So, has everybody heard of CRISPR? I would be shocked if you hadn't.
Da li su svi 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 izmenjivanje genoma - i toliko je raznovrsna i kontroverzna da zbog nje počinju svakakve zanimljive rasprave. Da li da vratimo runastog mamuta? Da li da izmenimo ljudski embrion? I moje omiljeno: kako možemo da opravdamo brisanje čitave vrste koju smatramo štetnom za ljude sa lica planete 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 nauke napreduje mnogo brže od mehanizama koji regulišu upravljanje njome. I tako, proteklih šest godina, moja je lična misija da se postaram da što je više moguće ljudi razume ovu vrstu tehnologije i njene 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.
CRISPR je bio tema velike medijske pomame i najčešće se koriste reči "lako" i "jeftino". Želim da malo produbim temu i pogledam neke od mitova i realnosti koji se tiču CRISPR-a.
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.
Ukoliko želite da izmenite genom CRISPR-om, prvo morate da oštetite DNK. Šteta nastaje tako što prelomite dupli niz kroz duplu spiralu. Onda kreću procesi popravke ćelije i onda te procese ubedimo da naprave izmenu koju želimo a ne prirodnu izmenu. Tako funkcioniše. To je sistem od dva dela. Imate protein Cas9 i nešto što se zove RNK vodič. Volim da ga posmatram kao raketu na navođenje. Cas9 onda - volim da stvarima dajem ljudske karakteristike - Cas9 liči na nekog Pekmena koji želi da žvaće DNK, a RNK vodič je povodac koji ga drži van genoma dok ne pronađe tačno mesto gde se uklapa. Kombinacija ove dve stvari naziva se CRISPR. To je sistem koji smo ukrali od drevnog bakterijskog imunog sistema.
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 neverovatno kod svega je da RNK vodič, samo 20 slova, je ono što napada sistem. Ovo je lako za osmisliti i veoma je jeftino. Ovo je deo koji je modularan u sistemu, sve ostalo ostaje isto. Ovo ga čini neverovatno moćnim i lakim sistemom za korišćenje.
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.
RNK vodič i kompleks Cas9 proteina zajedno kruže po genomu i kada naiđu na mesto gde se vodič RNK podudara, onda se ubacuju između dva niza duple spirale, kidaju ih, to natera protein Cas9 da seče i odjednom imate ćeliju u panici jer sada ima polomljen komad 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.
Šta onda radi? Zove hitnu pomoć. Postoje dva glavna načina popravke. U prvom se samo uzima DNK i dva komada se ponovo prilepe. Ovo nije veoma efikasan sistem jer se dešava da ponekad ispadne baza ili se doda. To je dobar sistem da se možda izbaci neki gen, ali nije način na koji zaista želimo da menjamo 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 način popravke mnogo je zanimljiviji. Kod ovog načina popravke, uzima se odgovarajući komad DNK. I sada, kod diploidnog organizma poput ljudi, imamo jedan primerak genoma od majke i jedan od oca, pa ako se jedan ošteti, drugi hromozom se može iskoristiti za popravku. Odatle potiče ovo. Vrši se popravka i genom je opet bezbedan.
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 možemo ovo prisvojiti je taj da mu damo komad lažne DNK, komad koji je homologan na oba kraja, ali je drugačiji na sredini. Sada možete staviti šta god želite u sredinu i namagarčićete ćeliju. Možete izmeniti slovo, možete vaditi slova, ali što je najbitnije, možete ubaciti novu DNK, poput trojanskog konja.
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 neverovatan, što se tiče broja raznih naučnih otkrića koje će katalisati. Ono što je kod njega posebno je ovaj modularni sistem za ciljanje. Mislim, već godinama trpamo DNK u različite organizme, zar ne? Ali zbog modularnog sistema za ciljanje, zapravo možemo da je stavimo tačno tamo gde 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 mnogo priča o tome da je CRISPR jeftin i da je jednostavan. Ja vodim otvorenu laboratoriju. Počinjem da dobijam mejlove od ljudi ovakvog sadržaja:
"Hey, can I come to your open night and, like, maybe use CRISPR and engineer my genome?"
"Hej, mogu li da dođem na otvoreno veče i da kao, možda koristim CRISPR i izmenim svoj genom?"
(Laugher)
(Smeh)
Like, seriously.
Kao, zaista.
I'm, "No, you can't."
Kažem: "Ne, ne možeš."
(Laughter)
(Smeh)
"But I've heard it's cheap. I've heard it's easy."
"Ali čuo sam da je jeftino. Čuo sam da je jednostavno."
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.
Malo ćemo da istražimo to. Koliko je jeftino? Jeftino je u poređenju sa drugim stvarima, da. Trošak materijala za eksperimente koštaće od na hiljade dolara do na stotine dolara i uštedeće dosta vremena. Skratiće vreme s nedelja na dane. To je sjajno. Još uvek vam je potrebna profesionalna laboratorija za rad, nećete uraditi ništa smisleno van profesionalne laboratorije. Mislim, ne slušajte bilo koga ko kaže da nešto ovako može da se uradi na vašem kuhinjskom stolu. Zaista nije lako baviti se ovakvim poslom. Da ne spominjem to da se trenutno vodi bitka oko patenta, pa i da izmislite nešto, Institut Brod i Univerzitet Berkli su u neverovatnoj bici oko patenta. Zaista je fascinantno gledati kako se to dešava jer optužuju jedni druge za prevaru i onda ljudi govore stvari poput: "O, pa ja sam potpisao svesku tu i tamo." Ovo se neće rešiti godinama. A kada se reši, možete da se kladite da ćete nekome plaćati ogromnu svotu za licenciranje da biste koristili ove stvari. Da li je onda zaista jeftino? Pa jeftino je ako radite osnovno istraživanje i imate laboratoriju.
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 lako? Hajde da istražimo to. Uvek se neki vrag ispreči. Zapravo ne znamo toliko toga o ćelijama. Još su nešto poput crnih kutija. Na primer, ne znamo zašto neki RNK vodiči funkcionišu veoma dobro, a neki RNK vodiči ne funkcionišu. Ne znamo zašto neke ćelije žele da poprave niz na jedan način, a neke ćelije na drugi.
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.
Pored toga, tu je i ceo problem da uopšte ubacite sistem u ćeliju. U petrijevoj posudi, to nije tako teško, ali ako to želite da uradite na celom organizmu, postaje prilično komplikovano. U redu je ako koristite nešto poput krvi ili koštane srži - to su mete raznih istraživanja trenutno.
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?
Bila je sjajna priča o nekoj devojčici koju su spasili od leukemije tako što su izvadili krv, izmenili je i vratili je uz prethodnika CRISPR-a. Ovo je vrsta istraživanja kakve će ljudi raditi. Ali trenutno, ako želite da pristupite celom telu, verovatno ćete morati da korstite virus. Uzmete virus, u njega ubacite CRISPR, date virusu da zarazi ćeliju. Ali sada tu imate virus, i ne znamo šta su dugotrajne posledice ovoga. Pored toga, CRISPR ima neke nuspojave, veoma mali broj njih, ali ipak su tu. Šta će se tokom vremena desiti s time?
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 naučnici koji pokušavaju na njih da odgovore, i to će se desiti pre ili kasnije. Ali nije prosto kao pritiskanje dugmeta, ni blizu toga. Da li je onda zaista lako? Pa, ako provedete nekoliko godina radeći na tome u svom posebnom sistemu, da, onda jeste.
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, zaista ne znamo mnogo o tome kako da nateramo da se desi jedna stvar tako što ćemo izmeniti određena mesta u genomu. Još nam dosta treba da otkrijemo kako da svinji damo krila, na primer. Ili čak nogu viška - zadovoljila bih se time. To bi bilo kul, zar ne? Ali dešava se to da CRISPR koriste hiljade i hiljade naučnika da bi obavljali zaista bitan posao poput toga da prave bolje modele bolesti kod životinja, na primer ili stvaranja načina za proizvođenje dragocenih hemikalija i njihovo dovođenje u bačve u industrijskoj proizvodnji i fermentaciji ili samo jednostavnog istraživanja o tome šta rade 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.
Ovo je priča o CRISPR-u koju bi trebalo da pričamo i ne dopada mi se što blještavije strane svega ovoga ne daju da izađe na videlo ostalo. Mnogo naučnika radilo je na tome da se desi CRISPR i meni je zanimljivo to da ove naučnike podržava naše društvo.
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 broju ljudi da provode vreme baveći se istraživanjem. To sve nas čini izumiteljima CRISPR-a, i rekla bih da to sve nas čini 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.
Pozvala bih vas sve da zaista naučite više o ovakvim tehnologijama jer zaista, jedino na taj način možemo zaista da vodimo razvoj ovih tehnologija, upotrebu ovih tehnologija i da se postaramo da sve ima srećan kraj - i za planetu i za nas.
Thanks.
Hvala.
(Applause)
(Aplauz)