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.
Dobro, mislio sam da će ovdje biti podij pa sam malo prestravljen. (Smijeh) Chris me zamolio da ponovno ispričam kako smo otkrili strukturu DNK. I s obzirom da ja, kao što znate, slijedim njegova naređenja, to ću i učiniti. Ali to mi je malo dosadno. (Smijeh) I, kao što znate, napisao sam knjigu. Pa ću reći nešto— (Smijeh) – reći ću malo o, znate, tome kako se dogodilo otkriće te zašto smo Francis i ja to otkrili. I onda, možda ću imati barem pet minuta da kažem što me sada zaokuplja.
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.
Iza mene je moja fotografija kad sam imao 17 godina. Bio sam na Sveučilištu Chicago, na trećoj godini zato što vam Sveučilište Chicago dozvoljava upis nakon dvije godine srednje škole. Dakle – bilo je zabavno pobjeći iz srednje škole. Zato što sam bio jako malen i nisu mi išli sportovi ili bilo što poput toga.
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.
No moram reći da je moj odgoj – znate, moj otac je bio odgojen kao episkopejac i republikanac. No nakon prve godine fakulteta postao je ateist i demokrat. (Smijeh) A moja majka bila je irska katolkinja, no - nije uzimala religiju previše ozbiljno. I tako nakon 11-te godine, više nisam pohađao nedjeljnu misu niti išao promatrati ptice sa svojim ocem. Vrlo rano čuo sam za Charlesa Darwina. Pretpostavljam da znate, on je bio veliki heroj. I, kao što znate, današnje shvaćanje života podrazumijeva evoluciju.
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?
A na Sveučilištu Chicago moj glavni predmet bila je biologija. I mislio sam da ću završiti, znate, ako budem dovoljno bistar, sa doktoratom iz ornitologije na Cornell-u. Tada je u čikaškim novinama izašao osvrt na knjigu „Što je život?“ slavnog fizičara Schrodingera. I to je, naravno, bilo pitanje na koje sam htio znati odgovor. Kao što znate, Darwin je objasnio život nakon što je on već započeo, ali što je osnova života?
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?
A Schrodinger je rekao da je osnova informacija sadržana u našim kromosomima, te da mora biti sadržana u molekulama. Nikad prije nisam pomišljao na molekule. Znate kromosomi su ustvari molekule, a informacija je vjerojatno bila prisutna u digitalnom obliku. I veliko je pitanje bilo, kako kopirate tu informaciju?
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.
To je bila knjiga. I tako sam od tog trenutka htio biti genetičar – razumjeti gene i kroz njih razumjeti život. Tako sam, znate, imao svog heroja na distanci. To nije bio igrač bejzbola, to je bio Linus Pauling. I tako sam predao molbu na Caltech, a oni su me odbili. (Smijeh) Onda sam otišao na Indianu koja je bila jednako dobra kao i Caltech u genetici, a osim toga imali su i stvarno dobru košarkašku momčad. Imao sam stvarno sretan život u Indiani. I upravo sam u Indiani dobio utisak da bi, znate, geni mogli biti DNK. I zato sam, kad sam obranio doktorat, otišao u potragu za DNK.
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.
Tako sam prvo otišao u Copenhagen zato što sam mislio, dobro, možda bih mogao postati biokemičar. No otkrio sam da je biokemija jako dosadna. Nije išla prema ničemu, znate, onome što su geni. Bila je samo znanost o jezgri. I onda, tu je bila knjiga, mala knjiga. Možete ju pročitati za oko dva sata. I - tada sam otišao na skup u Italiji. A tamo je bio neočekivani predavač, kojega nije bilo u programu, a on je govorio o DNK. Bio je to Maurice Wilkins. On je bio školovani fizičar, a nakon rata htio se baviti biofizikom i odabrao je DNK jer je DNK bila utvrđena na Institutu Rockefeller kao moguća molekula genetičkog materijala u kromosomima. Većina ljudi vjerovala je da su to bili proteini. No Wilkins je, znate, mislio da je to najvjerojatnije DNK i pokazao je tu fotografiju X-zrakama. Neka vrsta kristala. Dakle taj je DNK imao strukturu, premda se radilo vjerojatno o različitim molekulama koje su nosile različite setove uputa. I tako je bilo nešto univerzalno u DNK molekulama. I zato sam želio raditi s njim, ali on nije htio bivšeg promatrača ptica pa sam završio na Cambridge-u u Engleskoj.
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?
Dakle, otišao sam na Cambridge zato što je to tada bilo stvarno najbolje mjesto na svijetu za kristalografiju x-zrakama. A kristalografija x-zrakama sada je predmet, kao što znate, odjela za kemiju. Mislim, u to vrijeme, bila je domena fizičara. Zato je najbolje mjesto za kristalografiju x-zrakama bio Cavendish-ov laboratorij na Cambridge-u. I tamo sam upoznao Francisa Cricka. Otišao sam tamo, a da ga prije nisam poznavao. Bilo mu je 35, meni 23. I u samo jednom danu, odlučili smo da bismo možda trebali prečicom pronaći strukturu DNK. Ne riješiti ju, znate, u onom krutom značenju, već izgraditi model. Jedan atomski model koristeći se nekim koordinatama, znate, duljinama i tom vrstom podataka iz fotografija x-zrakama. Samo se pitati što je ta molekula - kako bi trebala izgledati?
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.
A razlog da to napravimo, u središtu ove fotografije, je Linus Pauling. Otprilike šest mjeseci prije, on je predložio strukturu alfa uzvojnice za proteine. I radeći to, on je isključio čovjeka sa desne strane, Sir Lawrencea Bragga, koji je bio Cavendishov profesor. Ovo je fotografija nekoliko godina kasnije, kad je Bragg dobio razlog da se nasmije. On se svakako nije smijao kad sam ja došao tamo, zato što je bio donekle ponižen Paulingovom alfa uzvojnicom, a ljudi sa Cambridgea su podbacili jer nisu bili kemičari. I svakako, niti Crick niti ja nismo bili kemičari te smo samo pokušali izraditi model. A on je znao, Francis je poznavao Wilkinsa. Tako je Wilkins rekao kako on misli da je uzvojnica. Prikaz x-zrakama, on je mislio, usporediv je sa uzvojnicom.
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.
Tako smo izgradili model od tri niti. Došli su nam ljudi iz Londona. Wilkins i njegova suradnica, ili moguća suradnica, Rosalind Franklin, došli su i na neki način ismijali naš model. Rekli su da je loš, a i bio je. Rekli su nam da više ne izrađujemo modele; da smo nesposobni. (Smijeh). I tako mi nismo izgradili više modela, a Francis se na neki način vratio poslu na proteinima. U osnovi, ja nisam radio ništa. Osim što sam čitao. Kao što znate, čitanje je dobra stvar; dođete do činjenica. I nastavili smo govoriti ljudima u Londonu kako će Linus Pauling prijeći na DNK. Ako je DNK toliko važna, Linus bi znao. On će izraditi model i onda ćemo mi opet biti pometeni.
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)
A, u stvari, on je pisao ljudima u Londonu: Može li vidjeti njihove fotografije x-zrakama? A oni su bili dovoljno mudri da odgovore "ne." I tako ih on nije vidio. Ali bilo ih je u literaturi. Ustvari, Linus ih nije dovoljno pažljivo pogledao. A onda, otprilike 15 mjeseci nakon što sam došao na Cambridge, počele su se širiti glasine od sina Linus Paulinga, koji je bio na Cambridge-u, koji je govorio da njegov otac sad radi na DNK. I tako, jednog je dana Peter navratio i rekao kako je on Peter Pauling i dao mi je kopiju očevih rukopisa. I čovječe, al sam bio preplašen jer sam mislio, znate, opet bismo mogli biti pometeni. A ja nisam imao ništa za raditi, ni predispozicije za bilo što. (Smijeh)
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)
I tako bio je taj članak u kojem je on pretpostavio strukturu od tri niti. I ja sam pročitao, i to je bila – obična besmislica. (Smijeh) To je to bilo neočekivano od svjetski – (Smijeh) – držalo se skupa vodikovim vezama između fosfatnih skupina. Dakle, ako je maksimalni pH u stanici oko sedam, te vodikove veze ne mogu postojati. Požurili smo na zavod za kemiju i pitali, „Može li Pauling biti u pravu?“ A Alex Hust je odgovorio, „Ne.“ I mi smo bili sretni. (Smijeh)
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.
I kao što znate, još smo bili u igri, ali nas je plašilo da će netko sa Caltech-a Linusu reći da nije u pravu. A onda je Bragg rekao, „Izgradite modele.“ I samo mjesec dana nakon što smo vidjeli Paulingov rukopis – trebao bih reći da sam odnio rukopis u London i pokazao ga ljudima. Dakle, rekao sam kako Linus nije bio u pravu i da smo mi još uvijek u igri i da smjesta moraju početi raditi modele. No Wilkins je rekao ne, Rosalind Frenklin je odlazila za dva mjeseca i nakon što ona ode on će početi graditi modele. I tako sam ja došao natrag u Cambridge s tom vijesti, a Bragg je rekao, „Izgradite modele.“ Dakle, naravno, ja sam htio napraviti modele. A evo slike Rosalind. Ona je stvarno, znate, na neki način bila kemičarka, ali trebala je biti poučena - nije znala ništa organske kemije ili kvantne kemije. Ona je bila kristalograf.
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.
Mislim da je dio razloga što nije htjela praviti modele bio taj što ona nije bila kemičar, a Pauling jest. Tako smo Crick i ja, znate, počeli praviti modele i ja sam naučio malo kemije, ali ne dovoljno. Dobili smo odgovor 28. veljače 1953. I to zbog pravila, koje je za mene jako dobro pravilo: Nikad nemoj biti najpametnija osoba u prostoriji, a mi to nismo bili. Nismo bili najbolji kemičari u prostoriji. Ušao sam i pokazao sparivanje koje sam napravio i Jerry Donohue - koji je bio kemičar - rekao mi je da je to krivo. Imaš - atome vodika na krivim mjestima. Stavio sam ih kako su stajali u knjigama. Rekao je da je krivo.
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)
Sljedeći dan, znate, nakon što sam pomislio, „Mogao bi biti u pravu.“ Promijenio sam mjesta i onda smo otkrili sparivanje baza i Francis je odmah rekao da lanci idu u suprotnim smjerovima. I znali smo da smo u pravu. Bilo je to prilično, znate, sve se dogodilo u otprilike dva sata. Od ničega do nečega. I znali smo da je veliko jer, znate, ako samo stavite A do T i G do C, imate mehanizam kopiranja. Vidjeli smo kako se genetska informacija prenosi. To je redoslijed četiriju baza. To je, na jedan način, digitalan oblik informacija. Kopirate ih krenuvši od razdvajanja lanaca. Tako da, znate, ako nije radilo na ovaj način, mogli biste i vjerovati u to jer niste imali ni jedan drugi model. (Smijeh)
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)
Ali to nije način na koji većina znanstvenika razmišlja. Većina znanstvenika je prilično dosadna. Rekli su, nećemo razmišljati o tome dok ne znamo da je to točno. Ali, znate, mislili smo, pa, to je barem 95 posto točno ili 99 posto točno. Zato razmislite o tome. Sljedećih pet godina, imali smo praktički pet referenci na naš rad u Nature-u - to je ništa. Bili smo ostavljeni sami sebi i pokušavali smo otkriti zadnji dio trojca: kako - što ta genetska informacija radi? Bilo je prilično jasno da daje informaciju za RNK molekulu, a kako dođeš od RNK do proteina? Otprilike tri godine smo samo - pokušao sam riješiti strukturu RNK. Nije išlo. Nije davala dobre rengenske slike. Bio sam izrazito nesretan; djevojka se nije udala za mene. Bilo je to, znate, priično loše razdoblje. (Smijeh)
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)
Evo slike Francisa i mene prije nego što sam upoznao tu djevojku pa još uvijek izgledam sretno. (Smijeh) Evo što smo radili kad nismo znali što raditi dalje: osnovali smo klub i zvali smo ga Klub RNK kravata. George Gamow, sjajan fizičar, dizajnirao je kravatu. Bio je jedan od naših članova. Pitanje je bilo: kako doći od četveroznamenkastog koda do dvadeseteroznamenkastog koda proteina? Feynman je bio član i Teller i Gamowljevi prijatelji. Ali ovo je jedini - ne, samo su nas dvaput slikali. I oba puta netko od nas nije imao kravatu. Evo Francis gore desno i Alex Rich – liječnik koji je postao kristalograf – je kraj mene. Ovo je slikano na Cambridgeu u rujnu 1955. Smješkam se, pomalo nasilu, barem mislim, jer je djevojka koju sam imao otišla. (Smijeh)
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)
Tako da nisam baš bio sretan do 1960., jer smo onda zapravo otkrili, znate, da postoje tri oblika RNK. Znali smo, u biti, da DNK daje informaciju za RNK. RNK daje informaciju za proteine. I to je dovelo Marshalla Nirenberga, znate, da uzme RNK - sintetičku RNK - i stavi ju u sustav za stvaranje proteina. Stvorio je polifenilalanin, polifenilalanin. To je bilo prvo razbijanje genetskog koda. I završilo je 1966. Eto, to je ono što je Chris htio da radim - što se dogodilo otad? Pa, u to vrijeme trebao bih se vratiti. Kad smo otkrili strukturu DNK, održao sam prvi govor u Cold Springs Harboru. Fizičar, Leo Szilard me pogledao i rekao, „Hoćeš li ovo patentirati?“ A - znao je zakon o patentima, nismo to mogli patentirati jer nije bilo koristi od toga. (Smijeh)
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?
I tako DNK nije postala korisna melekula i odvjetnici ju nisu uzeli u računicu do 1973. 20 godina kasnije kad su Boyer i Cohen iz San Francisca i Stanforda došli do metode rekombinantne DNK i Stanford ju je patentirao i zaradio mnogo novca. Barem su patentirali nešto što može, znate, raditi korisne stvari. I onda, naučili su čitati slova koda. I, bum, odjednom smo imali biotehnološku industriju. Ali, bili smo još uvijek daleko od odgovora na pitanje koje je dominiralo mojim djetinjstvom, a to je: Kako se priroda razvija?
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.
Nastavit ću. Već sam ostao bez vremena, ali ovo je Michael Wigler, vrlo, vrlo pametan matematičar koji je postao fizičar. Razvio je tehniku koja nam omogućava da pogledamo uzorak DNK i milijun točaka po njoj. Evo ondje čip, jedan uobičajeni. Eno i jednog napravljenog fotolitografijom tvrtke Madison a zove se NimbleGen, koji je znatno napredniji od Affymetrixa. Koristimo njihovu tehnologiju. I ono što možemo raditi je uspoređivati normalne odsječke DNK i odsječke raka. Možete vidjeti na vrhu da odsječci raka koji su loši pokazuju ubacivanja i brisanja. Tako da je DNK prilično uništena, ali ako imate šansu za preživljavanje, DNK i nije toliko uništena. Mislimo da će nas ovo na kraju dovesti do nečega što zovemo "DNK biopsije." Prije nego što se počneš liječiti od raka, trebao bi proučiti ovu metodu i steći sliku o svom neprijatelju. Nije to - to je samo djelomičan pogled, ali je - mislim da će biti jako korisno.
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.
Počeli smo s rakom dojke jer ima mnogo novca za njega, bez vladinog novca. Sad imam osobni interes: želim to napraviti za rak prostate. Tako vas neće liječiti ako nije opasno. Ali Wigler je, osim gledanja u stanice raka pogledao i u normalne stanice i donio iznenađujuće opažanje. To je da svi mi imamo otprilike 10 mjesta u genomu gdje smo dobili ili izgubili gen. Tako da smo svi na neki način nesavršeni. Pitanje je, ako smo već ovdje, znate, ovi mali gubitci ili dobitci možda nisu tako strašni. Ali ako se brisanje ili amplifikacija dogode u krivom genu, možda ćemo se razboljeti.
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.
Prva bolest koju smo pogledali je autizam. Razlog zbog kojeg smo proučavali autizam je taj što smo imali novaca za to. Proučavanje pojedinca stoji otprilike 3.000 dolara. A roditelj djeteta s Aspergerovom bolesti, autizma s visokom inteligencijom, poslao je svoju stvar nekoj tvrtci koja to nije obavila. Nismo to mogli obaviti konvencionalnom genetikom, već samo skenirajući počeli smo otkrivati gene za autizam. Možete ovdje vidjeti da ih ima mnogo. Mnogo je djece autistično zato što su izgubili velike dijelove DNK. Mislim, velike dijelove na molekularnoj razini. Vidjeli smo jedno autistično dijete kojemu je otprilike pet milijuna baza nedostajalo iz kromosoma. Nismo još proučili roditelje, iako vjerojatno roditelji nemaju taj gubitak jer inače ne bi bili roditelji. Sad, dakle, naše proučavanje autizma tek počinje. Dobili smo 3 milijuna dolara. Mislim da će koštati barem 10 ili 20 prije nego što ćemo biti u poziciji pomoći roditeljima koji imaju autistično dijete ili misle da bi mogli imati autistično dijete, a da mi možemo otkriti razliku? Ova bi tehnika trebala vjerojatno gledati na sve. To je prekrasan način traženja gena.
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.
I tako, završit ću tako što ću reći da smo proučili 20 osoba sa shizofrenijom. I mislili smo da ćemo morati proučiti nekoliko stotina prije nego što shvatimo bit. Ali kako možete vidjeti, sedam od dvadeset ima veliku vjerojatnost. A opet, u kontrolnoj grupi bilo ih je troje. Koje je značenje kontrolne skupine? Jesu li i oni također ludi, a mi to nismo znali? Ili su, znate, ipak normalni? Rekao bih da su normalni. I što mislimo o shizofreniji je to da postoje geni za predispoziciju, i ovisno je li ovaj taj koji predisponira - onda postoji samo subsegment populacije koji je sposoban biti shizofreničan.
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)
Sad, nemamo doista dokaze za to, ali mislim, dat ću vam hipotezu, ako ste ljevak, skloniji ste shizofreniji. 30 posto shizofreničara su ljevaci, a shizofrenija ima vrlo smiješnu genetiku, što znači da su 60 posto ljudi genetski ljevaci, ali samo polovica od njih to i pokazuje. Nemam vremena objašnjavati. Ali neki ljudi koji misle da su dešnjaci zapravo su genetski ljevaci. OK. Samo kažem da ako mislite, o, ne nosim gen za ljevorukost, i tako,znate, moja djeca neće imati rizik za shizofreniju. Mogli biste. OK? (Smijeh)
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.
Tako da je to, za mene, iznimno uzbudljivo vrijeme. Trebali bismo moći naći gene za bipolarnost; postoji povezanost. A kad bismo imali dovoljno novca, pronašli bismo ih sve ove godine. Hvala vam.