Ladies and gentlemen, I present to you the human genome.
Dame i gospodo, predstavljam vam ljudski genom.
(Applause)
(Pljesak)
Chromosome one -- top left, bottom right -- are the sex chromosomes. Women have two copies of that big X chromosome; men have the X and, of course, that small copy of the Y. Sorry boys, but it's just a tiny little thing that makes you different. So if you zoom in on this genome, then what you see, of course, is this double-helix structure -- the code of life spelled out with these four biochemical letters, or we call them bases: A, C, G and T. How many are there in the human genome? Three billion. Is that a big number? Well, everybody can throw around big numbers. But in fact, if I were to place one base on each pixel of this 1280x800-resolution screen, we would need 3,000 screens to take a look at the genome. So it's really quite big.
Prvi kromosom u gornjem lijevom kutu. U donjem desnom kutu su spolni kromosomi . Žene imaju dvije kopije velikog X kromosoma, muškarci imaju X, i naravno, jedan mali Y kromosom. Žao mi je, dečki, ali od žena vas čini različitim samo sićušna malena stvarčica. Dakle, ako povećate prikaz ovog genoma, primjetit ćete oblik dvostruke zavojnice -- životni kod sastoji se od ova četiri biokemijska slova, kojima nazivamo baze. To su A, C, G i T. Koliko ih ima u ljudskom genomu? Tri milijarde. Je li to velik broj? Pa, svatko se može razbacivati velikim brojevima. Ali, zapravo, ako bismo mogli zamisliti jednu bazu kao jedan pixel na ovom ekranu rezolucije 1.280x800, bilo bi nam potrebno 3.000 takvih ekrana da bismo mogli imati pregled cijeloga genoma. Znači, prilično je to velika brojka.
And perhaps because of its size, a group of people -- all, by the way, with Y chromosomes -- decided they would want to sequence it.
Možda je baš u pitanju veličina, zbog čega je grupa ljudi -- od kojih svi, kad smo već kod toga, posjeduju Y kromosom -- odlučila sekvencionirati genom.
(Laughter)
(Smijeh)
And so 15 years, actually, and about four billion dollars later, the genome was sequenced and published. In 2003, the final version was published, and they keep working on it. That was all done on a machine like this. It costs about a dollar for each base -- a very slow way of doing it.
I tako, 15 godina i četiri milijarde dolara kasnije, genom je sekvencioniran i objavljen. U 2003.godini objavljena je završna verzija, ali i dalje se nastavlja rad na tom projektu. Cijeli proces sekvencioniranja učinjen je na uređaju koji izgleda ovako. Dođe otprilike jedan dolar po bazi -- i to je vrlo spor način sekvencioniranja.
Well, folks, I'm here to tell you that the world has completely changed, and none of you know about it. So now what we do is take a genome, we make maybe 50 copies of it, we cut all those copies up into little 50-base reads, and then we sequence them, massively parallel. Then we bring that into software and reassemble it, and tell you what the story is. So to give you a picture of what this looks like, the Human Genome Project: 3 gigabases, right? One run on one of these modern machines: 200 gigabases in a week. And that 200 is going to change to 600 this summer, and there's no sign of this pace slowing. The price of a base, to sequence a base, has fallen 100 million times. That's the equivalent of you filling up your car with gas in 1998, waiting until 2011, and now you can drive to Jupiter and back twice.
Dakle, ljudi, danas sam ovdje kako bih vam rekao kako se svijet potpuno promjenio, a nitko od vas ne zna za to. Sada zapravo, uzmemo genom, napravimo 50-ak kopija tog genoma, isiječemo sve te kopije u male 50-bazne dijelove, i sekvencioniramo ih većinom paralelno. Onda rezultat unesemo u softver, i ponovno ga sastavimo, i proučimo. Samo da vam dam sliku kako to otprilike izgleda. Projekt Ljudski genom: 3 gigabaze. Pri radu ovog stroja možemo sekvencionirati 200 gigabaza tjedno. Taj broj od 200 gigabaza, promjenit će se u 600 ovog ljeta, a nema znakova da će se taj proces napredovanja i ubrzavanja usporiti. Tako je cijena za sekvencioniranje baze pala 100 milijuna puta. To je ekvivalentno punjenju automobila plinom u 1998.godini, da biste čekali do 2011. kako biste se odvezli od Jupitera i nazad dva puta.
(Laughter)
(Smijeh)
World population, PC placements, the archive of all of medical literature, Moore's law, the old way of sequencing, and here's all the new stuff. Guys, this is a long scale; you don't typically see lines that go up like that. So the worldwide capacity to sequence human genomes is something like 50,000 to 100,000 human genomes this year. We know this based on the machines that are being placed. This is expected to double, triple or maybe quadruple year over year for the foreseeable future. In fact, there's one lab in particular that represents 20 percent of all that capacity: It's called the Beijing Genomics Institute. The Chinese are absolutely winning this race to the new Moon, by the way. What does this mean for medicine?
Svjetska populacija, PC prostori, arhiva cijele medicinske literature, Mooreov zakon, stari način sekvencioniranja i sve ove novine. Ljudi, ovo je logaritamska skala, obično se ne viđaju tako strme skale koje idu prema gore. Dakle, svjetski kapacitet za sekvencioniranje ljudskih genoma je otprilike od 50.000 do 100.000 genoma godišnje. Znamo to na temelju broja strojeva koji postoje. Očekuje se da će se taj broj povećati dva, tri ili čak četiri puta svake godine u doglednoj budućnosti. Zapravo, postoji jedan laboratorij u kojem se odrađuje 20 posto svih kapaciteta za sekvencioniranje genoma. Zove se Pekinški institut genomike. Kinezi, kad smo već kod toga, apsolutno vode u ovoj utrci do 'novog mjeseca'. Kakvo to značenje ima za medicinu?
So a woman, age 37, presents with stage 2 estrogen receptor-positive breast cancer. She is treated with surgery, chemotherapy and radiation. She goes home. Two years later, she comes back with stage 3C ovarian cancer, unfortunately; treated again with surgery and chemotherapy. She comes back three years later at age 42 with more ovarian cancer, more chemotherapy. Six months later, she comes back with acute myeloid leukemia. She goes into respiratory failure and dies eight days later.
Dakle, žena od 37 godina. Ona dolazi s drugom fazom raka dojke pozitivnog na estrogenske receptore. Liječi se kirurški, kemoterapijom i zračenjem. Odlazi kući. Dvije godine kasnije, vraća se s trećom fazom karcinoma jajnika. Nažalost, opet ju se podvrgava kirurškim zahvatima i kemoterapiji. Ponovno dolazi tri godine poslije u dobi od 42 godine s još više raka jajnika, više kemoterapije. Šest mjeseci poslije, dolazi s akutnom mijeloidnom leukemijom. Dolazi do zatajenja respiratornog sustava i osam dana kasnije umire.
So first: the way in which this woman was treated, in as little as 10 years, will look like bloodletting. And it's because of people like my colleague, Rick Wilson, at the Genome Institute at Washington University, who decided to take a look at this woman postmortem. And he took skin cells, healthy skin and cancerous bone marrow, and sequenced the whole genomes of both of them in a couple of weeks, no big deal. Then he compared those two genomes in software, and what he found, among other things, was a deletion -- a 2,000-base deletion across three billion bases in a particular gene called TP53. If you have this deleterious mutation in this gene, you're 90 percent likely to get cancer in your life.
Dakle, ovaj način liječenja žene, za desetak godina djelovat će poput puštanja krvi. I to zato što su ljudi, poput mojega kolege, Ricka Wilsona, koji radi u Genome Institute-u na sveučilištu u Washingtonu, odlučili pregledati tu ženu poslije smrti. Uzeo je neke zdrave stanice kože i nekoliko kancerogenih stanica koštane srži, te sekvencionirao cijeli genom obiju vrsta stanica u nekoliko tjedana, što nije velika stvar. Onda je usporedio ta dva genoma u softveru, i našao je, izmeđuostalog, deleciju -- deleciju 2.000 baza -- u cijelom genomu od tri milijarde baza -- u jednom određenom genu koji se zove TP53. Ako imate štetnu mutaciju u ovom genu, 90 posto je vjerojatnost da ćete oboljeti od karcinoma tijekom svojega života.
So unfortunately, this doesn't help this woman, but it does have severe -- profound, if you will -- implications to her family. I mean, if they have the same mutation, and they get this genetic test and they understand it, then they can get regular screens and can catch cancer early, and potentially live a significantly longer life.
Nažalost, to neće pomoći toj ženi, ali imat će ozbiljne implikacije za njezinu obitelj. Mislim, ako članovi njezine obitelji imaju istu tu mutaciju i naprave ovaj genetski test, te razumiju što takav rezultat pretraga za njih znači, ići će na česte preglede i na taj način mogu rak otkriti u ranoj fazi i uz to imati veće šanse za znatno duži životni vijek.
Let me introduce you to the Beery twins, diagnosed with cerebral palsy at the age of two. Their mom is a very brave woman who didn't believe it; the symptoms weren't matching up. And through some heroic efforts and a lot of Internet searching, she was able to convince the medical community that, in fact, they had something else. They had dopa-responsive dystonia. And so they were given L-Dopa, and their symptoms did improve, but they weren't totally asymptomatic. Significant problems remained.
Dopustite mi predstaviti vam blizance Beery, kojima je dijagnosticirana cerebralna paraliza kada su imali dvije godine. Njihova je majka bila vrlo hrabra žena, koja nije vjerovala dijagnozi jer se sistemi nisu poklapali sa simptomima bolesti, i uz pomoć herojskih napora i jako puno pretraživanja po internetu, uspjela je uvjeriti medicinsku zajednicu da boluju od nečega drugoga. Imali su distoniju koja reagira na dopu. Tako da su se primanjem L-Dopa, njihovi simptomi znatno poboljšali, ali nisu ostali bez simptoma. Značajan je problem ostao.
Turns out the gentleman in this picture is a guy named Joe Beery, who was lucky enough to be the CIO of a company called Life Technologies. They're one of two companies that makes these massive whole-genome sequencing tools. And so he got his kids sequenced. What they found was a series of mutations in a gene called SPR, which is responsible for producing serotonin, among other things. So on top of L-Dopa, they gave these kids a serotonin precursor drug, and they're effectively normal now. Guys, this would never have happened without whole-genome sequencing. At the time -- this was a few years ago -- it cost $100,000. Today it's $10,000, next year, $1,000, the year after, $100, give or take a year. That's how fast this is moving.
Gospodin na ovoj slici je čovjek zvan Joe Beery, sretnik je koji je CIO tvrtke koja se zove Life Technologies. To je jedna od dvije kompanije koja se bavi masovnim sekvencioniranjem ljudskih genoma. On je sekvencionirao genome svoje djece. Ono što je pronašao su bile serije mutacija u genu SPR, koji je odgovoran za proizvodnju serotonina, uz neke ostale funkcije. Tako da je uz L-Dopa, terapija pojačana serotonin-prekursorskim lijekovima i sada su potpuno bez simptoma. Ovo se nikada ne bi dogodilo bez potpunog sekvencioniranja genoma. U to vrijeme -- to je bilo prije nekoliko godina -- koštalo je oko 100.000 dolara. Danas se za sekvencioniranje mora izdvojiti 10.000 dolara. Iduće godine će biti 1.000. Godina nakon nje, 100 dolara, godina prije ili poslije. Toliko brzo napreduje taj odsječak medicine.
So here's little Nick -- likes Batman and squirt guns. And it turns out Nick shows up at the children's hospital with this distended belly, like a famine victim. And it's not that he's not eating; it's that when he eats, his intestine basically opens up and feces spill out into his gut. So a hundred surgeries later, he looks at his mom and says, "Mom, please pray for me. I'm in so much pain." His pediatrician happens to have a background in clinical genetics and he has no idea what's going on, but he says, "Let's get this kid's genome sequenced." And what they find is a single-point mutation in a gene responsible for controlling programmed cell death. So the theory is that he's having some immunological reaction to what's going on -- to the food, essentially. And that's a natural reaction, which causes some programmed cell death, but the gene that regulates that down is broken. And so this informs, among other things, of course, a treatment for bone marrow transplant, which he undertakes. And after nine months of grueling recovery, he's now eating steak with A1 sauce.
Dakle, ovo je mali Nick -- voli Batmana i oružje. Nick se u dječjoj bolnici pojavio s proširenim trbuhom, kakvoga imaju inače žrtve gladi. Razlog tome nije glad, već to što, kada jede -- njegovi se probavni organi jednostavno otvore i neprobavljena hrana odlazi direktno u crijeva. I tako, sto operacija poslije, on pogleda majku i kaže: ''Mama, molim te, moli se za mene. Užasno me boli'.' Njegov pedijatar ima iskustva u kliničkoj genetici, no ne razumije što se događa, ali kaže: “Hajdemo sekvencionirati dječakov genom”. I ono što su pronašli bila je točkasta mutacija u genu odgovornom za kontrolu programirane stanične smrti (apoptoze). Znači, teorija je da on ima nekakvu imunološku reakciju na ono što se u organizmu događa s hranom, a to je prirodna reakcija koja uzrokuje neke apoptoze. Ali gen koji regulira tu reakciju je “pokvaren”. Ovo nas upućuje, između ostalih stvari, naravno, na tretman transplantacije koštane srži, kojem se dječak podvrgava. I nakon devet mjeseci napornog oporavka, on sada jede odrezak s “A1 umakom”.
(Laughter)
(Smijeh)
The prospect of using the genome as a universal diagnostic is upon us today. Today. It's here. And what it means for all of us is that everybody in this room could live an extra 5, 10, 20 years, just because of this one thing. Which is a fantastic story, unless you think about humanity's footprint on the planet, and our ability to keep up food production. So it turns out that the very same technology is also being used to grow new lines of corn, wheat, soybean and other crops that are highly tolerant of drought, of flood, of pests and pesticides. Now, look -- as long as we continue to increase the population, we'll have to continue to grow and eat genetically modified foods. And that's the only position I'll take today. Unless there's anybody in the audience who'd like to volunteer to stop eating? None, not one.
Mogućnost korištenja genoma kao univerzalne dijagnoze je pred nama. Danas je to moguće. I to znači da bi svaka osoba u ovoj prostoriji mogla živjeti dodatnih pet, 10 ili 20 godina samo zbog ove mogućnosti. Ovo je fantastična priča, ukoliko ne razmišljate o proizvodnji hrane isključivo „ljudskom rukom“. Jer se ista tehnologija koristi za uzgoj novih linija kukuruza, pšenice, soje i drugih usjeva koji su visoko tolerantni na sušu, poplave, štetnike i pesticide. Gledajte, dokle god nastavljamo povećavati populaciju, morat ćemo nastaviti s uzgojem i konzumiranjem genetski modificirane hrane i to je stajalište za koje se ja danas zauzimam. Osim ako ne postoji netko u publici tko bi volio dobrovoljno prestati jesti? Ne, nitko. Ovo je pisaći stroj,
This is a typewriter, a staple of every desktop for decades. And, in fact, the typewriter was essentially deleted by this thing. And then more general versions of word processors came about. But ultimately, it was a disruption on top of a disruption. It was Bob Metcalfe inventing the Ethernet, and the connection of all these computers that fundamentally changed everything. Suddenly we had Netscape, we had Yahoo. And we had, indeed, the entire dot-com bubble.
glavni stroj svake radne površine desetljećima. U biti, pisaći je stroj prvotno zamjenjen ovim uređajem. Tada dolaze druge verzije procesora. Ali u konačnici, prijelom nad svime bio je Bob Metcalfe koji je izumio „Ethernet“ i omogućio povezivanje svih ovih kompjutera, koje je sve iz temelja promijenilo. I odjednom, imali smo Netscape, imali smo Yahoo, imali smo cijelu dot.com zavrzlamu.
(Laughter)
(Smijeh)
Not to worry though, that was quickly rescued by the iPod, Facebook and, indeed, Angry Birds.
Ne brinite, i to sve su brzo zamijenili iPod, Facebook i ljute ptice.
(Laughter)
(Smijeh)
Look, this is where we are today. This is the genomic revolution today. This is where we are. What I'd like you to consider is: What does it mean when these dots don't represent the individual bases of your genome, but they connect to genomes all across the planet? I just recently had to buy life insurance, and I was required to answer: A. I have never had a genetic test; B. I've had one, here you go; or C. I've had one and I'm not telling. Thankfully, I was able to answer A, and I say that honestly, in case my life insurance agent is listening. But what would have happened if I had said C?
Gledajte, ovo je mjesto na kojem smo danas. Ovo je revolucija genoma danas. Ovako danas stojimo. Volio bih da razmislite o ovome: Što bi značilo kada ove točkice ne bi predstavljale pojedinačne baze vašeg genoma, već bi bile povezane sa svim genomima diljem planeta? Nedavno sam kupovao životno osiguranje. I morao sam odgovoriti na pitanje s A. nikad nisam napravio genetički test, B. testiran sam, izvolite rezultate ili C. testiran sam, ali ne želim podijeliti rezultat. Hvala Bogu, mogao sam odabrati odgovor pod A i to je istinit odgovor, u slučaju da me moj agent za osiguranje sada sluša. Ali što bi se dogodilo da sam odgovorio s C? Potrošačke aplikacije vezane za genomiku, one će procvasti.
Consumer applications for genomics will flourish. Do you want to see if you're genetically compatible with your girlfriend? DNA sequencing on your iPhone? There's an app for that.
Želite vidjeti jeste li genetički kompatibilni sa svojom djevojkom? Svakako. DNK sekvenciranje na vašem iPhoneu? Evo aplikacije. (Smijeh)
(Laughter)
Personalized genomic massage, anyone? There's already a lab today that tests for allele 334 of the AVPR1 gene, the so-called cheating gene.
Personalizirana genomska masaža, možda? Danas već imamo laboratorij koji radi testove na alelu 334 gena AVPR1, takozvanog „gena za varanje“.
(Laughter)
Zato se svi vi koji ste danas ovdje sa svojom boljom polovicom
So anybody who's here today with your significant other, just turn over to them, swab their mouth, send it to the lab and you'll know for sure.
jednostavno okrenite prema njima i uzmite obris iz usta, pošaljite u laboratorij i znat ćete za sigurno. (Smijeh)
(Laughter)
Želite li uistinu glasovati za predsjednika
Do you really want to elect a president whose genome suggests cardiomyopathy? Think of it -- it's 2016, and the leading candidate releases not only her four years of back-tax returns, but also her personal genome. And it looks really good. Then she challenges all her competitors to do the same. Do you think that's not going to happen? Do you think it would have helped John McCain?
čiji genom otkriva kardiomiopatiju? Sad razmislite o ovome, godina je 2016. i vodeći kandidat objavljuje ne samo svoje četiri godine plaćanja i povrata poreza, već i svoj osobni genom. I on izgleda jako dobro. A tada izaziva sve ostale kandidate da učine isto. Mislite li da se to neće dogoditi? Mislite li da je to moglo pomoći Johnu McCainu? (Smijeh)
(Laughter)
Koliko se ljudi u publici
How many people in the audience have the last name Resnick, like me? Raise your hand. Anybody? Nobody. Typically, there's one or two. So my father's father was one of 10 Resnick brothers. They all hated each other, and all moved to different parts of the planet. So it's likely I'm related to every Resnick that I ever meet, but I don't know. So imagine if my genome were De-identified, sitting in software, And a third cousin's genome was also sitting there, and there was software that could compare the two and make these associations. Not hard to imagine. My company has software that does this right now. Imagine one more thing, that that software is able to ask both parties for mutual consent: "Would you be willing to meet your third cousin?" And if we both say yes -- voilà! Welcome to Chromosomally LinkedIn.
preziva Resnick poput mene? Podignite ruku. Itko? Nitko. Obično postoji jedan ili dva. Moj je djed bio jedan od desetoro braće Resnick. I svi su se međusobno mrzili. Svaki se preselio na drugi dio planeta. Zato je vrlo vjerojatno da sam u rodu sa svakim Resnickom kojeg sam ikad upoznao, samo ja to ne znam. Ali zamislite kako bi bilo kad bi moj genom bio identificiran, ubačen u softver, softver u kojemu se nalazi i genom mog bratića u trećem koljenu. I taj isti softver može usporediti ova dva genoma i otkriti njihovu povezanost. Nije to tako teško za zamisliti. Moje poduzeće ima softver koji to već radi. I zamislite još jednu stvar: zamislite da taj softver može upitati obje strane za međusobnu suglasnost, „ Želite li upoznati svog bratića u trećem koljenu?“ I ako oboje kažemo „DA“ -- voila! Dobrodošli na kromosomski Linkedln.
(Laughter)
(Smijeh)
Now this is probably a good thing, right? Bigger clan gatherings and so on. But maybe it's a bad thing as well. How many fathers in the room? Raise your hands. OK, so experts think that one to three percent of you are not actually the father of your child.
Ovo je vjerojatno dobra stvar, zar ne? Imat ćete veća obiteljska okupljanja i sve to. Ali, možda je, ujedno, i loša stvar. Koliko očeva imamo u prostoriji? Podignite ruke. Ok, stručnjaci procjenjuju da jedan do tri posto vas nije biološki otac svog djeteta.
(Laughter)
(Smijeh)
Look --
Pogledajte.
(Laughter)
(Smijeh)
These genomes, these 23 chromosomes, they don't in any way represent the quality of our relationships or the nature of our society -- at least not yet. And like any new technology, it's really in humanity's hands to wield it for the betterment of mankind or not. And so I urge you all to wake up and to tune in and to influence the genomic revolution that's happening all around you.
Ovi genomi, ova 23 kromosoma, ni na koji način ne predstavljaju kvalitetu naših odnosa ili prirodu našeg društva -- barem ne još. I kao kod svake nove tehnologije, u ljudskim je rukama hoćemo li ju iskoristiti za poboljšanje čovječanstva ili ne. I zato vas sve potičem da se probudite, uključite i utječete na genomsku revoluciju koja se događa svuda oko vas. Hvala vam.
Thank you.
(Applause)
(Pljesak)