So, has everybody heard of CRISPR? I would be shocked if you hadn't.
Da li su svi ovdje čuli za CRISPR? Bila bih šokirana da niste.
This is a technology -- it's for genome editing -- and it's so versatile and so controversial that it's sparking all sorts of really interesting conversations. Should we bring back the woolly mammoth? Should we edit a human embryo? And my personal favorite: How can we justify wiping out an entire species that we consider harmful to humans off the face of the Earth, using this technology?
Ovo je tehnologija -- za uređivanje gena -- i tako je prilagodljiva i kontroverzna da potiče svakakve zaista zanimljive razgovore. Trebamo li vratiti mamuta? Trebamo li uređivati ljudski embrij? I moj najdraži: Kako možemo opravdati brisanje čitave vrste, koju smatramo štetnima za ljude, sa lica zemlje, koristeći ovu tehnologiju?
This type of science is moving much faster than the regulatory mechanisms that govern it. And so, for the past six years, I've made it my personal mission to make sure that as many people as possible understand these types of technologies and their implications.
Ova vrsta znanosti kreće se puno brže od regulatornih mehanizama koji njome upravljaju. I tako, posljednjih šest godina, moja osobna misija je osigurati da što više ljudi razumije ove tipove tehnologija i njihove implikacije.
Now, CRISPR has been the subject of a huge media hype, and the words that are used most often are "easy" and "cheap." So what I want to do is drill down a little bit deeper and look into some of the myths and the realities around CRISPR.
Sada, CRISPR je bio predmet velike pompe u medijima, i riječi koje se najčešće koriste su "jednostavno" i "povoljno." I ono što želim je otići malo dublje i pogledati neke mitove i stvarnost vezanu uz CRISPR.
If you're trying to CRISPR a genome, the first thing that you have to do is damage the DNA. The damage comes in the form of a double-strand break through the double helix. And then the cellular repair processes kick in, and then we convince those repair processes to make the edit that we want, and not a natural edit. That's how it works. It's a two-part system. You've got a Cas9 protein and something called a guide RNA. I like to think of it as a guided missile. So the Cas9 -- I love to anthropomorphize -- so the Cas9 is kind of this Pac-Man thing that wants to chew DNA, and the guide RNA is the leash that's keeping it out of the genome until it finds the exact spot where it matches. And the combination of those two is called CRISPR. It's a system that we stole from an ancient, ancient bacterial immune system.
Ako pokušavate CRISPRirati genom, prva stvar koju morate napraviti je oštetiti DNK. Šteta dolazi u obliku pucanja dva vlakna kroz dvostruku uzvojnicu. I onda se jave procesi za popravljanje stanica, i onda uvjerimo te procese za popravljanje da naprave uređivanje koje želimo, a ne prirodno uređivanje. Tako to radi. To je sustav iz dva dijela. Imate Cas9 protein i nešto što se zove vodička RNK. Volim zamišljati to kao navođenu raketu. Dakle Cas9 -- volim antropomorfozirati -- tako da je Cas9 neka vrsta stvari poput Pac-Mana koja želi žvakati DNK, i vodička RNK je uzica koja ga drži izvan genoma dok ne nađe točno mjestso gdje se uklapa. I kombinacija te dvije stvari zove se CRISPR. To je sustav koji smo ukrali od drevnih, drevnih bakterijskih imunosnih sustava.
The part that's amazing about it is that the guide RNA, only 20 letters of it, are what target the system. This is really easy to design, and it's really cheap to buy. So that's the part that is modular in the system; everything else stays the same. This makes it a remarkably easy and powerful system to use.
Ono što je fascinanto je da vodička RNK, samo 20 slova nje, je ono što cilja sustav. To je jako jednostavno za dizajnirati, i vrlo povoljno za kupiti. To je dio koji je modularan u sustavu, sve ostalo ostaje isto. Tako nastaje nevjerojatno jednostavan i snažan sustav za korištenje.
The guide RNA and the Cas9 protein complex together go bouncing along the genome, and when they find a spot where the guide RNA matches, then it inserts between the two strands of the double helix, it rips them apart, that triggers the Cas9 protein to cut, and all of a sudden, you've got a cell that's in total panic because now it's got a piece of DNA that's broken.
Vodička RNK i Cas9 kompleks bjelančevina skupa skakuću po genomu, i kada nađu mjesto na koje pristaje RNK, umeće se između dvije niti dvostruke uzvojnice, kida ih, i to uzrokuje da Cas9 bjelančevina reže, i odjednom, imate stanicu koja je u panici jer sada ima komad pokidane DNK.
What does it do? It calls its first responders. There are two major repair pathways. The first just takes the DNA and shoves the two pieces back together. This isn't a very efficient system, because what happens is sometimes a base drops out or a base is added. It's an OK way to maybe, like, knock out a gene, but it's not the way that we really want to do genome editing.
Što mora učiniti? Poziva prve intervente. Postoje dva puta za popravak. PRvi samo uzima DNK i spoji ta dva komada. Ovo nije učinkovit sistem jer ponekad baza ispadne ili je dodana. To je OK način za izbacivanje gena, ali to nije način na koji želite uređivati genom.
The second repair pathway is a lot more interesting. In this repair pathway, it takes a homologous piece of DNA. And now mind you, in a diploid organism like people, we've got one copy of our genome from our mom and one from our dad, so if one gets damaged, it can use the other chromosome to repair it. So that's where this comes from. The repair is made, and now the genome is safe again.
Drugi put popravka je puno zanimljiviji. Ovim putem, trebate homologni komad DNK. I sad, u diploidnih organizama kao što su ljudi, imamo jednu kopiju našeg genoma od mame i jednu od tate, tako da ako se jedna ošteti, može koristiti drugi kromosom za popravak. Dakle odavde to dolazi. Popravak je napravljen, i sada je genom ponovno siguran.
The way that we can hijack this is we can feed it a false piece of DNA, a piece that has homology on both ends but is different in the middle. So now, you can put whatever you want in the center and the cell gets fooled. So you can change a letter, you can take letters out, but most importantly, you can stuff new DNA in, kind of like a Trojan horse.
Način na koji ovo želimo oteti je da ga hranimo lažnim komadom DNK, komadom koji ima homologiju na oba kraja ali je drugačiji u sredini. Sada, možete u sredinu staviti što god želite i stanica će biti zavarana. Tako da možete mijenjati slovo, možete izvaditi slovo, ali najvažnije, možete nagurati novu DNK unutra, nešto kao Trojanski konj.
CRISPR is going to be amazing, in terms of the number of different scientific advances that it's going to catalyze. The thing that's special about it is this modular targeting system. I mean, we've been shoving DNA into organisms for years, right? But because of the modular targeting system, we can actually put it exactly where we want it.
CRISPR će biti nevjerojatan u pogledu broja različitih znanstvenih napredaka koje će katalizirati. Stvar koja je posebna u tome je ovaj modularni sustav za ciljanje. Mislim, guramo DNK u organizme godinama, zar ne? Ali zbog modularnog sustava za ciljanje, možemo ju zapravo staviti gdje god želimo.
The thing is that there's a lot of talk about it being cheap and it being easy. And I run a community lab. I'm starting to get emails from people that say stuff like,
Stvar je u tome da se puno priča o tome da je povoljan i lak za shvatiti. I ja vodim društveni laboratorij. Počinjem dobivati mailove ljudi koji kažu sljedeće,
"Hey, can I come to your open night and, like, maybe use CRISPR and engineer my genome?"
"Mogu li doći na vašu otvorenu večer i možda koristiti CRISPR i urediti moj genom?"
(Laugher)
(Smijeh)
Like, seriously.
Kao, ozbiljno.
I'm, "No, you can't."
Ja kažem, "Ne, ne možete."
(Laughter)
(Smijeh)
"But I've heard it's cheap. I've heard it's easy."
"Ali čuo sam da je povoljno i lako."
We're going to explore that a little bit. So, how cheap is it? Yeah, it is cheap in comparison. It's going to take the cost of the average materials for an experiment from thousands of dollars to hundreds of dollars, and it cuts the time a lot, too. It can cut it from weeks to days. That's great. You still need a professional lab to do the work in; you're not going to do anything meaningful outside of a professional lab. I mean, don't listen to anyone who says you can do this sort of stuff on your kitchen table. It's really not easy to do this kind of work. Not to mention, there's a patent battle going on, so even if you do invent something, the Broad Institute and UC Berkeley are in this incredible patent battle. It's really fascinating to watch it happen, because they're accusing each other of fraudulent claims and then they've got people saying, "Oh, well, I signed my notebook here or there." This isn't going to be settled for years. And when it is, you can bet you're going to pay someone a really hefty licensing fee in order to use this stuff. So, is it really cheap? Well, it's cheap if you're doing basic research and you've got a lab.
To ćemo malo istraživati. Pa, koliko je to povoljno? Da, povoljan je u usporedbi s drugima. Smanjit će troškove prosječnih materijala za eksperimente sa tisuća i tisuća dolara na stotine dolara, i skraćuje potrebno vrijeme također. Može skratiti vrijeme od tjedana do dana. To je fantastično. Još uvijek trebate profesionalni laboratorij u kojem ćete raditi; nećete ništa značajno napraviti izvan profesionalnog laboratorija. Mislim, nemojte slušati nikoga tko kaže da možete ove stvari raditi na vašem kuhinjskom stolu. Nije lako raditi ovakve stvari. Da ne spominjem da postoji bitka za patente trenutno, tako da i ako nešto izumimo, Broad Institut, ili Berkeley se bore u ovoj bitci za patent. Zaista je fascinantno gledati je kako se razvija jer se optužuju međusobno za lažne tvrdnje i onda ljudi dolaze i govore, "Pa potpisao sam bilježnicu tu ili tu." To se neće riješiti godinama. A i kada se riješi, možete se gladiti da ćete nekome plaćati pozamašnu svotu za licencu kako biste koristili ove stvari. Pa, je li zaista povoljno? Pa, povoljno je ako radite osnovno istraživanje i imate laboratorij.
How about easy? Let's look at that claim. The devil is always in the details. We don't really know that much about cells. They're still kind of black boxes. For example, we don't know why some guide RNAs work really well and some guide RNAs don't. We don't know why some cells want to do one repair pathway and some cells would rather do the other.
A što s time da je jednostavno? Pogledajmo tu tvrdnju. Vrag je uvijek u detaljima. Zaista ne znamo tako puno o stanicama. One su još uvijek crne kutije. Na primjer, ne znamo zašto neka vodička RNK radi dobro, a druge ne. Ne znam zašto neke stanice rade popravke jednim putem a neke druge drugim putem.
And besides that, there's the whole problem of getting the system into the cell in the first place. In a petri dish, that's not that hard, but if you're trying to do it on a whole organism, it gets really tricky. It's OK if you use something like blood or bone marrow -- those are the targets of a lot of research now.
I osim toga, postoji čitav problem stavljanja sustava u stanicu na prvom mjestu. U petrijevoj zdjelici, to nije teško, ali ako pokušavate to napraviti čitavom organizmu, postaje dosta nezgodno. U redu je ako koristite nešto kao koštanu srž -- to je predmet dosta istraživanja.
There was a great story of some little girl who they saved from leukemia by taking the blood out, editing it, and putting it back with a precursor of CRISPR. And this is a line of research that people are going to do. But right now, if you want to get into the whole body, you're probably going to have to use a virus. So you take the virus, you put the CRISPR into it, you let the virus infect the cell. But now you've got this virus in there, and we don't know what the long-term effects of that are. Plus, CRISPR has some off-target effects, a very small percentage, but they're still there. What's going to happen over time with that?
Postojala je odlična priča o djevojčici koju su spasili od leukemije uzimajući krv, uređujući je i vrativši je sa pretečom CRISPR-a. I ovo je istraživanje koje će ljudi raditi. Ali sada, ako želite doći u cijelo tijelo, morat ćete koristiti virus. Uzmete virus, stavite CRISPR u njega, dozvolite virusu da zarazi stanicu. Ali sada tu imate taj virus, i ne znamo kako će dugoročno utjecati na okruženje. A i CRISPR ima neke neželjene učinke, vrlo malen postotak, ali oni su još uvijek tamo. Što će se s njima dogoditi kroz vrijeme?
These are not trivial questions, and there are scientists that are trying to solve them, and they will eventually, hopefully, be solved. But it ain't plug-and-play, not by a long shot. So: Is it really easy? Well, if you spend a few years working it out in your particular system, yes, it is.
OVo nisu trivijalna pitanja, i postoje znanstvenici koji na njih pokušavaju odgovoriti, i s vremenom će, nadamo se, biti riješeni. Ali to nije uključi i igraj, ni u kom slučaju. Dakle, je li zaista lako? Pa, ako potrošite nekoliko godina radeći s tim u određenom sustavu, da, jest.
Now the other thing is, we don't really know that much about how to make a particular thing happen by changing particular spots in the genome. We're a long way away from figuring out how to give a pig wings, for example. Or even an extra leg -- I'd settle for an extra leg. That would be kind of cool, right? But what is happening is that CRISPR is being used by thousands and thousands of scientists to do really, really important work, like making better models of diseases in animals, for example, or for taking pathways that produce valuable chemicals and getting them into industrial production in fermentation vats, or even doing really basic research on what genes do.
Druga stvar je, mi ne znamo puno o tome kako učiniti da se određena stvar dogodi mjenjajući određena mjesta u genomu. Daleko smo od shvaćanja kako svinjama dati krila, na primjer. Ili samo dodatnu nogu -- zadovoljila bih se dodatnom nogom. To bi bilo pomalo kul, zar ne? Ali ono što se događa je da CRISPR koriste tisuće i tisuće znanstvenika kako bi radili vrlo, vrlo važan posao, radeći bolje modele bolesti kod životinja na primjer, ili koristeći putanje koje proizvode vrijedne kemikalije i uvode ih u industrijsku proizvodnju u fermentacijskim kacama, ili rade osnovna istraživanja o tome što čine geni.
This is the story of CRISPR we should be telling, and I don't like it that the flashier aspects of it are drowning all of this out. Lots of scientists did a lot of work to make CRISPR happen, and what's interesting to me is that these scientists are being supported by our society.
To je priča CRISPR-a koju bismo trebali pričati i ne volim što ovi blještavi dijelovi zasjenjuju sve ovo. Puno znanstvenika radilo je na tome da se CRISPR dogodi, i ono što mi je zanimljivo mi je da su ovi znanstvenici poduprti od strane društva.
Think about it. We've got an infrastructure that allows a certain percentage of people to spend all their time doing research. That makes us all the inventors of CRISPR, and I would say that makes us all the shepherds of CRISPR. We all have a responsibility.
Razmislite o tome. Imamo infrastrukturu koja dozvoljava određenom postotku ljudi da troši svo svoje vrijeme istraživajući. To nas sve čini izumiteljima CRISPR-a, i čini nas pastirima CRISPR-a. Svi imamo odgovornost.
So I would urge you to really learn about these types of technologies, because, really, only in that way are we going to be able to guide the development of these technologies, the use of these technologies and make sure that, in the end, it's a positive outcome -- for both the planet and for us.
Tako da bih urgirala da zaista naučite nešto o ovim tehnologijama, jer, zapravo, samo na taj način ćemo moći voditi razvoj ovih tehnologija, uporabu ovih tehnologija i biti sigurni da je na kraju rezultat pozitivan -- i za planet i za nas.
Thanks.
Hvala.
(Applause)
(Pljesak)