What you need to know about CRISPR | Ellen Jorgensen

Prevoditelj: Ivan Stamenković Recezent: Senzos Osijek

So, has everybody heard of CRISPR?

Da li su svi ovdje čuli za CRISPR?

I would be shocked if you hadn't.

Bila bih šokirana da niste.

This is a technology -- it's for genome editing --

Ovo je tehnologija -- za uređivanje gena --

and it's so versatile and so controversial

i tako je prilagodljiva i kontroverzna

that it's sparking all sorts of really interesting conversations.

da potiče svakakve zaista zanimljive razgovore.

Should we bring back the woolly mammoth?

Trebamo li vratiti mamuta?

Should we edit a human embryo?

Trebamo li uređivati ljudski embrij?

And my personal favorite:

I moj najdraži:

How can we justify wiping out an entire species

Kako možemo opravdati brisanje čitave vrste,

that we consider harmful to humans

koju smatramo štetnima za ljude,

off the face of the Earth,

sa lica zemlje,

using this technology?

koristeći ovu tehnologiju?

This type of science is moving much faster

Ova vrsta znanosti kreće se puno brže

than the regulatory mechanisms that govern it.

od regulatornih mehanizama koji njome upravljaju.

And so, for the past six years,

I tako, posljednjih šest godina,

I've made it my personal mission

moja osobna misija je

to make sure that as many people as possible understand

osigurati da što više ljudi razumije

these types of technologies and their implications.

ove tipove tehnologija i njihove implikacije.

Now, CRISPR has been the subject of a huge media hype,

Sada, CRISPR je bio predmet velike pompe u medijima,

and the words that are used most often are "easy" and "cheap."

i riječi koje se najčešće koriste su "jednostavno" i "povoljno."

So what I want to do is drill down a little bit deeper

I ono što želim je otići malo dublje

and look into some of the myths and the realities around CRISPR.

i pogledati neke mitove i stvarnost vezanu uz CRISPR.

If you're trying to CRISPR a genome,

Ako pokušavate CRISPRirati genom,

the first thing that you have to do is damage the DNA.

prva stvar koju morate napraviti je oštetiti DNK.

The damage comes in the form of a double-strand break

Šteta dolazi u obliku pucanja dva vlakna

through the double helix.

kroz dvostruku uzvojnicu.

And then the cellular repair processes kick in,

I onda se jave procesi za popravljanje stanica,

and then we convince those repair processes

i onda uvjerimo te procese za popravljanje

to make the edit that we want,

da naprave uređivanje koje želimo,

and not a natural edit.

a ne prirodno uređivanje.

That's how it works.

Tako to radi.

It's a two-part system.

To je sustav iz dva dijela.

You've got a Cas9 protein and something called a guide RNA.

Imate Cas9 protein i nešto što se zove vodička RNK.

I like to think of it as a guided missile.

Volim zamišljati to kao navođenu raketu.

So the Cas9 -- I love to anthropomorphize --

Dakle Cas9 -- volim antropomorfozirati --

so the Cas9 is kind of this Pac-Man thing

tako da je Cas9 neka vrsta stvari poput Pac-Mana

that wants to chew DNA,

koja želi žvakati DNK,

and the guide RNA is the leash that's keeping it out of the genome

i vodička RNK je uzica koja ga drži izvan genoma

until it finds the exact spot where it matches.

dok ne nađe točno mjestso gdje se uklapa.

And the combination of those two is called CRISPR.

I kombinacija te dvije stvari zove se CRISPR.

It's a system that we stole

To je sustav koji smo ukrali

from an ancient, ancient bacterial immune system.

od drevnih, drevnih bakterijskih imunosnih sustava.

The part that's amazing about it is that the guide RNA,

Ono što je fascinanto je da vodička RNK,

only 20 letters of it,

samo 20 slova nje,

are what target the system.

je ono što cilja sustav.

This is really easy to design,

To je jako jednostavno za dizajnirati,

and it's really cheap to buy.

i vrlo povoljno za kupiti.

So that's the part that is modular in the system;

To je dio koji je modularan u sustavu,

everything else stays the same.

sve ostalo ostaje isto.

This makes it a remarkably easy and powerful system to use.

Tako nastaje nevjerojatno jednostavan i snažan sustav za korištenje.

The guide RNA and the Cas9 protein complex together

Vodička RNK i Cas9 kompleks bjelančevina skupa

go bouncing along the genome,

skakuću po genomu,

and when they find a spot where the guide RNA matches,

i kada nađu mjesto na koje pristaje RNK,

then it inserts between the two strands of the double helix,

umeće se između dvije niti dvostruke uzvojnice,

it rips them apart,

kida ih,

that triggers the Cas9 protein to cut,

i to uzrokuje da Cas9 bjelančevina reže,

and all of a sudden,

i odjednom,

you've got a cell that's in total panic

imate stanicu koja je u panici

because now it's got a piece of DNA that's broken.

jer sada ima komad pokidane DNK.

What does it do?

Što mora učiniti?

It calls its first responders.

Poziva prve intervente.

There are two major repair pathways.

Postoje dva puta za popravak.

The first just takes the DNA and shoves the two pieces back together.

PRvi samo uzima DNK i spoji ta dva komada.

This isn't a very efficient system,

Ovo nije učinkovit sistem

because what happens is sometimes a base drops out

jer ponekad baza ispadne

or a base is added.

ili je dodana.

It's an OK way to maybe, like, knock out a gene,

To je OK način za izbacivanje gena,

but it's not the way that we really want to do genome editing.

ali to nije način na koji želite uređivati genom.

The second repair pathway is a lot more interesting.

Drugi put popravka je puno zanimljiviji.

In this repair pathway,

Ovim putem,

it takes a homologous piece of DNA.

trebate homologni komad DNK.

And now mind you, in a diploid organism like people,

I sad, u diploidnih organizama kao što su ljudi,

we've got one copy of our genome from our mom and one from our dad,

imamo jednu kopiju našeg genoma od mame i jednu od tate,

so if one gets damaged,

tako da ako se jedna ošteti,

it can use the other chromosome to repair it.

može koristiti drugi kromosom za popravak.

So that's where this comes from.

Dakle odavde to dolazi.

The repair is made,

Popravak je napravljen,

and now the genome is safe again.

i sada je genom ponovno siguran.

The way that we can hijack this

Način na koji ovo želimo oteti

is we can feed it a false piece of DNA,

je da ga hranimo lažnim komadom DNK,

a piece that has homology on both ends

komadom koji ima homologiju na oba kraja

but is different in the middle.

ali je drugačiji u sredini.

So now, you can put whatever you want in the center

Sada, možete u sredinu staviti što god želite

and the cell gets fooled.

i stanica će biti zavarana.

So you can change a letter,

Tako da možete mijenjati slovo,

you can take letters out,

možete izvaditi slovo,

but most importantly, you can stuff new DNA in,

ali najvažnije, možete nagurati novu DNK unutra,

kind of like a Trojan horse.

nešto kao Trojanski konj.

CRISPR is going to be amazing,

CRISPR će biti nevjerojatan

in terms of the number of different scientific advances

u pogledu broja različitih znanstvenih napredaka

that it's going to catalyze.

koje će katalizirati.

The thing that's special about it is this modular targeting system.

Stvar koja je posebna u tome je ovaj modularni sustav za ciljanje.

I mean, we've been shoving DNA into organisms for years, right?

Mislim, guramo DNK u organizme godinama, zar ne?

But because of the modular targeting system,

Ali zbog modularnog sustava za ciljanje,

we can actually put it exactly where we want it.

možemo ju zapravo staviti gdje god želimo.

The thing is that there's a lot of talk about it being cheap

Stvar je u tome da se puno priča o tome da je povoljan

and it being easy.

i lak za shvatiti.

And I run a community lab.

I ja vodim društveni laboratorij.

I'm starting to get emails from people that say stuff like,

Počinjem dobivati mailove ljudi koji kažu sljedeće,

"Hey, can I come to your open night

"Mogu li doći na vašu otvorenu večer

and, like, maybe use CRISPR and engineer my genome?"

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.

To ćemo malo istraživati.

So, how cheap is it?

Pa, koliko je to povoljno?

Yeah, it is cheap in comparison.

Da, povoljan je u usporedbi s drugima.

It's going to take the cost of the average materials for an experiment

Smanjit će troškove prosječnih materijala za eksperimente

from thousands of dollars to hundreds of dollars,

sa tisuća i tisuća dolara na stotine dolara,

and it cuts the time a lot, too.

i skraćuje potrebno vrijeme također.

It can cut it from weeks to days.

Može skratiti vrijeme od tjedana do dana.

That's great.

To je fantastično.

You still need a professional lab to do the work in;

Još uvijek trebate profesionalni laboratorij u kojem ćete raditi;

you're not going to do anything meaningful outside of a professional lab.

nećete ništa značajno napraviti izvan profesionalnog laboratorija.

I mean, don't listen to anyone who says

Mislim, nemojte slušati nikoga tko kaže

you can do this sort of stuff on your kitchen table.

da možete ove stvari raditi na vašem kuhinjskom stolu.

It's really not easy to do this kind of work.

Nije lako raditi ovakve stvari.

Not to mention, there's a patent battle going on,

Da ne spominjem da postoji bitka za patente trenutno,

so even if you do invent something,

tako da i ako nešto izumimo,

the Broad Institute and UC Berkeley are in this incredible patent battle.

Broad Institut, ili Berkeley se bore u ovoj bitci za patent.

It's really fascinating to watch it happen,

Zaista je fascinantno gledati je kako se razvija

because they're accusing each other of fraudulent claims

jer se optužuju međusobno za lažne tvrdnje

and then they've got people saying,

i onda ljudi dolaze i govore,

"Oh, well, I signed my notebook here or there."

"Pa potpisao sam bilježnicu tu ili tu."

This isn't going to be settled for years.

To se neće riješiti godinama.

And when it is,

A i kada se riješi,

you can bet you're going to pay someone a really hefty licensing fee

možete se gladiti da ćete nekome plaćati pozamašnu svotu za licencu

in order to use this stuff.

kako biste koristili ove stvari.

So, is it really cheap?

Pa, je li zaista povoljno?

Well, it's cheap if you're doing basic research and you've got a lab.

Pa, povoljno je ako radite osnovno istraživanje i imate laboratorij.

How about easy? Let's look at that claim.

A što s time da je jednostavno? Pogledajmo tu tvrdnju.

The devil is always in the details.

Vrag je uvijek u detaljima.

We don't really know that much about cells.

Zaista ne znamo tako puno o stanicama.

They're still kind of black boxes.

One su još uvijek crne kutije.

For example, we don't know why some guide RNAs work really well

Na primjer, ne znamo zašto neka vodička RNK radi dobro,

and some guide RNAs don't.

a druge ne.

We don't know why some cells want to do one repair pathway

Ne znam zašto neke stanice rade popravke jednim putem

and some cells would rather do the other.

a neke druge drugim putem.

And besides that,

I osim toga,

there's the whole problem of getting the system into the cell

postoji čitav problem stavljanja sustava u stanicu

in the first place.

na prvom mjestu.

In a petri dish, that's not that hard,

U petrijevoj zdjelici, to nije teško,

but if you're trying to do it on a whole organism,

ali ako pokušavate to napraviti čitavom organizmu,

it gets really tricky.

postaje dosta nezgodno.

It's OK if you use something like blood or bone marrow --

U redu je ako koristite nešto kao koštanu srž --

those are the targets of a lot of research now.

to je predmet dosta istraživanja.

There was a great story of some little girl

Postojala je odlična priča o djevojčici

who they saved from leukemia

koju su spasili od leukemije

by taking the blood out, editing it, and putting it back

uzimajući krv, uređujući je i vrativši je

with a precursor of CRISPR.

sa pretečom CRISPR-a.

And this is a line of research that people are going to do.

I ovo je istraživanje koje će ljudi raditi.

But right now, if you want to get into the whole body,

Ali sada, ako želite doći u cijelo tijelo,

you're probably going to have to use a virus.

morat ćete koristiti virus.

So you take the virus, you put the CRISPR into it,

Uzmete virus, stavite CRISPR u njega,

you let the virus infect the cell.

dozvolite virusu da zarazi stanicu.

But now you've got this virus in there,

Ali sada tu imate taj virus,

and we don't know what the long-term effects of that are.

i ne znamo kako će dugoročno utjecati na okruženje.

Plus, CRISPR has some off-target effects,

A i CRISPR ima neke neželjene učinke,

a very small percentage, but they're still there.

vrlo malen postotak, ali oni su još uvijek tamo.

What's going to happen over time with that?

Što će se s njima dogoditi kroz vrijeme?

These are not trivial questions,

OVo nisu trivijalna pitanja,

and there are scientists that are trying to solve them,

i postoje znanstvenici koji na njih pokušavaju odgovoriti,

and they will eventually, hopefully, be solved.

i s vremenom će, nadamo se, biti riješeni.

But it ain't plug-and-play, not by a long shot.

Ali to nije uključi i igraj, ni u kom slučaju.

So: Is it really easy?

Dakle, je li zaista lako?

Well, if you spend a few years working it out in your particular system,

Pa, ako potrošite nekoliko godina radeći s tim u određenom sustavu,

yes, it is.

da, jest.

Now the other thing is,

Druga stvar je,

we don't really know that much about how to make a particular thing happen

mi ne znamo puno o tome kako učiniti da se određena stvar dogodi

by changing particular spots in the genome.

mjenjajući određena mjesta u genomu.

We're a long way away from figuring out

Daleko smo od shvaćanja kako

how to give a pig wings, for example.

svinjama dati krila, na primjer.

Or even an extra leg -- I'd settle for an extra leg.

Ili samo dodatnu nogu -- zadovoljila bih se dodatnom nogom.

That would be kind of cool, right?

To bi bilo pomalo kul, zar ne?

But what is happening

Ali ono što se događa

is that CRISPR is being used by thousands and thousands of scientists

je da CRISPR koriste tisuće i tisuće znanstvenika

to do really, really important work,

kako bi radili vrlo, vrlo važan posao,

like making better models of diseases in animals, for example,

radeći bolje modele bolesti kod životinja na primjer,

or for taking pathways that produce valuable chemicals

ili koristeći putanje koje proizvode vrijedne kemikalije

and getting them into industrial production in fermentation vats,

i uvode ih u industrijsku proizvodnju u fermentacijskim kacama,

or even doing really basic research on what genes do.

ili rade osnovna istraživanja o tome što čine geni.

This is the story of CRISPR we should be telling,

To je priča CRISPR-a koju bismo trebali pričati

and I don't like it that the flashier aspects of it

i ne volim što ovi blještavi dijelovi

are drowning all of this out.

zasjenjuju sve ovo.

Lots of scientists did a lot of work to make CRISPR happen,

Puno znanstvenika radilo je na tome da se CRISPR dogodi,

and what's interesting to me

i ono što mi je zanimljivo mi je

is that these scientists are being supported by our society.

da su ovi znanstvenici poduprti od strane društva.

Think about it.

Razmislite o tome.

We've got an infrastructure that allows a certain percentage of people

Imamo infrastrukturu koja dozvoljava određenom postotku ljudi

to spend all their time doing research.

da troši svo svoje vrijeme istraživajući.

That makes us all the inventors of CRISPR,

To nas sve čini izumiteljima CRISPR-a,

and I would say that makes us all the shepherds of CRISPR.

i čini nas pastirima CRISPR-a.

We all have a responsibility.

Svi imamo odgovornost.

So I would urge you to really learn about these types of technologies,

Tako da bih urgirala da zaista naučite nešto o ovim tehnologijama,

because, really, only in that way

jer, zapravo, samo na taj način

are we going to be able to guide the development of these technologies,

ćemo moći voditi razvoj ovih tehnologija,

the use of these technologies

uporabu ovih tehnologija

and make sure that, in the end, it's a positive outcome --

i biti sigurni da je na kraju rezultat pozitivan --

for both the planet and for us.

i za planet i za nas.

Thanks.

Hvala.

(Applause)

(Pljesak)