Gene editing can now change an entire species -- forever | Jennifer Kahn

Translator: Sahi Rahman Reviewer: Sarmoko Sarmoko

So this is a talk about gene drives,

Ceramah ini adalah tentang gene-drive (penggerak gen)

but I'm going to start by telling you a brief story.

tapi akan saya mulai dengan cerita singkat.

20 years ago, a biologist named Anthony James

20 tahun lalu, ahli biologi bernama Anthony James

got obsessed with the idea of making mosquitos

terobsesi dengan ide membuat nyamuk

that didn't transmit malaria.

yang tidak menularkan malaria.

It was a great idea, and pretty much a complete failure.

Sebuah ide hebat, dan cukup besar untuk gagal total.

For one thing, it turned out to be really hard

Ternyata sangat sulit

to make a malaria-resistant mosquito.

untuk membuat nyamuk kebal malaria.

James managed it, finally, just a few years ago,

James akhirnya berhasil, beberapa tahun belakangan ini,

by adding some genes that make it impossible

dengan menambahkan gen yang mencegah

for the malaria parasite to survive inside the mosquito.

parasit malaria untuk hidup di dalam tubuh nyamuk.

But that just created another problem.

Tapi itu membuat masalah baru.

Now that you've got a malaria-resistant mosquito,

Kini saat Anda mendapati nyamuk yang kebal terhadap malaria,

how do you get it to replace all the malaria-carrying mosquitos?

bagaimana cara menggantikan semua nyamuk pembawa malaria?

There are a couple options,

Ada beberapa pilihan.

but plan A was basically to breed up

Rencana A pada intinya mengembangbiakkan

a bunch of the new genetically-engineered mosquitos

sekelompok nyamuk hasil rekayasa genetika

release them into the wild

melepaskannya di alam liar

and hope that they pass on their genes.

dan berharap gen mereka diturunkan.

The problem was that you'd have to release

Masalahnya adalah Anda harus melepas

literally 10 times the number of native mosquitos to work.

dengan jumlah 10 kali lebih banyak dari nyamuk alami agar berhasil.

So in a village with 10,000 mosquitos,

Jadi di sebuah desa dengan 10.000 nyamuk,

you release an extra 100,000.

Anda harus membuat 100.000.

As you might guess,

Seperti yang Anda tebak,

this was not a very popular strategy with the villagers.

hal ini bukanlah strategi populer di masyarakat.

(Laughter)

(Tawa)

Then, last January, Anthony James got an email

Januari lalu, Anthony James menerima surat elektronik

from a biologist named Ethan Bier.

dari ahli biologi bernama Ethan Bier.

Bier said that he and his grad student Valentino Gantz

Bier bercerita bahwa dia dan muridnya, Valentino Gantz,

had stumbled on a tool that could not only guarantee

menemukan alat yang tidak hanya menjamin

that a particular genetic trait would be inherited,

bahwa satu sifat gen dapat diturunkan,

but that it would spread incredibly quickly.

tapi juga dapat menyebar amat cepat.

If they were right, it would basically solve the problem

Jika mereka benar, itu adalah solusi dari masalah

that he and James had been working on for 20 years.

yang dia dan James coba selesaikan selama 20 tahun.

As a test, they engineered two mosquitos to carry the anti-malaria gene

Sebagai pengujian, mereka merekayasa dua nyamuk membawa gen anti-malaria

and also this new tool, a gene drive,

dan alat baru ini, sebuah gene-drive,

which I'll explain in a minute.

yang akan saya jelaskan.

Finally, they set it up so that any mosquitos

Akhirnya, mereka mengondisikan nyamuk

that had inherited the anti-malaria gene

yang membawa gen anti-malaria

wouldn't have the usual white eyes, but would instead have red eyes.

agar memiliki mata berwarna merah, bukan putih seperti warna aslinya.

That was pretty much just for convenience

Itu agar memudahkan

so they could tell just at a glance which was which.

untuk mengamati nyamuk hasil rekayasa dan yang bukan.

So they took their two anti-malarial, red-eyed mosquitos

Jadi mereka mengambil dua nyamuk anti-malaria bermata merah

and put them in a box with 30 ordinary white-eyed ones,

mencampurnya di kotak dengan 30 nyamuk bermata putih,

and let them breed.

untuk berkembang biak.

In two generations, those had produced 3,800 grandchildren.

Pada dua generasi, nyamuk-nyamuk itu menghasilkan 3.800 keturunan.

That is not the surprising part.

Bukan itu yang mengejutkan.

This is the surprising part:

Inilah yang mengejutkan:

given that you started with just two red-eyed mosquitos

hanya dengan mencampurkan dua nyamuk bermata merah

and 30 white-eyed ones,

dan 30 nyamuk bermata putih,

you expect mostly white-eyed descendants.

Anda mengira mata-putih lah yang dominan.

Instead, when James opened the box,

Namun, saat James membuka kotak itu,

all 3,800 mosquitos had red eyes.

keseluruhan dari 3.800 nyamuk bermata merah.

When I asked Ethan Bier about this moment,

Saat saya bertanya pada Ethan Bier,

he became so excited that he was literally shouting into the phone.

dia sangat gembira sampai-sampai berteriak di telpon.

That's because getting only red-eyed mosquitos

Itu karena keseluruhan nyamuk bermata merah

violates a rule that is the absolute cornerstone of biology,

menyalahi aturan mutlak biologi,

Mendelian genetics.

genetika Mendel.

I'll keep this quick,

Saya persingkat,

but Mendelian genetics says when a male and a female mate,

tapi genetika Mendel berdalil saat jantan dan betina kawin,

their baby inherits half of its DNA from each parent.

bayi mendapat sifat turunan DNA dari kedua induk.

So if our original mosquito was aa and our new mosquito is aB,

Jadi, jika nyamuk alami adalah aa dan nyamuk rekayasa adalah aB,

where B is the anti-malarial gene,

di mana B adalah gen anti-malaria,

the babies should come out in four permutations:

keturunan harusnya selaras permutasi berikut:

aa, aB, aa, Ba.

aa, aB, aa, Ba.

Instead, with the new gene drive,

Sedangkan, dengan gene-drive baru ini,

they all came out aB.

semuanya adalah aB.

Biologically, that shouldn't even be possible.

Secara biologis, hal itu tidaklah mungkin.

So what happened?

Jadi apa yang terjadi?

The first thing that happened

Hal pertama yang terjadi

was the arrival of a gene-editing tool known as CRISPR in 2012.

adalah ditemukannya alat penyunting gen bernama CRISPR di tahun 2012.

Many of you have probably heard about CRISPR,

Sebagian besar Anda mungkin tahu CRISPR,

so I'll just say briefly that CRISPR is a tool that allows researchers

jadi saya persingkat bahwa CRISPR memungkinkan ilmuwan

to edit genes very precisely, easily and quickly.

menyunting gen secara akurat, mudah, dan cepat.

It does this by harnessing a mechanism that already existed in bacteria.

Alat ini bekerja dengan memanfaatkan mekanisme pada bakteri.

Basically, there's a protein that acts like a scissors

Terutamanya, ada protein yang berfungsi seperti gunting

and cuts the DNA,

dan memotong DNA,

and there's an RNA molecule that directs the scissors

dan ada molekul RNA yang mengarahkan gunting itu

to any point on the genome you want.

ke titik manapun yang Anda mau.

The result is basically a word processor for genes.

Hasilnya seperti perangkat pengolah kata untuk gen.

You can take an entire gene out, put one in,

Anda dapat mengambil seluruh gen, memasukkan satu,

or even edit just a single letter within a gene.

atau hanya mengubah satu huruf (nukleotida) pada gen

And you can do it in nearly any species.

Dan dapat dilakukan pada semua spesies.

OK, remember how I said that gene drives originally had two problems?

Baiklah, ingatkah Anda tentang dua masalah gene-drive di awal?

The first was that it was hard to engineer a mosquito

Pertama, adalah sulit untuk merekayasa nyamuk

to be malaria-resistant.

agar kebal malaria.

That's basically gone now, thanks to CRISPR.

Masalah itu sudah hilang, berkat CRISPR.

But the other problem was logistical.

Tapi tersisa masalah logistik.

How do you get your trait to spread?

Bagaimana menyebarluaskannya?

This is where it gets clever.

Di sinilah kecerdikan dimulai.

A couple years ago, a biologist at Harvard named Kevin Esvelt

Beberapa tahun lalu, ahli biologi Harvard bernama Kevin Esvelt

wondered what would happen

memikirkan apa yang terjadi

if you made it so that CRISPR inserted not only your new gene

jika Anda berhasil memasukkan CRISPR tak hanya ke dalam gen baru

but also the machinery that does the cutting and pasting.

tapi juga mesin yang melakukan pemotongan dan penyisipan.

In other words, what if CRISPR also copied and pasted itself.

Dengan kata lain, bagaimana jika CRISPR melipatgandakan dirinya sendiri.

You'd end up with a perpetual motion machine for gene editing.

Semua berakhir dengan mesin penyunting gen yang bekerja abadi.

And that's exactly what happened.

Dan itulah yang benar terjadi.

This CRISPR gene drive that Esvelt created

Gene-drive CRISPR yang dibuat Esvelt

not only guarantees that a trait will get passed on,

tak hanya menjamin sifat yang diturunkan,

but if it's used in the germline cells,

tapi jika digunakan pada sel germline,

it will automatically copy and paste your new gene

alat itu secara otomatis melipatgandakan gen baru Anda

into both chromosomes of every single individual.

pada dua kromosom dari setiap individu.

It's like a global search and replace,

Hal ini seperti pencarian dan penggantian global,

or in science terms, it makes a heterozygous trait homozygous.

dalam istilah ilmiah, itu membuat heterozigot menjadi homozigot.

So, what does this mean?

Jadi, apa artinya?

For one thing, it means we have a very powerful,

Di satu sisi, kita memiliki alat yang sangat ampuh,

but also somewhat alarming new tool.

namun juga mengkhawatirkan.

Up until now, the fact that gene drives didn't work very well

Hingga kini, fakta bahwa gene-drive tak berfungsi dengan baik

was actually kind of a relief.

sebenarnya melegakan.

Normally when we mess around with an organism's genes,

Biasanya, saat kita ikut campur dengan gen organisme,

we make that thing less evolutionarily fit.

kita membuatnya evolusinya terancam.

So biologists can make all the mutant fruit flies they want

Ahli biologi dapat membuat lalat buah mutan semau mereka

without worrying about it.

tanpa mengkhawatirkannya.

If some escape, natural selection just takes care of them.

Jika beberapa lepas, seleksi alam akan mengurusnya.

What's remarkable and powerful and frightening about gene drives

Apa yang menakjubkan, ampuh, dan menakutkan dari gene-drive

is that that will no longer be true.

adalah itu akan segera sempurna.

Assuming that your trait does not have a big evolutionary handicap,

Dengan asumsi sifat alami Anda tidak cacat secara evolusi,

like a mosquito that can't fly,

seperti nyamuk yang tak dapat terbang,

the CRISPR-based gene drive will spread the change relentlessly

gene-drive berbasis CRISPR akan menyebarkan rekayasanya tanpa henti

until it is in every single individual in the population.

hingga setiap individu di satu populasi memilikinya.

Now, it isn't easy to make a gene drive that works that well,

Kini, tidak mudah membuat gene-drive yang dapat berfungsi,

but James and Esvelt think that we can.

tapi James dan Esvelt percaya kita mampu.

The good news is that this opens the door to some remarkable things.

Kabar baiknya adalah hal ini membuka pintu pada hal hebat lainnya.

If you put an anti-malarial gene drive

Saat memasukkan gene-drive anti-malaria

in just 1 percent of Anopheles mosquitoes,

pada 1 persen nyamuk Anopheles,

the species that transmits malaria,

spesies yang menularkan malaria,

researchers estimate that it would spread to the entire population in a year.

peneliti memperkirakan itu akan menyebar ke seluruh populasi dalam setahun.

So in a year, you could virtually eliminate malaria.

Jadi dalam satu tahun, Anda dapat melenyapkan malaria.

In practice, we're still a few years out from being able to do that,

Praktiknya, kita masih berjarak beberapa tahun untuk mampu melakukannya,

but still, a 1,000 children a day die of malaria.

tetap, 1000 anak-anak mati karena malaria setiap harinya.

In a year, that number could be almost zero.

Dalam setahun, angka itu dapat mendekati nol.

The same goes for dengue fever, chikungunya, yellow fever.

Hal sama untuk demam berdarah, chikunguya, demam kuning.

And it gets better.

Dan kebaikan lainnya.

Say you want to get rid of an invasive species,

Taruhlah Anda ingin melenyapkan spesies invasif,

like get Asian carp out of the Great Lakes.

seperti ikan Karper dari Great Lakes.

All you have to do is release a gene drive

Dapat dilakukan dengan melepas gene-drive

that makes the fish produce only male offspring.

yang membuat keturunannya jantan semua.

In a few generations, there'll be no females left, no more carp.

Hanya dalam beberapa generasi, tak akan ada betina, tak ada lagi karper.

In theory, this means we could restore hundreds of native species

Secara teori, ratusan spesies alami yang terancam punah

that have been pushed to the brink.

dapat dipulihkan.

OK, that's the good news,

Baiklah, itu kabar baiknya,

this is the bad news.

dan ini kabar buruknya.

Gene drives are so effective

Gene-drive sangat efektif

that even an accidental release could change an entire species,

hingga pelepasan yang tidak disengaja dapat mengubah seluruh spesies,

and often very quickly.

dengan sangat cepat.

Anthony James took good precautions.

Tindak pencegahan Anthony James cukup bagus.

He bred his mosquitos in a bio-containment lab

Dia membiakkan nyamuknya di lab bio terisolasi

and he also used a species that's not native to the US

dan dia memakai spesies yang tidak berasal dari Amerika

so that even if some did escape,

jadi meski beberapa lepas,

they'd just die off, there'd be nothing for them to mate with.

mereka akan mati, karena tak ada pasangannya.

But it's also true that if a dozen Asian carp with the all-male gene drive

Tapi juga benar adanya jika selusin Karper yang tak dapat menghasilkan betina

accidentally got carried from the Great Lakes back to Asia,

secara tak sengaja lepas ke Asia,

they could potentially wipe out the native Asian carp population.

mereka dapat memusnahkan seluruh populasi spesies karper asli.

And that's not so unlikely, given how connected our world is.

Dan itu sangatlah mungkin, mengingat keterhubungan dunia kita.

In fact, it's why we have an invasive species problem.

Sebenarnya, itulah penyebab adanya spesies invasif.

And that's fish.

Dan itu hanyalah ikan.

Things like mosquitos and fruit flies,

Hewan seperti nyamuk dan lalat buah,

there's literally no way to contain them.

tidak ada cara untuk mengisolasi mereka.

They cross borders and oceans all the time.

Mereka melintasi samudra setiap saat.

OK, the other piece of bad news

OK, kabar buruk lainnya

is that a gene drive might not stay confined

adalah gene-drive tidak hanya terbatas

to what we call the target species.

pada spesies target.

That's because of gene flow,

Itu karena aliran gen,

which is a fancy way of saying that neighboring species

dengan kata lain, spesies terdekat darinya

sometimes interbreed.

dapat kawin silang.

If that happens, it's possible a gene drive could cross over,

Jika itu terjadi, satu gen dapat melintasi satu spesies,

like Asian carp could infect some other kind of carp.

seperti Karper Asia mengontaminasi Karper lainnya.

That's not so bad if your drive just promotes a trait, like eye color.

Bukan hal yang buruk jika drive hanya membawa sifat seperti warna mata.

In fact, there's a decent chance that we'll see

Faktnya, ada kemungkinan kita akan melihat

a wave of very weird fruit flies in the near future.

gelombang lalat buah aneh dalam waktu dekat.

But it could be a disaster

Tapi akan jadi petaka

if your drive is deigned to eliminate the species entirely.

jika drive dirancang untuk memusnahkan suatu spesies.

The last worrisome thing is that the technology to do this,

Hal mengkhawatirkan terakhir adalah teknologi ini,

to genetically engineer an organism and include a gene drive,

untuk merekayasa gen organisme dan termasuk gene-drive,

is something that basically any lab in the world can do.

mudah dilakukan di lab manapun.

An undergraduate can do it.

Mahasiswa bisa membuatnya.

A talented high schooler with some equipment can do it.

Murid SMA yang cerdas, dengan peralatan memadai dapat membuatnya.

Now, I'm guessing that this sounds terrifying.

Kini, saya tebak hal ini terdengar mengerikan.

(Laughter)

(Tawa)

Interestingly though, nearly every scientist I talk to

Namun yang menarik, hampir setiap ilmuwan yang saya temui

seemed to think that gene drives were not actually that frightening or dangerous.

tidak berpendapat bahwa gene-drive menakutkan ataupun membahayakan.

Partly because they believe that scientists will be

Sebagian, mungkin karena mereka percaya ilmuwan

very cautious and responsible about using them.

akan awas dan bertanggungjawab menggunakannya.

(Laughter)

(Tawa)

So far, that's been true.

Sejauh ini, memang benar.

But gene drives also have some actual limitations.

Tapi gene-drive juga mempunyai beberapa batasan nyata.

So for one thing, they work only in sexually reproducing species.

Ini hanya bekerja pada spesies yang bereproduksi secara seksual.

So thank goodness, they can't be used to engineer viruses or bacteria.

Syukurlah, tak dapat digunakan pada virus atau bakteri.

Also, the trait spreads only with each successive generation.

Dan lagi, sifat rekayasa hanya menyebar pada keturunan.

So changing or eliminating a population

Jadi mengubah atau mengeliminasi populasi

is practical only if that species has a fast reproductive cycle,

hanya mungkin jika spesies itu memiliki siklus reproduksi yang cepat,

like insects or maybe small vertebrates like mice or fish.

seperti serangga, vertebrata kecil: tikus atau ikan.

In elephants or people, it would take centuries

Pada gajah dan manusia, butuh berabad-abad

for a trait to spread widely enough to matter.

agar satu sifat menyebar secara signifikan.

Also, even with CRISPR, it's not that easy to engineer a truly devastating trait.

Lagi pun, meski dengan CRISPR, tidak mudah membuat sifat yang benar-benar cacat.

Say you wanted to make a fruit fly

Misalkan Anda ingin lalat buah

that feeds on ordinary fruit instead of rotting fruit,

yang makan buah segar, bukan buah busuk,

with the aim of sabotaging American agriculture.

dengan tujuan menyabotase pertanian Amerika.

First, you'd have to figure out

Pertama Anda harus temukan

which genes control what the fly wants to eat,

gen mana mengendalikan pilihan makanan lalat itu,

which is already a very long and complicated project.

yang mana adalah proyek yang sangat sulit dan lama.

Then you'd have to alter those genes to change the fly's behavior

Lalu Anda harus mengubah gen yang dapat mengubah sifat alami lalat

to whatever you'd want it to be,

sesuai dengan keinginan Anda,

which is an even longer and more complicated project.

yang juga merupakan proyek yang lebih lama dan sulit.

And it might not even work,

Dan mungkin juga gagal,

because the genes that control behavior are complex.

karena gen pengendali perilaku adalah kompleks.

So if you're a terrorist and have to choose

Jadi jika Anda teroris dan harus memilih

between starting a grueling basic research program

antara program penelitian awal yang melelahkan,

that will require years of meticulous lab work and still might not pan out,

membutuhkan tahunan kerja lab, dengan kemungkinan gagal,

or just blowing stuff up?

atau membuat bom?

You'll probably choose the later.

Opsi terakhir yang paling mungkin.

This is especially true because at least in theory,

Khusus hal ini adalah benar karena dalam teori,

it should be pretty easy to build what's called a reversal drive.

seharusnya mudah pula membuat drive-pembalik.

That's one that basically overwrites the change made by the first gene drive.

Drive yang dapat menghapus dan mengganti rekayasa gene-drive pertama.

So if you don't like the effects of a change,

Jadi saat satu perubahan tidak dikehendakki,

you can just release a second drive that will cancel it out,

Anda dapat melepas drive ke dua yang berfungsi berlawanan,

at least in theory.

setidaknya dalam teori.

OK, so where does this leave us?

Ok, jadi sampai di mana kita?

We now have the ability to change entire species at will.

Kita bisa mengubah keseluruhan suatu spesies sesuai kehendak.

Should we?

Haruskah?

Are we gods now?

Apakah kita Tuhan, sekarang?

I'm not sure I'd say that.

Saya tidak yakin.

But I would say this:

Tapi saya yakin hal ini:

first, some very smart people

Pertama, beberapa genius

are even now debating how to regulate gene drives.

bahkan berdebat tentang bagaimana meregulasi gene-drive.

At the same time, some other very smart people

Di saat yang sama, genius lainnya

are working hard to create safeguards,

bekerja membuat pengaman gene-drive,

like gene drives that self-regulate or peter out after a few generations.

seperti regulasi otomatis; mampu lenyap dalam beberapa generasi.

That's great.

Itu bagus.

But this technology still requires a conversation.

Tapi teknologi ini masih membutuhkan diskusi.

And given the nature of gene drives,

Dan mengingat hakikat gene-drive,

that conversation has to be global.

diskusi itu haruslah global.

What if Kenya wants to use a drive but Tanzania doesn't?

Bagaimana jika drive Kenya tak disetujui Tanzania?

Who decides whether to release a gene drive that can fly?

Siapa memutuskan untuk melepaskan sebuah gene-drive yang dapat terbang?

I don't have the answer to that question.

Saya tak bisa menjawabnya.

All we can do going forward, I think,

Yang dapat kita lakukan untuk terus maju

is talk honestly about the risks and benefits

adalah berdiskusi tentang risiko dan manfaat

and take responsibility for our choices.

dan bertanggung-jawab atas pilihan kita.

By that I mean, not just the choice to use a gene drive,

Tak hanya pilihan untuk menggunakan gene-drive,

but also the choice not to use one.

tapi juga untuk tidak menggunakannya.

Humans have a tendency to assume that the safest option

Manusia berkecenderungan untuk percaya bahwa pilihan terbaik

is to preserve the status quo.

adalah mempertahankan status-quo.

But that's not always the case.

Tapi itu tidak selamanya benar.

Gene drives have risks, and those need to be discussed,

Gene-drive berisiko, dan itu butuh didiskusikan,

but malaria exists now and kills 1,000 people a day.

tapi malaria masih ada saat ini dan membunuh 1000 orang per hari.

To combat it, we spray pesticides that do grave damage to other species,

Untuk melawannya, kita semprotkan pestisida yang membahayakan spesies lain,

including amphibians and birds.

termasuk amfibi dan burung.

So when you hear about gene drives in the coming months,

Jadi saat Anda mendengar gene-drive bulan depan,

and trust me, you will be hearing about them,

dan percayalah, Anda akan mendengarnya,

remember that.

ingatlah hal itu.

It can be frightening to act,

Beraksi memang menakutkan,

but sometimes, not acting is worse.

tapi kadang berdiam diri adalah lebih buruk.

(Applause)

(Tepuk tangan)