James Watson: How we discovered DNA

譯者: Zachary Lin Zhao 審譯者: Bill Hsiung

Well, I thought there would be a podium, so I'm a bit scared.

我本來以為那裡會有一個講臺的，所以現在我有點害怕了。

(Laughter)

（笑聲）

Chris asked me to tell again how we found the structure of DNA.

克里斯邀請我再講一次我們破解 DNA 結構的經過。

And since, you know, I follow his orders, I'll do it.

因為我遵照他的指示，所以我就來了。

But it slightly bores me.

但這令我感到有些無趣。

(Laughter)

（笑聲）

And, you know, I wrote a book. So I'll say something --

你知道的，我已經寫了一本關於這個發現的書。所以我將說說...

(Laughter)

（笑聲）

-- I'll say a little about, you know, how the discovery was made,

我將簡單提一下那次發現的經過，

and why Francis and I found it.

以及令法蘭西斯與我做出這項發現的原因。

And then, I hope maybe I have at least five minutes to say

然後我希望至少能有五分鐘的剩餘時間，

what makes me tick now.

讓我談談我現在的興趣所在。

In back of me is a picture of me when I was 17.

我身後是一張我 17 歲時的照片。

I was at the University of Chicago, in my third year,

我那時在芝加哥大學，讀大三。

and I was in my third year because the University of Chicago

我之所以能在 17 歲時就讀大三，是因為芝加哥大學

let you in after two years of high school.

在我讀了兩年高中之後就錄取我了。

So you -- it was fun to get away from high school -- (Laughter) --

擺脫高中生活對我來說樂趣無窮，

because I was very small, and I was no good in sports,

因為我長得很矮小，又不擅長體育，

or anything like that.

或任何跟體能有關的特長。

But I should say that my background -- my father was, you know,

但我得提一下我的生長背景：我的父親從小到大

raised to be an Episcopalian and Republican,

都是一名聖公會教徒和共和黨員。

but after one year of college, he became an atheist and a Democrat.

結果才上了一年大學，他變成了一名民主黨員與無神論者。

(Laughter)

（笑聲）

And my mother was Irish Catholic,

我母親是愛爾蘭天主教徒，

and -- but she didn't take religion too seriously.

但她沒把宗教看得很重。

And by the age of 11, I was no longer going to Sunday Mass,

所以 11 歲那年開始，我就不再去做禮拜了，

and going on birdwatching walks with my father.

反而是跟我的父親去到處賞鳥。

So early on, I heard of Charles Darwin.

因此我很早就聽說過達爾文，

I guess, you know, he was the big hero.

我想，他是我心中的大英雄。

And, you know, you understand life as it now exists through evolution.

你們也都知道現今的生命是通過漫長的演化而來的。

And at the University of Chicago I was a zoology major,

而我當時在芝加哥大學又是主修動物學，

and thought I would end up, you know, if I was bright enough,

所以我就想，要是我夠聰明的話，

maybe getting a Ph.D. from Cornell in ornithology.

搞不好最後能從康乃爾大學拿個鳥類學博士學位。

Then, in the Chicago paper, there was a review of a book

恰巧當時在芝加哥的報紙上有一篇書評，

called "What is Life?" by the great physicist, Schrodinger.

是由偉大的物理學家薛丁格寫的一本叫做《何謂生命？》的書。

And that, of course, had been a question I wanted to know.

當然了，那也是我一直都在探索的一個問題。

You know, Darwin explained life after it got started,

達爾文是解釋了生命的演變沒錯，

but what was the essence of life?

但生命的本質到底是什麼呢？

And Schrodinger said the essence was information

薛丁格認為這本質就是資訊，

present in our chromosomes, and it had to be present

我們染色體裡的資訊，而且這些資訊必須由分子來承載。

on a molecule. I'd never really thought of molecules before.

我之前從沒認真思考過分子的可能，

You know chromosomes, but this was a molecule,

大家都聽過染色體，但我們現在是在說一個分子，

and somehow all the information was probably present

而且不知怎地，所有資訊都可能以數位的形式

in some digital form. And there was the big question

儲存在這分子中。然後，問題就來了，

of, how did you copy the information?

你要怎麼複製這些資訊呢？

So that was the book. And so, from that moment on,

那本書就是討論這些問題。所以從那時起，

I wanted to be a geneticist --

我就立志要成為一名遺傳學家，

understand the gene and, through that, understand life.

通過了解基因來認識生命。

So I had, you know, a hero at a distance.

因此，我有了仰慕的偶像。

It wasn't a baseball player; it was Linus Pauling.

不是什麼棒球明星，而是化學家鮑林。

And so I applied to Caltech and they turned me down.

所以我就申請進入加州理工學院，然後被拒絕了。

(Laughter)

（笑聲）

So I went to Indiana,

因此我去了印第安納大學，

which was actually as good as Caltech in genetics,

其實那裡的遺傳學研究和加州理工學院一樣好，

and besides, they had a really good basketball team. (Laughter)

除此以外，他們有個非常棒的籃球隊。

So I had a really quite happy life at Indiana.

所以我在那裡的生活也非常愉快。

And it was at Indiana I got the impression

而且正是在印第安納的時候，我開始覺得

that, you know, the gene was likely to be DNA.

DNA 很有可能就是我們的基因。

And so when I got my Ph.D., I should go and search for DNA.

因此等我拿到博士學位後，我應該去研究 DNA。

So I first went to Copenhagen because I thought, well,

哥本哈根成了我的第一站，因為我覺得

maybe I could become a biochemist,

也許我可以成為一個生化學家。

but I discovered biochemistry was very boring.

但後來我發現生化真的是相當無趣。

It wasn't going anywhere toward, you know, saying what the gene was;

生化研究對於了解基因的本質完全無關，

it was just nuclear science. And oh, that's the book, little book.

它就好像是另一種原子科學。哦，原子科學就是我之前提到的那本書，

You can read it in about two hours.

不長，兩個小時就可以讀完。

And -- but then I went to a meeting in Italy.

但我之後在義大利參加一個會議的時候，

And there was an unexpected speaker who wasn't on the program,

遇到了一個原本不在節目單上的講者，

and he talked about DNA.

他演講的主題恰好是 DNA。

And this was Maurice Wilkins. He was trained as a physicist,

那是莫里斯‧威爾金斯，物理學家出身。

and after the war he wanted to do biophysics, and he picked DNA

二戰後他決定從事生物物理研究，而 DNA 正是他的研究對象，

because DNA had been determined at the Rockefeller Institute

因為當時洛克菲勒研究所已經發現

to possibly be the genetic molecules on the chromosomes.

染色體上的遺傳物質很有可能就是 DNA，

Most people believed it was proteins.

但多數人認為應該是蛋白質。

But Wilkins, you know, thought DNA was the best bet,

不過威爾金斯還是認為 DNA 才最有可能是遺傳物質，

and he showed this x-ray photograph.

並且展示了這張 X 光照片。

Sort of crystalline. So DNA had a structure,

有點像個結晶體。所以DNA是有這樣的一個結構，

even though it owed it to probably different molecules

儘管說不同的分子

carrying different sets of instructions.

攜帶著不同的指令，

So there was something universal about the DNA molecule.

但這些 DNA 分子具有某種一致性。

So I wanted to work with him, but he didn't want a former birdwatcher,

所以我當時就想跟他合作，但他並不需要一個退休鳥類觀察家。

and I ended up in Cambridge, England.

所以我到了英國劍橋。

So I went to Cambridge,

我之所以會去劍橋，

because it was really the best place in the world then

是因為那裡是當時研究射線晶體學的最好地方。

for x-ray crystallography. And x-ray crystallography is now a subject

現在的射線晶體學，

in, you know, chemistry departments.

通常是化學系中的一個研究主題。

I mean, in those days it was the domain of the physicists.

不過在當時，那可是物理學家的天下。

So the best place for x-ray crystallography

所以研究射線晶體學最好的地方

was at the Cavendish Laboratory at Cambridge.

是劍橋的卡文迪許實驗室。

And there I met Francis Crick.

而我就是在那遇見了法蘭西斯‧克立克。

I went there without knowing him. He was 35. I was 23.

當時我並不認識他。他當年 35 歲，我 23 歲。

And within a day, we had decided that

不過一天之內，我們就決定

maybe we could take a shortcut to finding the structure of DNA.

也許我們可以通過一條捷徑來破解 DNA 的結構。

Not solve it like, you know, in rigorous fashion, but build a model,

並不是以一般嚴謹死板的方法來解答這個問題，而是直接建造一個結構模型。

an electro-model, using some coordinates of, you know,

用X光照片裡的那些長度坐標什麼的

length, all that sort of stuff from x-ray photographs.

來建造電子模型。

But just ask what the molecule -- how should it fold up?

直接思考這個分子應該怎麼折疊？

And the reason for doing so, at the center of this photograph,

為什麼我們會想走捷徑？這個照片中間的那位

is Linus Pauling. About six months before, he proposed

就是鮑林。大概六個月前，他已經提出了

the alpha helical structure for proteins. And in doing so,

蛋白質的阿爾法螺旋結構。也正因此，

he banished the man out on the right,

他徹底擊垮了站在他右邊的勞倫斯‧布拉格爵士。

Sir Lawrence Bragg, who was the Cavendish professor.

布拉格當時是卡文迪許實驗室的教授。

This is a photograph several years later,

這張照片是幾年後拍的，

when Bragg had cause to smile.

布拉格只是強顏歡笑。

He certainly wasn't smiling when I got there,

我剛到那裡的時候，他可是完全笑不出來。

because he was somewhat humiliated by Pauling getting the alpha helix,

因為他覺得讓鮑林搶先發表阿爾法螺旋結構讓他丟臉了，

and the Cambridge people failing because they weren't chemists.

劍橋人輸在他們並不是化學家。

And certainly, neither Crick or I were chemists,

當然了，我和克立克也不是化學家。

so we tried to build a model. And he knew, Francis knew Wilkins.

所以我們才想要直接搭建模型。而布拉格知道法蘭西斯與威爾金斯是舊識。

So Wilkins said he thought it was the helix.

威爾金斯當時覺得 DNA 應該是個螺旋結構，

X-ray diagram, he thought was comparable with the helix.

他覺得那個 X 光圖片看上去像是個螺旋。

So we built a three-stranded model.

所以我們建了個三股螺旋結構。

The people from London came up.

倫敦的那幫人就過來看，

Wilkins and this collaborator, or possible collaborator,

威爾金斯和他（可能）的合作夥伴羅莎琳‧富蘭克林，

Rosalind Franklin, came up and sort of laughed at our model.

過來看過我們的模型後，對它有點嗤之以鼻。

They said it was lousy, and it was.

他們覺得我們的模型爛透了，我也承認。

So we were told to build no more models; we were incompetent.

他們告訴我們不要再造模型了，我們沒這個能力。

(Laughter)

（笑聲）

And so we didn't build any models,

於是乎，我們就不再造模型了。

and Francis sort of continued to work on proteins.

法蘭西斯重拾蛋白質的研究。

And basically, I did nothing. And -- except read.

我則是除了讀書以外，什麼都沒做。

You know, basically, reading is a good thing; you get facts.

要知道讀書是件好事，你可以增長知識。

And we kept telling the people in London

我們當時就一直告訴倫敦的那些人，

that Linus Pauling's going to move on to DNA.

鮑林要著手研究 DNA 了。

If DNA is that important, Linus will know it.

如果 DNA 真的那麼重要的話，鮑林會發現什麼的。

He'll build a model, and then we're going to be scooped.

他肯定會建造一個模型，到時候我們一定會輸的。

And, in fact, he'd written the people in London:

事實上，他的確是給倫敦的人寫了封信，

Could he see their x-ray photograph?

他想看看他們的 X 光照片。

And they had the wisdom to say "no." So he didn't have it.

還好他們有拒絕的智慧。因此他沒看到那張照片。

But there was ones in the literature.

不過當時各種文獻中都有類似的照片，

Actually, Linus didn't look at them that carefully.

事實上鮑林也沒有仔細地去研究那些照片。

But about, oh, 15 months after I got to Cambridge,

可是在我到了劍橋 15 個月後，

a rumor began to appear from Linus Pauling's son,

鮑林在劍橋的兒子開始散播傳聞，

who was in Cambridge, that his father was now working on DNA.

說他的爸爸正在研究 DNA。

And so, one day Peter came in and he said he was Peter Pauling,

結果有一天彼得找到我，他說他是彼得‧鮑林，

and he gave me a copy of his father's manuscripts.

然後他就給了我一份他老爸論文初稿的副本。

And boy, I was scared because I thought, you know, we may be scooped.

我當時就嚇傻了，我以為他比我們搶先一步。

I have nothing to do, no qualifications for anything.

我沒有了目標，一無是處的。這下子可完了。

(Laughter)

（笑聲）

And so there was the paper, and he proposed a three-stranded structure.

這就是那篇論文，他在裡面提出了一個三股的結構，

And I read it, and it was just -- it was crap.

我讀完之後覺得這篇論文簡直就是垃圾。

(Laughter)

（笑聲）

So this was, you know, unexpected from the world's --

對於他這位世界知名的學者來說，有失水準。

(Laughter)

（笑聲）

-- and so, it was held together by hydrogen bonds

他認為 DNA 是通過磷酸基之間的氫鍵

between phosphate groups.

所組合起來的。

Well, if the peak pH that cells have is around seven,

可是，如果細胞中的 pH 值大概是在 7 左右的話，

those hydrogen bonds couldn't exist.

那些氫鍵根本就無法存在嘛。

We rushed over to the chemistry department and said,

我們直奔化學系，問那裡的人：「鮑林有可能是正確的嗎？」

"Could Pauling be right?" And Alex Hust said, "No." So we were happy.

亞歷克斯回答說：「沒可能！」我們這下可樂壞了。

(Laughter)

（笑聲）

And, you know, we were still in the game, but we were frightened

我們還是有機會的，不過我們也是有點擔心。

that somebody at Caltech would tell Linus that he was wrong.

擔心加州工學院的那些人會告訴鮑林他搞錯了。

And so Bragg said, "Build models."

於是布拉格就說：「我們得造模型。」

And a month after we got the Pauling manuscript --

在我們收到鮑林初稿的一個月後，

I should say I took the manuscript to London, and showed the people.

我該提一下，我把初稿帶到了倫敦，給那裡的人看過。

Well, I said, Linus was wrong and that we're still in the game

我跟他們說鮑林錯了，我們還有機會。

and that they should immediately start building models.

因此他們應該馬上開始建造模型。

But Wilkins said "no." Rosalind Franklin was leaving in about two months,

但威爾金斯拒絕了。而羅莎琳再兩個月左右就要離開了，

and after she left he would start building models.

等她走後，他就會開始造模型。

And so I came back with that news to Cambridge,

沒辦法，我只能把消息如實地傳達給劍橋，

and Bragg said, "Build models."

而布拉格還是說：「造—模—型」

Well, of course, I wanted to build models.

當然了，我是一直都想要建造模型的。

And there's a picture of Rosalind. She really, you know,

這是羅莎琳的照片。她其實，怎麼說呢，

in one sense she was a chemist,

就某個程度上來說，是個化學家。

but really she would have been trained --

但其實，她只是...

she didn't know any organic chemistry or quantum chemistry.

她對有機化學或量子化學一竅不通。

She was a crystallographer.

她只是一個結晶學家。

And I think part of the reason she didn't want to build models

而且我覺得她不想建造模型的一部分原因

was, she wasn't a chemist, whereas Pauling was a chemist.

就是因為她不是化學家，而鮑林則是位十足的化學家。

And so Crick and I, you know, started building models,

於是克立克和我就開始建造模型。

and I'd learned a little chemistry, but not enough.

我學過一點化學，但不夠用。

Well, we got the answer on the 28th February '53.

不管怎樣，我們在 1953 年的 2 月 28 日終於破解了 DNA 的謎團。

And it was because of a rule, which, to me, is a very good rule:

這一切都是因為我始終堅信的一條法則：

Never be the brightest person in a room, and we weren't.

永遠別做最聰明的人，我們也的確不是。

We weren't the best chemists in the room.

我們不是那裡最優秀的化學家。

I went in and showed them a pairing I'd done,

我有一次把我剛剛做好的分子配對圖給那些化學家們看，

and Jerry Donohue -- he was a chemist -- he said, it's wrong.

唐納修 — 一名化學家 — 看了之後就說：「你畫錯了。

You've got -- the hydrogen atoms are in the wrong place.

你把氫原子放錯地方了。」

I just put them down like they were in the books.

我是按照書裡面畫的。

He said they were wrong.

他說那書上畫錯了。

So the next day, you know, after I thought, "Well, he might be right."

於是隔天，我想了想：「搞不好他是對的。」

So I changed the locations, and then we found the base pairing,

所以我更改了氫原子的位置，然後我們就發現了鹼基配對的規則，

and Francis immediately said the chains run in absolute directions.

而法蘭西斯也立即意識到，雙螺旋鏈可以此方式無限延伸。

And we knew we were right.

我們當時就知道我們肯定是對的。

So it was a pretty, you know, it all happened in about two hours.

這真是太美了，我是說，而這一切就發生在兩個小時間。

From nothing to thing.

從無到有。

And we knew it was big because, you know, if you just put A next to T

我們也知道這是個重大的發現，因為如果你把 A 鹼基和 T 鹼基放在一起，

and G next to C, you have a copying mechanism.

G 和 C 放在一起，你就可以實現 DNA 的複製了。

So we saw how genetic information is carried.

所以我們了解了遺傳資訊是如何被儲存的。

It's the order of the four bases.

就是利用這 4 個鹼基的排列組合。

So in a sense, it is a sort of digital-type information.

所以說，這也算得上是一種數位化的資訊。

And you copy it by going from strand-separating.

把這螺旋的兩股分開，就可以開始複製了。

So, you know, if it didn't work this way, you might as well believe it,

就算它不是這麼回事，我們也只能相信它是這麼回事，

because you didn't have any other scheme.

因為你也沒有什麼其他的選擇。

(Laughter)

（笑聲）

But that's not the way most scientists think.

但大多數的科學家都不是這麼想的，

Most scientists are really rather dull.

大多數的科學家都是相當呆板的。

They said, we won't think about it until we know it's right.

他們認為，除非被證實是對的，不然他們是不會考慮的。

But, you know, we thought, well, it's at least 95 percent right or 99 percent right.

但我們知道這理論至少是 95% 甚至是 99% 正確的。

So think about it. The next five years,

所以想想看，在隨後的五年裡，

there were essentially something like five references

我們在《自然》雜誌中所提出的理論

to our work in "Nature" -- none.

只被引用了五次。

And so we were left by ourselves,

沒辦法，我們只能靠自己了。

and trying to do the last part of the trio: how do you --

而我們也只剩下一個待解決的問題—

what does this genetic information do?

這些遺傳資訊到底是用來做什麼的呢？

It was pretty obvious that it provided the information

很明顯地，它為 RNA 分子提供資訊，

to an RNA molecule, and then how do you go from RNA to protein?

但這資訊又是怎樣從 RNA 傳達到蛋白質的呢？

For about three years we just -- I tried to solve the structure of RNA.

我用了大概三年的時間，希望能破解 RNA 的結構，

It didn't yield. It didn't give good x-ray photographs.

但是卻一無所獲。RNA 的 X 光片毫無價值。

I was decidedly unhappy; a girl didn't marry me.

我是相當得不開心。我愛的女人又不想嫁給我。

It was really, you know, sort of a shitty time.

那真是一段黑暗的時期。

(Laughter)

（笑聲）

So there's a picture of Francis and I before I met the girl,

這裡有一張我和法蘭西斯的照片，是在我遇到那個女人之前拍的，

so I'm still looking happy.

所以我看起來還很開心。

(Laughter)

（笑聲）

But there is what we did when we didn't know

當我們不知道下一步該怎麼走的時候，

where to go forward: we formed a club and called it the RNA Tie Club.

我們成立了一個俱樂部，稱作「RNA 領帶團」。

George Gamow, also a great physicist, he designed the tie.

偉大的物理學家喬治‧伽莫夫負責設計領帶。

He was one of the members. The question was:

他也是我們的團員之一。我們探討的問題是：

How do you go from a four-letter code

由四個字母組成的 DNA 密碼

to the 20-letter code of proteins?

是怎麼轉變成由 20 個字母組成的蛋白質密碼呢？

Feynman was a member, and Teller, and friends of Gamow.

費曼、泰勒和一些伽莫夫的朋友們當時都是團員。

But that's the only -- no, we were only photographed twice.

我們在一起只拍過一次，不不，是兩次照片。

And on both occasions, you know, one of us was missing the tie.

每次總有人忘記戴我們的領帶。

There's Francis up on the upper right,

右上角的是法蘭西斯。

and Alex Rich -- the M.D.-turned-crystallographer -- is next to me.

艾力克斯‧里奇就坐在我旁邊。他之前是醫生，不過後來變成結晶學家。

This was taken in Cambridge in September of 1955.

這張照片是 1995 年的九月在劍橋拍的。

And I'm smiling, sort of forced, I think,

我當時在笑，不過我想應該是被強迫的，

because the girl I had, boy, she was gone.

因為我愛的那個女人，離我遠去了。

(Laughter)

（笑聲）

And so I didn't really get happy until 1960,

我直到 1960 年才變得真正開心起來，

because then we found out, basically, you know,

因為那一年我們發現了

that there are three forms of RNA.

RNA 的三種形式。

And we knew, basically, DNA provides the information for RNA.

我們基本上也明白了是 DNA 把資訊傳給 RNA，

RNA provides the information for protein.

RNA 再把資訊傳給蛋白質。

And that let Marshall Nirenberg, you know, take RNA -- synthetic RNA --

馬歇爾‧尼倫伯格也因此可以把人工合成的 RNA

put it in a system making protein. He made polyphenylalanine,

放進系統裡製造出蛋白質出來。他當時做出的是

polyphenylalanine. So that's the first cracking of the genetic code,

多聚苯基丙氨酸。那就是遺傳密碼被破解的第一步，

and it was all over by 1966.

到了 1966 年，所有的密碼就已經完全被破解了。

So there, that's what Chris wanted me to do, it was --

好了，克里斯要我講的都講完了。

so what happened since then?

那之後又發生了什麼事呢？

Well, at that time -- I should go back.

我得回到我們剛發現 DNA 的時候，

When we found the structure of DNA, I gave my first talk

我在冷泉港給了我人生第一場演講，

at Cold Spring Harbor. The physicist, Leo Szilard,

物理學家列奧·聖拉多望著我問到：

he looked at me and said, "Are you going to patent this?"

「你打算申請專利嗎？」

And -- but he knew patent law, and that we couldn't patent it,

他其實是懂專利法的，他也知道我們不可能申請到什麼專利，

because you couldn't. No use for it.

因為我們的發現沒什麼實用價值。

(Laughter)

（笑聲）

And so DNA didn't become a useful molecule,

於是DNA沒有變成有用的分子，

and the lawyers didn't enter into the equation until 1973,

律師也跟我們毫無瓜葛，直到 1973 年，

20 years later, when Boyer and Cohen in San Francisco

當舊金山和史丹佛的保耶和科亨

and Stanford came up with their method of recombinant DNA,

發明了 DNA 重組技術時，

and Stanford patented it and made a lot of money.

史丹佛大學申請了專利，並且賺了一大筆錢。

At least they patented something

至少他們申請的專利

which, you know, could do useful things.

是有用的。

And then, they learned how to read the letters for the code.

之後，他們發現了怎麼解譯 DNA 密碼，

And, boom, we've, you know, had a biotech industry. And,

然後，突然間，我們就有了生物科技產業。

but we were still a long ways from, you know,

但我童年的一個問題

answering a question which sort of dominated my childhood,

卻一直沒有得到解決，

which is: How do you nature-nurture?

這個問題是：先天與後天如何合二為一？

And so I'll go on. I'm already out of time,

因此我要接著講下去，雖然說我已經超時了。

but this is Michael Wigler, a very, very clever mathematician

這是邁克爾‧威革勒，一個非常非常聰明的數學家。

turned physicist. And he developed a technique

後來變成了一名物理學家。他發明了一項技術

which essentially will let us look at sample DNA

讓我們可以觀察 DNA 樣本，

and, eventually, a million spots along it.

和沿著它的上萬個點。

There's a chip there, a conventional one. Then there's one

這是一個傳統的生物晶片。而旁邊的那個

made by a photolithography by a company in Madison

則是麥迪遜一家叫做 NimbleGen 的公司利用光蝕刻法製造出來的，

called NimbleGen, which is way ahead of Affymetrix.

技術上遠比 Affymetrix 的生物晶片先進。

And we use their technique.

所以我們使用他們的技術。

And what you can do is sort of compare DNA of normal segs versus cancer.

你所能做的基本上就是比較正常和癌症 DNA 分子的序列，

And you can see on the top

你在上方可以看到

that cancers which are bad show insertions or deletions.

這些惡性的癌症 DNA 不是多一塊就是少一塊，

So the DNA is really badly mucked up,

是相當雜亂的。

whereas if you have a chance of surviving,

但如果你有機會幸存的話，

the DNA isn't so mucked up.

你的 DNA 就不會這麼雜亂。

So we think that this will eventually lead to what we call

我們覺得這最終會帶我們走上「DNA活體檢測」的道路。

"DNA biopsies." Before you get treated for cancer,

在你接受癌症治療前，

you should really look at this technique,

真的應該好好看看這項技術。

and get a feeling of the face of the enemy.

至少讓你知道你所需面對的是什麼，

It's not a -- it's only a partial look, but it's a --

哪怕只是知道一點點也好。

I think it's going to be very, very useful.

我覺得這將會是非常非常有用的。

So, we started with breast cancer

因此我們就從乳癌開始著手，

because there's lots of money for it, no government money.

因為這領域已經擁有許多研究經費，不需政府額外補助。

And now I have a sort of vested interest:

現在我對此有很大的興趣，

I want to do it for prostate cancer. So, you know,

我想將之應用在前列腺癌上。因為，

you aren't treated if it's not dangerous.

如果不危險的話，你並不會被醫治。

But Wigler, besides looking at cancer cells, looked at normal cells,

但威革勒除了研究癌細胞外，也研究正常的細胞，

and made a really sort of surprising observation.

並且有了驚人的發現。

Which is, all of us have about 10 places in our genome

那就是，我們所有人的基因組中都有大概 10 個地方

where we've lost a gene or gained another one.

要麼多了個基因，要麼少了個基因。

So we're sort of all imperfect. And the question is well,

所以說，我們都是不完美的。

if we're around here, you know,

不過既然我們都活得好好的，

these little losses or gains might not be too bad.

就說明這些增減可能沒什麼大不了的。

But if these deletions or amplifications occurred in the wrong gene,

但如果這一切發生在錯誤的基因上，

maybe we'll feel sick.

我們就有可能因此而生病。

So the first disease he looked at is autism.

所以他首先研究自閉症。

And the reason we looked at autism is we had the money to do it.

原因在於我們有足夠的資金來研究自閉症。

Looking at an individual is about 3,000 dollars. And the parent of a child

看一位病人大概需要 3 千美元。

with Asperger's disease, the high-intelligence autism,

有個艾斯伯格症（高智商自閉症）孩子的家長

had sent his thing to a conventional company; they didn't do it.

把他孩子的基因送到一個傳統的生技公司，但他們並沒有這樣比對。

Couldn't do it by conventional genetics, but just scanning it

傳統的基因科技做不了什麼。但通過簡單的掃描，

we began to find genes for autism.

我們就可以找到自閉症的基因。

And you can see here, there are a lot of them.

不難看到，與自閉症相關的基因有很多個。

So a lot of autistic kids are autistic

所以很多有自閉症的孩子之所以會有自閉症，

because they just lost a big piece of DNA.

是因為他們遺失了一大塊的 DNA。

I mean, big piece at the molecular level.

當然了，我是指分子層面上的一大塊。

We saw one autistic kid,

我們曾經看過一個自閉症兒童，

about five million bases just missing from one of his chromosomes.

在他的一條染色體上就缺少了約 5 百萬個鹼基。

We haven't yet looked at the parents, but the parents probably

我們還沒檢查他的父母，不過他的父母很有可能

don't have that loss, or they wouldn't be parents.

並不缺少這些鹼基，不然他們也不會為人父母。

Now, so, our autism study is just beginning. We got three million dollars.

自閉症的研究才剛剛開始。我們有 3 百萬美元研究經費，

I think it will cost at least 10 to 20 before you'd be in a position

但我覺得我們至少需要 1 千到 2 千萬美元，

to help parents who've had an autistic child,

才能真正幫助那些有自閉症子女的父母，

or think they may have an autistic child,

或者是那些認為自己有自閉症子女的父母。

and can we spot the difference?

我們能把他們區別開來嗎？

So this same technique should probably look at all.

這項技術也許應該大範圍地推廣，

It's a wonderful way to find genes.

因為它是尋找基因很有效的方法。

And so, I'll conclude by saying

我最後想說的是，

we've looked at 20 people with schizophrenia.

我們已經研究了 20 位精神分裂症患者，

And we thought we'd probably have to look at several hundred

我們可能總共需要研究幾百個

before we got the picture. But as you can see,

才能有所收穫。不過你在這裡可以看到，

there's seven out of 20 had a change which was very high.

這 20 名患者中，有 7 名的基因都有異變。這可是相當高的比例。

And yet, in the controls there were three.

不過我們的對照組中，也有三個人的基因有異變，

So what's the meaning of the controls?

那麼，對照組的意義又在哪裡呢？

Were they crazy also, and we didn't know it?

難不成他們的精神也有問題，只不過我們不知道罷了？

Or, you know, were they normal? I would guess they're normal.

還是說他們是正常人？我猜他們是正常的。

And what we think in schizophrenia is there are genes of predisposure,

我們現在所知的是精神分裂患者是有易患基因的，

and whether this is one that predisposes --

我們也能區分某個基因是否是罪魁禍首。

and then there's only a sub-segment of the population

然而只有一小部分的人群，

that's capable of being schizophrenic.

是真正會得精神分裂的。

Now, we don't have really any evidence of it,

我們現在還沒有確鑿的證據，

but I think, to give you a hypothesis, the best guess

不過我的猜想是，

is that if you're left-handed, you're prone to schizophrenia.

如果你是個左撇子，你會比較容易得精神分裂症。

30 percent of schizophrenic people are left-handed,

30% 的精神分裂症患者是左撇子，

and schizophrenia has a very funny genetics,

而精神分裂症的基因又是很滑稽的，

which means 60 percent of the people are genetically left-handed,

滑稽之處在於，其實 60% 的患者是有左撇子基因的，

but only half of it showed. I don't have the time to say.

不過他們當中只有一半成為左撇子。我沒有時間具體地解釋。

Now, some people who think they're right-handed

總之，有些人覺得他們是右撇子，

are genetically left-handed. OK. I'm just saying that, if you think,

但他們卻有著左撇子基因。所以說，你要是覺得

oh, I don't carry a left-handed gene so therefore my, you know,

你沒有左撇子基因，因此你的孩子不會患上精神分裂症。

children won't be at risk of schizophrenia. You might. OK?

我只想說：一切皆有可能。

(Laughter)

（笑聲）

So it's, to me, an extraordinarily exciting time.

對我來說，我們處在一個非常令人興奮的時代。

We ought to be able to find the gene for bipolar;

我們應該可以找到躁鬱症的基因。

there's a relationship.

這其中是有關聯的。

And if I had enough money, we'd find them all this year.

如果我有足夠的錢的話，我今年就能把它們給找出來。

I thank you.

謝謝大家。