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.
Pre nekoliko godina, sa kolegom Emanuelom Šarpentjeom, otkrila sam novu tehnologiju za preuređenje genoma. Ona se zove CRISPR-Cas9. Ova tehnologija omogućava naučnicima da prave promene u DNK u ćelijama, koje nam mogu omogućiti da izlečimo genetske 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 je CRISPR tehnologija nastala iz jednog jednostavnog istraživanja koje je za cilj imalo da otkrije kako se bakterije bore protiv virusa. Bakterije u svojim okruženjima moraju da se susreću sa virusima i virusne infekcije možemo zamisliti kao tempirane bombe - bakterija ima samo nekoliko minuta da deaktivira bombu pre nego što je ona uništi. I tako mnoge bakterije u svojim ćelijama image adaptivni imuni sistem, CRISPR, koji im omogućava da otkriju i unište virusnu DNK.
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.
Deo CRISPR sistema je protein pod nazivom Cas9, koji može da pronađe, razdvoji i na kraju degradira virusnu DNK na jedan poseban način. Kroz naše istraživanje kojim smo želeli da razumemo aktivnost ovog proteina, Cas9, shvatili smo da možemo da iskoristimo njegovu funkciju kao tehnologiju genetskog inženjeringa - način na koji naučnici odstrane ili ubace određene delove DNK u ćelije sa izuzetnom preciznošću - kojom bismo dobili mogućnosti da radimo stvari koje uopšte nisu bile moguće u prošlosti.
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 tehnologija je već korišćena da promeni DNK u ćelijama miševa i majmuna, kao i drugih organizama. Kineski naučnici su nedavno pokazali da CRISPR tehnologiju mogu da koriste čak i da promene gene u ljudskim embrionima. A naučnici u Filadelfiji su pokazali da mogu da koriste CRISPR da odstrane DNK integrisanih HIV virusa iz zaraženih ljudskih ćelija.
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.
Prilika da se na ovaj način preuređuje genom povlači za sobom etička pitanja koja moramo da razmotrimo, jer ova tehnologija može da se primeni ne samo na odraslim ćelijama, nego i na embrionima organizama, uključujući i našu vrstu. I tako, zajedno sa kolegama, pozvala sam na globalni razgovor o ovoj tehnologiji čiji sam su-osnivač, kako bismo razmotrili sve etičke i društvene implikacije jedne ovakve tehnologije.
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.
Sada želim da vam ispričam šta je CRISPR tehnologija, šta može da uradi, gde smo danas i zašto mislim da moramo mudro da postupamo u načinu na koji ovu tehnologiju primenjujemo.
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 neku ćeliju, oni ubace svoju DNK. A u bakteriji, CRISPR sistem dozvoljava da se DNK iznese iz virusa i u malim delovima ubaci u hromozom - u DNK bakterije. Ovi integrisani delovi virusne DNK umeću se na mestu pod nazivom CRISPR. CRISPR znači grupisana, pravilno raspoređena kratka palindromska ponavljanja.
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.
Složen pojam - shvatate zašto koristimo akronim CRISPR. To je mehanizam koji dozvoljava ćelijama da tokom vremena beleže viruse kojima su bile izložene. I, što je važno, ti delovi DNK se prenose na potomke tih ćelija, tako da su ćelije od virusa zaštićene ne samo u jednoj generaciji, nego tokom mnogo generacija. Ovo dozvoljava ćeliji da prati zaraze i kako moj kolega, Blejk Videnheft, voli da kaže, CRISPR je efikasna genetska karta vakcine u ćeliji. Jednom kada se ti delovi DNK ubace u bakterijski hromozom, ćelija tada pravi malu kopiju molekula zvanog RNK, koji je na ovoj slici narandžast, koji je doslovna replika virusne DNK. RNK je hemijski rođak DNK i dozvoljava interakciju sa molekulima DNK koji imaju sličnu sekvencu.
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.
Dakle, ti delići RNK iz CRISPR-a vezuju se za protein pod nazivom Cas9, koji je na slici bele boje, i formiraju sastav koji u ćeliji funkcioniše kao stražar. On pretražuje svu DNK u ćeliji kako bi našao mesta koja se poklapaju sa sekvencama vezane RNK. I kada ta mesta pronađe - kao što ovde vidite, plavi molekul je DNK - ovaj sastav se udružuje sa tom DNK i dozvoljava da sečivo Cas9 ispreseca virusnu DNK. On pravi veoma precizan rez. Ovaj sastav Cas9 RNK stražara možemo da posmatramo kao par makaza koje mogu da seku DNK; on pravi dvostrani presek u DNK spirali. Ono što je važno je da je ovaj sastav moguće programirati, da prepozna određene sekvence DNK i preseče DNK na tom mestu.
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.
I kao što ću vam sad reći, prepoznali smo da ta aktivnost može da se iskoristi za genetski inženjering, da dozvoli ćelijama da prave vrlo precizne promene u DNK na mestu gde se napravi ovaj rez. Ovo je donekle analogno načinu na koji koristimo programe za obradu teksta kako bismo popravili grešku u nekom dokumentu.
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.
Razlog zašto smo zamislili korišćenje CRISPR-a za genetski inženjering je zato što ćelije imaju sposobnost da otkriju i poprave oštećenu DNK. Kad ćelija biljke ili životinje otkrije dvostrani prekid u svojoj DNK, ona može da ga popravi, ili tako što sastavi krajeve oštećene DNK malom, sitnom promenom u sekvenci te pozicije, ili integrisanjem novog komada DNK na mestu oštećenja. Dakle, ako imamo način da unesemo dvostrane prekide u DNK na određenim mestima, možemo podstaći ćelije da poprave ta oštećenja, ili prekidom ili uklapanjem nove genetske informacije. Dakle, da možemo da isprogramiramo CRISPR tehnologiju da preseče DNK na mestu ili u blizini mutacije koja uzrokuje cističnu fibrozu, recimo, podstakli bismo ćelije da poprave tu mutaciju.
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.
Genetski inženjering nije novost; razvija se od 1970-ih. Postoje tehnologije za sekvenciranje DNK, za kopiranje DNK, i čak za manipulisanje DNK. One su mnogo obećavale, ali je problem bio što nisu bile efikasne ili su bile toliko složene za upotrebu da ih većina naučnika nije usvojila u svom radu u laboratorijama, a kamoli za kliničke primene. Dakle, prilika da se koristi tehnologija kao što je CRISPR je privlačna, zbog svoje relativne jednostavnosti. Starije tehnologije genetskog inženjeringa možemo porediti sa ponovnim instaliranjem računara svaki put kada želite da pokrenete novi program, dok je CRISPR kao softver za genom; možemo ga lako programirati koristeći ove male delove 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 kad se napravi dvostrani presek u DNK, možemo da pokrenemo popravku i tako potencijalno postignemo izuzetne stvari, npr. da ispravimo mutacije koje uzrokuju anemiju ćelija ili Hantingtonovu bolest. Ja mislim da će se ova tehnologija prvo upotrebljavati na krvi, gde je relativno lakše dovesti je u ćelije u poređenju sa čvrstim tkivima.
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.
Trenutno, mnogo se radi na životinjskim modelima ljudskih bolesti, npr. miševima. Ova tehnologija se koristi da se naprave vrlo precizne promene koje dozvoljavaju da proučavamo način na koji one u ćelijskoj DNK utiču na tkivo ili, u ovom slučaju, na ceo 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 primeru, CRISPR tehnologija je korišćena da poremeti gen pravljenjem male promene u DNK u genu koji je odgovoran za crnu boju ovih miševa. Zamislite da se ovi beli miševi razlikuju od svojih obojenih rođaka samo u maloj promeni jednog gena u celom genomu, a inače su potpuno normalni. I kad sekvenciramo DNK onih životinja, otkrivamo da je ta promena u DNK nastala tačno na onom mestu gde smo je uveli koristeći CRISPR tehnologiju.
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 eksperimenti se vrše na drugim životinjama, koji su korisni za pravljenje modela ljudskih bolesti, kao što su majmuni. I ovde otkrivamo da možemo da koristimo ove sisteme da testiramo primenu ove tehnologije na određenim tkivima, na primer, da razumemo kako da dostavimo CRISPR u ćelije. Takođe želimo bolje da razumemo kako da kontrolišemo način na koji se DNK popravlja posle oštećenja, i da razumemo kako da kontrolišemo i ograničimo bilo kakvo odstupanje ili neželjene efekte korišćenja ove tehnologije.
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 kliničku primenu ove tehnologije, sigurno kod odraslih, videti u narednih 10 godina. Mislim da je verovatno da ćemo u tom vremenskom okviru videti klinička testiranja i možda odobrene terapije, što je veoma uzbudljivo za razmišljanje. I zbog uzbuđenja u vezi sa ovom tehnologijom, mnoge startap kompanije su veoma zainteresovane i osnovane radi komercijalizacije CRISPR tehnologije, i mnogo investitora ulaže u te kompanije.
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.
Međutim, moramo takođe da uzmemo u obzir da CRISPR tehnologija može da se koristi za npr. poboljšanja. Zamislite da pokušamo da napravimo ljude koji imaju pojačane osobine, kao što su jače kosti, manja podložnost kardiovaskularnoj bolesti ili čak koji imaju osobine koje bismo smatrali poželjnim, na primer drugačija boja očiju ili visina, takve stvari. „Dizajnirani ljudi“, da tako kažem. Trenutno, genetske informacije kojima bismo znali koje vrste gena bi podstakle ove osobine uglavnom su nepoznate. Međutim, važno je znati da nam CRISPR tehnologija daje alat da takve promene pravimo, jednom kada budemo imali znanje.
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 pokreće mnoga etička pitanja koja pažljivo moramo da razmotrimo i zato smo ja i moje kolege pozvali na globalnu pauzu u bilo kakvoj kliničkoj primeni ove tehnologije na ljudskim embrionima, da bismo dobili vremena da stvarno razmotrimo različite implikacije toga. U stvari, postoji važan presedan za takvu pauzu iz 1970-ih kada su se naučnici okupili da pozovu na moratorijum u korišćenju molekularnog kloniranja, dok bezbednost te tehnologije nije bila pažljivo testirana i potvrđena.
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.
Dakle, genetski izmenjeni ljudi još uvek nisu među nama, ali to više nije naučna fantastika. Genetski modifikovane životinje i biljke se upravo dešavaju. A to pred sve nas stavlja ogromnu odgovornost, da pažljivo razmotrimo neželjene posledice, ali i željene efekte nekog naučnog otkrića.
Thank you.
Hvala vam.
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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 Đuzani: Dženifer, ovo je tehnoloija sa ogromnim posledicama, kao što ste istakli. Vaš stav u vezi sa traženjem pauze, moratorijuma ili karantina je izuzetno odgovoran. Naravno, postoje terapijski rezultati ovoga, ali i neterapijski, a oni izgleda dobijaju pažnju, posebno u medijima. Ovo je jedno od poslednjih izdanja „Ekonomista“ - „Menjanje čovečanstva“. Priča se o genetskim poboljšanjima, ne o lečenjima. Kakve reakcije ste dobili u martu, od Vaših kolega iz naučnog sveta, kada ste tražili ili preporučili da bi trebalo da zastanemo i razmislimo na trenutak?
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.
Dženifer Daudna: Mislim da su kolege u stvari bile oduševljene što imaju priliku da o ovome otvoreno razgovaraju. Zanimljivo je da, dok razgovaram sa ljudima, mojim kolegama naučnicima i ostalima, postoji širok spektar viđenja ovoga. Jasno je da je to tema koju je potrebno pažljivo razmotriti i o njoj pričati.
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?
BĐ: U decembru će se održati veliki sastanak koji ste organizovali Vi i Vaše kolege, zajedno sa Nacionalnom naučnom akademijom i drugima. Šta se nadate da će biti ishod tog sastanka, u praktičnom smislu?
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.
DžD: Nadam se da ćemo izneti stavove mnogih pojedinaca i zainteresovanih strana koje žele da razmišljaju o odgovornom korišćenju ove tehnologije. Možda neće biti moguće postići konsenzus, ali mislim da bi trebalo makar da razumemo koji su sve problemi u daljem radu.
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?
BĐ: Vaše kolege, kao što je Džordž Čerč, na primer, sa Harvarda, kažu: „Da, etička pitanja su u osnovi pitanja sigurnosti. Testiramo iznova i iznova, na životinjama u laboratoriji, i kad osetimo da je dovoljno bezbedno, prelazimo na ljude.“ To je druga struja razmišljanja, da možemo da iskoristimo ovu priliku i prihvatimo je. Da li možda ovo podstiče razdor u naučnoj zajednici? Mislim, da li ćemo videti da se neki uzdržavaju zbog etičkih pitanja, a neki samo idu napred jer neke zemlje imaju slabu ili nikakvu regulativu?
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.
DžD: Mislim da će sa svakom novom tehnologijom, posebno ovakvom, biti različitih stavova i mislim da je to potpuno razumljivo. Mislim da će na kraju ova tehnologija biti korišćena za inženjering ljudskog genoma, ali mislim da ne bi bilo odgovorno to uraditi bez pažljive diskusije i razmatranja rizika i potencijalnih komplikacija.
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?
BĐ: Postoje mnoge tehnologije i druga naučna polja koja se razvijaju eksponencijalno, skoro kao vaše polje. Mislim na veštačku inteligenciju, autonomne robote itd. Niko izgleda - osim autonomnih robota za ratovanje - niko nije pokrenuo sličnu diskusiju u tim poljima, pozvao na moratorijum. Da li mislite da će vaša diskusija poslužiti kao primer drugima?
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.
DžD: Mislim da je naučnicima teško da izađu iz laboratorije. Govoreći u svoje ime, to je pomalo neprijatno. Međutim, mislim da, biti deo nastanka ovoga, stavlja mene i moje kolege u poziciju odgovornosti. Rekla bih da se zaista nadam da će ostale tehnologije biti razmatrane na isti način, kao što bismo želeli da razmotrimo nešto što bi moglo imati posledice u drugim poljima osim biologije.
BG: Jennifer, thanks for coming to TED.
BĐ: Dženifer, hvala što ste došli na TED.
JD: Thank you.
DžD: Hvala vama.
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