James Watson: How we discovered DNA

286,291 views ・ 2007-05-16

TED


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翻译人员: Zachary Lin Zhao 校对人员: Tony Yet
00:25
Well, I thought there would be a podium, so I'm a bit scared.
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我本来以为那里会有一个讲台的,现在我有点害怕了。
00:28
(Laughter)
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(笑声)
00:31
Chris asked me to tell again how we found the structure of DNA.
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克里斯让我再讲一次我们是怎么破解DNA的结构的。
00:34
And since, you know, I follow his orders, I'll do it.
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我一向都是听从他的指令,这一次自然也不例外。
00:37
But it slightly bores me.
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但说实话,我是觉得挺无聊的。
00:39
(Laughter)
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(笑声)
00:41
And, you know, I wrote a book. So I'll say something --
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我写了一整本书,所以我不得不说点什么——
00:46
(Laughter)
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(笑声)
00:48
-- I'll say a little about, you know, how the discovery was made,
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——我打算讲一讲我和弗朗西斯是怎么发现DNA的结构的,
00:51
and why Francis and I found it.
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以及我们搞这项研究的原因所在。
00:53
And then, I hope maybe I have at least five minutes to say
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然后我希望能至少有五分钟的时间,
00:57
what makes me tick now.
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让我讨论一下我现在的动力所在。
01:01
In back of me is a picture of me when I was 17.
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我身后是一张我17岁时的照片。
01:06
I was at the University of Chicago, in my third year,
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我那时在芝加哥大学,读大三。
01:09
and I was in my third year because the University of Chicago
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我之所以能在17岁时就读大三,是因为芝加哥大学
01:15
let you in after two years of high school.
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在我读了两年高中之后就录取我了。
01:17
So you -- it was fun to get away from high school -- (Laughter) --
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摆脱高中对我来说是件好事,
01:23
because I was very small, and I was no good in sports,
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因为我长得很矮小,又不擅长体育,
01:26
or anything like that.
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也没其他的特长。
01:27
But I should say that my background -- my father was, you know,
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但我得提一下我的生长背景——我的父亲从小到大
01:33
raised to be an Episcopalian and Republican,
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都是一名圣公会教徒,是一名共和党员。
01:35
but after one year of college, he became an atheist and a Democrat.
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结果才上了一年大学,他不仅不信神了,还变成了一名民主党员。
01:40
(Laughter)
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(笑声)
01:43
And my mother was Irish Catholic,
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我母亲是爱尔兰天主教徒,
01:45
and -- but she didn't take religion too seriously.
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但她从来没把宗教太当回儿事。
01:50
And by the age of 11, I was no longer going to Sunday Mass,
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所以11岁那年,我就不再去听星期天的弥撒了,
01:54
and going on birdwatching walks with my father.
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反而是跟我的父亲去到处观察鸟。
01:58
So early on, I heard of Charles Darwin.
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我很早就听说过达尔文,
02:02
I guess, you know, he was the big hero.
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我那时候猜他也算是个大英雄。
02:05
And, you know, you understand life as it now exists through evolution.
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你们也都知道现今的生命是通过漫长的演化而来的。
02:11
And at the University of Chicago I was a zoology major,
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而我当时在芝加哥大学又是主修动物学,
02:15
and thought I would end up, you know, if I was bright enough,
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所以我就想,要是我够聪明的话,
02:18
maybe getting a Ph.D. from Cornell in ornithology.
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搞不好最后能从康奈尔大学得到个鸟类学博士学位。
02:23
Then, in the Chicago paper, there was a review of a book
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恰巧当时在芝加哥的报纸上有一篇书评,
02:29
called "What is Life?" by the great physicist, Schrodinger.
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是介绍伟大的物理学家薛定谔写的一本叫做《何谓生命?》的书。
02:33
And that, of course, had been a question I wanted to know.
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当然了,那也是我一直都在探求的一个问题。
02:36
You know, Darwin explained life after it got started,
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达尔文是解释了生命的演变,没错,
02:39
but what was the essence of life?
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但生命的精髓到底是什么呢?
02:41
And Schrodinger said the essence was information
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薛定谔认为这精髓就是信息,
02:45
present in our chromosomes, and it had to be present
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是我们染色体里的信息,而且这些信息必须由一个分子来承载。
02:49
on a molecule. I'd never really thought of molecules before.
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我只前从来没怎么想过分子。
02:55
You know chromosomes, but this was a molecule,
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是,我听说过染色体,但我们现在是在说一个分子,
02:59
and somehow all the information was probably present
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而且所有的生命信息都很有可能以数码的形式
03:02
in some digital form. And there was the big question
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被写进这个分子中。啊,问题就来了,
03:06
of, how did you copy the information?
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你要怎么复制这些信息呢?
03:08
So that was the book. And so, from that moment on,
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那本书就是讨论这些问题。所以从那时起,
03:13
I wanted to be a geneticist --
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我就立志要成为一名遗传学家——
03:18
understand the gene and, through that, understand life.
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通过理解基因来理解生命。
03:20
So I had, you know, a hero at a distance.
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我当时也有了自己仰慕的英雄。
03:25
It wasn't a baseball player; it was Linus Pauling.
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不是什么棒球英豪,而是鲍林。
03:27
And so I applied to Caltech and they turned me down.
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所以我就申请进入加州理工学院,没想到他们竟然没要我。
03:33
(Laughter)
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(笑声)
03:35
So I went to Indiana,
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没办法,我只好去印第安纳大学。
03:36
which was actually as good as Caltech in genetics,
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其实那里的基因专业和加州工学院没什么差别。
03:39
and besides, they had a really good basketball team. (Laughter)
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再说了,印第安纳的篮球队可是相当不错。
03:43
So I had a really quite happy life at Indiana.
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所以我在那里的生活也算得上是快乐。
03:46
And it was at Indiana I got the impression
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而且正是在印第安纳的时候,我开始觉得
03:49
that, you know, the gene was likely to be DNA.
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我们的DNA很有可能就是我们的基因。
03:51
And so when I got my Ph.D., I should go and search for DNA.
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等到我拿到我的博士学位后,我就可以去研究DNA了。
03:55
So I first went to Copenhagen because I thought, well,
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哥本哈根成了我的第一站,因为我觉得
04:01
maybe I could become a biochemist,
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也许我可以成为一个生物化学家。
04:02
but I discovered biochemistry was very boring.
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但后来我才发现生物化学真的是相当无聊。
04:05
It wasn't going anywhere toward, you know, saying what the gene was;
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它跟基因的本质完全没什么关联,
04:09
it was just nuclear science. And oh, that's the book, little book.
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只是一味地探讨核科学。哦,这就是我之前提到的那本书,
04:13
You can read it in about two hours.
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不长,两个小时就可以读完。
04:15
And -- but then I went to a meeting in Italy.
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但我之后在意大利参加一个会议的时候,
04:19
And there was an unexpected speaker who wasn't on the program,
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遇到了一个原本不在节目单上的演讲者,
04:24
and he talked about DNA.
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而他演讲的主题恰恰是DNA。
04:26
And this was Maurice Wilkins. He was trained as a physicist,
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这是莫里斯·威尔金斯,物理学家出身。
04:29
and after the war he wanted to do biophysics, and he picked DNA
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二战后他决定从事生物物理学,而DNA正是他的研究对象,
04:33
because DNA had been determined at the Rockefeller Institute
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因为当时洛克菲勒研究所已经证实
04:36
to possibly be the genetic molecules on the chromosomes.
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染色体上的基因分子很有可能就是DNA。
04:40
Most people believed it was proteins.
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但很多人却觉得应该是蛋白质。
04:41
But Wilkins, you know, thought DNA was the best bet,
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不过威尔金斯还是认为DNA才是最有可能的遗传物质,
04:45
and he showed this x-ray photograph.
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并且展示了这张X光照片。
04:49
Sort of crystalline. So DNA had a structure,
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有点像个结晶体。所以DNA是有这样的一个结构,
04:53
even though it owed it to probably different molecules
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尽管说不同的分子
04:56
carrying different sets of instructions.
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很可能肩负着不同的职责。
04:58
So there was something universal about the DNA molecule.
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但至少所有DNA分子的结构都是一致的。
05:00
So I wanted to work with him, but he didn't want a former birdwatcher,
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所以我当时就很想跟他合作,但他并不需要一个鸟类观察家。
05:05
and I ended up in Cambridge, England.
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没办法,我只好去英国剑桥。
05:06
So I went to Cambridge,
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我之所以会去剑桥,
05:08
because it was really the best place in the world then
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是因为那里才是研究射线晶体学的最好地方。
05:11
for x-ray crystallography. And x-ray crystallography is now a subject
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现在的射线晶体学,
05:15
in, you know, chemistry departments.
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通常是化学系的研究对象。
05:17
I mean, in those days it was the domain of the physicists.
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不过在当时,那可是物理学家的天下。
05:20
So the best place for x-ray crystallography
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所以研究射线晶体学最好的地方
05:24
was at the Cavendish Laboratory at Cambridge.
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就是剑桥的卡文迪许实验室。
05:27
And there I met Francis Crick.
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而我就是在那里结识了弗朗西斯·克里克。
05:33
I went there without knowing him. He was 35. I was 23.
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当时我并不认识他。他那时候35岁,我23岁。
05:36
And within a day, we had decided that
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不过一天之内,我们就决定
05:41
maybe we could take a shortcut to finding the structure of DNA.
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也许我们可以通过一条捷径来破解DNA的结构。
05:46
Not solve it like, you know, in rigorous fashion, but build a model,
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并不是一步一步按部就班地来破解,而是直接构建一个结构模型。
05:52
an electro-model, using some coordinates of, you know,
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用X光照片里的那些长度坐标什么的
05:56
length, all that sort of stuff from x-ray photographs.
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来构建一个电子模型。
05:59
But just ask what the molecule -- how should it fold up?
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直接来思考这个分子应该怎么叠起来?
06:02
And the reason for doing so, at the center of this photograph,
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为什么这么叠?这个照片中间的那位
06:06
is Linus Pauling. About six months before, he proposed
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就是鲍林。大概六个月前,他已经提出了
06:09
the alpha helical structure for proteins. And in doing so,
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蛋白质的阿尔法螺旋结构。也正因此,
06:13
he banished the man out on the right,
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是彻底击垮了站在他右边的劳伦斯·布拉格爵士。
06:15
Sir Lawrence Bragg, who was the Cavendish professor.
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布拉格当时是卡文迪许的教授。
06:18
This is a photograph several years later,
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这张照片是几年后拍的,
06:20
when Bragg had cause to smile.
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布拉格只能是强颜欢笑。
06:22
He certainly wasn't smiling when I got there,
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我到那里的时候,他可是完全笑不出来。
06:24
because he was somewhat humiliated by Pauling getting the alpha helix,
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因为他觉得鲍林的阿尔法螺旋发现让他丢脸了,
06:28
and the Cambridge people failing because they weren't chemists.
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剑桥人的失败让他丢脸了,毕竟他们并不是化学家。
06:32
And certainly, neither Crick or I were chemists,
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当然了,我和克里克也不是什么化学家。
06:37
so we tried to build a model. And he knew, Francis knew Wilkins.
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所以我们才想要直接搭建模型。弗朗西斯那时候认识威尔金斯。
06:43
So Wilkins said he thought it was the helix.
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威尔金斯当时觉得DNA应该是个螺旋结构,
06:45
X-ray diagram, he thought was comparable with the helix.
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他觉得那个X光图片看上去像是个螺旋。
06:48
So we built a three-stranded model.
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所以我们就构建了个三股的螺旋结构。
06:50
The people from London came up.
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伦敦的那帮人就过来看,
06:52
Wilkins and this collaborator, or possible collaborator,
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威尔金斯和他的合作伙伴罗莎琳·富兰克林
06:57
Rosalind Franklin, came up and sort of laughed at our model.
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过来看过我们的模型后,对它有点嗤之以鼻。
07:00
They said it was lousy, and it was.
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他们觉得我们的模型相当烂。它确实是挺烂的。
07:02
So we were told to build no more models; we were incompetent.
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他们告诉我们不要再造模型了,我们没这个能力。
07:07
(Laughter)
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(笑声)
07:11
And so we didn't build any models,
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于是乎,我们就不再造模型了。
07:13
and Francis sort of continued to work on proteins.
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弗朗西斯继续研究他的蛋白质。
07:16
And basically, I did nothing. And -- except read.
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我则是除了读书以外,什么都没干。
07:22
You know, basically, reading is a good thing; you get facts.
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要知道读书总是件好事,你可以增长知识。
07:25
And we kept telling the people in London
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我们当时就一直告诉伦敦的那些人
07:28
that Linus Pauling's going to move on to DNA.
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鲍林要着手研究DNA了。
07:30
If DNA is that important, Linus will know it.
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如果DNA真的那么重要,鲍林肯定是知道的呀。
07:32
He'll build a model, and then we're going to be scooped.
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他肯定会构造一个模型,到时候我们就都算是落伍了。
07:34
And, in fact, he'd written the people in London:
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事实上,他的确是给伦敦的人写了封信:
07:36
Could he see their x-ray photograph?
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他想看看他们的X光照片。
07:39
And they had the wisdom to say "no." So he didn't have it.
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还好伦敦的那帮人算是聪明,拒绝了他。他也因此没看到那张照片。
07:42
But there was ones in the literature.
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不过当时各种文献中都有那张照片,
07:44
Actually, Linus didn't look at them that carefully.
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只不过鲍林没有看得那么仔细。
07:46
But about, oh, 15 months after I got to Cambridge,
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可是当我到达剑桥15个月后,
07:52
a rumor began to appear from Linus Pauling's son,
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鲍林在剑桥的儿子开始散播传闻,
07:55
who was in Cambridge, that his father was now working on DNA.
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说他的爸爸正在研究DNA。
07:59
And so, one day Peter came in and he said he was Peter Pauling,
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结果有一天彼得找到我,他说他是彼得·鲍林,
08:03
and he gave me a copy of his father's manuscripts.
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然后他就把他老爸的手稿递给了我。
08:05
And boy, I was scared because I thought, you know, we may be scooped.
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我当时就吓傻了,我以为他比我们抢先一步。
08:11
I have nothing to do, no qualifications for anything.
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我没有文凭,一无是处的。这下子可完了。
08:14
(Laughter)
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(笑声)
08:16
And so there was the paper, and he proposed a three-stranded structure.
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这就是那篇论文,他在里面提出了一个三股的结构,
08:22
And I read it, and it was just -- it was crap.
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我读完了之后就觉得他根本是在胡言乱语。
08:24
(Laughter)
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(笑声)
08:29
So this was, you know, unexpected from the world's --
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这对于他这位世界级的人物来说,的确是有失水准。
08:32
(Laughter)
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(笑声)
08:34
-- and so, it was held together by hydrogen bonds
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他认为DNA是通过磷酸团之间的氢键
08:37
between phosphate groups.
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来支撑起来的。
08:39
Well, if the peak pH that cells have is around seven,
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可是,如果细胞中的pH峰值大概是在7左右的话,
08:43
those hydrogen bonds couldn't exist.
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那些氢键根本就无法存在嘛。
08:46
We rushed over to the chemistry department and said,
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我们是直奔化学系,去问那里的人:“鲍林有可能是正确的吗?”
08:48
"Could Pauling be right?" And Alex Hust said, "No." So we were happy.
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亚历克斯回答说:“没可能。”我们这下可是乐坏了。
08:54
(Laughter)
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(笑声)
08:56
And, you know, we were still in the game, but we were frightened
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我们还是有机会的,不过我们也是有点担心
08:59
that somebody at Caltech would tell Linus that he was wrong.
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担心加州工学院的那些人会告诉鲍林他搞错了。
09:03
And so Bragg said, "Build models."
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于是布拉格就说,“我们得造模型。”
09:05
And a month after we got the Pauling manuscript --
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在我们收到鲍林手稿的一个月后——
09:09
I should say I took the manuscript to London, and showed the people.
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确切地说,是我把手稿带到了伦敦,给那里的人看过。
09:14
Well, I said, Linus was wrong and that we're still in the game
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我当时就说鲍林是错的,我们还有机会。
09:17
and that they should immediately start building models.
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我还告诉他们应该马上开始构造模型。
09:19
But Wilkins said "no." Rosalind Franklin was leaving in about two months,
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但威尔克斯却把我给否决了。他说罗莎琳两个月之后就要离开了,
09:24
and after she left he would start building models.
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等她走了,他就开始造模型。
09:27
And so I came back with that news to Cambridge,
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没办法,我只能把消息如实地传达给剑桥,
09:31
and Bragg said, "Build models."
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当时布拉格就说,“造——模——型。”
09:32
Well, of course, I wanted to build models.
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当然了,我是一直都想要构造模型的。
09:33
And there's a picture of Rosalind. She really, you know,
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这就是罗莎琳的照片。她其实,怎么说呢,
09:39
in one sense she was a chemist,
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从某个意义上讲,算是个化学家。
09:41
but really she would have been trained --
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但她从没有接受过专业的训练。
09:43
she didn't know any organic chemistry or quantum chemistry.
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有机化学、量子化学她都是一窍不通。
09:46
She was a crystallographer.
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她其实是一个结晶学家。
09:47
And I think part of the reason she didn't want to build models
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而我觉得她不想建造模型的一部分原因
09:52
was, she wasn't a chemist, whereas Pauling was a chemist.
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就是因为她不是化学家,而鲍林则是位十足的化学家。
09:55
And so Crick and I, you know, started building models,
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于是克里克和我就开始构造模型。
10:00
and I'd learned a little chemistry, but not enough.
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我学过一丁点的化学,但不够用。
10:03
Well, we got the answer on the 28th February '53.
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不管怎样,我们在1953年的2月28日终于破解了DNA的谜团。
10:07
And it was because of a rule, which, to me, is a very good rule:
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这一切都是因为我始终坚信的一条法则:
10:11
Never be the brightest person in a room, and we weren't.
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永远别做最聪明的人。我们也的确不是。
10:17
We weren't the best chemists in the room.
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我们不是那里最优秀的化学家。
10:19
I went in and showed them a pairing I'd done,
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我有一次把我刚刚做好的分子配对图给那些化学家们看,
10:21
and Jerry Donohue -- he was a chemist -- he said, it's wrong.
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唐诺休——他是名化学家——看了之后就说:“你画错了。
10:25
You've got -- the hydrogen atoms are in the wrong place.
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你把氢原子放错地方了。”
10:28
I just put them down like they were in the books.
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我其实就是按照书里面画的。
10:31
He said they were wrong.
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但他说我画错了。
10:32
So the next day, you know, after I thought, "Well, he might be right."
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于是第二天,我想了想,“搞不好他是对的。”
10:36
So I changed the locations, and then we found the base pairing,
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所以我就更改了那些氢原子的位置。之后我们就发现了碱基之间的搭配组合。
10:40
and Francis immediately said the chains run in absolute directions.
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而弗朗西斯也立即意识到这双螺旋中的链条是以绝对方向延伸的。
10:43
And we knew we were right.
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我们当时就知道我们肯定是对的。
10:45
So it was a pretty, you know, it all happened in about two hours.
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而这一切就发生在两个小时间。
10:52
From nothing to thing.
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从无到有。
10:56
And we knew it was big because, you know, if you just put A next to T
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我们也知道这是个重大的发现,因为如果你把A碱基和T碱基放在一起,
11:01
and G next to C, you have a copying mechanism.
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G和C放在一起,你就可以实现DNA的复制了。
11:04
So we saw how genetic information is carried.
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我们总算弄明白了所谓的基因信息
11:08
It's the order of the four bases.
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是由这4个碱基的排列顺序决定的。
11:09
So in a sense, it is a sort of digital-type information.
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所以说,这也算得上是一种数码信息。
11:13
And you copy it by going from strand-separating.
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把这螺旋中的两股分开,就可以开始复制了。
11:18
So, you know, if it didn't work this way, you might as well believe it,
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就算它不是这么回事,我们也只能相信它是这么回事,
11:26
because you didn't have any other scheme.
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因为你也没有什么其他的选择。
11:27
(Laughter)
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(笑声)
11:30
But that's not the way most scientists think.
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但大多数的科学家都不是这么看待事物的。
11:33
Most scientists are really rather dull.
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大多数的科学家都是相当木讷的。
11:36
They said, we won't think about it until we know it's right.
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他们认为,除非这已经被证实是对的,他们是绝对不会考虑它的。
11:38
But, you know, we thought, well, it's at least 95 percent right or 99 percent right.
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但我们知道我们的理论至少是百分之九十五、九十九正确的。
11:44
So think about it. The next five years,
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所以还是考虑一下吧。在随后的五年里,
11:48
there were essentially something like five references
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我们的理论在《自然》杂志中
11:50
to our work in "Nature" -- none.
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只被提到了五次。
11:53
And so we were left by ourselves,
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没办法,我们只能靠自己了。
11:55
and trying to do the last part of the trio: how do you --
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而我们也只剩下一个待解决的问题——
12:00
what does this genetic information do?
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这些基因信息到底是用来做什么的呢?
12:04
It was pretty obvious that it provided the information
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很明显,它为RNA分子提供信息,
12:08
to an RNA molecule, and then how do you go from RNA to protein?
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但这信息又是怎样从RNA传达到蛋白质的呢?
12:11
For about three years we just -- I tried to solve the structure of RNA.
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我用了大概三年的时间,希望能破解RNA的结构,
12:16
It didn't yield. It didn't give good x-ray photographs.
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但却是一无所获。RNA的X光照片毫无价值。
12:19
I was decidedly unhappy; a girl didn't marry me.
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我是相当得不开心。我爱的女人又不想嫁给我。
12:22
It was really, you know, sort of a shitty time.
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我算是走狗屎运了。
12:25
(Laughter)
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(笑声)
12:28
So there's a picture of Francis and I before I met the girl,
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这是我和弗朗西斯的一张照片,是在我遇到那个女人之前拍的,
12:32
so I'm still looking happy.
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我那时看上去还挺开心的。
12:33
(Laughter)
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(笑声)
12:36
But there is what we did when we didn't know
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当我们不知所措的时候,我们所能做的
12:39
where to go forward: we formed a club and called it the RNA Tie Club.
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也只有成立个小团体,叫做“RNA领带团”。
12:45
George Gamow, also a great physicist, he designed the tie.
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伟大的物理学家乔治·伽莫夫负责设计领带。
12:49
He was one of the members. The question was:
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他也是我们的团员之一。我们探讨的问题是:
12:52
How do you go from a four-letter code
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由四个字母组成的DNA密码
12:54
to the 20-letter code of proteins?
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是怎么转变成由20个字母组成的蛋白质的呢?
12:56
Feynman was a member, and Teller, and friends of Gamow.
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费曼和伽莫夫的朋友泰勒当时都是团员。
13:01
But that's the only -- no, we were only photographed twice.
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我们在一起只拍过一次,不不,是两次照片。
13:07
And on both occasions, you know, one of us was missing the tie.
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每次都会有个人忘记带我们的团队领带。
13:10
There's Francis up on the upper right,
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右上角的是弗朗西斯。
13:13
and Alex Rich -- the M.D.-turned-crystallographer -- is next to me.
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阿里克斯·里奇就坐在我旁边。他之前是医学博士,不过后来变成结晶学家。
13:18
This was taken in Cambridge in September of 1955.
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这张照片是在1955年的九月在剑桥拍的。
13:22
And I'm smiling, sort of forced, I think,
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我当时有在笑,不过是被强迫的,
13:28
because the girl I had, boy, she was gone.
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因为我爱的那个女人,离我远去了。
13:31
(Laughter)
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(笑声)
13:35
And so I didn't really get happy until 1960,
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我直到1960年才变得真正开心起来
13:40
because then we found out, basically, you know,
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因为那一年我们发现了
13:44
that there are three forms of RNA.
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RNA的三种形式。
13:46
And we knew, basically, DNA provides the information for RNA.
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我们也基本上是明白了DNA把信息传给RNA,
13:49
RNA provides the information for protein.
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RNA再把信息传给蛋白质。
13:51
And that let Marshall Nirenberg, you know, take RNA -- synthetic RNA --
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马歇尔·尼伦伯格也因此可以把人造RNA
13:56
put it in a system making protein. He made polyphenylalanine,
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放进培养系统里制造蛋白质出来。他当时合成的是
14:02
polyphenylalanine. So that's the first cracking of the genetic code,
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多聚苯基丙氨酸。那也算是基因密码破解的第一步,
14:10
and it was all over by 1966.
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而到了1966年,一切的密码就都已经被破解了。
14:12
So there, that's what Chris wanted me to do, it was --
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好了,克里斯让我讲的我都讲完了。
14:15
so what happened since then?
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那之后又发生了什么呢?
14:19
Well, at that time -- I should go back.
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我得回过头来讲一下我们刚发现DNA的时候。
14:22
When we found the structure of DNA, I gave my first talk
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当时我的第一个讲座是在冷泉港实验室。
14:27
at Cold Spring Harbor. The physicist, Leo Szilard,
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那里的物理学家列奥·圣拉多就问我:
14:30
he looked at me and said, "Are you going to patent this?"
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“你打算申请专利吗?”
14:33
And -- but he knew patent law, and that we couldn't patent it,
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他其实是懂专利法的,他也知道我们申请不到什么专利,
14:38
because you couldn't. No use for it.
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因为我们的发现根本就没什么大用处。
14:40
(Laughter)
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(笑声)
14:42
And so DNA didn't become a useful molecule,
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于是DNA并没有变成什么有用的分子,
14:46
and the lawyers didn't enter into the equation until 1973,
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律师也是跟我们毫无关联。直到20年后的1973年,
14:51
20 years later, when Boyer and Cohen in San Francisco
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当旧金山和斯坦福的保耶和科亨
14:56
and Stanford came up with their method of recombinant DNA,
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发明了DNA重组技术时,
14:58
and Stanford patented it and made a lot of money.
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斯坦福申请了专利,并且赚了一大笔钱。
15:01
At least they patented something
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至少他们申请的专利
15:02
which, you know, could do useful things.
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还算是有用处。
15:05
And then, they learned how to read the letters for the code.
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之后,他们发现了怎么看懂DNA的编码,
15:08
And, boom, we've, you know, had a biotech industry. And,
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整个生物工程产业也是随之拔地而起。
15:13
but we were still a long ways from, you know,
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但我童年的一个问题
15:20
answering a question which sort of dominated my childhood,
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却一直没有得到解决:
15:22
which is: How do you nature-nurture?
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先天与后天如何合二为一?
15:27
And so I'll go on. I'm already out of time,
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我会接着讲下去,虽然说我已经超时了。
15:31
but this is Michael Wigler, a very, very clever mathematician
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这是迈克尔·威革勒,一个非常非常聪明的数学家。
15:34
turned physicist. And he developed a technique
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后来变成了一名物理学家。他发明了一项技术
15:37
which essentially will let us look at sample DNA
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让我们可以观察DNA样本
15:41
and, eventually, a million spots along it.
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和沿着它的上万个点。
15:43
There's a chip there, a conventional one. Then there's one
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这是一个传统的芯片。而旁边的那个
15:46
made by a photolithography by a company in Madison
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则是麦迪逊一家叫做罗氏的公司利用光刻法制造出来的,
15:49
called NimbleGen, which is way ahead of Affymetrix.
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要比昂飞公司的好得多。
15:54
And we use their technique.
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所以我们使用他们的技术。
15:56
And what you can do is sort of compare DNA of normal segs versus cancer.
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你所能做的基本上就是比较DNA的分子次序。
16:01
And you can see on the top
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这是癌症的DNA。你在上方可以看到
16:05
that cancers which are bad show insertions or deletions.
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这些癌症DNA不是多一块就是少一块,
16:10
So the DNA is really badly mucked up,
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是相当杂乱的。
16:13
whereas if you have a chance of surviving,
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但如果你有幸存的机会的话,
16:15
the DNA isn't so mucked up.
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你的DNA就不会这么杂乱。
16:17
So we think that this will eventually lead to what we call
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我们觉得这最终会引领我们走上“DNA活体检测”的道路。
16:20
"DNA biopsies." Before you get treated for cancer,
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在你治疗癌症前,
16:24
you should really look at this technique,
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真的应该好好看看这项技术。
16:26
and get a feeling of the face of the enemy.
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至少让你知道你所面对的是什么,
16:29
It's not a -- it's only a partial look, but it's a --
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哪怕只是知道一点点也好。
16:32
I think it's going to be very, very useful.
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我觉得这将会是非常非常有用的。
16:35
So, we started with breast cancer
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于是我们就从乳腺癌下手,
16:37
because there's lots of money for it, no government money.
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因为利润丰厚,不需要政府的钱。
16:40
And now I have a sort of vested interest:
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现在我对此有很大的兴趣,
16:44
I want to do it for prostate cancer. So, you know,
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我想研究前列腺癌。因为如果不严重的话,
16:46
you aren't treated if it's not dangerous.
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你就没有必要接受治疗。
16:49
But Wigler, besides looking at cancer cells, looked at normal cells,
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但威革勒不仅仅是研究了癌细胞,他也研究了正常的细胞,
16:55
and made a really sort of surprising observation.
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并且有了惊人的发现。
16:58
Which is, all of us have about 10 places in our genome
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那就是,我们所有人的基因组中都有大概10个地方
17:02
where we've lost a gene or gained another one.
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要么多了个基因,要么少了个基因。
17:05
So we're sort of all imperfect. And the question is well,
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所以说,我们都是不完美的。
17:11
if we're around here, you know,
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不过既然我们都活得好好的,
17:13
these little losses or gains might not be too bad.
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就证明这些多多少少其实没什么大不了的。
17:16
But if these deletions or amplifications occurred in the wrong gene,
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但如果这一切是发生在错误的基因上,
17:21
maybe we'll feel sick.
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我们就有可能因此而生病。
17:22
So the first disease he looked at is autism.
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所以他首先研究的就是自闭症。
17:26
And the reason we looked at autism is we had the money to do it.
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原因在于我们有足够的资金来研究自闭症。
17:31
Looking at an individual is about 3,000 dollars. And the parent of a child
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看一位病人大概需要3千美元。
17:36
with Asperger's disease, the high-intelligence autism,
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有个艾斯伯格症候群(高智商自闭症)孩子的家长
17:38
had sent his thing to a conventional company; they didn't do it.
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把他孩子的基因送到一个传统的公司,但他们什么也做不了。
17:43
Couldn't do it by conventional genetics, but just scanning it
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传统的基因科技做不了什么。但我们通过简单的扫描,
17:46
we began to find genes for autism.
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就可以找到自闭症的基因。
17:49
And you can see here, there are a lot of them.
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不难看到,这些基因有很多个。
17:53
So a lot of autistic kids are autistic
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所以很多有自闭症的孩子之所以会有自闭症,
17:57
because they just lost a big piece of DNA.
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是因为他们遗失了一大块的DNA。
17:59
I mean, big piece at the molecular level.
305
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当然了,我是指分子层面上的一大块。
18:01
We saw one autistic kid,
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我们曾经看过一个自闭症患儿,
18:03
about five million bases just missing from one of his chromosomes.
307
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在他的一条染色体上就缺少了5百万个碱基。
18:06
We haven't yet looked at the parents, but the parents probably
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我们还没检查他的父母,不过他的父母很有可能
18:09
don't have that loss, or they wouldn't be parents.
309
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并不缺少这些碱基,不然的话他们也不可能成为父母。
18:12
Now, so, our autism study is just beginning. We got three million dollars.
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自闭症的研究才刚刚开始。我们有3百万美元研究经费,
18:19
I think it will cost at least 10 to 20 before you'd be in a position
311
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但我觉得我们至少需要1千到2千万美元,才能真正帮助那些
18:23
to help parents who've had an autistic child,
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有自闭症子女的父母,
18:26
or think they may have an autistic child,
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或者是那些认为自己有自闭症子女的父母。
18:28
and can we spot the difference?
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我们能把他们区别开来吗?
18:30
So this same technique should probably look at all.
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这项技术也许应该大范围地推广,
18:33
It's a wonderful way to find genes.
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因为它是寻找基因很有效的方法。
18:37
And so, I'll conclude by saying
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我最后想说的是,
18:39
we've looked at 20 people with schizophrenia.
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我们已经研究了20位精神分裂症患者,
18:41
And we thought we'd probably have to look at several hundred
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我们可能还需要再研究几百个
18:45
before we got the picture. But as you can see,
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才能有所收获。不过你在这里可以看到,
18:47
there's seven out of 20 had a change which was very high.
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这20名患者中有7名的基因都有变动。这可是相当高的比例。
18:51
And yet, in the controls there were three.
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不过我们的对照组中,也有三个人的基因有变动,
18:54
So what's the meaning of the controls?
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即如此,我们对照组的意义又何在呢?
18:56
Were they crazy also, and we didn't know it?
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难不成他们的精神也有问题,只不过我们不知道罢了?
18:58
Or, you know, were they normal? I would guess they're normal.
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还是说他们是正常人?我猜他们是正常的。
19:02
And what we think in schizophrenia is there are genes of predisposure,
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我们现在所知的是精神分裂患者是有易患基因的,
19:09
and whether this is one that predisposes --
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我们也能区分某个基因是否是罪魁祸首。
19:15
and then there's only a sub-segment of the population
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而只有一小部分的人群,
19:19
that's capable of being schizophrenic.
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是可以患上精神分裂的。
19:21
Now, we don't have really any evidence of it,
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我们现在还没有确凿的证据,
19:25
but I think, to give you a hypothesis, the best guess
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不过我的猜想是,
19:30
is that if you're left-handed, you're prone to schizophrenia.
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如果你是个左撇子,你就有可能会患上精神分裂症。
19:36
30 percent of schizophrenic people are left-handed,
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百分之三十的精神分裂症患者都是左撇子,
19:39
and schizophrenia has a very funny genetics,
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而精神分裂症的基因又是很滑稽的,
19:42
which means 60 percent of the people are genetically left-handed,
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这就意味着百分之六十的患者是有左撇子基因的,
19:46
but only half of it showed. I don't have the time to say.
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不过他们中只有一半成为了左撇子。我没有时间来具体地解释。
19:49
Now, some people who think they're right-handed
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总之,有些人觉得他们是右撇子,
19:52
are genetically left-handed. OK. I'm just saying that, if you think,
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但他们却有着左撇子基因。所以说,你要是觉得
19:58
oh, I don't carry a left-handed gene so therefore my, you know,
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你没有左撇子基因,因此你的孩子不会患上精神分裂症。
20:02
children won't be at risk of schizophrenia. You might. OK?
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我只想说:一切皆有可能。
20:05
(Laughter)
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(笑声)
20:08
So it's, to me, an extraordinarily exciting time.
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对我来说,现在真的是个非常激动人心的时代。
20:11
We ought to be able to find the gene for bipolar;
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我们应该可以找到躁郁症的基因。
20:13
there's a relationship.
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这其中是有关联的。
20:14
And if I had enough money, we'd find them all this year.
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如果我有足够的钱的话,我能在一年之内把它们都给找出来。
20:18
I thank you.
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谢谢大家。
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