0:00:00.844,0:00:03.306
So this is a talk about gene drives,

0:00:03.330,0:00:05.883
but I'm going to start[br]by telling you a brief story.

0:00:06.621,0:00:09.844
20 years ago, a biologist[br]named Anthony James

0:00:09.868,0:00:12.187
got obsessed with the idea[br]of making mosquitos

0:00:12.211,0:00:14.790
that didn't transmit malaria.

0:00:15.683,0:00:19.739
It was a great idea,[br]and pretty much a complete failure.

0:00:20.596,0:00:23.256
For one thing, it turned out[br]to be really hard

0:00:23.280,0:00:25.287
to make a malaria-resistant mosquito.

0:00:26.286,0:00:29.913
James managed it, finally,[br]just a few years ago,

0:00:29.937,0:00:32.008
by adding some genes[br]that make it impossible

0:00:32.032,0:00:34.746
for the malaria parasite[br]to survive inside the mosquito.

0:00:35.551,0:00:37.373
But that just created another problem.

0:00:38.043,0:00:40.885
Now that you've got[br]a malaria-resistant mosquito,

0:00:40.909,0:00:44.495
how do you get it to replace[br]all the malaria-carrying mosquitos?

0:00:46.107,0:00:47.580
There are a couple options,

0:00:47.604,0:00:49.627
but plan A was basically to breed up

0:00:49.651,0:00:52.738
a bunch of the new[br]genetically-engineered mosquitos

0:00:52.762,0:00:54.088
release them into the wild

0:00:54.112,0:00:56.079
and hope that they pass on their genes.

0:00:56.673,0:00:58.787
The problem was that you'd have to release

0:00:58.811,0:01:03.111
literally 10 times the number[br]of native mosquitos to work.

0:01:03.135,0:01:05.222
So in a village with 10,000 mosquitos,

0:01:05.246,0:01:07.325
you release an extra 100,000.

0:01:08.229,0:01:09.379
As you might guess,

0:01:09.403,0:01:12.157
this was not a very popular strategy[br]with the villagers.

0:01:12.181,0:01:13.331
(Laughter)

0:01:14.963,0:01:18.667
Then, last January,[br]Anthony James got an email

0:01:18.691,0:01:20.642
from a biologist named Ethan Bier.

0:01:21.400,0:01:24.259
Bier said that he[br]and his grad student Valentino Gantz

0:01:24.283,0:01:27.227
had stumbled on a tool[br]that could not only guarantee

0:01:27.251,0:01:29.925
that a particular genetic trait[br]would be inherited,

0:01:29.949,0:01:32.028
but that it would spread[br]incredibly quickly.

0:01:32.734,0:01:35.400
If they were right,[br]it would basically solve the problem

0:01:35.424,0:01:37.805
that he and James had been[br]working on for 20 years.

0:01:38.450,0:01:43.108
As a test, they engineered two mosquitos[br]to carry the anti-malaria gene

0:01:43.132,0:01:45.291
and also this new tool, a gene drive,

0:01:45.315,0:01:46.806
which I'll explain in a minute.

0:01:47.506,0:01:49.839
Finally, they set it up[br]so that any mosquitos

0:01:49.863,0:01:51.801
that had inherited the anti-malaria gene

0:01:51.825,0:01:55.824
wouldn't have the usual white eyes,[br]but would instead have red eyes.

0:01:56.682,0:01:58.732
That was pretty much just for convenience

0:01:58.756,0:02:01.293
so they could tell just at a glance[br]which was which.

0:02:02.192,0:02:04.949
So they took their two[br]anti-malarial, red-eyed mosquitos

0:02:04.973,0:02:07.632
and put them in a box[br]with 30 ordinary white-eyed ones,

0:02:07.656,0:02:08.830
and let them breed.

0:02:09.383,0:02:13.240
In two generations, those had produced[br]3,800 grandchildren.

0:02:14.217,0:02:16.010
That is not the surprising part.

0:02:16.716,0:02:18.638
This is the surprising part:

0:02:18.662,0:02:21.569
given that you started[br]with just two red-eyed mosquitos

0:02:21.593,0:02:22.927
and 30 white-eyed ones,

0:02:22.951,0:02:25.712
you expect mostly white-eyed descendants.

0:02:26.514,0:02:29.538
Instead, when James opened the box,

0:02:29.562,0:02:32.903
all 3,800 mosquitos had red eyes.

0:02:33.315,0:02:35.355
When I asked Ethan Bier about this moment,

0:02:35.379,0:02:38.894
he became so excited that he was literally[br]shouting into the phone.

0:02:39.886,0:02:42.049
That's because getting[br]only red-eyed mosquitos

0:02:42.073,0:02:45.021
violates a rule that is the absolute[br]cornerstone of biology,

0:02:45.045,0:02:46.287
Mendelian genetics.

0:02:46.912,0:02:48.081
I'll keep this quick,

0:02:48.105,0:02:50.869
but Mendelian genetics[br]says when a male and a female mate,

0:02:50.893,0:02:53.535
their baby inherits half[br]of its DNA from each parent.

0:02:53.559,0:02:57.154
So if our original mosquito was aa[br]and our new mosquito is aB,

0:02:57.178,0:02:58.980
where B is the anti-malarial gene,

0:02:59.004,0:03:01.391
the babies should come out[br]in four permutations:

0:03:01.415,0:03:03.988
aa, aB, aa, Ba.

0:03:04.884,0:03:07.173
Instead, with the new gene drive,

0:03:07.197,0:03:08.709
they all came out aB.

0:03:09.900,0:03:12.452
Biologically, that shouldn't[br]even be possible.

0:03:12.476,0:03:13.780
So what happened?

0:03:14.709,0:03:16.153
The first thing that happened

0:03:16.177,0:03:19.447
was the arrival of a gene-editing tool[br]known as CRISPR in 2012.

0:03:20.701,0:03:22.811
Many of you have probably[br]heard about CRISPR,

0:03:22.835,0:03:26.136
so I'll just say briefly that CRISPR[br]is a tool that allows researchers

0:03:26.160,0:03:28.739
to edit genes very precisely,[br]easily and quickly.

0:03:29.533,0:03:33.262
It does this by harnessing a mechanism[br]that already existed in bacteria.

0:03:33.286,0:03:35.912
Basically, there's a protein[br]that acts like a scissors

0:03:35.936,0:03:37.170
and cuts the DNA,

0:03:37.194,0:03:39.677
and there's an RNA molecule[br]that directs the scissors

0:03:39.701,0:03:41.419
to any point on the genome you want.

0:03:41.443,0:03:44.133
The result is basically[br]a word processor for genes.

0:03:44.157,0:03:46.783
You can take an entire gene[br]out, put one in,

0:03:46.807,0:03:49.252
or even edit just a single[br]letter within a gene.

0:03:49.646,0:03:51.599
And you can do it in nearly any species.

0:03:53.328,0:03:57.042
OK, remember how I said that gene drives[br]originally had two problems?

0:03:57.835,0:04:00.955
The first was that it was hard[br]to engineer a mosquito

0:04:00.979,0:04:02.366
to be malaria-resistant.

0:04:02.390,0:04:04.517
That's basically gone now,[br]thanks to CRISPR.

0:04:05.117,0:04:06.879
But the other problem was logistical.

0:04:07.307,0:04:09.109
How do you get your trait to spread?

0:04:10.196,0:04:11.672
This is where it gets clever.

0:04:12.943,0:04:16.545
A couple years ago, a biologist[br]at Harvard named Kevin Esvelt

0:04:16.569,0:04:17.919
wondered what would happen

0:04:17.943,0:04:21.570
if you made it so that[br]CRISPR inserted not only your new gene

0:04:21.594,0:04:24.435
but also the machinery[br]that does the cutting and pasting.

0:04:25.233,0:04:29.073
In other words, what if CRISPR[br]also copied and pasted itself.

0:04:30.145,0:04:33.276
You'd end up with a perpetual[br]motion machine for gene editing.

0:04:34.458,0:04:36.192
And that's exactly what happened.

0:04:37.037,0:04:39.915
This CRISPR gene drive that Esvelt created

0:04:39.939,0:04:43.582
not only guarantees[br]that a trait will get passed on,

0:04:43.606,0:04:46.044
but if it's used in the germline cells,

0:04:46.068,0:04:48.644
it will automatically copy and paste[br]your new gene

0:04:48.668,0:04:51.314
into both chromosomes[br]of every single individual.

0:04:51.743,0:04:54.140
It's like a global search and replace,

0:04:54.164,0:04:57.385
or in science terms, it makes[br]a heterozygous trait homozygous.

0:04:59.045,0:05:01.656
So, what does this mean?

0:05:01.680,0:05:04.404
For one thing, it means we have[br]a very powerful,

0:05:04.428,0:05:07.085
but also somewhat alarming new tool.

0:05:08.576,0:05:11.465
Up until now, the fact that gene drives[br]didn't work very well

0:05:11.489,0:05:12.972
was actually kind of a relief.

0:05:13.425,0:05:16.107
Normally when we mess around[br]with an organism's genes,

0:05:16.131,0:05:18.480
we make that thing[br]less evolutionarily fit.

0:05:18.504,0:05:21.337
So biologists can make[br]all the mutant fruit flies they want

0:05:21.361,0:05:22.614
without worrying about it.

0:05:22.638,0:05:25.645
If some escape, natural selection[br]just takes care of them.

0:05:26.750,0:05:29.973
What's remarkable and powerful[br]and frightening about gene drives

0:05:29.997,0:05:31.757
is that that will no longer be true.

0:05:33.092,0:05:36.656
Assuming that your trait does not have[br]a big evolutionary handicap,

0:05:36.680,0:05:38.759
like a mosquito that can't fly,

0:05:38.783,0:05:42.236
the CRISPR-based gene drive[br]will spread the change relentlessly

0:05:42.260,0:05:45.266
until it is in every single individual[br]in the population.

0:05:47.101,0:05:49.990
Now, it isn't easy to make[br]a gene drive that works that well,

0:05:50.014,0:05:52.188
but James and Esvelt think that we can.

0:05:53.339,0:05:57.163
The good news is that this opens[br]the door to some remarkable things.

0:05:57.187,0:05:59.091
If you put an anti-malarial gene drive

0:05:59.115,0:06:01.315
in just 1 percent of Anopheles mosquitoes,

0:06:01.339,0:06:03.091
the species that transmits malaria,

0:06:03.488,0:06:07.607
researchers estimate that it would spread[br]to the entire population in a year.

0:06:08.178,0:06:11.047
So in a year, you could virtually[br]eliminate malaria.

0:06:11.455,0:06:15.327
In practice, we're still a few years out[br]from being able to do that,

0:06:15.351,0:06:18.069
but still, a 1,000 children[br]a day die of malaria.

0:06:18.093,0:06:20.283
In a year, that number[br]could be almost zero.

0:06:20.966,0:06:23.862
The same goes for dengue fever,[br]chikungunya, yellow fever.

0:06:25.211,0:06:26.616
And it gets better.

0:06:27.215,0:06:29.691
Say you want to get rid[br]of an invasive species,

0:06:29.715,0:06:31.838
like get Asian carp[br]out of the Great Lakes.

0:06:32.434,0:06:34.458
All you have to do is release a gene drive

0:06:34.482,0:06:36.799
that makes the fish produce[br]only male offspring.

0:06:37.386,0:06:41.584
In a few generations,[br]there'll be no females left, no more carp.

0:06:41.608,0:06:44.687
In theory, this means we could restore[br]hundreds of native species

0:06:44.711,0:06:46.378
that have been pushed to the brink.

0:06:47.410,0:06:50.697
OK, that's the good news,

0:06:50.721,0:06:52.013
this is the bad news.

0:06:53.070,0:06:55.098
Gene drives are so effective

0:06:55.122,0:06:58.947
that even an accidental release[br]could change an entire species,

0:06:58.971,0:07:00.161
and often very quickly.

0:07:01.178,0:07:03.304
Anthony James took good precautions.

0:07:03.328,0:07:05.494
He bred his mosquitos[br]in a bio-containment lab

0:07:05.518,0:07:08.106
and he also used a species[br]that's not native to the US

0:07:08.130,0:07:09.685
so that even if some did escape,

0:07:09.709,0:07:12.724
they'd just die off, there'd be nothing[br]for them to mate with.

0:07:12.748,0:07:16.771
But it's also true that if a dozen[br]Asian carp with the all-male gene drive

0:07:16.795,0:07:20.724
accidentally got carried[br]from the Great Lakes back to Asia,

0:07:20.748,0:07:24.177
they could potentially wipe out[br]the native Asian carp population.

0:07:25.930,0:07:28.842
And that's not so unlikely,[br]given how connected our world is.

0:07:28.866,0:07:31.437
In fact, it's why we have[br]an invasive species problem.

0:07:31.912,0:07:33.080
And that's fish.

0:07:33.428,0:07:36.016
Things like mosquitos and fruit flies,

0:07:36.040,0:07:38.000
there's literally no way to contain them.

0:07:38.024,0:07:40.135
They cross borders[br]and oceans all the time.

0:07:41.754,0:07:43.936
OK, the other piece of bad news

0:07:43.960,0:07:46.278
is that a gene drive[br]might not stay confined

0:07:46.302,0:07:48.115
to what we call the target species.

0:07:48.556,0:07:50.055
That's because of gene flow,

0:07:50.079,0:07:52.676
which is a fancy way of saying[br]that neighboring species

0:07:52.700,0:07:53.948
sometimes interbreed.

0:07:53.972,0:07:57.123
If that happens, it's possible[br]a gene drive could cross over,

0:07:57.147,0:07:59.674
like Asian carp could infect[br]some other kind of carp.

0:07:59.698,0:08:03.413
That's not so bad if your drive[br]just promotes a trait, like eye color.

0:08:03.437,0:08:05.684
In fact, there's a decent[br]chance that we'll see

0:08:05.708,0:08:08.279
a wave of very weird fruit flies[br]in the near future.

0:08:09.390,0:08:10.653
But it could be a disaster

0:08:10.677,0:08:13.581
if your drive is deigned[br]to eliminate the species entirely.

0:08:14.351,0:08:17.879
The last worrisome thing[br]is that the technology to do this,

0:08:17.903,0:08:21.594
to genetically engineer an organism[br]and include a gene drive,

0:08:21.618,0:08:24.952
is something that basically any lab[br]in the world can do.

0:08:24.976,0:08:26.316
An undergraduate can do it.

0:08:27.209,0:08:30.491
A talented high schooler[br]with some equipment can do it.

0:08:32.526,0:08:34.835
Now, I'm guessing[br]that this sounds terrifying.

0:08:35.351,0:08:37.557
(Laughter)

0:08:37.581,0:08:40.471
Interestingly though,[br]nearly every scientist I talk to

0:08:40.495,0:08:44.376
seemed to think that gene drives were not[br]actually that frightening or dangerous.

0:08:44.400,0:08:47.028
Partly because they believe[br]that scientists will be

0:08:47.052,0:08:49.256
very cautious and responsible[br]about using them.

0:08:49.280,0:08:50.294
(Laughter)

0:08:50.318,0:08:51.548
So far, that's been true.

0:08:52.302,0:08:54.998
But gene drives also have[br]some actual limitations.

0:08:55.022,0:08:58.331
So for one thing, they work[br]only in sexually reproducing species.

0:08:58.704,0:09:02.132
So thank goodness, they can't be used[br]to engineer viruses or bacteria.

0:09:02.156,0:09:05.346
Also, the trait spreads[br]only with each successive generation.

0:09:05.370,0:09:07.363
So changing or eliminating a population

0:09:07.387,0:09:10.713
is practical only if that species[br]has a fast reproductive cycle,

0:09:10.737,0:09:13.537
like insects or maybe[br]small vertebrates like mice or fish.

0:09:14.438,0:09:16.699
In elephants or people,[br]it would take centuries

0:09:16.723,0:09:19.103
for a trait to spread[br]widely enough to matter.

0:09:20.079,0:09:25.221
Also, even with CRISPR, it's not that easy[br]to engineer a truly devastating trait.

0:09:26.079,0:09:27.808
Say you wanted to make a fruit fly

0:09:27.832,0:09:30.387
that feeds on ordinary fruit[br]instead of rotting fruit,

0:09:30.411,0:09:33.044
with the aim of sabotaging[br]American agriculture.

0:09:33.068,0:09:34.598
First, you'd have to figure out

0:09:34.622,0:09:37.394
which genes control[br]what the fly wants to eat,

0:09:37.418,0:09:39.965
which is already a very long[br]and complicated project.

0:09:40.489,0:09:43.793
Then you'd have to alter those genes[br]to change the fly's behavior

0:09:43.817,0:09:45.355
to whatever you'd want it to be,

0:09:45.379,0:09:48.180
which is an even longer[br]and more complicated project.

0:09:48.204,0:09:49.522
And it might not even work,

0:09:49.546,0:09:52.040
because the genes[br]that control behavior are complex.

0:09:52.064,0:09:54.072
So if you're a terrorist[br]and have to choose

0:09:54.096,0:09:56.454
between starting a grueling[br]basic research program

0:09:56.478,0:10:00.005
that will require years of meticulous[br]lab work and still might not pan out,

0:10:00.029,0:10:01.376
or just blowing stuff up?

0:10:01.400,0:10:03.055
You'll probably choose the later.

0:10:03.498,0:10:05.918
This is especially true[br]because at least in theory,

0:10:05.942,0:10:09.076
it should be pretty easy[br]to build what's called a reversal drive.

0:10:09.100,0:10:12.798
That's one that basically overwrites[br]the change made by the first gene drive.

0:10:12.822,0:10:15.116
So if you don't like[br]the effects of a change,

0:10:15.140,0:10:17.973
you can just release a second drive[br]that will cancel it out,

0:10:17.997,0:10:19.147
at least in theory.

0:10:21.374,0:10:23.096
OK, so where does this leave us?

0:10:24.604,0:10:28.199
We now have the ability[br]to change entire species at will.

0:10:29.017,0:10:30.183
Should we?

0:10:30.552,0:10:31.917
Are we gods now?

0:10:33.972,0:10:35.305
I'm not sure I'd say that.

0:10:36.094,0:10:37.321
But I would say this:

0:10:38.329,0:10:40.187
first, some very smart people

0:10:40.211,0:10:43.067
are even now debating[br]how to regulate gene drives.

0:10:43.598,0:10:46.162
At the same time,[br]some other very smart people

0:10:46.186,0:10:48.297
are working hard to create safeguards,

0:10:48.321,0:10:51.873
like gene drives that self-regulate[br]or peter out after a few generations.

0:10:52.644,0:10:53.844
That's great.

0:10:54.313,0:10:56.860
But this technology still requires[br]a conversation.

0:10:58.059,0:10:59.789
And given the nature of gene drives,

0:10:59.813,0:11:01.503
that conversation has to be global.

0:11:02.131,0:11:04.838
What if Kenya wants to use a drive[br]but Tanzania doesn't?

0:11:05.241,0:11:08.608
Who decides whether to release[br]a gene drive that can fly?

0:11:10.874,0:11:12.828
I don't have the answer to that question.

0:11:13.618,0:11:15.626
All we can do going forward, I think,

0:11:15.650,0:11:18.484
is talk honestly[br]about the risks and benefits

0:11:18.508,0:11:20.730
and take responsibility for our choices.

0:11:21.817,0:11:25.730
By that I mean, not just the choice[br]to use a gene drive,

0:11:25.754,0:11:27.753
but also the choice not to use one.

0:11:29.111,0:11:32.088
Humans have a tendency to assume[br]that the safest option

0:11:32.112,0:11:33.904
is to preserve the status quo.

0:11:34.905,0:11:36.477
But that's not always the case.

0:11:37.711,0:11:41.112
Gene drives have risks,[br]and those need to be discussed,

0:11:41.136,0:11:44.286
but malaria exists now[br]and kills 1,000 people a day.

0:11:44.977,0:11:48.541
To combat it, we spray pesticides[br]that do grave damage to other species,

0:11:48.565,0:11:50.135
including amphibians and birds.

0:11:51.668,0:11:54.532
So when you hear about gene drives[br]in the coming months,

0:11:54.556,0:11:56.810
and trust me, you will[br]be hearing about them,

0:11:56.834,0:11:58.378
remember that.

0:11:58.402,0:12:00.422
It can be frightening to act,

0:12:00.446,0:12:02.583
but sometimes, not acting is worse.

0:12:04.746,0:12:12.566
(Applause)