WEBVTT

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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 by the idea
of making mosquitos

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that didn't transmit malaria.

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It was a great idea,
but 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 gene
to survive inside the mosquito.

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But that just created another problem.

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Now that you've got 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
a bunch of the new genetically-engineered mosquotos,

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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 gene trait
would not 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 eye 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
says when a male and 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 and 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
of 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 is 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,

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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.