Well, I thought there would be a podium, so I'm a bit scared. (Laughter) Chris asked me to tell again how we found the structure of DNA. And since, you know, I follow his orders, I'll do it. But it slightly bores me. (Laughter) And, you know, I wrote a book. So I'll say something -- (Laughter) -- I'll say a little about, you know, how the discovery was made, and why Francis and I found it. And then, I hope maybe I have at least five minutes to say what makes me tick now.
我本來以為那裡會有一個講臺的,所以現在我有點害怕了。 (笑聲) 克里斯邀請我再講一次我們破解 DNA 結構的經過。 因為我遵照他的指示,所以我就來了。 但這令我感到有些無趣。 (笑聲) 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... (笑聲) 我將簡單提一下那次發現的經過, 以及令法蘭西斯與我做出這項發現的原因。 然後我希望至少能有五分鐘的剩餘時間, 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. I was at the University of Chicago, in my third year, and I was in my third year because the University of Chicago let you in after two years of high school. So you -- it was fun to get away from high school -- (Laughter) -- because I was very small, and I was no good in sports, or anything like that.
我身後是一張我 17 歲時的照片。 我那時在芝加哥大學,讀大三。 我之所以能在 17 歲時就讀大三,是因為芝加哥大學 在我讀了兩年高中之後就錄取我了。 擺脫高中生活對我來說樂趣無窮, 因為我長得很矮小,又不擅長體育, 或任何跟體能有關的特長。
But I should say that my background -- my father was, you know, raised to be an Episcopalian and Republican, but after one year of college, he became an atheist and a Democrat. (Laughter) And my mother was Irish Catholic, and -- but she didn't take religion too seriously. And by the age of 11, I was no longer going to Sunday Mass, and going on birdwatching walks with my father. So early on, I heard of Charles Darwin. I guess, you know, he was the big hero. And, you know, you understand life as it now exists through evolution.
但我得提一下我的生長背景:我的父親從小到大 都是一名聖公會教徒和共和黨員。 結果才上了一年大學,他變成了一名民主黨員與無神論者。 (笑聲) 我母親是愛爾蘭天主教徒, 但她沒把宗教看得很重。 所以 11 歲那年開始,我就不再去做禮拜了, 反而是跟我的父親去到處賞鳥。 因此我很早就聽說過達爾文, 我想,他是我心中的大英雄。 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, and thought I would end up, you know, if I was bright enough, maybe getting a Ph.D. from Cornell in ornithology. Then, in the Chicago paper, there was a review of a book called "What is Life?" by the great physicist, Schrodinger. And that, of course, had been a question I wanted to know. You know, Darwin explained life after it got started, but what was the essence of life?
而我當時在芝加哥大學又是主修動物學, 所以我就想,要是我夠聰明的話, 搞不好最後能從康乃爾大學拿個鳥類學博士學位。 恰巧當時在芝加哥的報紙上有一篇書評, 是由偉大的物理學家薛丁格寫的一本叫做《何謂生命?》的書。 當然了,那也是我一直都在探索的一個問題。 達爾文是解釋了生命的演變沒錯, 但生命的本質到底是什麼呢?
And Schrodinger said the essence was information present in our chromosomes, and it had to be present on a molecule. I'd never really thought of molecules before. You know chromosomes, but this was a molecule, and somehow all the information was probably present in some digital form. And there was the big question of, how did you copy the information?
薛丁格認為這本質就是資訊, 我們染色體裡的資訊,而且這些資訊必須由分子來承載。 我之前從沒認真思考過分子的可能, 大家都聽過染色體,但我們現在是在說一個分子, 而且不知怎地,所有資訊都可能以數位的形式 儲存在這分子中。然後,問題就來了, 你要怎麼複製這些資訊呢?
So that was the book. And so, from that moment on, I wanted to be a geneticist -- understand the gene and, through that, understand life. So I had, you know, a hero at a distance. It wasn't a baseball player; it was Linus Pauling. And so I applied to Caltech and they turned me down. (Laughter) So I went to Indiana, which was actually as good as Caltech in genetics, and besides, they had a really good basketball team. (Laughter) So I had a really quite happy life at Indiana. And it was at Indiana I got the impression that, you know, the gene was likely to be DNA. And so when I got my Ph.D., I should go and search for DNA.
那本書就是討論這些問題。所以從那時起, 我就立志要成為一名遺傳學家, 通過了解基因來認識生命。 因此,我有了仰慕的偶像。 不是什麼棒球明星,而是化學家鮑林。 所以我就申請進入加州理工學院,然後被拒絕了。 (笑聲) 因此我去了印第安納大學, 其實那裡的遺傳學研究和加州理工學院一樣好, 除此以外,他們有個非常棒的籃球隊。 所以我在那裡的生活也非常愉快。 而且正是在印第安納的時候,我開始覺得 DNA 很有可能就是我們的基因。 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, maybe I could become a biochemist, but I discovered biochemistry was very boring. It wasn't going anywhere toward, you know, saying what the gene was; it was just nuclear science. And oh, that's the book, little book. You can read it in about two hours. And -- but then I went to a meeting in Italy. And there was an unexpected speaker who wasn't on the program, and he talked about DNA. And this was Maurice Wilkins. He was trained as a physicist, and after the war he wanted to do biophysics, and he picked DNA because DNA had been determined at the Rockefeller Institute to possibly be the genetic molecules on the chromosomes. Most people believed it was proteins. But Wilkins, you know, thought DNA was the best bet, and he showed this x-ray photograph. Sort of crystalline. So DNA had a structure, even though it owed it to probably different molecules carrying different sets of instructions. So there was something universal about the DNA molecule. So I wanted to work with him, but he didn't want a former birdwatcher, and I ended up in Cambridge, England.
哥本哈根成了我的第一站,因為我覺得 也許我可以成為一個生化學家。 但後來我發現生化真的是相當無趣。 生化研究對於了解基因的本質完全無關, 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, 不長,兩個小時就可以讀完。 但我之後在義大利參加一個會議的時候, 遇到了一個原本不在節目單上的講者, 他演講的主題恰好是 DNA。 那是莫里斯‧威爾金斯,物理學家出身。 二戰後他決定從事生物物理研究,而 DNA 正是他的研究對象, 因為當時洛克菲勒研究所已經發現 染色體上的遺傳物質很有可能就是 DNA, 但多數人認為應該是蛋白質。 不過威爾金斯還是認為 DNA 才最有可能是遺傳物質, 並且展示了這張 X 光照片。 有點像個結晶體。所以DNA是有這樣的一個結構, 儘管說不同的分子 攜帶著不同的指令, 但這些 DNA 分子具有某種一致性。 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。 所以我到了英國劍橋。
So I went to Cambridge, because it was really the best place in the world then for x-ray crystallography. And x-ray crystallography is now a subject in, you know, chemistry departments. I mean, in those days it was the domain of the physicists. So the best place for x-ray crystallography was at the Cavendish Laboratory at Cambridge. And there I met Francis Crick. I went there without knowing him. He was 35. I was 23. And within a day, we had decided that maybe we could take a shortcut to finding the structure of DNA. Not solve it like, you know, in rigorous fashion, but build a model, an electro-model, using some coordinates of, you know, length, all that sort of stuff from x-ray photographs. But just ask what the molecule -- how should it fold up?
我之所以會去劍橋, 是因為那裡是當時研究射線晶體學的最好地方。 現在的射線晶體學, 通常是化學系中的一個研究主題。 不過在當時,那可是物理學家的天下。 所以研究射線晶體學最好的地方 是劍橋的卡文迪許實驗室。 而我就是在那遇見了法蘭西斯‧克立克。 當時我並不認識他。他當年 35 歲,我 23 歲。 不過一天之內,我們就決定 也許我們可以通過一條捷徑來破解 DNA 的結構。 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。 用X光照片裡的那些長度坐標什麼的 來建造電子模型。 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, is Linus Pauling. About six months before, he proposed the alpha helical structure for proteins. And in doing so, he banished the man out on the right, Sir Lawrence Bragg, who was the Cavendish professor. This is a photograph several years later, when Bragg had cause to smile. He certainly wasn't smiling when I got there, because he was somewhat humiliated by Pauling getting the alpha helix, and the Cambridge people failing because they weren't chemists. And certainly, neither Crick or I were chemists, so we tried to build a model. And he knew, Francis knew Wilkins. So Wilkins said he thought it was the helix. X-ray diagram, he thought was comparable with the helix.
為什麼我們會想走捷徑?這個照片中間的那位 就是鮑林。大概六個月前,他已經提出了 蛋白質的阿爾法螺旋結構。也正因此, 他徹底擊垮了站在他右邊的勞倫斯‧布拉格爵士。 布拉格當時是卡文迪許實驗室的教授。 這張照片是幾年後拍的, 布拉格只是強顏歡笑。 我剛到那裡的時候,他可是完全笑不出來。 因為他覺得讓鮑林搶先發表阿爾法螺旋結構讓他丟臉了, 劍橋人輸在他們並不是化學家。 當然了,我和克立克也不是化學家。 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。 威爾金斯當時覺得 DNA 應該是個螺旋結構, 他覺得那個 X 光圖片看上去像是個螺旋。
So we built a three-stranded model. The people from London came up. Wilkins and this collaborator, or possible collaborator, Rosalind Franklin, came up and sort of laughed at our model. They said it was lousy, and it was. So we were told to build no more models; we were incompetent. (Laughter) And so we didn't build any models, and Francis sort of continued to work on proteins. And basically, I did nothing. And -- except read. You know, basically, reading is a good thing; you get facts. And we kept telling the people in London that Linus Pauling's going to move on to DNA. If DNA is that important, Linus will know it. He'll build a model, and then we're going to be scooped.
所以我們建了個三股螺旋結構。 倫敦的那幫人就過來看, 威爾金斯和他(可能)的合作夥伴羅莎琳‧富蘭克林, 過來看過我們的模型後,對它有點嗤之以鼻。 他們覺得我們的模型爛透了,我也承認。 他們告訴我們不要再造模型了,我們沒這個能力。 (笑聲) 於是乎,我們就不再造模型了。 法蘭西斯重拾蛋白質的研究。 我則是除了讀書以外,什麼都沒做。 要知道讀書是件好事,你可以增長知識。 我們當時就一直告訴倫敦的那些人, 鮑林要著手研究 DNA 了。 如果 DNA 真的那麼重要的話,鮑林會發現什麼的。 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: Could he see their x-ray photograph? And they had the wisdom to say "no." So he didn't have it. But there was ones in the literature. Actually, Linus didn't look at them that carefully. But about, oh, 15 months after I got to Cambridge, a rumor began to appear from Linus Pauling's son, who was in Cambridge, that his father was now working on DNA. And so, one day Peter came in and he said he was Peter Pauling, and he gave me a copy of his father's manuscripts. And boy, I was scared because I thought, you know, we may be scooped. I have nothing to do, no qualifications for anything. (Laughter)
事實上,他的確是給倫敦的人寫了封信, 他想看看他們的 X 光照片。 還好他們有拒絕的智慧。因此他沒看到那張照片。 不過當時各種文獻中都有類似的照片, 事實上鮑林也沒有仔細地去研究那些照片。 可是在我到了劍橋 15 個月後, 鮑林在劍橋的兒子開始散播傳聞, 說他的爸爸正在研究 DNA。 結果有一天彼得找到我,他說他是彼得‧鮑林, 然後他就給了我一份他老爸論文初稿的副本。 我當時就嚇傻了,我以為他比我們搶先一步。 我沒有了目標,一無是處的。這下子可完了。 (笑聲)
And so there was the paper, and he proposed a three-stranded structure. And I read it, and it was just -- it was crap. (Laughter) So this was, you know, unexpected from the world's -- (Laughter) -- and so, it was held together by hydrogen bonds between phosphate groups. Well, if the peak pH that cells have is around seven, those hydrogen bonds couldn't exist. We rushed over to the chemistry department and said, "Could Pauling be right?" And Alex Hust said, "No." So we were happy. (Laughter)
這就是那篇論文,他在裡面提出了一個三股的結構, 我讀完之後覺得這篇論文簡直就是垃圾。 (笑聲) 對於他這位世界知名的學者來說,有失水準。 (笑聲) 他認為 DNA 是通過磷酸基之間的氫鍵 所組合起來的。 可是,如果細胞中的 pH 值大概是在 7 左右的話, 那些氫鍵根本就無法存在嘛。 我們直奔化學系,問那裡的人:「鮑林有可能是正確的嗎?」 亞歷克斯回答說:「沒可能!」我們這下可樂壞了。 (笑聲)
And, you know, we were still in the game, but we were frightened that somebody at Caltech would tell Linus that he was wrong. And so Bragg said, "Build models." And a month after we got the Pauling manuscript -- I should say I took the manuscript to London, and showed the people. Well, I said, Linus was wrong and that we're still in the game and that they should immediately start building models. But Wilkins said "no." Rosalind Franklin was leaving in about two months, and after she left he would start building models. And so I came back with that news to Cambridge, and Bragg said, "Build models." Well, of course, I wanted to build models. And there's a picture of Rosalind. She really, you know, in one sense she was a chemist, but really she would have been trained -- she didn't know any organic chemistry or quantum chemistry. She was a crystallographer.
我們還是有機會的,不過我們也是有點擔心。 擔心加州工學院的那些人會告訴鮑林他搞錯了。 於是布拉格就說:「我們得造模型。」 在我們收到鮑林初稿的一個月後, 我該提一下,我把初稿帶到了倫敦,給那裡的人看過。 我跟他們說鮑林錯了,我們還有機會。 因此他們應該馬上開始建造模型。 但威爾金斯拒絕了。而羅莎琳再兩個月左右就要離開了, 等她走後,他就會開始造模型。 沒辦法,我只能把消息如實地傳達給劍橋, 而布拉格還是說:「造—模—型」 當然了,我是一直都想要建造模型的。 這是羅莎琳的照片。她其實,怎麼說呢, 就某個程度上來說,是個化學家。 但其實,她只是... 她對有機化學或量子化學一竅不通。 她只是一個結晶學家。
And I think part of the reason she didn't want to build models was, she wasn't a chemist, whereas Pauling was a chemist. And so Crick and I, you know, started building models, and I'd learned a little chemistry, but not enough. Well, we got the answer on the 28th February '53. And it was because of a rule, which, to me, is a very good rule: Never be the brightest person in a room, and we weren't. We weren't the best chemists in the room. I went in and showed them a pairing I'd done, and Jerry Donohue -- he was a chemist -- he said, it's wrong. You've got -- the hydrogen atoms are in the wrong place. I just put them down like they were in the books. He said they were wrong.
而且我覺得她不想建造模型的一部分原因 就是因為她不是化學家,而鮑林則是位十足的化學家。 於是克立克和我就開始建造模型。 我學過一點化學,但不夠用。 不管怎樣,我們在 1953 年的 2 月 28 日終於破解了 DNA 的謎團。 這一切都是因為我始終堅信的一條法則: 永遠別做最聰明的人,我們也的確不是。 我們不是那裡最優秀的化學家。 我有一次把我剛剛做好的分子配對圖給那些化學家們看, 唐納修 — 一名化學家 — 看了之後就說:「你畫錯了。 你把氫原子放錯地方了。」 我是按照書裡面畫的。 他說那書上畫錯了。
So the next day, you know, after I thought, "Well, he might be right." So I changed the locations, and then we found the base pairing, and Francis immediately said the chains run in absolute directions. And we knew we were right. So it was a pretty, you know, it all happened in about two hours. From nothing to thing. And we knew it was big because, you know, if you just put A next to T and G next to C, you have a copying mechanism. So we saw how genetic information is carried. It's the order of the four bases. So in a sense, it is a sort of digital-type information. And you copy it by going from strand-separating. So, you know, if it didn't work this way, you might as well believe it, because you didn't have any other scheme. (Laughter)
於是隔天,我想了想:「搞不好他是對的。」 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, 而法蘭西斯也立即意識到,雙螺旋鏈可以此方式無限延伸。 我們當時就知道我們肯定是對的。 這真是太美了,我是說,而這一切就發生在兩個小時間。 從無到有。 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, G 和 C 放在一起,你就可以實現 DNA 的複製了。 所以我們了解了遺傳資訊是如何被儲存的。 就是利用這 4 個鹼基的排列組合。 所以說,這也算得上是一種數位化的資訊。 把這螺旋的兩股分開,就可以開始複製了。 就算它不是這麼回事,我們也只能相信它是這麼回事, 因為你也沒有什麼其他的選擇。 (笑聲)
But that's not the way most scientists think. Most scientists are really rather dull. They said, we won't think about it until we know it's right. But, you know, we thought, well, it's at least 95 percent right or 99 percent right. So think about it. The next five years, there were essentially something like five references to our work in "Nature" -- none. And so we were left by ourselves, and trying to do the last part of the trio: how do you -- what does this genetic information do? It was pretty obvious that it provided the information to an RNA molecule, and then how do you go from RNA to protein? For about three years we just -- I tried to solve the structure of RNA. It didn't yield. It didn't give good x-ray photographs. I was decidedly unhappy; a girl didn't marry me. It was really, you know, sort of a shitty time. (Laughter)
但大多數的科學家都不是這麼想的, 大多數的科學家都是相當呆板的。 他們認為,除非被證實是對的,不然他們是不會考慮的。 但我們知道這理論至少是 95% 甚至是 99% 正確的。 所以想想看,在隨後的五年裡, 我們在《自然》雜誌中所提出的理論 只被引用了五次。 沒辦法,我們只能靠自己了。 而我們也只剩下一個待解決的問題— 這些遺傳資訊到底是用來做什麼的呢? 很明顯地,它為 RNA 分子提供資訊, 但這資訊又是怎樣從 RNA 傳達到蛋白質的呢? 我用了大概三年的時間,希望能破解 RNA 的結構, 但是卻一無所獲。RNA 的 X 光片毫無價值。 我是相當得不開心。我愛的女人又不想嫁給我。 那真是一段黑暗的時期。 (笑聲)
So there's a picture of Francis and I before I met the girl, so I'm still looking happy. (Laughter) But there is what we did when we didn't know where to go forward: we formed a club and called it the RNA Tie Club. George Gamow, also a great physicist, he designed the tie. He was one of the members. The question was: How do you go from a four-letter code to the 20-letter code of proteins? Feynman was a member, and Teller, and friends of Gamow. But that's the only -- no, we were only photographed twice. And on both occasions, you know, one of us was missing the tie. There's Francis up on the upper right, and Alex Rich -- the M.D.-turned-crystallographer -- is next to me. This was taken in Cambridge in September of 1955. And I'm smiling, sort of forced, I think, because the girl I had, boy, she was gone. (Laughter)
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, 所以我看起來還很開心。 (笑聲) 當我們不知道下一步該怎麼走的時候, 我們成立了一個俱樂部,稱作「RNA 領帶團」。 偉大的物理學家喬治‧伽莫夫負責設計領帶。 他也是我們的團員之一。我們探討的問題是: 由四個字母組成的 DNA 密碼 是怎麼轉變成由 20 個字母組成的蛋白質密碼呢? 費曼、泰勒和一些伽莫夫的朋友們當時都是團員。 我們在一起只拍過一次,不不,是兩次照片。 每次總有人忘記戴我們的領帶。 右上角的是法蘭西斯。 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。 這張照片是 1995 年的九月在劍橋拍的。 我當時在笑,不過我想應該是被強迫的, 因為我愛的那個女人,離我遠去了。 (笑聲)
And so I didn't really get happy until 1960, because then we found out, basically, you know, that there are three forms of RNA. And we knew, basically, DNA provides the information for RNA. RNA provides the information for protein. And that let Marshall Nirenberg, you know, take RNA -- synthetic RNA -- put it in a system making protein. He made polyphenylalanine, polyphenylalanine. So that's the first cracking of the genetic code, and it was all over by 1966. So there, that's what Chris wanted me to do, it was -- so what happened since then? Well, at that time -- I should go back. When we found the structure of DNA, I gave my first talk at Cold Spring Harbor. The physicist, Leo Szilard, he looked at me and said, "Are you going to patent this?" And -- but he knew patent law, and that we couldn't patent it, because you couldn't. No use for it. (Laughter)
我直到 1960 年才變得真正開心起來, 因為那一年我們發現了 RNA 的三種形式。 我們基本上也明白了是 DNA 把資訊傳給 RNA, RNA 再把資訊傳給蛋白質。 馬歇爾‧尼倫伯格也因此可以把人工合成的 RNA 放進系統裡製造出蛋白質出來。他當時做出的是 多聚苯基丙氨酸。那就是遺傳密碼被破解的第一步, 到了 1966 年,所有的密碼就已經完全被破解了。 好了,克里斯要我講的都講完了。 那之後又發生了什麼事呢? 我得回到我們剛發現 DNA 的時候, 我在冷泉港給了我人生第一場演講, 物理學家列奧·聖拉多望著我問到: 「你打算申請專利嗎?」 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, 因為我們的發現沒什麼實用價值。 (笑聲)
And so DNA didn't become a useful molecule, and the lawyers didn't enter into the equation until 1973, 20 years later, when Boyer and Cohen in San Francisco and Stanford came up with their method of recombinant DNA, and Stanford patented it and made a lot of money. At least they patented something which, you know, could do useful things. And then, they learned how to read the letters for the code. And, boom, we've, you know, had a biotech industry. And, but we were still a long ways from, you know, answering a question which sort of dominated my childhood, which is: How do you nature-nurture?
於是DNA沒有變成有用的分子, 律師也跟我們毫無瓜葛,直到 1973 年, 當舊金山和史丹佛的保耶和科亨 發明了 DNA 重組技術時, 史丹佛大學申請了專利,並且賺了一大筆錢。 至少他們申請的專利 是有用的。 之後,他們發現了怎麼解譯 DNA 密碼, 然後,突然間,我們就有了生物科技產業。 但我童年的一個問題 卻一直沒有得到解決, 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, but this is Michael Wigler, a very, very clever mathematician turned physicist. And he developed a technique which essentially will let us look at sample DNA and, eventually, a million spots along it. There's a chip there, a conventional one. Then there's one made by a photolithography by a company in Madison called NimbleGen, which is way ahead of Affymetrix. And we use their technique. And what you can do is sort of compare DNA of normal segs versus cancer. And you can see on the top that cancers which are bad show insertions or deletions. So the DNA is really badly mucked up, whereas if you have a chance of surviving, the DNA isn't so mucked up. So we think that this will eventually lead to what we call "DNA biopsies." Before you get treated for cancer, you should really look at this technique, and get a feeling of the face of the enemy. It's not a -- it's only a partial look, but it's a -- I think it's going to be very, very useful.
因此我要接著講下去,雖然說我已經超時了。 這是邁克爾‧威革勒,一個非常非常聰明的數學家。 後來變成了一名物理學家。他發明了一項技術 讓我們可以觀察 DNA 樣本, 和沿著它的上萬個點。 這是一個傳統的生物晶片。而旁邊的那個 則是麥迪遜一家叫做 NimbleGen 的公司利用光蝕刻法製造出來的, 技術上遠比 Affymetrix 的生物晶片先進。 所以我們使用他們的技術。 你所能做的基本上就是比較正常和癌症 DNA 分子的序列, 你在上方可以看到 這些惡性的癌症 DNA 不是多一塊就是少一塊, 是相當雜亂的。 但如果你有機會幸存的話, 你的 DNA 就不會這麼雜亂。 我們覺得這最終會帶我們走上「DNA活體檢測」的道路。 在你接受癌症治療前, 真的應該好好看看這項技術。 至少讓你知道你所需面對的是什麼, 哪怕只是知道一點點也好。 我覺得這將會是非常非常有用的。
So, we started with breast cancer because there's lots of money for it, no government money. And now I have a sort of vested interest: I want to do it for prostate cancer. So, you know, you aren't treated if it's not dangerous. But Wigler, besides looking at cancer cells, looked at normal cells, and made a really sort of surprising observation. Which is, all of us have about 10 places in our genome where we've lost a gene or gained another one. So we're sort of all imperfect. And the question is well, if we're around here, you know, these little losses or gains might not be too bad. But if these deletions or amplifications occurred in the wrong gene, maybe we'll feel sick.
因此我們就從乳癌開始著手, 因為這領域已經擁有許多研究經費,不需政府額外補助。 現在我對此有很大的興趣, 我想將之應用在前列腺癌上。因為, 如果不危險的話,你並不會被醫治。 但威革勒除了研究癌細胞外,也研究正常的細胞, 並且有了驚人的發現。 那就是,我們所有人的基因組中都有大概 10 個地方 要麼多了個基因,要麼少了個基因。 所以說,我們都是不完美的。 不過既然我們都活得好好的, 就說明這些增減可能沒什麼大不了的。 但如果這一切發生在錯誤的基因上, 我們就有可能因此而生病。
So the first disease he looked at is autism. And the reason we looked at autism is we had the money to do it. Looking at an individual is about 3,000 dollars. And the parent of a child with Asperger's disease, the high-intelligence autism, had sent his thing to a conventional company; they didn't do it. Couldn't do it by conventional genetics, but just scanning it we began to find genes for autism. And you can see here, there are a lot of them. So a lot of autistic kids are autistic because they just lost a big piece of DNA. I mean, big piece at the molecular level. We saw one autistic kid, about five million bases just missing from one of his chromosomes. We haven't yet looked at the parents, but the parents probably don't have that loss, or they wouldn't be parents. Now, so, our autism study is just beginning. We got three million dollars. I think it will cost at least 10 to 20 before you'd be in a position to help parents who've had an autistic child, or think they may have an autistic child, and can we spot the difference? So this same technique should probably look at all. It's a wonderful way to find genes.
所以他首先研究自閉症。 原因在於我們有足夠的資金來研究自閉症。 看一位病人大概需要 3 千美元。 有個艾斯伯格症(高智商自閉症)孩子的家長 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。 傳統的基因科技做不了什麼。但通過簡單的掃描, 我們就可以找到自閉症的基因。 不難看到,與自閉症相關的基因有很多個。 所以很多有自閉症的孩子之所以會有自閉症, 是因為他們遺失了一大塊的 DNA。 當然了,我是指分子層面上的一大塊。 我們曾經看過一個自閉症兒童, 在他的一條染色體上就缺少了約 5 百萬個鹼基。 我們還沒檢查他的父母,不過他的父母很有可能 並不缺少這些鹼基,不然他們也不會為人父母。 自閉症的研究才剛剛開始。我們有 3 百萬美元研究經費, 但我覺得我們至少需要 1 千到 2 千萬美元, 才能真正幫助那些有自閉症子女的父母, 或者是那些認為自己有自閉症子女的父母。 我們能把他們區別開來嗎? 這項技術也許應該大範圍地推廣, 因為它是尋找基因很有效的方法。
And so, I'll conclude by saying we've looked at 20 people with schizophrenia. And we thought we'd probably have to look at several hundred before we got the picture. But as you can see, there's seven out of 20 had a change which was very high. And yet, in the controls there were three. So what's the meaning of the controls? Were they crazy also, and we didn't know it? Or, you know, were they normal? I would guess they're normal. And what we think in schizophrenia is there are genes of predisposure, and whether this is one that predisposes -- and then there's only a sub-segment of the population that's capable of being schizophrenic.
我最後想說的是, 我們已經研究了 20 位精神分裂症患者, 我們可能總共需要研究幾百個 才能有所收穫。不過你在這裡可以看到, 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。 不過我們的對照組中,也有三個人的基因有異變, 那麼,對照組的意義又在哪裡呢? 難不成他們的精神也有問題,只不過我們不知道罷了? 還是說他們是正常人?我猜他們是正常的。 我們現在所知的是精神分裂患者是有易患基因的, 我們也能區分某個基因是否是罪魁禍首。 然而只有一小部分的人群, 是真正會得精神分裂的。
Now, we don't have really any evidence of it, but I think, to give you a hypothesis, the best guess is that if you're left-handed, you're prone to schizophrenia. 30 percent of schizophrenic people are left-handed, and schizophrenia has a very funny genetics, which means 60 percent of the people are genetically left-handed, but only half of it showed. I don't have the time to say. Now, some people who think they're right-handed are genetically left-handed. OK. I'm just saying that, if you think, oh, I don't carry a left-handed gene so therefore my, you know, children won't be at risk of schizophrenia. You might. OK? (Laughter)
我們現在還沒有確鑿的證據, 不過我的猜想是, 如果你是個左撇子,你會比較容易得精神分裂症。 30% 的精神分裂症患者是左撇子, 而精神分裂症的基因又是很滑稽的, 滑稽之處在於,其實 60% 的患者是有左撇子基因的, 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。 總之,有些人覺得他們是右撇子, 但他們卻有著左撇子基因。所以說,你要是覺得 你沒有左撇子基因,因此你的孩子不會患上精神分裂症。 我只想說:一切皆有可能。 (笑聲)
So it's, to me, an extraordinarily exciting time. We ought to be able to find the gene for bipolar; there's a relationship. And if I had enough money, we'd find them all this year. I thank you.
對我來說,我們處在一個非常令人興奮的時代。 我們應該可以找到躁鬱症的基因。 這其中是有關聯的。 如果我有足夠的錢的話,我今年就能把它們給找出來。 謝謝大家。