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 with the idea
of making mosquitos

that didn't transmit malaria.

It was a great idea, and 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 parasite
to survive inside the mosquito.

But that just created another problem.

Now that you've got a
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 mosquitos

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 genetic trait
would 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-eyed 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 a 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, 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
word processor for 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 was 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 good 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.

Okay, the other piece
of bad news is that

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

That's because of gene flow,

which is a fancy way of saying
that neighboring species

sometimes inter-breed.

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

like Asian Carp could infect
some other kind of Carp.

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

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

of very weird fruit flies
in the near future.

But it could be a disaster
if your drive is deigned

to eliminate the species entirely.

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

to genetically engineer an organism
and include a gene drive,

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

An undergraduate can do it.

A talented high schooler
with some equipment can do it.

Now I'm guessing that
this sounds terrifying.

Interestingly though, nearly
every scientist I talk to

seems to think that gene drives
were not actually

that frightening or dangerous.

Partly because they believe that
scientists will be

very cautious and responsible
about using them.

(Laughter)

So far, that's been true.

But gene drives also have
some actual limitations.

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

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

Also, the trait spreads only with each
succesive genertion.

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

has a fast reproductive cycle,

like insects or maybe small vertebrates
like mice or fish.

In elephants or people, it would
take centuries

for a trait to spread widely enough
to matter.

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

Say you wanted to make a fruit fly

that feeds on ordinary fruit instead
of rotting fruit

with the aim of sabotaging
American agriculture.

First you'd have to figure out
which genes control

what the fly wants to eat,

which is already a very long
and complicated project.

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

to whatever you'd want it to be,

which is an even longer
and more complicated project.

And it might not even work because

the genes that control
behavior are complex.

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

starting a grueling basic research program

that will require years
of meticulous lab work

and still might not pan out,

or just blowing stuff up?

You'll probably choose the later.

This is especially true because
at least in theory,

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

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

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

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

at least in theory.

Okay, so where does this leave us?

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

Should we?

Are we gods now?

I'm not sure I'd say that.

But I would say this:

First, some very smart people
are even now debating

how to regulate gene drives.

At the same time, some other
very smart people

are working hard to create
safeguards,

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

That's great.

But this technology still requires
a conversation.

And given the nature of gene drives,

that conversation has to be global.

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

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

I don't have the answer to that question.

All we can do going forward, I think,

is talk honestly about
the risks and benefits

and take responsibility for our choices.

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

but also the choice not to use one.

Humans have a tendency to assume
that the safest option

is to preserve the status quo.

But that's not always the case.

Gene drives have risks and those
need to be discussed,

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

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

including amphibians and birds.

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

and trust me, you will be
hearing about them,

remember that.

It can be frightening to act,

but sometimes, not acting
is worse.

(Applause)