A few years ago, with my colleague, Emmanuelle Charpentier, I invented a new technology for editing genomes. It's called CRISPR-Cas9. The CRISPR technology allows scientists to make changes to the DNA in cells that could allow us to cure genetic disease.
Prije nekoliko godina, kolegica, Emmanuelle Charpentier, i ja, izumile smo novu metodu za uređivanje genoma. Zove se CRISPR-Cas9. CRISPR metoda omogućuje znanstvenicima da mijenjaju DNK u stanicama što bi moglo pomoći u liječenju genetskih bolesti.
You might be interested to know that the CRISPR technology came about through a basic research project that was aimed at discovering how bacteria fight viral infections. Bacteria have to deal with viruses in their environment, and we can think about a viral infection like a ticking time bomb -- a bacterium has only a few minutes to defuse the bomb before it gets destroyed. So, many bacteria have in their cells an adaptive immune system called CRISPR, that allows them to detect viral DNA and destroy it.
Možda će vas zanimati da smo do CRISPR metode došli preko osnovnog istraživanja koji je bio usmjeren na otkrivanje načina otpornosti bakterija na virusne infekcije. Bakterije se bore s virusima u njihovom okolišu i virusnu infekciju možemo zamisliti kao tempiranu bombu - bakterija ima samo nekoliko minuta detonirati bombu prije nego što eksplodira. Mnoge bakterije u svojim stanicama imaju adaptivni imunosustav koji se zove CRISPR, koji im omogućava da otkriju virusni DNK i unište ga.
Part of the CRISPR system is a protein called Cas9, that's able to seek out, cut and eventually degrade viral DNA in a specific way. And it was through our research to understand the activity of this protein, Cas9, that we realized that we could harness its function as a genetic engineering technology -- a way for scientists to delete or insert specific bits of DNA into cells with incredible precision -- that would offer opportunities to do things that really haven't been possible in the past.
Dio CRISPR sustava je protein koji se zove Cas9, a koji može pretražiti, izrezivati i na kraju i uništiti virusni DNK na specifičan način. Kroz naše istraživanje pokušali smo razumjeti aktivnosti ovog proteina, Cas9, da bi shvatili kako možemo iskoristiti njegovu funkciju za genetski inženjering - način kojim znanstvenici brišu ili umeću specifične dijelove DNK u stanice s nevjerojatnom preciznošću - što bi stvorilo mogućnost da radimo stvari koje su prije bile nemoguće.
The CRISPR technology has already been used to change the DNA in the cells of mice and monkeys, other organisms as well. Chinese scientists showed recently that they could even use the CRISPR technology to change genes in human embryos. And scientists in Philadelphia showed they could use CRISPR to remove the DNA of an integrated HIV virus from infected human cells.
CRISPR metoda već se počela koristiti za izmjenu DNK u stanicama miševa i majmuna, kao i drugih organizama. Kineski su znanstvenici nedavno otkrili da bi mogli koristiti CRISPR metodu za izmjenu gena u ljudskim embrijima. Znanstvenici iz Philadelphije koristili su CRISPR za uklanjanje DNK integriranog virusa HIV-a iz inficirane ljudske stanice.
The opportunity to do this kind of genome editing also raises various ethical issues that we have to consider, because this technology can be employed not only in adult cells, but also in the embryos of organisms, including our own species. And so, together with my colleagues, I've called for a global conversation about the technology that I co-invented, so that we can consider all of the ethical and societal implications of a technology like this.
Mogućnost ovakve vrste uređivanja gena postavlja različita etička pitanja koja trebamo razmotriti zato što se ova metoda može koristiti ne samo na odraslim stanicama, nego i na embrijskim stanicama, uključujući i našu vrstu. Tako sam, zajedno sa svojim kolegama, pokrenula globalnu raspravu o ovoj metodi koju smo izumile, kako bi razmotrili sve etičke i društvene implikacije ovakve metode.
What I want to do now is tell you what the CRISPR technology is, what it can do, where we are today and why I think we need to take a prudent path forward in the way that we employ this technology.
Ono što želim učiniti je opisati vam CRISPR, što može činiti, gdje smo danas, i zašto mislim da trebamo razborito napredovati u načinu korištenja ove metode.
When viruses infect a cell, they inject their DNA. And in a bacterium, the CRISPR system allows that DNA to be plucked out of the virus, and inserted in little bits into the chromosome -- the DNA of the bacterium. And these integrated bits of viral DNA get inserted at a site called CRISPR. CRISPR stands for clustered regularly interspaced short palindromic repeats. (Laughter)
Kada virusi zaraze stanicu ubace svoj DNK. U bakteriji CRISPR sustav omogućava da se DNK izvadi iz virusne stanice, i umetne u malim dijelovima u kromosom - DNK bakterijske stanice. Ovi se integrirani dijelovi virusnog DNK umeću u dio koji se zove CRISPR. CRISPR je naziv za sljedove između kojih su kratke ponavljajuće palindromske sekvence. (Smijeh)
A big mouthful -- you can see why we use the acronym CRISPR. It's a mechanism that allows cells to record, over time, the viruses they have been exposed to. And importantly, those bits of DNA are passed on to the cells' progeny, so cells are protected from viruses not only in one generation, but over many generations of cells. This allows the cells to keep a record of infection, and as my colleague, Blake Wiedenheft, likes to say, the CRISPR locus is effectively a genetic vaccination card in cells. Once those bits of DNA have been inserted into the bacterial chromosome, the cell then makes a little copy of a molecule called RNA, which is orange in this picture, that is an exact replicate of the viral DNA. RNA is a chemical cousin of DNA, and it allows interaction with DNA molecules that have a matching sequence.
Mnogo riječi – vidite zašto koristimo akronim CRISPR. To je mehanizam kojim stanice mogu tijekom vremena bilježiti viruse kojima su bile izložene. A što je najvažnije, dijelovi DNK prenose se na stanice potomke te su tako zaštićene od virusa ne samo u jednoj generaciji, već i u sljedećim generacijama stanica. To je način kojim stanice mogu zapamtiti neku infekciju, i kao što moj kolega, Blake Wiedenheft, voli reći, CRISPR je efektivan način za genetsko cijepljenje stanica. Jednom kada su dijelovi DNK umetnuti u bakterijski kromosom, stanica može napraviti kopiju molekule koja se zove RNK, narančasta je na ovoj slici, i točna je kopija virusnog DNK. RNK je kemijski rođak DNK, i omogućava interakciju između molekula DNK koje imaju odgovarajuće sekvence.
So those little bits of RNA from the CRISPR locus associate -- they bind -- to protein called Cas9, which is white in the picture, and form a complex that functions like a sentinel in the cell. It searches through all of the DNA in the cell, to find sites that match the sequences in the bound RNAs. And when those sites are found -- as you can see here, the blue molecule is DNA -- this complex associates with that DNA and allows the Cas9 cleaver to cut up the viral DNA. It makes a very precise break. So we can think of the Cas9 RNA sentinel complex like a pair of scissors that can cut DNA -- it makes a double-stranded break in the DNA helix. And importantly, this complex is programmable, so it can be programmed to recognize particular DNA sequences, and make a break in the DNA at that site.
Ti mali dijelovi RNK na CRISPR sekvenci pridružuju se -- vežu na -- protein koji se zove Cas9, ovo bijelo na slici, i formiraju kompleks koji funkcionira kao stražar u stanici. Pretražuje redom DNK u stanici kako bi pronašao odgovarajuće sekvence na vezanim RNK. Kada pronađe te sekvence - kao što možete vidjeti, DNK je plava molekula - ovaj se kompleks veže za DNK i omogućava proteinu Cas9 da izreže virusni DNK. To čini vrlo precizno. Možemo zamisliti Cas9 RNK stražarski kompleks kao par škara koji reže DNK - i čini dvolančani rez na uzvojnici DNK. Što je najvažnije, ovaj je kompleks programabilan i može biti programiran da prepozna određene sekvence DNK, i napravi rez na tom mjestu na DNK.
As I'm going to tell you now, we recognized that that activity could be harnessed for genome engineering, to allow cells to make a very precise change to the DNA at the site where this break was introduced. That's sort of analogous to the way that we use a word-processing program to fix a typo in a document.
Kao što ću vam sada reći, prepoznali smo da se ta funkcija može iskoristiti za genetički inženjering, što omogućuje stanicama preciznu izmjenu vlastitog DNK na mjestu gdje je potrebna promjena. To je djelomično slično načinu na koji koristimo program za obradu teksta kako bi ispravili tipografsku grešku.
The reason we envisioned using the CRISPR system for genome engineering is because cells have the ability to detect broken DNA and repair it. So when a plant or an animal cell detects a double-stranded break in its DNA, it can fix that break, either by pasting together the ends of the broken DNA with a little, tiny change in the sequence of that position, or it can repair the break by integrating a new piece of DNA at the site of the cut. So if we have a way to introduce double-stranded breaks into DNA at precise places, we can trigger cells to repair those breaks, by either the disruption or incorporation of new genetic information. So if we were able to program the CRISPR technology to make a break in DNA at the position at or near a mutation causing cystic fibrosis, for example, we could trigger cells to repair that mutation.
Ono što nas je navelo na korištenje CRISPR sustava za genetički inženjering je to što stanice imaju sposobnost otkriti oštećeni DNK i popraviti ga. Kad biljna ili životinjska stanica otkrije grešku na dvostrukom lancu DNK, može to ispraviti tako da zalijepi krajeve slomljenog DNK s vrlo malom promjenom u sekvenci na tom mjestu ili može ispraviti oštećenje umetanjem novih sekvenci DNK na mjestu loma. Ako imamo način kojim možemo inducirati dvolančane lomove na DNK na određenom mjestu, možemo potaknuti stanicu na popravak tih lomova poremećajem ili ugradnjom nove genetske informacije. Ako možemo pomoću CRISPR metode inducirati oštećenje DNK na mjestu ili blizu mjesta mutacijekoja uzrokuje, primjerice, cističnu fibrozu, mogli bismo potaknuti stanicu na ispravak mutacije.
Genome engineering is actually not new, it's been in development since the 1970s. We've had technologies for sequencing DNA, for copying DNA, and even for manipulating DNA. And these technologies were very promising, but the problem was that they were either inefficient, or they were difficult enough to use that most scientists had not adopted them for use in their own laboratories, or certainly for many clinical applications. So, the opportunity to take a technology like CRISPR and utilize it has appeal, because of its relative simplicity. We can think of older genome engineering technologies as similar to having to rewire your computer each time you want to run a new piece of software, whereas the CRISPR technology is like software for the genome, we can program it easily, using these little bits of RNA.
Genetički inženjering nije nova stvar, u razvoju je od 1970-ih. Postoje metode za sekvenciranje, kopiranje, čak i za manipuliranje DNK. Ove su metode bile vrlo obećavajuće, ali problem je što su ili nedovoljno učinkovite ili problematične za upotrebu pa ih mnogi znanstvenici nisu usvojili za upotrebu u svojim laboratorijima, a zasigurno ni za mnoge kliničke primjene. Mogućnost da se metoda kao što je CRISPR upotrijebi je privlačna zbog svoje relativne jednostavnosti. Možemo starije metode genetskog inženjeringa usporediti s prespajanjem vašeg računala svaki put kada želite pokrenuti novi softver, a CRISPR je metoda kao stoftver za genom, možemo ju lako isprogramirati, korištenjem dijelića RNK.
So once a double-stranded break is made in DNA, we can induce repair, and thereby potentially achieve astounding things, like being able to correct mutations that cause sickle cell anemia or cause Huntington's Disease. I actually think that the first applications of the CRISPR technology are going to happen in the blood, where it's relatively easier to deliver this tool into cells, compared to solid tissues.
Jednom kada je dvostruki lom napravljen na DNK, možemo potaknuti popravak i time postići potencijalno zapanjujuće stvari, kao što su popravljanje mutacija koje uzrokuje anemiju srpastih stanica ili Huntigtonovu bolest. Zapravo mislim da će se prve primjene CRISPR metode dogoditi u krvožilnom sustavu, gdje je relativno lakše koristiti ovu metodu na stanicama u odnosu na čvrsta tkiva.
Right now, a lot of the work that's going on applies to animal models of human disease, such as mice. The technology is being used to make very precise changes that allow us to study the way that these changes in the cell's DNA affect either a tissue or, in this case, an entire organism.
Puno se posla koji se sada odvija odnosi na životinjske modele ljudskih bolesti, kao što su miševi. Metoda se koristi kako bi napravili vrlo precizne promjene koje omogućavaju proučavanje načina na koji ove promjene u staničnom DNK utječu na tkiva ili, u ovom slučaju, na cijeli organizam.
Now in this example, the CRISPR technology was used to disrupt a gene by making a tiny change in the DNA in a gene that is responsible for the black coat color of these mice. Imagine that these white mice differ from their pigmented litter-mates by just a tiny change at one gene in the entire genome, and they're otherwise completely normal. And when we sequence the DNA from these animals, we find that the change in the DNA has occurred at exactly the place where we induced it, using the CRISPR technology.
U ovom smo primjeru, CRISPR metodom poremetili gene učinivši malu promjenu u DNK u genu koji je odgovoran za crnu boju krzna ovog miša. Zamislite da se ovaj bijeli miš razlikuje od svojih obojanih sustanara samo po maloj genskoj promjeni u cijelom genomu, a po svemu je ostalome sasvim normalan. Kada sekvencioniramo DNK ovih životinja, uočavamo da se promjena u DNK nalazi na upravo onom mjestu na kojem smo ju inducirali koristeći CRISPR metodu.
Additional experiments are going on in other animals that are useful for creating models for human disease, such as monkeys. And here we find that we can use these systems to test the application of this technology in particular tissues, for example, figuring out how to deliver the CRISPR tool into cells. We also want to understand better how to control the way that DNA is repaired after it's cut, and also to figure out how to control and limit any kind of off-target, or unintended effects of using the technology.
Dodatni se pokusi vrše na drugim životinjama koje su korisne za stvaranje modela za ljudske bolesti, kao naprimjer majmunima. Zaključili smo da ovakav sustav možemo koristiti za testiranje uporabe ove metode u određenim tkivima, primjerice, kako dostaviti CRISPR u stanice. Također želimo bolje razumjeti kako kontrolirati način na koji je DNK popravljen nakon reza, ali i shvatiti kako ćemo kontrolirati i ograničiti bilo koji neciljan ili nenamjeran učinak korištenja ove metode.
I think that we will see clinical application of this technology, certainly in adults, within the next 10 years. I think that it's likely that we will see clinical trials and possibly even approved therapies within that time, which is a very exciting thing to think about. And because of the excitement around this technology, there's a lot of interest in start-up companies that have been founded to commercialize the CRISPR technology, and lots of venture capitalists that have been investing in these companies.
Mislim da ćemo vidjeti ovu metodu u kliničkoj uporabi, zasigurno kod odraslih, u sljedećih 10 godina. Mislim da je moguće da će postojati klinička ispitivanja, a vjerojatno i odobrene terapije unutar tog vremena, što je vrlo uzbudljiva stvar, kad razmislite. Zbog uzbuđenja oko ove metode, mnogo je zanimanja u novim tvrtkama koje su osnovane kako bi komercijalizirale CRISPR metodu, ali i puno smjelih kapitalista koji ulažu u ove tvrtke.
But we have to also consider that the CRISPR technology can be used for things like enhancement. Imagine that we could try to engineer humans that have enhanced properties, such as stronger bones, or less susceptibility to cardiovascular disease or even to have properties that we would consider maybe to be desirable, like a different eye color or to be taller, things like that. "Designer humans," if you will. Right now, the genetic information to understand what types of genes would give rise to these traits is mostly not known. But it's important to know that the CRISPR technology gives us a tool to make such changes, once that knowledge becomes available.
Moramo još razumjeti da se CRISPR metoda može koristiti za stvari kao što je poboljšanje. Zamislite da probamo stvoriti ljude koji bi imali poboljšane značajke, kao što su jače kosti, ili manju sklonost kardiovaskularnim bolestima ili imaju značajke koje bismo možda smatrali poželjnijima, kao što je druga boja očiju ili visina, takve stvari. Nazovimo to dizajniranim ljudima. Upravo sada, genetske informacije za razumijevanje tipa gena koji bi doveli do takvih osobina uglavnom su nepoznate. Ali važno je znati da je CRISPR metoda alat koji će omogućiti takvu vrstu promjene, jednom kada znanje postane dostupno.
This raises a number of ethical questions that we have to carefully consider, and this is why I and my colleagues have called for a global pause in any clinical application of the CRISPR technology in human embryos, to give us time to really consider all of the various implications of doing so. And actually, there is an important precedent for such a pause from the 1970s, when scientists got together to call for a moratorium on the use of molecular cloning, until the safety of that technology could be tested carefully and validated.
Ovo postavlja brojna etička pitanja koja je potrebno pomno razmotriti, i to je razlog zašto smo kolege i ja pozvali na globalnu stanku u kliničkoj primjeni CRISPR metode na ljudskim embrijima, kako bismo uspjeli razmotriti različite implikacije za to. Zapravo, postoji važan presedan za takvu stanku iz 1970-ih, kada su se znanstvenici sastali i zatražili moratorij na korištenje molekularnog kloniranja, dok se sigurnost metode pažljivo ne testira i opravda.
So, genome-engineered humans are not with us yet, but this is no longer science fiction. Genome-engineered animals and plants are happening right now. And this puts in front of all of us a huge responsibility, to consider carefully both the unintended consequences as well as the intended impacts of a scientific breakthrough.
Genski uređeni ljudi još ne postoje, no to više nije znanstvena fantastika. Genski uređene životinje i biljke sada su stvarnost. Ovo nam svima nameće veliku odgovornost da pažljivo razmotrimo neželjene posljedice kao i željene učinke ovog znanstvenog otkrića.
Thank you.
Hvala.
(Applause)
(Pljesak)
(Applause ends)
(Pljesak završava)
Bruno Giussani: Jennifer, this is a technology with huge consequences, as you pointed out. Your attitude about asking for a pause or a moratorium or a quarantine is incredibly responsible. There are, of course, the therapeutic results of this, but then there are the un-therapeutic ones and they seem to be the ones gaining traction, particularly in the media. This is one of the latest issues of The Economist -- "Editing humanity." It's all about genetic enhancement, it's not about therapeutics. What kind of reactions did you get back in March from your colleagues in the science world, when you asked or suggested that we should actually pause this for a moment and think about it?
Bruno Giussani: Jennifer, ovo je metoda koja nosi velike posljedice, kao što ste istaknuli. Vaš stav i molba za stankom ili moratorijem ili karantenom izuzetno je odgovoran. Postoje, naravno, terapijski rezultati ovoga, ali postoje i oni neterapijski, a oni, čini se, dobivaju najviše pažnje, posebice u medijima. Ovo je jedan od zadnjih brojeva The Economista – „Uređivanje čovječanstva“ Sve je o genetskom poboljšanju, a ne o liječenju. Kakve ste reakcije dobili u ožujku od svojih kolega u znanstvenom svijetu, kada ste pitali, predložili da bi trebali napraviti stanku na trenutak i razmisliti o svemu?
Jennifer Doudna: My colleagues were actually, I think, delighted to have the opportunity to discuss this openly. It's interesting that as I talk to people, my scientific colleagues as well as others, there's a wide variety of viewpoints about this. So clearly it's a topic that needs careful consideration and discussion.
Jennifer Doudna: Moje su kolege, zapravo bili oduševljeni što imaju priliku otvoreno razgovarati. Zanimljivo je da u razgovoru s ljudima, kolegama znanstvenicima, ali i drugima, vidim da postoje razni pogledi na sve ovo. Jasno je da su za ovu temu potrebni pažljivo razmatranje i rasprava.
BG: There's a big meeting happening in December that you and your colleagues are calling, together with the National Academy of Sciences and others, what do you hope will come out of the meeting, practically?
BG: Važan se sastanak održava u prosincu ove godine koji ste sazvali vi i vaši kolege, zajedno s Nacionalnom akademijom znanosti i drugima, što mislite, što će proizaći iz njega?
JD: Well, I hope that we can air the views of many different individuals and stakeholders who want to think about how to use this technology responsibly. It may not be possible to come up with a consensus point of view, but I think we should at least understand what all the issues are as we go forward.
JD: Nadam se da možemo obznaniti poglede različitih individualaca i dioničara koji žele razmišljati o tome kako ovu metodu odgovorno upotrebljavati. Možda neće biti moguće doći do zajedničkog stajališta, ali mislim da, kako napredujemo, trebamo razumjeti svu materiju.
BG: Now, colleagues of yours, like George Church, for example, at Harvard, they say, "Yeah, ethical issues basically are just a question of safety. We test and test and test again, in animals and in labs, and then once we feel it's safe enough, we move on to humans." So that's kind of the other school of thought, that we should actually use this opportunity and really go for it. Is there a possible split happening in the science community about this? I mean, are we going to see some people holding back because they have ethical concerns, and some others just going forward because some countries under-regulate or don't regulate at all?
BG: Neke vaše kolege, kao što je George Church s Harvada, primjerice, kažu, „Etička su pitanja samo pitanja sigurnosti. Mi neprestano testiramo na životinjama i u laboratoriju, i kada pomislimo da je dovoljno sigurno, prijeći ćemo na ljude.“ Ovo je drugačiji način razmišljanja, da bi trebali ovu priliku u potpunosti iskoristiti. Je li moguće u znanstvenoj zajednici imati podijeljena mišljenja o ovome? Hoćemo li vidjeti neke ljude kako se suzdržavaju jer imaju etičke brige, a druge kako grabe priliku jer neke zemlje slabo ili uopće ne reguliraju etička pitanja?
JD: Well, I think with any new technology, especially something like this, there are going to be a variety of viewpoints, and I think that's perfectly understandable. I think that in the end, this technology will be used for human genome engineering, but I think to do that without careful consideration and discussion of the risks and potential complications would not be responsible.
JD: Mislim da sa svakom novom metodom, a posebno nekom kao što je ova, uvijek postoje različita stajališta, i mislim da je to sasvim razumljivo. Mislim da će na kraju ova metoda biti korištena za genomski inženjering ljudi, ali raditi to bez pažljivog razmatranja i rasprave o rizicima i mogućim komplikacijama ne bi bilo odgovorno.
BG: There are a lot of technologies and other fields of science that are developing exponentially, pretty much like yours. I'm thinking about artificial intelligence, autonomous robots and so on. No one seems -- aside from autonomous warfare robots -- nobody seems to have launched a similar discussion in those fields, in calling for a moratorium. Do you think that your discussion may serve as a blueprint for other fields?
BG: Postoje mnoge metode i druga znanstvena polja koja se eksponencijalno razvijaju, slično kao i vaše. Govorim o umjetnoj inteligenciji, samoupravljajućim robotima i tako dalje. Čini se da ništa - osim ratnih samoupravljajućih robota -- nije pokrenulo sličnu raspravu na tim poljima, i pozvao na moratorij. Mislite li da će vaša rasprava možda poslužiti kao predložak za ostala polja?
JD: Well, I think it's hard for scientists to get out of the laboratory. Speaking for myself, it's a little bit uncomfortable to do that. But I do think that being involved in the genesis of this really puts me and my colleagues in a position of responsibility. And I would say that I certainly hope that other technologies will be considered in the same way, just as we would want to consider something that could have implications in other fields besides biology.
JD: Mislim da je znanstvenicima teško napustiti laboratorij. Govoreći o sebi, malo je nelagodno to učiniti. Ali mislim da uključenost u nastanak ovoga mene i moje kolege stavlja na odgovornu poziciju. Mogu reći da se iskreno nadam da će ostale metode biti razmotrene na isti način, kao što bismo mi htjeli razmotriti nešto što bi moglo imati implikacije u drugim poljima, a ne samo u biologiji.
BG: Jennifer, thanks for coming to TED.
BG: Jennifer, hvala ti na dolasku na TED.
JD: Thank you.
JD: Hvala vama.
(Applause)
(Pljesak)