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.
Haya ni mazungumzo ya ubadilishaji jeni, ila nitaanza kwa kuwaelezea hadithi fupi miaka 20 iliyopita, mwanabiolojia aliyeitwa Anthony James alijawa na wazo la kutengeneza mbu ambao hawaambukizi malaria.
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.
lilikuwa wazo zuri, na lilishindikana kabisa. Kwani, ilikuja kuwa vigumu sana kutengeneza mbu asiyestahimili malaria. James hatimaye aliweza, miaka michache iliyopita, kwa kuongeza jeni zinazofanya isiwezekane kwa vimelea vya malaria kushindwa kuishi ndani ya mbu.
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.
lakini hiyo ilileta tatizo lingine. Sasa umeshapata mbu asiyestahimili malaria, utamfanyaje aweze kubadilisha mbu wote wanaobeba malaria? Kuna chaguzi kadhaa, lakini mpango A ulikuwa wa uzalishaji kiasi cha mbu wapya waliotengenezwa kijenetiki waachilie mwituni na utegemee kwamba wataeneza jeni zao. Tatizo lilikuwa kwamba ulitakiwa uachilie kiasi cha mara 10 ya namba ya mbu wenyeji kufanyakazi Hivyo katika kijiji chenye mbu 10,000. unaachilia 100,000 wa ziada. Kama unavyoweza kuhisi, mkakati huu haukukubalika kwa wanakijiji.
(Laughter)
(Kicheko)
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.
Kisha, Januari iliyopita, Anthony James akapata barua pepe kutoka kwa mbiolojia aitwaye Ethan Bier. Bier akasema kwamba yeye na mwanafunzi wake Valentino Gantz walikutana na kifaa ambacho kiweza sio tu kuhakikisha kwamba kibainisho cha jenetiki fulani kitarithiwa lakini hiyo itaeneza kwa haraka mno. kama wangekuwa sahihi, ingeweza kutatua tatizo yeye na James walilolifanyia kazi kwa miaka 20.
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.
kama majaribio, walitengeneza mbu wawili kubeba jeni isiyo na malaria na pia kifaa kipya cha ubadilishaji jeni, ambayo nitaielezea hivi punde. wakakiandaa ili mbu yeyote ambaye alirithi jeni isiyo na malaria asiwe na macho meupe, awe na macho mekundu. Hiyo ilikuwa tu kwa ajili ya urahisi ili waweze kujua kwa kuangalia yupi ni yupi.
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.
Hivyo walichukua mbu 2 wasio na malaria wenye macho mekundu na kuwaweka ndani ya boksi na mbu 30 wenye macho meupe, na kuwaacha wazaliane. Ndani ya vizazi viwili, hao walizalisha wajukuu 3,800. Hiyo sio sehemu ya kushangaza. Hii ndio sehemu ya kushangaza: kutokana na kwamba ulianza na mbu 2 tu wenye macho mekundu na 30 wenye macho meupe, unategemea wenye macho meupe kuzaana zaidi Badala yake, wakati James akifungua boksi, mbu wote 3,800 walikuwa na macho mekundu.
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.
Nilipo muuliza Ethan Bier kuhusu hili, alipatwa msisimko mkubwa sana kiasi kwamba alipiga makelele kwenye simu. Ni kwasababu kupata mbu wenye macho mekundu tu inakiuka kanuni ambayo ni msingi thabiti wa biolojia, Jenetiki za Mendelia. Nitaieleza hii haraka, jenetiki za Mendelia zadai mwanamke na mwanaume wakipandana mtoto wao hurithi nusu ya DNA kutoka kwa kila mzazi. ikiwa mbu wetu asilia alikuwa aa na mbu wetu mpya ni aB, na B ni jeni isiyostahimili malaria, watoto wanatakiwa watoke katika hitari nne: aa, aB, aa, Ba. Badala yake katika ubadilishaji jeni, wote walitokea aB. Kibiolojia, hiyo haitakiwi hata kuwezekana.
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.
Sasa nini kilichotokea? Kitu cha kwanza kilichotokea ni kuwasili kifaa cha kuhakiki jeni kilichoitwa CRISPR mwaka 2012. wengi wenu pengine mmesikia kuhusu CRISPR, hivyo kwa kifupi hiyo CRISPR ni kifaa kinachoruhusu watafiti kuhakiki jeni kwa uhakika, kirahisi na haraka. Inafanya hivi kwa kuunganisha utaratibu ambao ulikuwepo ndani ya bakteria. Kimsingi,kuna protini ambayo hutumika kama mkasi na kukata DNA, na kuna molekuli ya RNA ambayo huelekeza mkasi upande wowote kwenye jenome. Matokeo kimsingi ni uchakataji neno kwa ajili ya jeni. Unaweza kutoa jeni yote nje, na kuweka nyingine ndani, au hata kuhakiki herufi moja ndani ya jeni. unaweza kufanya hivyo kwa spishi yoyote.
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.
OK, kumbuka nilivyosema ubadilishaji jeni mwanzo ulikuwa na matatizo mawili? La kwanza ilikuwa ni vigumu kutengeneza mbu aweze kutostahimili malaria. Hiyo imeondoka sasa, shukrani kwa CRISPR. Ila tatizo lingine ni la kiutaratibu. Unawezaje kufanya kibainisho kienee? Hapa ndipo panpoleta usumbufu.
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.
Miaka michache iliyopita, mwanabiolojia wa Harvard Kevin Esvelt alifikiria itatokea nini Ikiwa utaifanya ili kwamba CRISPR iingizwe sio tu kwenye jeni mpya ila pia kwenye mashine ambayo hukata na kubandika. Kwa maneno mengine itakuwaje CRISPR ikijinakili na kujibandika yenyewe. Utaishia kuwa na mashine inayozunguka kuhakiki jeni. Na hicho ndicho kilichotokea Hii CRISPR ya ubadilishaji jeni iliyoundwa na Esvelt sio tu inakuhakikishia kwamba kibainisho kitarithishwa, ikitumika kwenye seli za vijidudu vinavyobadilika, itanakili na kubandika moja kwa moja jeni yako mpya kuwa kromosomu zote za kila kiumbe pekee. Ni kama utafutaji duniani na ubadilishaji, au kisayansi, hufanya kibainisho heterezaigosi kuwa homozaigosi.
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.
Hivyo, hii inamaanisha nini? kwa namna moja, inamaanisha tuna chombo chenye nguvu sana, lakini pia chombo kipya chakutia hofu. Hadi sasa, kwakuwa ubadilishaji jeni haukufanya kazi vizuri ilikuwa na uahueni kidogo. Kawaida tunapovuruga jeni za viumbe, tunafanya kile kitu kisifae kinadharia ya mageuko wanabiolojia wanaweza kutengeneza nzi wa matunda wanaotaka bila kuhofia lolote kama baadhi watatoroka, uchaguzi asilia utawashughulikia.
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.
Kinachosifika na chenye nguvu na kutisha kuhusu ubadilishaji jeni ni kwamba haitakuwa tena kweli. Chukulia kibainisho chako hakina ulemavu mkubwa wa nadharia ya mageuko, kama vile mbu ambao hawawezi kuruka CRISPR-yenye ubadilishaji jeni itaeneza mabadiliko kwa kasi kubwa mno hadi itakapokuwa ndani ya kila kitu katika kundi tafiti. Si rahisi kuunda ubadilishaji jeni ufanye kazi vizuri hivyo, lakini James na Esvelt wanadhani tunaweza.
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.
Habari njema ni kuwa hii inafungua mlango kwa mambo yasiyo ya kawaida. Ukitia ubadilishaji jeni usio na malaria katika asilimia 1 ya mbu wa Anofelesi, spishi inayoambukiza malaria, watafiti wanakadiria kwamba utaenea kwa mbu wote kwa muda wa mwaka mmoja. Hivyo kwa mwaka, unaweza kukaribia kuitokomeza malaria. Kiutendaji tupo bado miaka michache kuweza kufanikisha hilo, lakini bado watoto 1,000 hufa kwa malaria kwa siku. Kwa mwaka, namba hiyo yaweza kukaribia sifuri. hivyo pia kwa homa ya dengue, chikungunya na homa ya manjano.
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.
Na inazidi kuwa bora. Ikiwa unataka kuondoa spishi zinazoenea kwa kasi, kama Kamongo wa Asia kwenye Maziwa Makuu. Unatakiwa kuachilia ubadilishaji jeni ambao utafanya samaki wazaliane madume tu. kwa vizazi vijavyo hakutakuwa na majike na kamongo wataisha. kinadharia, inamaanisha tunaweza rudisha mamia ya spishi asilia zilikuwa zimesukumwa ukingoni.
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.
OK, hiyo ni habari njema, hii ni habari mbaya. Ubadilishaji jeni hufanyakazi kwa ufanisi hata ukiachiwa kwa bahati mbaya unaweza kubadili spishi nzima, mara zote kwa haraka mno Anthony James alichukua tahadhari vizuri. Alizalisha mbu wake kwenye maabara madhubuti na pia alitumia spishi zisizo asilia kwa Marekani ili hata baadhi zikiponyoka, zitakufa tu, kutakuwa hakuna spishi za kuzaliana nao. Lakini pia ni kweli ikiwa dazeni ya Kamongo wa Asia wenye jeni za kiume tu bahati mbaya wakachukuliwa kutoka Maziwa Makuu na kurudishwa Asia, wanaweza kufuta idadi yote ya Kamongo wa Asia asilia. Nahiyo inawezekana, kwa jinsi dunia yetu ilivyounganika. ndio maana tuna tatizo la spishi zinazoenea kwa kasi. Na hiyo ni samaki. Vitu kama mbu na nzi wa matunda, Hakuna kabisa njia ya kuwadhibiti. Wanavuka mipaka na bahari wakati wote.
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.
OK, kipande kingine cha habari mbaya ubadilishaji jeni hauwezi kufungwa sehemu moja kwa kile tunachokiita spishi lengwa. Husababishwa na kuhama kwa jeni ambayo tunaweza kusema pia ni spishi jirani wakati mwingine huzaliana. kama itatokea,inawezekana ubadilishaji jeni kwenda upande mwingine, kama Kamongo wa Asia wataambukiza Kamongo wengine. Si vibaya ubadilishaji wako ukisaidia kibainisho kama rangi ya macho. Kwa kweli,kuna nafasi kubwa kwa tutaona wimbi la nzi wa matunda wasio kawaida kwa siku zijazo Lakini inaweza kuwa janga Ikiwa ubadilishaji wake umetengenezwa kutokomeza spishi yote.
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.
Kitu cha mwisho cha kutia hofu ni kwamba teknolojia ya kufanya hivi, kutengeneza viumbe kijenetiki na kutumia ubadilishaji jeni, ni kitu ambacho maabara yoyote duniani inaweza kufanya. Mhitimu wa chuo ataweza. Mwanafunzi wa sekondari mwenye kipaji na vifaa anaweza kufanya.
Now, I'm guessing that this sounds terrifying.
Sasa naona kwamba inaonekana inatisha sana.
(Laughter)
(Kicheko)
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.
Chakufurahisha, karibia kila mwanasayansi ninayeongea naye anafikiria kwamba ubadilishaji jeni sio wa kutisha au hatari kiasi hicho. Upande mmoja kwasababu wanaamini wanasayansi watakuwa makini sana na kuwajibika kuhusu kuzitumia.
(Laughter)
(Kicheko)
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.
Kwa hapo, hilo ni kweli. Ila ubadilishaji jeni pia una kikomo kilichopo. Kitu kimoja, unafanya kazi kwa spishi zinazozaliana kwa kupandana. Hivyo tushukuru, hauwezi kutumika kutengeneza virusi au bakteria. Pia, vibainisho huenea kwa kizazi kinachofuatia tu. Kubadilisha au kutokomeza kundi tafiti inawezekana tu ikiwa spishi hiyo ina mzunguko wa haraka wa kuzaliana, kama wadudu au labda wanyama wadogo kama panya au samaki. Kwa tembo au binadamu, itachukua karne kadhaa kibainishi kuenea kwa kiasi kikubwa kuleta maana.
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.
Pia hata kwa CRISPR, sio rahisi kutengeneza kibainishi kiharibifu. Sema ulitaka kutengeneza nzi matunda ambao hula matunda ya kawaida badala ya kuyaozesha, kwa nia ya kuhujumu kilimo cha Marekani. Kwanza, unatakiwa ujue ni jeni zipi zinaongoza kitu gani nzi wanataka kula, ambayo tayari ni mpango mrefu sana na mgumu. Kisha urekebishe hizo jeni kubadilisha tabia ya nzi kuwa chochote unachotaka kiwe ambayo ni mpango mrefu zaidi na mgumu zaidi. Na inaweza isifanye kazi, kwasababu jeni zinazoongoza tabia ni changamani Kama wewe ni gaidi na unatakiwa uchague kati ya kuanza programu ya utafiti yenye kuchosha itakayohitaji miaka mingi maabara na bado isitokee vizuri, au ulipue tu vitu? Pengine utachagua cha pili.
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.
Hii haswa ni kweli kwasababu angalau kinadharia inatakiwa iwe rahisi kujenga ubadilishaji kinyume. Hii ndio ile inayofunika mabadiliko ya ubadilishaji jeni wa kwanza Hivyo kama hupendi athari za mabadiliko, unaweza kutoa tu ubadilishaji wapili ambao utaifuta, angalau kinadharia.
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?
OK,hii inatuacha wapi? Sasa tunao uwezo wa kubadilisha spishi yoyote kwa hiari. Tufanye hivyo? Tumekuwa miungu sasa? Sijui kama ningesema hivyo. Ila ningesema hivi: kwanza, baadhi ya watu wenye akili sana sasa hivi wanajadili jinsi ya kudhibiti ubadilishaji jeni. Wakati huo huo watu wengine wenye akili sana wanafanyakazi kwa bidii kuunda uhifadhi, ikiwa uendeshaji jeni utajiendesha au kupotea baada ya vizazi vichache. Hivyo ni vizuri Lakini teknolojia hii bado inahitaji mazungunzo. Kutokana ubadilishaji jeni ulivyo mazungumzo hayo yawe ya kimataifa. Itakuwaje Kenya ikitaka kutumia ila Tanzania inakataa? Nani anayeamua iwe kuachia ubadilishaji jeni utakaopaa?
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.
Sina majibu kwa swali hilo. Tunachoweza kufanya mbeleni, nadhani, ni kuongea kwa uwazi kuhusu hatari na faida na kuwajibika kwa uchaguzi wetu. kwa hilo, namaanisha si uchaguzi tu wa kutumia ubadilishaji jeni, bali pia uchaguzi wa kutotumia. Binadamu wanatabia ya kudhania uchaguzi salama kuliko wote ni kutunza hali kama ilivyo. Lakini haiko hivyo siku zote. Ubadilishaji jeni una hatari na hizo zinahitaji kujadiliwa, lakini malaria ipo sasa na inaua watu 1,000 kila siku. kupambana nayo, tunapuliza dawa ambazo huharibu spishi nyingine, ikijumuisha amfibia na ndege.
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.
Hivyo utakaposikia ubadilishaji jeni miezi inayokuja, na niamini utasikia habari zake ila kutofanya kitu ni mbaya zaidi. kumbuka kwamba. inaweza kutia hofu kuchukua hatua,
(Applause)
(Makofi)