0:00:01.066,0:00:03.527
So this is a talk about gene drives,

0:00:03.527,0:00:06.801
but I'm going to start by [br]telling you a brief story.

0:00:06.801,0:00:09.868
20 years ago, a biologist[br]named Anthony James

0:00:09.868,0:00:12.211
got obsessed with the idea[br]of making mosquitos

0:00:12.211,0:00:15.857
that didn't transmit malaria.

0:00:15.857,0:00:20.803
It was a great idea, and pretty[br]much a complete failure.

0:00:20.803,0:00:23.427
For one thing, it turned [br]out to be really hard

0:00:23.427,0:00:26.469
to make a malaria resistant mosquito.

0:00:26.469,0:00:29.536
James managed it, finally,[br]just a few years ago

0:00:29.536,0:00:31.902
by adding some genes[br]that make it impossible

0:00:31.902,0:00:35.757
for the malaria parasite[br]to survive inside the mosquito.

0:00:35.757,0:00:38.218
But that just created another problem.

0:00:38.218,0:00:41.051
Now that you've got a [br]malaria-resistant mosquito,

0:00:41.051,0:00:46.322
how do you get it to replace[br]all the malaria-carrying mosquitos?

0:00:46.322,0:00:48.133
There are a couple options,

0:00:48.133,0:00:50.009
but plan A was basically to breed up[br]

0:00:50.009,0:00:52.459
a bunch of the new [br]genetically-engineered mosquitos

0:00:52.459,0:00:54.263
release them into the wild,

0:00:54.263,0:00:56.673
and hope that they pass on their genes.

0:00:56.673,0:00:58.811
The problem was that you'd [br]have to release

0:00:58.811,0:01:03.135
literally 10x the number of native[br]mosquitos to work.

0:01:03.135,0:01:05.246
So in a village with 10,000 mosquitos,

0:01:05.246,0:01:08.497
you release an extra 100,000.

0:01:08.497,0:01:11.004
As you might guess, this was not[br]a very popular strategy

0:01:11.004,0:01:12.514
with the villagers.

0:01:12.514,0:01:15.137
(Laughter)

0:01:15.137,0:01:18.829
Then, last January, Anthony James[br]got an email

0:01:18.829,0:01:21.639
from a biologist named [br]Ethan Bier.

0:01:21.639,0:01:24.272
Bier said that he and his grad student,[br]Valentino Gantz,

0:01:24.272,0:01:26.887
had stumbled on a tool that could [br]not only guarentee

0:01:26.887,0:01:30.161
that a particular genetic trait[br]would be inherited,

0:01:30.161,0:01:32.354
but that it would spread[br]incredibly quickly.

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If they were right, it would basically[br]solve the problem

0:01:35.223,0:01:38.752
that he and James had been[br]working on for 20 years.

0:01:38.752,0:01:41.562
As a test, they engineered[br]two mosquitos

0:01:41.562,0:01:43.257
to carry the anti-malaria gene

0:01:43.257,0:01:45.556
and also this new tool,[br]a gene drive,

0:01:45.556,0:01:47.506
which I'll explain in a minute.

0:01:47.506,0:01:49.712
Finally, they set it up so that[br]any mosquitos

0:01:49.712,0:01:51.825
that had inherited the[br]anti-malaria gene

0:01:51.825,0:01:55.585
wouldn't have the usual white eyes,[br]but would instead have red eyes.

0:01:55.585,0:01:58.280
That was pretty much just [br]for convenience

0:01:58.280,0:02:02.413
so they could tell just at a glance[br]which was which.

0:02:02.413,0:02:05.153
So they took their two [br]anti-malarial, red-eyed mosquitos

0:02:05.153,0:02:07.847
and put them in a box with 30[br]ordinary white-eyed ones

0:02:07.847,0:02:09.797
and let them breed.

0:02:09.797,0:02:14.534
In two generations, those had [br]produced 38,000 grandchildren.

0:02:14.534,0:02:16.972
That is not the surprising part.

0:02:16.972,0:02:18.923
This is the surprising part:

0:02:18.923,0:02:21.593
Given that you started with just[br]two red-eyed mosquitos

0:02:21.593,0:02:23.172
and 30 white-eyed ones,

0:02:23.172,0:02:26.725
you expect mostly white-eyed[br]descendents.

0:02:26.725,0:02:29.790
Instead, when James opened the box,

0:02:29.790,0:02:33.598
all 38,000 mosquitos had red eyes.

0:02:33.598,0:02:35.822
When I asked Ethan Bier[br]about this moment,

0:02:35.822,0:02:39.723
he became so excited, tht he was[br]literally shouting into the phone.

0:02:39.723,0:02:42.073
That's because getting only[br]red-eyed mosquitos

0:02:42.073,0:02:45.045
violates a rule that is the[br]absolute cornerstone of biology,

0:02:45.045,0:02:46.912
Mendelian genetics.

0:02:46.912,0:02:49.202
I'll keep this quick, [br]but Mendelian genetics

0:02:49.202,0:02:50.873
says when a male and a female mate,

0:02:50.873,0:02:53.753
their baby inherits half of its[br]DNA from each parent.

0:02:53.753,0:02:57.352
So if our original mosquito was aa[br]and our new mosquito is aB,

0:02:57.352,0:02:59.140
where B is the anti-malarial gene,

0:02:59.140,0:03:01.415
the babies should come out[br]in four permutations:

0:03:01.415,0:03:05.130
aa, aB, aa, Ba.

0:03:05.130,0:03:07.197
Instead, with the new gene drive,

0:03:07.197,0:03:10.123
they all came out aB.

0:03:10.123,0:03:12.723
Biologically, that shouldn't[br]even be possible.

0:03:12.723,0:03:14.906
So what happened?

0:03:14.906,0:03:17.197
The first thing that happened[br]was the arrival

0:03:17.197,0:03:20.055
of a gene-editing tool[br]known as CRISPR in 2012.

0:03:20.055,0:03:22.538
Many of you have probably heard[br]about CRISPR,

0:03:22.538,0:03:25.831
so I'll just say briefly that CRISPR[br]is a tool that allows researchers

0:03:25.831,0:03:29.038
to edit genes very precisely,[br]easily and quickly.

0:03:29.038,0:03:32.712
It does this by harnessing a mechanism[br]that already existed in bacteria.

0:03:32.712,0:03:35.409
Basically, there's a protein[br]that acts like a scissors

0:03:35.409,0:03:36.877
and cuts the DNA,

0:03:36.877,0:03:39.427
and there's an RNA molecule[br]that directs the scissors

0:03:39.427,0:03:41.237
to any point on the genome you want.

0:03:41.237,0:03:44.651
The result is basically a word processor[br]word processor for genes.

0:03:44.651,0:03:47.135
You can take an entire gene out,[br]put one in,

0:03:47.135,0:03:49.945
or even edit just a single letter[br]within a gene.

0:03:49.945,0:03:53.544
And you can do it in nearly any species.

0:03:53.544,0:03:55.641
Okay, remember how I said [br]that gene drives

0:03:55.641,0:03:57.914
originally had two problems?

0:03:57.914,0:04:01.137
The first was that it was hard[br]to engineer a mosquito

0:04:01.137,0:04:02.623
to be malaria resistant.

0:04:02.623,0:04:05.363
That's basically gone now,[br]thanks to CRISPR.

0:04:05.363,0:04:07.546
But the other problem was [br]logistical.

0:04:07.546,0:04:10.402
How do you get your trait to spread?

0:04:10.402,0:04:13.165
This is where it gets clever.

0:04:13.165,0:04:16.450
A couple years ago, a biologist[br]at Harvard named Kevin Esvelt

0:04:16.450,0:04:18.986
wondered what would happen[br]if you made it so that

0:04:18.986,0:04:21.803
CRISPR inserted not only[br]your new gene,

0:04:21.803,0:04:25.448
but also the machinery [br]that does the cutting and pasting.

0:04:25.448,0:04:30.185
In other words, what if CRISPR[br]also copy and pasted itself.

0:04:30.185,0:04:34.713
You'd end up with a perpetual[br]motion machine for gene editing.

0:04:34.713,0:04:37.267
And that's exactly what happened.

0:04:37.267,0:04:40.077
This CRISPR gene drive[br]that Esvelt created

0:04:40.077,0:04:43.606
not only guarantees that a trait [br]will get passed on,

0:04:43.606,0:04:46.068
but if its used in the germline cell,

0:04:46.068,0:04:48.668
it will automatically copy and paste[br]your new gene

0:04:48.668,0:04:51.989
into both chromosomes of every[br]single individual.

0:04:51.989,0:04:54.450
It's like a global search and replace,

0:04:54.450,0:04:58.666
or in science terms, it makes[br]a heterozygous trait homozygous.

0:04:58.666,0:05:01.927
So, what does this mean?

0:05:01.927,0:05:04.574
For one thing, it means we have[br]a very powerful,

0:05:04.574,0:05:08.576
but also somewhat alarming new tool.

0:05:08.576,0:05:11.586
Up until now, the fact that gene drives[br]didn't work very well

0:05:11.586,0:05:13.269
was actually kind of a relief.

0:05:13.269,0:05:15.898
Normally when we mess around[br]with an organisms's genes,

0:05:15.898,0:05:18.264
we make that thing [br]less evolutionarily fit.

0:05:18.264,0:05:21.264
So biologists can make all the mutant[br]fruit flies they want

0:05:21.264,0:05:22.500
without worrying about it.

0:05:22.500,0:05:27.004
If some escape, natural selection[br]just takes care of it.

0:05:27.004,0:05:30.302
What's remarkable and powerful[br]and frightening about gene drives

0:05:30.302,0:05:32.856
is that that will no longer be true.

0:05:32.856,0:05:36.943
Assuming that your trait does not[br]have a big evolutionary handicap,

0:05:36.943,0:05:39.009
like a mosquito that can't fly,

0:05:39.009,0:05:42.492
the CRISPR-based gene drive[br]will spread the change relentlessly

0:05:42.492,0:05:47.322
until it is in every single individual[br]in the population.

0:05:47.322,0:05:50.178
Now, it isn't easy to make[br]a gene drive that works that well,

0:05:50.178,0:05:53.568
but James and Esvelt think[br]that we can.

0:05:53.568,0:05:57.469
The good news is that this opens[br]the door to some remarkable things.

0:05:57.469,0:06:00.116
If you put an anti-malarial gene drive[br]in just 1 percent

0:06:00.116,0:06:03.143
of anopheles mosquitos,[br]the species that transmits malaria.

0:06:03.143,0:06:06.502
Researchers estimate that it would[br]spread to the entire population

0:06:06.502,0:06:08.406
in a year.

0:06:08.406,0:06:11.071
So in a year, you could virtually [br]eliminate malaria.

0:06:11.071,0:06:14.350
In practice, we're still a few years out[br]from being able to do that,

0:06:14.350,0:06:18.344
but sitll, a 1,000 children a day[br]die of malaria.

0:06:18.344,0:06:21.293
In a year, that number could be[br]almost zero.

0:06:21.293,0:06:25.426
The same goes for dengue fever,[br]chicken genuang (?), yellow fever.

0:06:25.426,0:06:27.469
And it gets better.

0:06:27.469,0:06:30.022
Say you want to get rid [br]of an invasive species,

0:06:30.022,0:06:32.670
like get Asian Carp out of[br]The Great Lakes.

0:06:32.670,0:06:34.692
All you have to do is release [br]a gene drive

0:06:34.692,0:06:37.570
that makes the fish produce[br]only male offspring.

0:06:37.570,0:06:41.419
In a few generations, there'll be[br]no females left, no more carp.

0:06:41.419,0:06:44.164
In theory, this means that we [br]could restore hundreds

0:06:44.164,0:06:47.601
of native species that have been[br]pushed to the brink.

0:06:47.601,0:06:50.968
Okay, that's the good news,

0:06:50.968,0:06:53.313
this is the bad news.

0:06:53.313,0:06:55.380
Gene drives are so effective,

0:06:55.380,0:06:59.234
that even an accidental release [br]could change an entire species,

0:06:59.234,0:07:01.440
and often very quickly.

0:07:01.440,0:07:03.530
Anthony James took good precautions.

0:07:03.530,0:07:05.746
He breed his mosquitos in[br]a bio-containment lab

0:07:05.746,0:07:08.427
and he also used a species[br]that's not native to the US

0:07:08.427,0:07:10.176
so that even if some did escape,

0:07:10.176,0:07:11.494
they'd just die off,

0:07:11.494,0:07:13.515
there'd be nothing for them[br]to mate with.

0:07:13.515,0:07:15.651
But it's also true that if [br]a dozen Asian Carp

0:07:15.651,0:07:19.482
with the all-male gene drive accidentally[br]got carried from The Great Lakes

0:07:19.482,0:07:20.968
back to Asia,

0:07:20.968,0:07:25.519
they could potentially wipe out [br]the native Asian Carp population.

0:07:25.519,0:07:29.048
And that's not so unlikely, given[br]how connected our world is.

0:07:29.048,0:07:32.230
In fact, it's why we have [br]an invasive species problem.

0:07:32.230,0:07:33.646
And that's fish.

0:07:33.646,0:07:37.826
Things like mosquitos and fruit flies,[br]there's literally no way to contain them.

0:07:37.826,0:07:41.982
They cross borders and oceans[br]all the time.

0:07:41.982,0:07:44.467
Okay, the other piece [br]of bad news is that

0:07:44.467,0:07:48.139
a gene drive might not stay confined[br]to what we call the target species.

0:07:48.139,0:07:50.079
That's because of gene flow,

0:07:50.079,0:07:52.874
which is a fancy way of saying[br]that neighboring species

0:07:52.874,0:07:54.103
sometimes inter-breed.

0:07:54.103,0:07:57.147
If that happens, it's possible[br]a gene drive could cross over,

0:07:57.147,0:07:59.861
like Asian Carp could infect[br]some other kind of Carp.

0:07:59.861,0:08:03.437
That's not so bad if your drive[br]just promotes a trait, like eye color.

0:08:03.437,0:08:06.372
In fact, there's a decent chance that[br]we'll see a wave

0:08:06.372,0:08:09.614
of very weird fruit flies [br]in the near future.

0:08:09.614,0:08:12.353
But it could be a disaster[br]if your drive is deigned

0:08:12.353,0:08:14.629
to eliminate the species entirely.

0:08:14.629,0:08:17.903
The last worrisome thing is that[br]the technology to do this,

0:08:17.903,0:08:21.618
to genetically engineer an organism[br]and include a gene drive,

0:08:21.618,0:08:25.543
is something that basically any lab[br]in the world can do.

0:08:25.543,0:08:27.423
An undergraduate can do it.

0:08:27.423,0:08:32.160
A talented high schooler[br]with some equipment can do it.

0:08:32.160,0:08:35.527
Now I'm guessing that [br]this sounds terrifying.

0:08:35.527,0:08:40.495
Interestingly though, nearly [br]every scientist I talk to

0:08:40.495,0:08:43.097
seems to think that gene drives[br]were not actually

0:08:43.097,0:08:44.583
that frightening or dangerous.

0:08:44.583,0:08:47.072
Partly because they believe that[br]scientists will be

0:08:47.072,0:08:49.444
very cautious and responsible[br]about using them.

0:08:49.444,0:08:50.318
(Laughter)

0:08:50.318,0:08:52.524
So far, that's been true.

0:08:52.524,0:08:55.380
But gene drives also have[br]some actual limitations.

0:08:55.380,0:08:58.399
For one thing, they work in only[br]sexually reproducing species.

0:08:58.399,0:09:01.882
So thank goodness, they can't be used[br]to engineer viruses or bacteria.

0:09:01.882,0:09:05.243
Also, the trait spreads only with each[br]succesive genertion.

0:09:05.243,0:09:08.732
So changing or eliminating a population[br]is practical only if that species

0:09:08.732,0:09:11.100
has a fast reproductive cycle,[br]

0:09:11.100,0:09:14.192
like insects or maybe small vertebrates[br]like mice or fish.

0:09:14.192,0:09:16.534
In elephants or people, it would[br]take centuries

0:09:16.534,0:09:20.342
for a trait to spread widely enough[br]to matter.

0:09:20.342,0:09:25.492
Also, even with CRISPR, it's not that easy[br]to engineer a truly devastating trait.

0:09:25.492,0:09:27.679
Say you wanted to make a fruit fly[br]

0:09:27.679,0:09:30.303
that feeds on ordinary fruit instead[br]of rotting fruit

0:09:30.303,0:09:33.068
with the aim of sabotaging [br]American agriculture.

0:09:33.068,0:09:35.481
First you'd have to figure out[br]which genes control

0:09:35.481,0:09:37.594
what the fly wants to eat,

0:09:37.594,0:09:40.636
which is already a very long [br]and complicated project.

0:09:40.636,0:09:43.817
Then you'd have to alter those genes[br]to change the fly's behavior

0:09:43.817,0:09:45.442
to whatever you'd want it to be,

0:09:45.442,0:09:48.087
which is an even longer [br]and more complicated project.

0:09:48.087,0:09:49.807
And it might not even work because[br]

0:09:49.807,0:09:52.024
the genes that control[br]behavior are complex.

0:09:52.024,0:09:54.591
So if you're a terrorist and have [br]to choose between

0:09:54.591,0:09:56.222
starting a grueling basic research program

0:09:56.222,0:09:57.726
that will require years [br]of meticulous lab work

0:09:57.726,0:09:59.398
and still might not pan out,

0:09:59.398,0:10:00.768
or just blowing stuff up?

0:10:00.768,0:10:03.237
You'll probably choose the later.

0:10:03.237,0:10:05.621
This is especially true because[br]at least in theory,

0:10:05.621,0:10:09.011
it should be pretty easy to build[br]what's called a reversal drive.

0:10:09.011,0:10:13.028
That's one that basically overwrites[br]the change made by the first gene drive.

0:10:13.028,0:10:15.303
So if you don't like the effects [br]of a change,

0:10:15.303,0:10:18.159
you can just release a second drive[br]that will cancel it out,

0:10:18.159,0:10:21.573
at least in theory.

0:10:21.573,0:10:24.847
Okay, so where does this leave us?

0:10:24.847,0:10:29.351
We now have the ability to change[br]entire species at will.

0:10:29.351,0:10:30.814
Should we?

0:10:30.814,0:10:34.251
Are we gods now?

0:10:34.251,0:10:36.317
I'm not sure I'd say that.

0:10:36.317,0:10:38.663
But I would say this:

0:10:38.663,0:10:41.426
First, some very smart people[br]are even now debating

0:10:41.426,0:10:43.841
how to regulate gene drives.

0:10:43.841,0:10:46.418
At the same time, some other[br]very smart people

0:10:46.418,0:10:48.601
are working hard to create[br]safeguards,

0:10:48.601,0:10:52.177
like gene drives that self regulate[br]or petter out after a few generations.

0:10:52.177,0:10:53.427
That's great.

0:10:53.427,0:10:56.471
But this technology still requires[br]a conversation.

0:10:56.471,0:10:59.723
And given the nature of gene drives,

0:10:59.723,0:11:02.370
that conversation has to be global.

0:11:02.370,0:11:05.528
What if Kenya wants to use a drive[br]that Tanzania doesn't?

0:11:05.528,0:11:09.557
Who decides whether to release[br]a gene drive that can fly?

0:11:11.287,0:11:13.841
I don't have the answer to that question.

0:11:13.841,0:11:15.884
All we can do going forward, I think,

0:11:15.884,0:11:18.671
is talk honestly about [br]the risks and benefits

0:11:18.671,0:11:21.945
and take responsibility for our choices.

0:11:21.945,0:11:25.962
By that I mean, not just the choice[br]to use a gene drive,

0:11:25.962,0:11:29.421
but also the choice not to use one.

0:11:29.421,0:11:32.347
Humans have a tendency to assume[br]that the safest option

0:11:32.347,0:11:35.064
is to preserve the status quo.

0:11:35.064,0:11:37.711
But that's not always the case.

0:11:37.711,0:11:41.356
Gene drives have risks and those[br]need to be discussed,

0:11:41.356,0:11:45.211
but malaria exists now and kills[br]1,000 people a day.

0:11:45.211,0:11:48.856
To combat it, we spray pesticides[br]that do grave damage to other species,

0:11:48.856,0:11:51.605
including amphibians and birds.

0:11:51.605,0:11:54.336
So when you hear about gene drives[br]in the coming months,

0:11:54.336,0:11:57.193
and trust me, you will be [br]hearing about them,

0:11:57.193,0:11:58.632
remember that.

0:11:58.632,0:12:00.675
It can be frightening to act,

0:12:00.675,0:12:04.925
but sometimes, not acting[br]is worse.

0:12:04.925,0:12:07.948
(Applause)