So this is a talk about gene drives, but I'm going to start by telling you a brief story. 20 years ago, a biologist named Anthony James got obsessed with the idea of making mosquitos that didn't transmit malaria.
Dakle, ovo je govor o genetskom pogonu, ali ću početi tako što ću vam ispričati kratku priču. Pre 20 godina, biolog po imenu Entoni Džejms je postao opsednut idejom stvaranja komaraca koji ne prenose malariju.
It was a great idea, and pretty much a complete failure. For one thing, it turned out to be really hard to make a malaria-resistant mosquito. James managed it, finally, just a few years ago, by adding some genes that make it impossible for the malaria parasite to survive inside the mosquito.
To je bila sjajna zamisao i gotovo potpuni fijasko. Ako ništa drugo, ispostavilo se da je veoma teško stvoriti komarca otpornog na malariju. Džejms je uspeo konačno u tome pre samo nekoliko godina, dodajući neke gene koji onemogućavaju malaričnom parazitu da preživi u komarcu.
But that just created another problem. Now that you've got a malaria-resistant mosquito, how do you get it to replace all the malaria-carrying mosquitos? There are a couple options, but plan A was basically to breed up a bunch of the new genetically-engineered mosquitos release them into the wild and hope that they pass on their genes. The problem was that you'd have to release literally 10 times the number of native mosquitos to work. So in a village with 10,000 mosquitos, you release an extra 100,000. As you might guess, this was not a very popular strategy with the villagers.
No to je samo stvorilo drugi problem. Sad kad imate komarca otpornog na malariju, kako da postignete da on zameni sve komarce nosioce malarije? Imate nekoliko opcija, ali je plan A u suštini bio uzgoj gomile novih genetski dizajniranih komaraca, njihovo puštanje u divljinu i nadanje da će da prenesu svoje gene. Problem je bio to što biste morali da pustite bukvalno 10 puta više tih komaraca nego što ima domaćih, da bi funkcionisalo. Pa biste u selu sa 10.000 komaraca, pustili dodatnih 100.000. Kao što pretpostavljate, ovo nije bila naročito popularna strategija među seljanima.
(Laughter)
(Smeh)
Then, last January, Anthony James got an email from a biologist named Ethan Bier. Bier said that he and his grad student Valentino Gantz had stumbled on a tool that could not only guarantee that a particular genetic trait would be inherited, but that it would spread incredibly quickly. If they were right, it would basically solve the problem that he and James had been working on for 20 years.
Potom je prošlog januara Entoni Džejms primio mejl od biologa po imenu Itan Bir. Bir je rekao da su on i njegov student Valentino Ganc nabasali na oruđe koje ne samo da garantuje da će određena genetska osobina da bude nasledna, već i da će se ona širiti neverovatno brzo. Ako su u pravu, to bi u suštini rešilo problem na kome su on i Džejms radili proteklih 20 godina.
As a test, they engineered two mosquitos to carry the anti-malaria gene and also this new tool, a gene drive, which I'll explain in a minute. Finally, they set it up so that any mosquitos that had inherited the anti-malaria gene wouldn't have the usual white eyes, but would instead have red eyes. That was pretty much just for convenience so they could tell just at a glance which was which.
Kao probu, dizajnirali su dva komarca da nose antimalarični gen kao i ovo novo oruđe, genetski pogon, koje ću ubrzo da objasnim. Konačno, podesili su to tako da bilo koji komarac koji je nasledio antimalarični gen nema uobičajene bele oči, već da umesto toga ima crvene oči. To je prosto bilo radi praktičnosti kako bi na prvi pogled mogli da kažu koji je koji.
So they took their two anti-malarial, red-eyed mosquitos and put them in a box with 30 ordinary white-eyed ones, and let them breed. In two generations, those had produced 3,800 grandchildren. That is not the surprising part. This is the surprising part: given that you started with just two red-eyed mosquitos and 30 white-eyed ones, you expect mostly white-eyed descendants. Instead, when James opened the box, all 3,800 mosquitos had red eyes.
Pa su uzeli svoja dva antimalarična, crvenooka komarca i stavili su ih u kutiju sa 30 običnih belookih da se razmnožavaju. Za dve generacije proizveli su 3.800 unučadi. To nije iznenađujući deo. Ovo je iznenađujući deo: kako ste počeli samo sa dva crvenooka komarca i 30 belookih, očekivali biste većinu belookih potomaka. Umesto toga, kad je Džejms otvorio kutiju, svih 3.800 komaraca je imalo crvene oči.
When I asked Ethan Bier about this moment, he became so excited that he was literally shouting into the phone. That's because getting only red-eyed mosquitos violates a rule that is the absolute cornerstone of biology, Mendelian genetics. I'll keep this quick, but Mendelian genetics says when a male and a female mate, their baby inherits half of its DNA from each parent. So if our original mosquito was aa and our new mosquito is aB, where B is the anti-malarial gene, the babies should come out in four permutations: aa, aB, aa, Ba. Instead, with the new gene drive, they all came out aB. Biologically, that shouldn't even be possible.
Kad sam upitala Itana Bira o ovom momentu, toliko je bio uzbuđen da je bukvalno vikao preko telefona. Zato što dobijanje samo crvenookih komaraca narušava zakon koji je apsolutni temelj biologije, Mendelovu genetiku. Sažeto ću o ovome, ali Mendelova genetika kaže da kada se mužjak i ženka pare, njihova beba nasleđuje polovinu DNK od oba roditelja. Pa, ako je naš prvobitni komarac aa, a naš novi komarac je aB, gde je B antimalarični gen, bebe bi trebalo da dolaze s četiri permutacije: aa, aB, aa, Ba. Umesto toga, novim genetskim pogonom, svi su bili aB. Biološki, to ne bi trebalo uopšte da bude moguće.
So what happened? The first thing that happened was the arrival of a gene-editing tool known as CRISPR in 2012. Many of you have probably heard about CRISPR, so I'll just say briefly that CRISPR is a tool that allows researchers to edit genes very precisely, easily and quickly. It does this by harnessing a mechanism that already existed in bacteria. Basically, there's a protein that acts like a scissors and cuts the DNA, and there's an RNA molecule that directs the scissors to any point on the genome you want. The result is basically a word processor for genes. You can take an entire gene out, put one in, or even edit just a single letter within a gene. And you can do it in nearly any species.
Pa šta se desilo? Prvo što se desilo je nastanak 2012. oruđa za redigovanje gena poznatog kao CRISPR. Mnogi od vas ste verovatno čuli za CRISPR, pa ću ukratko reći da je CRISPR oruđe koje omogućuje istraživačima da rediguju gene veoma precizno, lako i brzo. On to radi po uzoru na mehanizam koji već postoji kod bakterija. U suštini, imamo protein koji se ponaša poput makaza i seče DNK, a jedan molekul RNK upravlja makazama do bilo koje željene tačke genoma. Rezultat je u suštini procesor reči za gene. Možete da izvadite čitav gen, ubacite drugi, ili čak da redigujete samo jedno slovo unutar gena. A možete to da uradite skoro kod svih vrsta.
OK, remember how I said that gene drives originally had two problems? The first was that it was hard to engineer a mosquito to be malaria-resistant. That's basically gone now, thanks to CRISPR. But the other problem was logistical. How do you get your trait to spread? This is where it gets clever.
U redu, setite se kako sam rekla da je genetski pogon imao dva problema? Prvi je bio to što je teško stvoriti komarca da bude otporan na malariju. To je prosto nestalo, zahvaljujući CRISPR-u. No drugi problem je bio logistički. Kako da uspete u širenju željene osobine? Ovde je mudrolija.
A couple years ago, a biologist at Harvard named Kevin Esvelt wondered what would happen if you made it so that CRISPR inserted not only your new gene but also the machinery that does the cutting and pasting. In other words, what if CRISPR also copied and pasted itself. You'd end up with a perpetual motion machine for gene editing. And that's exactly what happened. This CRISPR gene drive that Esvelt created not only guarantees that a trait will get passed on, but if it's used in the germline cells, it will automatically copy and paste your new gene into both chromosomes of every single individual. It's like a global search and replace, or in science terms, it makes a heterozygous trait homozygous.
Pre nekoliko godina, biolog na Harvardu po imenu Kevin Esvelt se zapitao šta bi se desilo kad biste postigli da CRISPR umetne ne samo novi gen, već i mehanizam koji obavlja sečenje i lepljenje. Drugim rečima, šta ako bi CRISPR takođe kopirao i lepio samog sebe. Dobili biste mašinu koja konstantno izvršava redigovanje gena. A upravo to se desilo. Ovaj CRISPR genetski pogon koji je stvorio Esvelt, ne samo da garantuje da će osobina da se prenese, već, ako se koristi unutar embrionskih ćelija, on će automatski da kopira i lepi vaš novi gen u oba hromozoma svakog pojedinca. To je poput globalne potrage i zamene, ili naučnim rečnikom, heterozigotska osobina postaje homozigotska.
So, what does this mean? For one thing, it means we have a very powerful, but also somewhat alarming new tool. Up until now, the fact that gene drives didn't work very well was actually kind of a relief. Normally when we mess around with an organism's genes, we make that thing less evolutionarily fit. So biologists can make all the mutant fruit flies they want without worrying about it. If some escape, natural selection just takes care of them.
Pa, šta ovo znači? Ako ništa drugo, znači da imamo veoma moćno, ali takođe unekoliko uznemirujuće novo oruđe. Sve do sad je činjenica da genetski pogoni ne rade kako treba bila nekako umirujuća. Obično kad se mešamo u gene nekog organizma, to nešto postaje evolucijski lošije uklopljeno. Pa biolozi mogu da stvore koliko god žele mušica mutanata i da ne brinu zbog toga. Ako neke pobegnu, prirodna selekcija će da se postara za njih.
What's remarkable and powerful and frightening about gene drives is that that will no longer be true. Assuming that your trait does not have a big evolutionary handicap, like a mosquito that can't fly, the CRISPR-based gene drive will spread the change relentlessly until it is in every single individual in the population. Now, it isn't easy to make a gene drive that works that well, but James and Esvelt think that we can.
Zapanjujuće, moćno i zastrašujuće kod genetskog pogona je što ovo više neće biti tačno. Pod pretpostavkom da vaša osobina nema veliki evolucijski nedostatak, poput komarca koji ne leti, genetski pogon zasnovan na CRISPR-u će neumorno da širi promenu, dok ne bude u svakom pojedinačnom članu populacije. Sad, nije lako stvoriti genetski pogon koji tako dobro radi, ali Džejms i Esvelt misle da možemo.
The good news is that this opens the door to some remarkable things. If you put an anti-malarial gene drive in just 1 percent of Anopheles mosquitoes, the species that transmits malaria, researchers estimate that it would spread to the entire population in a year. So in a year, you could virtually eliminate malaria. In practice, we're still a few years out from being able to do that, but still, a 1,000 children a day die of malaria. In a year, that number could be almost zero. The same goes for dengue fever, chikungunya, yellow fever.
Dobre vesti su da ovo otvara vrata nekim izvanrednim stvarima. Ako ubacite antimalarični genetski pogon u samo jedan procenat komaraca Anopheles, vrstu koja prenosi malariju, istraživači procenjuju da bi se za godinu proširio u čitavoj populaciji. Pa biste za godinu dana praktično eliminisali malariju. U praksi, još uvek smo nekoliko godina daleko od te mogućnosti, ali ipak, 1.000 dece dnevno umre od malarije. Za godinu bi taj broj mogao da bude skoro nula. Isto se odnosi na groznicu denga, virus čikungunja, žutu groznicu.
And it gets better. Say you want to get rid of an invasive species, like get Asian carp out of the Great Lakes. All you have to do is release a gene drive that makes the fish produce only male offspring. In a few generations, there'll be no females left, no more carp. In theory, this means we could restore hundreds of native species that have been pushed to the brink.
I sve je bolje. Recimo da želite da se rešite invazivne vrste, poput azijskog šarana iz Velikih jezera. Samo treba da oslobodite genetski pogon zbog koga bi riba proizvodila samo muške potomke. Za nekoliko generacija, ne bi bilo ženki, ne bi bilo više šarana. U teoriji, to znači da bismo mogli da vratimo stotine autohtonih vrsta koje su dovedene do ivice.
OK, that's the good news, this is the bad news. Gene drives are so effective that even an accidental release could change an entire species, and often very quickly. Anthony James took good precautions. He bred his mosquitos in a bio-containment lab and he also used a species that's not native to the US so that even if some did escape, they'd just die off, there'd be nothing for them to mate with. But it's also true that if a dozen Asian carp with the all-male gene drive accidentally got carried from the Great Lakes back to Asia, they could potentially wipe out the native Asian carp population. And that's not so unlikely, given how connected our world is. In fact, it's why we have an invasive species problem. And that's fish. Things like mosquitos and fruit flies, there's literally no way to contain them. They cross borders and oceans all the time.
U redu, to su dobre vesti, ovo su loše vesti. Genetski pogoni su toliko efikasni da bi čak i nenamerno oslobađanje moglo da izmeni celokupnu vrstu i često veoma brzo. Entoni Džejms je vodio računa. Uzgajao je komarce u biozadržavajućoj laboratoriji i takođe je koristio vrstu koja nije autohtono američka pa čak i da su neki pobegli, prosto bi uginuli, ne bi imali sa čime da se pare. No takođe je istina da ako bi desetak azijskih šarana sa samo muškim genetskim pogonom slučajno bilo vraćeno iz Velikih jezera u Aziju, potencijalno bi mogli da izbrišu autohtonu populaciju azijskog šarana. A to nije toliko nemoguće, s obzirom na povezanost našeg sveta. Zapravo, zato i imamo problem s invazivnim vrstama. A radi se o ribi. Stvari poput komaraca i vinskih mušica bukvalno nemamo način da obuzdamo. Sve vreme prelaze granice i okeane.
OK, the other piece of bad news is that a gene drive might not stay confined to what we call the target species. That's because of gene flow, which is a fancy way of saying that neighboring species sometimes interbreed. If that happens, it's possible a gene drive could cross over, like Asian carp could infect some other kind of carp. That's not so bad if your drive just promotes a trait, like eye color. In fact, there's a decent chance that we'll see a wave of very weird fruit flies in the near future. But it could be a disaster if your drive is deigned to eliminate the species entirely.
U redu, drugi deo loših vesti je da genetski pogon možda ne ostane ograničen onim što nazivamo ciljnim vrstama. A to je zbog protoka gena, što je kitnjast način da se kaže da se susedne vrste ponekad međusobno pare. Ako se to desi, moguće je da se genetski pogon prenese, npr, azijski šaran može da zarazi druge vrste šarana. To nije tako loše, ako pogon samo promoviše osobinu, poput boje očiju. Zapravo, postoje skromne šanse da ćemo da vidimo talas veoma čudnih vinskih mušica u skorijoj budućnosti. Ali katastrofalno je ako je pogon osmišljen da u potpunosti eliminiše vrstu.
The last worrisome thing is that the technology to do this, to genetically engineer an organism and include a gene drive, is something that basically any lab in the world can do. An undergraduate can do it. A talented high schooler with some equipment can do it.
Poslednja zabrinjavajuća stvar je da je tehnologija za ovo, za genetski inženjering organizma i uključivanje genetskog pogona, nešto što u suštini svaka laboratorija u svetu može da napravi. Student to može da uradi. Talentovani srednjoškolac s nešto opreme može to da uradi.
Now, I'm guessing that this sounds terrifying.
Sad, pretpostavljam da ovo zvuči zastrašujuće.
(Laughter)
(Smeh)
Interestingly though, nearly every scientist I talk to seemed to think that gene drives were not actually that frightening or dangerous. Partly because they believe that scientists will be very cautious and responsible about using them.
Zanimljivo je pak, da skoro svaki naučnik s kojim razgovaram čini se da misli kako genetski pogoni zapravo i nisu toliko strašni, ni opasni. Delimično jer veruju da će naučnici da budu veoma oprezni i odgovorni kod njihove upotrebe.
(Laughter)
(Smeh)
So far, that's been true. But gene drives also have some actual limitations. So for one thing, they work only in sexually reproducing species. So thank goodness, they can't be used to engineer viruses or bacteria. Also, the trait spreads only with each successive generation. So changing or eliminating a population is practical only if that species has a fast reproductive cycle, like insects or maybe small vertebrates like mice or fish. In elephants or people, it would take centuries for a trait to spread widely enough to matter.
Do sad je to bilo tako. Ali genetski pogoni takođe imaju neka stvarna ograničenja. Kao na primer, funkcionišu jedino kod vrsta koje se razmnožavaju seksualno. Pa, srećom, ne mogu da se koriste za pravljenje virusa ili bakterija. Takođe, ciljana osobina se širi jedino kod svake naredne generacije. Pa je izmena ili eliminacija populacije praktična jedino ako ta vrsta ima brz reproduktivni ciklus, poput insekata ili pak manjih kičmenjaka, miševa ili riba. Kod slonova ili ljudi, trebalo bi vekovi da prođu da bi se osobina proširila dovoljno da ima značaj.
Also, even with CRISPR, it's not that easy to engineer a truly devastating trait. Say you wanted to make a fruit fly that feeds on ordinary fruit instead of rotting fruit, with the aim of sabotaging American agriculture. First, you'd have to figure out which genes control what the fly wants to eat, which is already a very long and complicated project. Then you'd have to alter those genes to change the fly's behavior to whatever you'd want it to be, which is an even longer and more complicated project. And it might not even work, because the genes that control behavior are complex. So if you're a terrorist and have to choose between starting a grueling basic research program that will require years of meticulous lab work and still might not pan out, or just blowing stuff up? You'll probably choose the later.
Takođe, čak ni uz CRISPR nije tako lako proizvesti istinski razornu osobinu. Recimo da želite stvoriti vinsku mušicu koja se hrani običnim voćem, a ne trulim voćem, u cilju sabotiranja američke poljoprivrede. Prvo biste morali da otkrijete koji geni kontrolišu šta mušica želi da jede, a to je već dug i složen projekat. Potom biste morali da izmenite te gene zarad izmene mušicinog ponašanja u ono koje je poželjno za vas, a to je čak i duži i još složeniji projekat. A možda čak i ne uspete jer su geni koji kontrolišu ponašanje složeni. Pa, ako ste terorista i morate da izaberete između pokretanja napornog istraživačkog programa koj bi zahtevao godine minucioznog laboratorijskog rada koji može da omane ili prostog raznošenja stvari? Verovatno ćete izabrati drugo.
This is especially true because at least in theory, it should be pretty easy to build what's called a reversal drive. That's one that basically overwrites the change made by the first gene drive. So if you don't like the effects of a change, you can just release a second drive that will cancel it out, at least in theory.
Ovo je naročito tačno jer, bar u teoriji, trebalo bi da je prilično lako napraviti reverzibilni pogon. To je pogon koji u suštini briše promenu koju je uzrokovao prvi pogon. Pa, ako vam se ne sviđaju efekti izmene, možete prosto da oslobodite drugi pogon koji će to da poništi, bar u teoriji.
OK, so where does this leave us? We now have the ability to change entire species at will. Should we? Are we gods now? I'm not sure I'd say that. But I would say this: first, some very smart people are even now debating how to regulate gene drives. At the same time, some other very smart people are working hard to create safeguards, like gene drives that self-regulate or peter out after a few generations. That's great. But this technology still requires a conversation. And given the nature of gene drives, that conversation has to be global. What if Kenya wants to use a drive but Tanzania doesn't? Who decides whether to release a gene drive that can fly?
U redu, šta nam preostaje? Sad imamo sposobnost da po želji promenimo čitavu vrstu. Da li bismo trebali? Da li smo sad bogovi? Nisam sigurna da bih to rekla. Ali bih rekla sledeće: pod jedan, neki veoma pametni ljudi čak i sad raspravljaju kako da regulišu genetske pogone. Istovremeno, neki drugi veoma pametni ljudi vredno rade na stvaranju obezbeđenja, kao genetski pogoni koji se samoregulišu ili nestaju nakon par generacija. To je sjajno. Ali ova tehnologija i dalje zahteva diskusiju. Shodno prirodi genetskih pogona, razgovor bi morao da bude globalan. Šta ako Kenija želi da koristi pogon, ali Tanzanija ne želi? Ko odlučuje da li da oslobodi genetski pogon koji leti?
I don't have the answer to that question. All we can do going forward, I think, is talk honestly about the risks and benefits and take responsibility for our choices. By that I mean, not just the choice to use a gene drive, but also the choice not to use one. Humans have a tendency to assume that the safest option is to preserve the status quo. But that's not always the case. Gene drives have risks, and those need to be discussed, but malaria exists now and kills 1,000 people a day. To combat it, we spray pesticides that do grave damage to other species, including amphibians and birds.
Nemam odgovor na to pitanje. Sve što možemo u buduće, mislim, je da iskreno razgovaramo o rizicima i prednostima i da preuzmemo odgovornost za naše izbore. Pod tim mislim, ne samo na izbor korišćenja genetskog pogona, već i na izbor njegove neupotrebe. Ljudi teže pretpostavci da je najbezbednija opcija da se čuva status kvo. Ali to nije uvek tako. Genetski pogoni nose rizike, a o njima mora da se raspravlja, ali malarija je sada prisutna i ubija svakodnevno 1000 ljudi. Protiv nje koristimo pesticide koji nanose ozbiljnu štetu drugim vrstama, uključujući vodozemce i ptice.
So when you hear about gene drives in the coming months, and trust me, you will be hearing about them, remember that. It can be frightening to act, but sometimes, not acting is worse.
Pa, kad narednih meseci budete slušali o genetskim pogonima, a verujte mi, slušaćete o njima, setite se ovoga. Može da bude zastrašujuće delati, ali je ponekad gore ne delati.
(Applause)
(Aplauz)