Nå, jeg troede der ville være et podium, så jeg er lidt bange. (Latter) Chris bad mig om igen at fortælle hvordan vi fandt strukturen på DNA. Og siden, I ved, jeg følger hans ordrer, vil jeg gøre det. Men det keder mig en smule. (Latter) Og, I ved, jeg skrev en bog. Så jeg vil sige noget -- (Latter) jeg vil fortælle lidt om, I ved, hvordan opdagelsen blev gjort, og hvorfor Francis og jeg fandt det. Og så, håber jeg at jeg i hvert fald har fem minutter til at fortælle noget om hvad der fanger mig nu.
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.
Bag mig er der et billede af mig fra da jeg var 17. Jeg gik på University of Chicago, i mit tredje år, og jeg var i mit tredje år, fordi University of Chicago giver en adgang efter to års gymnasium. Så man -- det var sjovt at komme væk fra gymnasiet -- (Latter) -- fordi jeg var meget lille, og jeg duede ikke til sport, eller noget i den retning.
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.
Men jeg bør sige at min baggrund -- min far var, I ved, opdraget til at være episkopal og republikaner, men efter et år på universitetet, blev han ateist og demokrat. (Latter) Og min mor var irsk katolsk, og -- men hun tog ikke religion alt for alvorligt. Og da jeg var 11 gik jeg ikke længere til søndagsmesse, og tog på gåture for at kigge på fugle med min far. Så jeg hørte tidligt om Charles Darwin. Jeg tror, I ved, at han var den store helt. Og, I ved, man forstår livet som det nu eksisterer gennem evolution.
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.
Og ved University of Chicago havde jeg zoologi som hovedfag, og troede jeg ville ende som, I ved, hvis jeg var kvik nok, måske få en Ph.D. fra Cornell i ornitologi. Så, i avisen i Chicago, var der en anmeldelse af en bog, der hed "Hvad er Liv?" af en stor fysiker, Schrodinger. Og det var, selvfølgelig, et spørgsmål som jeg ville kende svaret på. I ved, Darwin forklarede livet efter det begyndte, men hvad var livets essens?
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?
Og Schrodinger sagde at essensen var information der var tilstede i vores kromosomer, og den skulle være tilstede på et molekyle. Jeg havde aldrig rigtigt tænkt på molekyler før. Man kender kromosomer, men dette var et molekyle, og på en eller anden måde var den information formentlig til stede i en eller anden digital form. Og der var det store spørgsmål om, hvordan kopierede man den information?
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?
Så det var bogen. Så, fra det øjeblik, ville jeg være genetiker -- ville forstå genet og, gennem det, forstå liv. Så jeg havde, I ved, en helt på afstand. Det var ikke en baseball spiller; det var Linus Pauling. Så jeg søgte ind på Caltech og de afviste mig. (Latter) Så tog jeg til Indiana, hvilket faktisk var lige så godt som Caltech indenfor genetik, og derudover havde de et virkelig godt basketball team. (Latter) Så jeg havde virkelig et temmelig lykkeligt liv ved Indiana. Og det var ved Indiana at jeg fik indtrykket at, I ved, genet var sandsynligvis DNA. Så jeg fik min Ph.D., jeg burde tage ud og lede efter DNA.
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.
Så først tog jeg til København fordi jeg tænkte, jamen, måske kunne jeg blive biokemiker, men jeg opdagede at biokemi var meget kedeligt. Det var ikke på vej noget sted hen, I ved, og sagde at genet var; det var bare nuklear videnskab. Og øh, det er bogen, lille bog. Man kan læse den på cirka to timer. Og -- men så tog jeg til et møde i Italien. Og der var en uventet foredragsholder der ikke var på programmet, og han talte om DNA. Og dette var Maurice Wilkins. Han var trænet som fysiker, og efter krigen ville han lave biokemi, og han valgte DNA fordi DNA blev valgt ved Rockefeller Institutet til muligvis at være det genetiske molekyle på kromosomerne. De fleste mennesker mente det var proteiner. Men Wilkins, I ved, mente at DNA var det bedste gæt, og han viste dette røntgen billede. Krystalagtigt på en måde. Så DNA havde en struktur, selvom det skyldes det til sikkert forskellige molekyler der bar forskellige sæt instruktioner. Så der var noget universelt ved DNA molekylet. Så jeg ville arbejde med ham, men havde ikke lyst til en tidligere amatørornitolog, og jeg endte i Cambridge, England.
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.
Så jeg tog til Cambridge, fordi det var virkelig det bedste sted i verden dengang til røntgen krystallografi. Og røntgen krystallografi er nu et emne i, I ved, kemi afdelinger. Jeg mener, dengang var det fysikernes domæne. Så det bedste sted for røntgen krystallografi var ved Cavendish Laboratoriet ved Cambridge. Og der mødte jeg Francis Crick. Jeg tog derhen uden at kende ham. Han var 35. Jeg var 23. Og indenfor en dag, havde vi besluttet at måske kunne vi tage en smutvej til at finde DNAs struktur. Ikke løse det ligesom, I ved, på en rigoristisk måde, men bygge en model, en elektro-model, ved at bruge nogle koordinater til, I ved, længde, alle den slags ting fra røntgen fotografier. Men bare spørg hvad molekylet -- hvordan ville det folde sig?
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?
Og grunden til at gøre det på den måde, i midten af billedet, er Linus Pauling. Cirka seks måneder inden, foreslog han den alfa spiralformede struktur til proteiner. Og ved at gøre det, forviste han manden til højre, Sir Lawrence Bragg, der var professoren ved Cavendish. Dette er et billede fra adskillige år senere, da Bragg havde grund til at smile. Han smilede bestemt ikke da jeg kom, fordi han var blev noget ydmyget af at Pauling fandt alfa spiralen, og Cambridge folkene der fejlede fordi de ikke var kemikere. Og bestemt, hverken Crick eller jeg var kemikere, så vi prøvede at bygge en model. Og han kendte, Francis kendte Wilkins. Så Wilkins sagde han mente det var spiralformen. Røntgen diagrammet, han mente det var sammenligneligt med spiralformen.
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.
Så vi byggede en tre strenget model. Folkene fra London kom forbi. Wilkins og hans samarbejder, eller mulig samarbejder, Rosalind Franklin, kom forbi og mere eller mindre grinede af vores model. De sagde det var elendigt, og det var det. Så vi blev fortalt at vi ikke skulle bygge flere modeller; vi var inkompetente. (Latter) Så vi byggede ikke flere modeller, og Francis fortsatte på en eller anden måde arbejdet med proteinerne. Og i bund og grund, gjorde jeg ingenting. Og -- bortset fra at læse. I ved, dybest set, er det at læse en god ting; man får oplysninger. Og vi blev ved med at fortælle folkene i London at Linus Pauling vil flytte til DNA. Hvis DNA er så vigtigt, vil Linus vide det. Han bygger en model, og så bliver vi overhalet indenom.
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.
Og, faktisk, havde han skrevet til folkene i London: Kunne han se deres røntgen billede? Og de havde visheden til at sige "nej." Så han havde det ikke. Men der var nogen i litteraturen. Faktisk, kiggede Linus ikke omhyggeligt på dem. Men cirka, 15 måneder efter jeg kom til Cambridge, startede et rygte fra Linus Paulings søn, der var i Cambridge, at hans var nu arbejdede på DNA. Så, en dag kom Peter ind og sagde at han var Peter Pauling, og han gav mig en kopi af hans fars manuskripter. Og manner, jeg var skræmt fordi jeg troede, I ved, måske var vi blevet overhalet indenom. Jeg har ikke noget at lave, ingen kvalifikationer for noget. (Latter)
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)
Så der var afhandlingen, og han foreslog en tre strenget struktur. Og jeg læste den, og det var bare -- det var noget bras. (Latter) Så dette var, I ved, uventet fra verdens -- (Latter) -- så, det blev holdt sammen af hydrogen forbindelser mellem fosfat grupper. Jamen, hvis spids pH værdien som cellerne har er omkring syv, kunne de hydrogen forbindelser ikke eksistere. Vi skyndte os over til kemi afdelingen og sagde, "Kunne Pauling have ret?" Og Alex Hust sagde, "Nej." Så vi var glade. (Latter)
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)
Og, I ved, vi var stadig med i kampen, men vi var bange for at nogen ved Caltech ville fortælle Linus at han tog fejl. Så Bragg sagde, "Byg modeller." Og en måned efter vi fik Paulings afhandling -- jeg burde sige at jeg tog afhandlingen med til London, og viste det til folkene. Jamen, jeg sagde, Linus tog fejl og at vi stadig er med i kampen og at de burde i gang med at bygge modeller med det samme. Men Wilkins sagde "nej." Rosalind Franklin ville forlade os to måneder senere, og efter hun forlod os ville han begynde at bygge modeller. Så jeg kom tilbage til Cambridge med det nyt, og Bragg sagde, "Byg modeller." Jamen, selvfølgelig, ville jeg bygge modeller. Og her er et billede af Rosalind. Hun var virkelig, I ved, på en måde kemiker, men hun ville virkelig blive trænet -- hun kendte ikke noget til organisk kemi eller kvantekemi. Hun var krystallograf.
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.
Og jeg tror at en del af grunden til at hun ikke ville bygge modeller var, hun var ikke kemiker, hvorimod Pauling var kemiker. Så Crick og jeg, I ved, begyndte at bygge modeller, og jeg lærte en smule om kemi, men ikke nok. Jamen, vi fik svaret den 28 februar, 1953. Og det var på grund af en regel, der for mig, er en meget god regel: Vær aldrig den kvikkeste person i et lokale, og det var vi ikke. Vi var ikke de bedste kemikere i lokalet. Jeg tog ind og viste dem en pardannelse jeg havde lavet, og Jerry Donohue -- han var kemiker -- ha sagde, det er forkert. Man har -- hydrogen atomerne er det forkerte sted. Jeg havde placeret dem ligesom de var i bøgerne. Han sagde de var forkerte.
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.
Så den næste dag, I ved, efter jeg tænkte, "Jamen, måske har han ret." Så jeg ændrede placeringerne, og så fandt vi basis pardannelsen, og Francis sagde med det samme at kæderne løber i absolutte retninger. Og vi vidste vi havde ret. Så det var en temmelig, I ved, det skete alt sammen i løbet af et par timer. Fra ingenting til ting. Og vi vidste det var stort fordi, I ved, hvis man bare sætter A ved siden af T og G ved siden af C, har man en kopierende mekanisme. Så vi så hvordan genetisk information bliver båret videre. Det er ordenen på de fire baser. Så på en måde, er det en slags digital information. Og man kopierer den ved at gå fra at separere strenge. Så, I ved, hvis det ikke virkede på denne måde, kunne man lige så godt tro på det, fordi man havde ikke andre planer. (Latter)
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)
Men det er ikke sådan de fleste forskere tænker. De fleste forskere at faktisk ret kedelige. De sagde, vi vil ikke tænke på det før vi ved det er rigtigt. Men, I ved, vi tænkte, jamen, det er i hvert fald 95 procent rigtigt, eller 99 procent rigtigt. Så tænk på det. De næste fem år, var der i bund og grund noget i retningen af fem kildehenvisninger til vores arbejde i "Nature" -- ingen. Så vi var overladt til os selv, og prøvede at færdiggøre den sidste del i trioen: hvordan -- hvad gør denne genetiske information? Det var ret åbenlyst, at det gav os information til et RNA molekule, og hvordan går man så fra RNA til protein? I tre år var vi bare -- jeg prøvede at løse strukturen i RNA. Det gav sig ikke. Det gav ikke gode røntgen billeder. Jeg var udpræget ulykkelig; en pige giftede sig ikke med mig. Det var virkelig, I ved, en modbydelig tid. (Latter)
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)
Så der er et billede af Francis og jeg før jeg mødte pigen, så jeg ser stadig lykkelig ud. (Latter) Men her er hvad vi gjorde når vi ikke vidste hvordan vi skulle fortsætte: vi startede en klub og kaldte den RNA Tie Club. George Gamow, der også var en stor fysiker, han opfandt slipset. Han var et af medlemmerne. Spørgsmålet var: Hvordan går man fra en fire cifret kode til proteinets 20 ciffer kode? Feynman var medlem, og Teller, og Gamows venner. Med det er det eneste -- nej, vi blev kun fotograferet to gange. Og begge gange, I ved, manglede en af os slipset. Der er Francis øverst til højre, og Alex Rich -- lægen der blev krystallograf -- står ved siden af mig. Dette blev taget i Cambridge i september 1955. Og jeg smiler, anstrengt, tror jeg, fordi pigen jeg havde, manner, hun var væk. (Latter)
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)
Så jeg blev ikke rigtig lykkelig før 1960, fordi da fandt vi ud af, dybest set, I ved, at der er tre typer RNA. Og vi vidste, i bund og grund, at DNA giver information til RNA. RNA giver information til proteinet. Og det fik Marshall Nirenberg, I ved, til at tage RNA -- syntetisk RNA -- sætte det i et system og lave protein. Han lavede polyphenylalanine, polyphenylalanine. Så det er begyndelsen på at knække den genetiske kode, og det var alt sammen slut i 1966. Så der, det er hvad Chris vi have mig til, det var -- så hvad er der sket siden da? Jamen, dengang -- jeg burde gå tilbage. Da vi fandt DNAets struktur, holdte jeg mit første foredrag ved Cold Spring Harbor. Fysikeren, Leo Szilard, han kiggede på mig og sagde, "Vil du patentere dette?" Og -- men han kendte patentlovgivningen, og at vi ikke kunne patentere det, fordi det kunne man ikke. Ingen brug for det. (Latter)
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)
Så DNA blev ikke et brugbart molekyle, og advokaterne kom ikke ind i ligningen før 1973, 20 år senere, da Boyer og Cohen i San Fransisco og Stanford kom med deres metode til rekombinant DNA, og Stanford patenterede det og tjente en masse penge. De patenterede i det mindste noget som, I ved, kunne gøre brugbare ting. Og så, lærte de hvordan man læser bogstaverne til koden. Og, boom, vi, I ved, havde en biotech industri. Og, men vi var stadig langt fra, I ved, at besvare spørgsmålet der på en eller anden måde dominerede min barndom, som er: Hvordan nærer man naturen?
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?
Så jeg fortsætter. Jeg er allerede over tid, men dette er Michael Wigler, en meget, meget intelligent matematiker, der blev fysiker. Og han udviklede en teknik der i bund og grund vil lade os se på en DNA prøve og, i sidste ende, kommer der en million prikker. Der er en chip her, en konventionel en. Så er der en der er lavet af en fotolitograf af et firma i Madison der hedder NimbleGen, der er langt foran Affymetrix. Og vi bruger deres teknik. Og det man kan lave er en slags sammenligning af DNA af normale celler versus kræft. Og man kan se i toppen at kræft der er dårligt, viser indførelse eller deletion. Så DNAet kludret helt til, hvorimod hvis man har en chance for at overleve, er DNAet ikke så kludret. Så vi mener at dette i sidste ende vil lede til det vi kalder "DNA biopsi." Inden man bliver behandlet for kræft, bør man virkelig kigge på denne teknik, og få en følelse af at se fjenden i øjnene. Det er ikke en -- det er kun et delvist syn, men det er et -- jeg tror det bliver meget, meget brugbart.
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.
Så, vi begyndte med brystkræft fordi der er mange penge til det, ingen offentlige penge. Og nu har jeg lidt en egeninteresse: jeg gør det for prostatakræft. Så, I ved, man bliver ikke behandlet hvis det ikke er farligt. Men Wigler, foruden at kigge på kræftceller, kiggede på normale celler, og jeg lavede virkelig en slags overraskende observation. Hvilket er, vi har alle omkring 10 steder i vores genmasse hvor vi har mistet et gen eller fået endnu et. Så vi er alle lidt ufuldstændige. Og spørgsmålet er, hvis vi er her, I ved, disse små tab eller gevinster er måske ikke så slemme. Men hvis disse mangler og tilføjelser optræder i det forkerte gen, vil vi måske føle os syge.
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.
Så den første sygdom han kiggede på er autisme. Og grunden til at vi kiggede på autisme er at vi havde pengene til at gøre det. At se på et individ er omkring 3.000 dollars. Og en forælder til et barn med Aspergers syndrom, høj intelligens autisme, sendte denne ting til en konventionel virksomhed; de gjorde det ikke. De kunne ikke gøre det med konventionel genetik, men bare ved at scanne det begyndte vi at finde gener for autisme. Og man kan se her, at der er mange af dem. Så mange autistiske børn er autister fordi de har mistet et stort stykke DNA. Jeg mener, et stort stykke på molekylært niveau. Vi så et autistisk barn, omkring fem millioner baser mangler ved et af hans kromosomer. Vi har ikke kigget på forældrene, men forældrene har sikkert ikke det tab, ellers ville de ikke være forældrene. Så, nu, starter vores autisme studie kun. Vi har tre millioner dollars. Jeg tror det vil koste mindst 10 eller 20 før man vil være i en position til at hjælpe forældre der har fået et autistisk barn, eller tror de måske har et autistisk barn, og kan se forskellen? Så denne samme teknik burde nok kigge på alle. Det er en vidunderlig måde at finde gener på.
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.
Så, jeg vil slutte med at sige at vi har kigget på 20 mennesker med skizofreni. Og vi troede at vi muligvis havde kigget på adskillige hundrede før vi fik ideen. Men som I kan se, er der syv ud af tyve der havde en forandring der var meget høj. Og alligevel, i kontrollerne var der tre. Så hvad er meningen med kontroller? Var de også skøre, og vidste vi det ikke? Eller, I ved, var de normale? Jeg ville tro at de er normale. Og vi mener at der i skizofreni er gener der er prædisponerede, og om dette er en der prædisponerer -- og så er der kun en del segment af befolkningen der er i stand til at være skizofren.
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.
Nu har vi ikke rigtig noget bevis på det, men jeg mener, for at give jer en hypotese, det bedste gæt er at hvis man er venstrehåndet, så er der en tilbøjelighed til skizofreni. 30 procent af skizofrene mennesker er venstrehåndende, og og skizofreni har en meget sjov genetik, hvilket betyder at 60 procent af menneskerne genetisk set er venstrehåndede, men kun halvdelen viste det. Jeg har ikke tiden til at forklare. Nu er nogen mennesker der tror de er højrehåndede genetisk set venstrehåndede. OK. Jeg siger bare at, hvis man mener, oh, jeg bærer ikke på et venstrehåndet gen så derfor er mine, I ved, børn ikke i fare for at blive skizofrene. Måske jeres. (Latter)
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)
Så det er, for mig, en utrolig spændende tid. Vi bør være i stand til at finde genet for bipolar lidelse; der er et forhold. Og hvis jeg havde nok penge, ville vi finde dem alle i år. Jeg takker jer.
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.