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So this is a talk about gene drives,

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

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20 years ago, a biologist
named Anthony James

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got obsessed with the idea
of making mosquitos

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that didn't transmit malaria.

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

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For one thing, it turned 
out to be really hard

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to make a malaria resistant mosquito.

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James managed it, finally,
just a few years ago

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by adding some genes
that make it impossible

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for the malaria parasite
to survive inside the mosquito.

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But that just created another problem.

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

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

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There are a couple options,

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but plan A was basically to breed up


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a bunch of the new 
genetically-engineered mosquitos

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release them into the wild,

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and hope that they pass on their genes.

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The problem was that you'd 
have to release

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literally 10x the number of native
mosquitos to work.

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So in a village with 10,000 mosquitos,

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you release an extra 100,000.

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As you might guess, this was not
a very popular strategy

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with the villagers.

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(Laughter)

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Then, last January, Anthony James
got an email

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from a biologist named 
Ethan Bier.

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Bier said that he and his grad student,
Valentino Gantz,

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had stumbled on a tool that could 
not only guarentee

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that a particular genetic trait
would be inherited,

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but that it would spread
incredibly quickly.

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If they were right, it would basically
solve the problem

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

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As a test, they engineered
two mosquitos

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to carry the anti-malaria gene

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and also this new tool,
a gene drive,

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which I'll explain in a minute.

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Finally, they set it up so that
any mosquitos

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that had inherited the
anti-malaria gene

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

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That was pretty much just 
for convenience

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

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

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

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and let them breed.

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In two generations, those had 
produced 38,000 grandchildren.

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That is not the surprising part.

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This is the surprising part:

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Given that you started with just
two red-eyed mosquitos

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and 30 white-eyed ones,

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you expect mostly white-eyed
descendents.

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Instead, when James opened the box,

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all 38,000 mosquitos had red eyes.

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When I asked Ethan Bier
about this moment,

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he became so excited, tht he was
literally shouting into the phone.

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That's because getting only
red-eyed mosquitos

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violates a rule that is the
absolute cornerstone of biology,

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Mendelian genetics.

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I'll keep this quick, 
but Mendelian genetics

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says when a male and a female mate,

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their baby inherits half of its
DNA from each parent.

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

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where B is the anti-malarial gene,

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the babies should come out
in four permutations:

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aa, aB, aa, Ba.

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Instead, with the new gene drive,

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they all came out aB.

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Biologically, that shouldn't
even be possible.

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So what happened?

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The first thing that happened
was the arrival

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

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Many of you have probably heard
about CRISPR,

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

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to edit genes very precisely,
easily and quickly.

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

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

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and cuts the DNA,

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and there's an RNA molecule
that directs the scissors

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to any point on the genome you want.

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The result is basically a word processor
word processor for genes.

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

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or even edit just a single letter
within a gene.

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And you can do it in nearly any species.

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Okay, remember how I said 
that gene drives

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originally had two problems?

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The first was that it was hard
to engineer a mosquito

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to be malaria resistant.

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That's basically gone now,
thanks to CRISPR.

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But the other problem was 
logistical.

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How do you get your trait to spread?

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This is where it gets clever.

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

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wondered what would happen
if you made it so that

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CRISPR inserted not only
your new gene,

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but also the machinery 
that does the cutting and pasting.

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

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

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And that's exactly what happened.

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This CRISPR gene drive
that Esvelt created

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not only guarantees that a trait 
will get passed on,

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but if its used in the germline cell,

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it will automatically copy and paste
your new gene

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into both chromosomes of every
single individual.

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It's like a global search and replace,

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

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So, what does this mean?

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

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but also somewhat alarming new tool.

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

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was actually kind of a relief.

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

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we make that thing 
less evolutionarily fit.

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So biologists can make all the mutant
fruit flies they want

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without worrying about it.

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

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What's remarkable and powerful
and frightening about gene drives

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is that that will no longer be true.

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

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like a mosquito that can't fly,

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the CRISPR-based gene drive
will spread the change relentlessly

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until it is in every single individual
in the population.

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

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but James and Esvelt think
that we can.

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

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If you put an anti-malarial gene drive
in just 1 percent

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of anopheles mosquitos,
the species that transmits malaria.

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Researchers estimate that it would
spread to the entire population

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in a year.

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So in a year, you could virtually 
eliminate malaria.

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

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

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In a year, that number could be
almost zero.

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The same goes for dengue fever,
chicken genuang (?), yellow fever.

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And it gets better.

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Say you want to get rid 
of an invasive species,

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like get Asian Carp out of
The Great Lakes.

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All you have to do is release 
a gene drive

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that makes the fish produce
only male offspring.

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

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In theory, this means that we 
could restore hundreds

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of native species that have been
pushed to the brink.

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Okay, that's the good news,

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this is the bad news.

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Gene drives are so effective,

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that even an accidental release 
could change an entire species,

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and often very quickly.

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Anthony James took good precautions.

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He breed his mosquitos in
a bio-containment lab

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

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so that even if some did escape,

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they'd just die off,

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there'd be nothing for them
to mate with.

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But it's also true that if 
a dozen Asian Carp

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with the all-male gene drive accidentally
got carried from The Great Lakes

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back to Asia,

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they could potentially wipe out 
the native Asian Carp population.

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

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

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And that's fish.

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Things like mosquitos and fruit flies,
there's literally no way to contain them.

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They cross borders and oceans
all the time.

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Okay, the other piece 
of bad news is that

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a gene drive might not stay confined
to what we call the target species.

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That's because of gene flow,

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which is a fancy way of saying
that neighboring species

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sometimes inter-breed.

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

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like Asian Carp could infect
some other kind of Carp.

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

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

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of very weird fruit flies 
in the near future.

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But it could be a disaster
if your drive is deigned

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to eliminate the species entirely.

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

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to genetically engineer an organism
and include a gene drive,

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

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An undergraduate can do it.

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A talented high schooler
with some equipment can do it.

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Now I'm guessing that 
this sounds terrifying.

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Interestingly though, nearly 
every scientist I talk to

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seems to think that gene drives
were not actually

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that frightening or dangerous.

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Partly because they believe that
scientists will be

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very cautious and responsible
about using them.

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(Laughter)

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So far, that's been true.

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But gene drives also have
some actual limitations.

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For one thing, they work in only
sexually reproducing species.

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

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Also, the trait spreads only with each
succesive genertion.

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So changing or eliminating a population
is practical only if that species

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has a fast reproductive cycle,


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like insects or maybe small vertebrates
like mice or fish.

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In elephants or people, it would
take centuries

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for a trait to spread widely enough
to matter.

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

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Say you wanted to make a fruit fly


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that feeds on ordinary fruit instead
of rotting fruit

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with the aim of sabotaging 
American agriculture.

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First you'd have to figure out
which genes control

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what the fly wants to eat,

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which is already a very long 
and complicated project.

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

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to whatever you'd want it to be,

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which is an even longer 
and more complicated project.

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And it might not even work because


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the genes that control
behavior are complex.

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So if you're a terrorist and have 
to choose between

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starting a grueling basic research program

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that will require years 
of meticulous lab work

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and still might not pan out,

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or just blowing stuff up?

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You'll probably choose the later.

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This is especially true because
at least in theory,

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

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

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

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

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at least in theory.

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Okay, so where does this leave us?

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

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Should we?

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Are we gods now?

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I'm not sure I'd say that.

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But I would say this:

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First, some very smart people
are even now debating

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how to regulate gene drives.

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At the same time, some other
very smart people

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are working hard to create
safeguards,

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

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That's great.

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But this technology still requires
a conversation.

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And given the nature of gene drives,

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that conversation has to be global.

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

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

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I don't have the answer to that question.

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All we can do going forward, I think,

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is talk honestly about 
the risks and benefits

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and take responsibility for our choices.

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

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but also the choice not to use one.

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Humans have a tendency to assume
that the safest option

245
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is to preserve the status quo.

246
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But that's not always the case.

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Gene drives have risks and those
need to be discussed,

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

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

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including amphibians and birds.

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

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and trust me, you will be 
hearing about them,

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remember that.

254
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It can be frightening to act,

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but sometimes, not acting
is worse.

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(Applause)