Ladies and gentlemen, I present to you the human genome.
Dame i gospodo, ovo pred vama je ljudski genom.
(Applause)
(Aplauz)
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.
Hromozom jedan, u gornjem levom i donjem desnom uglu, to su polni hromozomi. Žene imaju dve kopije ovog velikog X hromozoma muškarci imaju jedan X i, naravno, malu kopiju hromozoma Y. Izvinite momci, ali samo ova jedna mala stvar vas čini drugačijim. Ukoliko zumirate u genom, ono što ćete videti, naravno, je ova struktura duplog heliksa - kod života koji je ispisan uz pomoć četiri biohemijska slova, ili kako ih mi zovemo baza: A, C, G i T. Koliko ovih baza ima u ljudskom genomu? Tri milijarde. Da li je to veliki broj? Pa, svako može da se razmeće velikim brojevima. Činjenica je da ukoliko bih postavio jednu bazu na svaki piksel ovog ekrana rezolucije 1280 puta 800, trebalo bi nam 3000 ekrana kako bismo sagledali genom. Dakle zaista je veliki.
And perhaps because of its size, a group of people -- all, by the way, with Y chromosomes -- decided they would want to sequence it.
I možda baš zbog njegove veličine, grupa ljudi - koja uzgred budi rečeno ima Y hromozom - je odlučila da želi da sekvencira genom.
(Laughter)
(Smeh)
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.
Tako da je nakon 15 godina i oko 4 milijarde dolara kasnije, genom sekvenciran i javno objavljen. Prva verzija genoma je objavljena 2003. godine i na njoj se i dalje se radi. Sve je to urađeno na mašini koja izgleda ovako. Košta otprilike dolar po sekvenciranoj bazi -
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.
veoma spor način za završavanje ovog posla. Pa narode, ovde sam kako bih vam saopštio da se svet potpuno promenio, a niko od vas ne zna za to. Ono što mi sada radimo jeste da uzmemo genom, napravimo otprilike 50 kopija istog, isečemo sve te kopije na deliće od 50 baznih parova, i onda ih sekvenciramo masivnim paralelnim reakcijama. A onda podatke prebacimo u softver i sastavimo ceo genom i ispričamo vam njegovu priču. Sve sa namerom da vam dam to dočaramo, vidite ovde Projekat Humani Genom od 3 gigabaza. A na ovim mašinama jedna reakcija čita 200 gigabaza nedeljno. A tih 200 će se promeniti u 600 ovog leta i ne postoji nijedan znak koji ukazuje da će se ovaj trend usporiti. Cena sekvenciranja jedne baze je pala 100 miliona puta. To je isto kao da napunite rezervoar kola 1998. sačekate do 2011. i onda možete da se odvezete do Jupitera i nazad dva puta.
(Laughter)
(Smeh)
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?
Svetska populacija, rasprostranjenost ličnih računara, arhive sve medicinske literature, Murov zakon, stari način sekvenciranja, i ovde su prikazana nova otkrića. Ljudi, ovo je logaritamska skala, i uobičajeno ne vidimo na njoj trend koji ide tako strmo na gore. Tako da je svetski kapacitet za sekvenciranje ljudskih genoma otprilike od 50.000 do 100.000 ljudskih genoma godišnje. Mi imamo tu informaciju na osnovu mašina koje su u upotrebi. Očekujemo da će se broj udvostručiti, utrostručiti ili možda učetvorostručiti iz godine u godinu u bliskoj budućnosti. U stvari, postoji jedna laboratorija koja sama ima 20% tog kapaciteta. Zove se Pekinški institut za genom. Kinezi apsolutno pobeđuju u ovoj trci za novi Mesec, uzgred budi rečeno. Šta ovo znači u svetu medicine?
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.
Žena ima 37 godina. Pokazuje simptome raka dojke drugog stepena koji je pozitivan za receptor estrogena. Tretman: operacija, hemoterapija i zračenje. Ona odlazi kuci. Dve godine kasnije, vraća se u bolnicu sa rakom jajnika trećeg stepena. Nažalost, terapija su ponovo operacija i hemoterapija. Vraća se ponovo tri godine kasnije u svojoj 42. godini i ima opet rak jajnika, još hemoterapije. Šest meseci kasnije, vraća se obolela od akutne mijeloidne leukemije. Razvija kolaps disajnih organa i umire 8 dana nakon toga.
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.
Prvo, način na koji je ova žena lečena, za samo 10 godina od sada, će izgledati kao krvoproliće. A to je zahvaljujući ljudima kao što je moj kolega, Rik Vilson, koji radi na Institutu za Genom Univerziteta u Vašingtonu, i koji je odlučio da analizira ovu ženu nakon smrti. On je sekvencirao, uzeo je uzorak ćelija kože, zdrave kože, i koštane srži žene obolele od raka i sekvencirao je potpuni genom oba uzorka u periodu od dve nedelje, to nije velika stvar. A potom je uporedio ova dva genoma uz pomoć softvera, i ono što je između ostalog pronašao je suzbijanje dugo 2000 baznih parova između tri milijarde baznih parova u tačno određenom genu koji se zove TP53. Ukoliko imate ovako štetnu mutaciju u tom genu,
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.
imate 90 odsto šanse da obolite od raka u svom životu. Nažalost, to nije pomoglo ovoj ženi, ali ima veoma ozbiljne, veoma značajne posledice za njenu porodicu. Mislim, ukoliko oni imaju istu mutaciju i urade ovaj genetički test, i razumeju ga, onda mogu redovno odlaziti na preglede, i mogu ustanoviti rak u ranom stadijumu i potencijalno mogu živeti znatno dužim životom.
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.
Upoznajte Biri blizance, kojima je dijagnostikovana cerebralna paraliza kada su imali dve godine. Njihova majka je veoma hrabra žena koja nije verovala u to, simptomi se nisu podudarali, i nakon herojske borbe i mnogo istraživanja na internetu, uspela je da ubedi doktore da njena deca boluju od druge bolesti. Bolovali su od distonije mišića osetljive na dopamin. Tako da im je dat L-Dopamin, i njihovi simptomi se se poboljšali, ali nisu svi simptomi bolesti nestali. Značajni problemi su ipak ostali.
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, $100, give or take a year. That's how fast this is moving.
Ispostavilo se da je gospodin na ovoj fotografiji, Džo Biri, imao sreće da bude Direktor informacija kompanije koja se zove "Žvotne tehnologije". To je jedna od dve kompanije koja proizvodi mašine za masivno sekvenciranje celih genoma. Rešio je da sekvencira genom svoje dece. I pronašli su čitav niz mutacija u genu koji zovemo SPR, koji, između ostalog, diktira proizvodnju serotonina. Tako da su deca pored L-Dopamina dobila i lek koji je prethodnik serotonina i oni su potpuno zdravi sada. Ljudi, ovo se nikada ne bi desilo da nije bilo sekvenciranja celog genoma. I tada, pre nekoliko godina, je to koštalo 100,000$. Danas košta 10,000$. Sledeće godine 1,000$. Godinu nakon sledeće koštaće 100 $, plus minus koja godina. To je brzina kojom se sve ovo pokreće.
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.
Ovo je mali Nik, voli Betmena i vodene pištolje. Ispostavilo se da je Nik došao u dečju bolnicu sa nadutim stomakom kao kod žrtava gladovanja. I nije da on ne jede, već je stvar u tome da kada jede, njegova creva se bukvalno otvore i izmet se izlije u njegov stomak. Tako da, stotinu operacija kasnije on pogleda u svoju majku i kaže joj: "Mama, molim te moli se za mene. Toliko me sve boli." Njegov pedijatar je igrom slučaja znao dosta o kliničkoj genetici i nije imao predstavu šta se dešava sa dečakom, ali on reče: "Hajde da sekvenciramo genom ovog deteta." I pronašli su mutaciju u jednoj bazi u genu koji kontroliše programiranu ćelijsku smrt. Tako da su došli do teorije da dete razvija neku imunološku reakciju na ono što se dešava - na hranu u principu, a to je prirodna reakcija, koja uzrukuje programiranu ćelijsku smrt. Ali gen koji reguliše taj proces nije funkcionalan. To znači da je, između ostalog naravno, neophodno uraditi transplantaciju koštane srži, što se i desilo. Nakon devet meseci napornog oporavka, dete sada jede šnicle sa sosom.
(Laughter)
(Smeh)
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 korišćenja genoma kao opšteg dijagnostičkog sredstva je tu pred nama danas. Danas, tu je, sada. I ono što to znači za sve nas jeste da svako ovde prisutan može živeti dodatnih 5, 10, 20 godina samo zahvaljujući sekvenciranju genoma. To je fantastična priča, osim ukoliko porazmislite o uticaju čovečanstva na planetu i našim mogućnostima da proizvedemo dovoljno hrane. Ispostavilo se da se ista ta tehnologija koristi takođe za proizovdnju novih sorti kukuruza, žita, soje i drugih žitarica koje su veoma otporne na sušu, poplave, na štetočine i pesticide. Sve dok mi nastavljamo da povećavamo svetsku populaciju, moraćemo i da nastavimo da gajimo i jedemo genetički modifikovanu hranu, i to je jedini stav koji ću danas izložiti. Osim ukoliko ima nekoga u publici ko bi želeo da volontira da prestane da jede? Niko, baš niko.
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.
Ovo je pisaća mašina, bila je obeležje svakog radnog stola decenijama. A činjenica je da je pisaću mašinu zamenila ova naprava. A potom su se pojavile već opšte verzije procesora reči. Na kraju, ono što je dovelo do promena nad svim promenama je Bob Metkalf koji je izumeo Eternet i način povezivanja svih tih kompjutera što je suštinski promenilo sve. I odjednom smo dobili "Netscape" i "Yahoo" i dobili smo, u principu, celu "dotcom" propast.
(Laughter)
(Smeh)
Not to worry though, that was quickly rescued by the iPod, Facebook and, indeed, Angry Birds.
Ali bez ikakvih briga, sve to je dovoljno brzo zamenjeno Ajpodima, Fejsbukom i, svakako, ljutim pticama.
(Laughter)
(Smeh)
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?
Shvatite, ovo je mesto gde se mi nalazimo danas. Ovo je genomska revolucija danas. Baš tu se nalazimo. Tako da bih ja voleo da obratite pažnju na ovo: šta bi značilo ukoliko ove tačke ne predstavljaju pojedinačne baze vašeg genoma, već povezuju genome na celoj planeti? Ja sam nedavno morao da kupim životno osiguranje. I zahtevano je od mene da odgovorim na pitanja: A. Nikada nisam radio genetički test; B. Radio sam ga, evo izvolite rezultate; C. Radio sam test, ali neću vam reći rezultat. Na sreću, mogao sam da odgovorim pod A, i zaista sam iskren, za slučaj da me agent životnog osiguranja sluša. Ali šta bi se desilo da sam odgovorio opcijom C?
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.
Korisničke primene genomike će procvetati. Želite da saznate da li ste genetički kompatibilni sa svojom devojkom? Naravno.
(Laughter)
Sekvenciranje DNK na telefonu? Postoji aplikacija za to.
Personalized genomic massage, anyone? There's already a lab today that tests for allele 334 of the AVPR1 gene, the so-called cheating gene.
(Smeh) Lična genetička masaža? Danas već postoji laboratorija u kojoj se radi test za prisustvo alela 334 gena AVPR1,
(Laughter)
poznatog i kao gen varanja.
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.
Tako da ko god je ovde danas sa svojim partnerom, samo uzmite bris iz njihovih usta i pošaljite to laboratoriji na analizu i znaćete zasigurno.
(Laughter)
(Smeh)
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?
Da li zaista želite da izaberete predsednika čiji genom sugeriše da će razviti kardiomiopatiju? Sada zamislite da je 2016. godina i vodeći kandidat obelodanjuje ne samo svoj izveštaj о porezima za poslednje 4 godine, već i svoj lični genom. I izgleda veoma dobro. A potom poziva sve svoje suparnike da urade isto. Da li mislite da se to neće desiti? Da li mislite da je to moglo da pomogne Džonu Mekejnu?
(Laughter)
(Smeh)
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.
Koliko ljudi u publici se preziva Reznik kao ja? Podignite svoje ruke. Bilo ko? Niko. Obično bude jedno ili dvoje ljudi. Moj deda je bio jedan od desetorice braće Reznik. Oni se međusobno nisu podnosili i raselili su se širom planete. Tako da postoji mogućnost da sam u srodstvu sa svakim Reznikom kojeg upoznam, ali to ne znam. Zamislite sada da je moj genom dekodiran, i da se nalazi u nekom softveru, i da je tu i genom mog daljeg rođaka i postoji softver koji može da uporedi ta ova genoma i uspostavi takve veze. To nije teško zamisliti. Moja firma ima softver koji već radi upravo to. I zamislite još jednu stvar, da je taj softver u stanju da upita obe strane za uzajamnu saglasnost, "Da li želite da upoznate svog daljeg rođaka?" I ukoliko obojica kažemo da, juhu!
(Laughter)
Dobrodošli na hromozomski "LinkedIn".
(Smeh)
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.
To je verovatno i dobra stvar, zar ne? Dolazi do okupljanja većeg klana i tako dalje. Ali možda je to i loša stvar. Koliko ima očeva ovde? Podignite svoje ruke. U redu, stručnjaci misle da 1 do 3 odsto očeva u stvari nisu očevi svoje dece.
(Laughter)
(Smeh)
Look --
Pogledajte.
(Laughter)
(Smeh)
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, ovih 23 hromozoma, ne predstavljaju ni na koji način kvalitet naših odnosa ili prirodu našeg društva, barem još uvek ne čine to. I kao svaka druga nova tehnologija, zaista je u rukama čovečanstva da njome upravlja u smeru njegovog poboljšanja ili pogoršanja. Tako da vas ja podstičem da se probudite i uključite i utičete na genomsku revoluciju koja se dešava svuda oko vas.
Thank you.
Hvala vam.
(Applause)
(Aplauz)