Gene editing can now change an entire species -- forever

So this is a talk about gene drives,

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

20 years ago, a biologist
named Anthony James

got obsessed by the idea
of making mosquitos

that didn't transmit malaria.

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

For one thing, it turned out to be
really hard

to make a malaria resistant mosquito.

James managed it, finally,
just a few years ago

by adding some genes
that make it impossible

for the malaria gene
to survive inside the mosquito.

But that just created another problem.

Now that you've got malaria-resistant
mosquito,

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

There are a couple options,

but plan A was basically to breed up
a bunch of the new genetically-engineered mosquotos,

release them into the wild,

and hope that they pass on their genes.

The problem was that you'd
have to release

literally 10x the number of native
mosquitos to work.

So in a village with 10,000 mosquitos,

you release an extra 100,000.

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

with the villagers.

(Laughter)

Then, last January, Anthony James
got an email

from a biologist named
Ethan Bier.

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

had stumbled on a tool that could not only
guarentee

that a particular gene trait
would not be inherited,

but that it would spread
incredibly quickly.

If they were right, it would basically
solve the problem

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

As a test, they engineered
two mosquitos

to carry the anti-malaria gene

and also this new tool,
a gene drive,

which I'll explain in a minute.

Finally, they set it up so that
any mosquitos

that had inherited the
anti-malaria gene

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

That was pretty much just
for convenience

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

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

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

and let them breed.

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

That is not the surprising part.

This is the surprising part:

given that you started with just
two red-eyed mosquitos

and 30 white-eyed ones,

you expect mostly white-eyed
descendents.

Instead, when James opened the box,

all 38,000 mosquitos had red eyes.

When I asked Ethan Bier
about this moment,

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

That's because getting only
red-eyed mosquitos

violates a rule that is the
absolute cornerstone of biology,

Mendelian genetics.

I'll keep this quick, but Mendelian genetics
says when a male and female mate,

their baby inherits half of its
DNA from each parent.

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

where B is the anti-malarial gene,

the babies should come out
in four permutations:

aa, aB, aa and Ba.

Instead, with the new gene drive,

they all came out aB.

Biologically, that shouldn't
even be possible.

So what happened?

The first thing that happened
was the arrival

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

Many of you have probably heard
about CRISPR,

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

to edit genes very precisely,
easily and quickly.

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

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

and cuts the DNA,

and there's an RNA molecule
that directs the scissors

to any point on the genome you want.

The result is basically a word processor
of genes.

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

or even edit just a single letter
within a gene.

And you can do it in nearly any species.

Okay, remember how I said
that gene drives

originally had two problems?

The first is that it was hard
to engineer a mosquito

to be malaria resistant.

That's basically gone now,
thanks to CRISPR.

But the other problem was
logistical.

How do you get your trait to spread?

This is where it gets clever.

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

wondered what would happen
if you made it so that

CRISPR inserted not only
your new gene,

but also the machinery
that does the cutting and pasting.

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

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

And that's exactly what happened.

This CRISPR gene drive
that Esvelt created

not only guarantees that a trait
will get passed on,

but if its used in the germline cell,

it will automatically copy and paste
your new gene

into both chromosomes of every
single individual.

It's like a global search and replace,

or in science terms,

it makes a heterozygous trait
homozygous.

So, what does this mean?

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

but also somewhat alarming new tool.

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

was actually kind of a relief.

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

we make that thing less evolutionarily fit.

So biologists can make all the mutant
fruit flies they want

without worrying about it.

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

What's remarkable and powerful
and frightening about gene drives

is that that will no longer be true.

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

like a mosquito that can't fly,

the CRISPR-based gene drive
will spread the change relentlessly

until it is in every single individual
in the population.

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

but James and Esvelt think
that we can.

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

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

of anopheles mosquitos,
the species that transmits malaria.

Researchers estimate that it would
spread to the entire population

in a year.

So in a year, you could virtually
eliminate malaria.

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

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

In a year, that number could be
almost zero.

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

And it gets better.

Say you want to get rid
of an invasive species,

like get Asian Carp out of
The Great Lakes.

All you have to do is release
a gene drive

that makes the fish produce
only male offspring.

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

In theory, this means that we
could restore hundreds

of native species that have been
pushed to the brink.

Okay, that's the good news,

this is the bad news.

Gene drives are so effective,

that even an accidental release
could change an entire species,

and often very quickly.

Anthony James took the precautions.

He breed his mosquitos in
a bio-containment lab

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

so that even if some did escape,

they'd just die off,

there'd be nothing for them
to mate with.

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

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

back to Asia,

they could potentially wipe out
the native Asian Carp population.

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

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

And that's fish.

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

They cross borders and oceans
all the time.