WEBVTT

99:59:59.999 --> 99:59:59.999
So this is a talk about gene drives,

99:59:59.999 --> 99:59:59.999
but I'm going to start by 
telling you a brief story.

99:59:59.999 --> 99:59:59.999
20 years ago, a biologist
named Anthony James

99:59:59.999 --> 99:59:59.999
got obsessed by the idea
of making mosquitos

99:59:59.999 --> 99:59:59.999
that didn't transmit malaria.

99:59:59.999 --> 99:59:59.999
It was a great idea,
but pretty much a complete failure.

99:59:59.999 --> 99:59:59.999
For one thing, it turned out to be
really hard

99:59:59.999 --> 99:59:59.999
to make a malaria resistant mosquito.

99:59:59.999 --> 99:59:59.999
James managed it, finally,
just a few years ago

99:59:59.999 --> 99:59:59.999
by adding some genes
that make it impossible


99:59:59.999 --> 99:59:59.999
for the malaria gene
to survive inside the mosquito.

99:59:59.999 --> 99:59:59.999
But that just created another problem.

99:59:59.999 --> 99:59:59.999
Now that you've got malaria-resistant
mosquito,

99:59:59.999 --> 99:59:59.999
how do you get it to replace
all the malaria-carrying mosquitos?

99:59:59.999 --> 99:59:59.999
There are a couple options,

99:59:59.999 --> 99:59:59.999
but plan A was basically to breed up
a bunch of the new genetically-engineered mosquotos,

99:59:59.999 --> 99:59:59.999
release them into the wild,

99:59:59.999 --> 99:59:59.999
and hope that they pass on their genes.

99:59:59.999 --> 99:59:59.999
The problem was that you'd 
have to release

99:59:59.999 --> 99:59:59.999
literally 10x the number of native
mosquitos to work.

99:59:59.999 --> 99:59:59.999
So in a village with 10,000 mosquitos,

99:59:59.999 --> 99:59:59.999
you release an extra 100,000.

99:59:59.999 --> 99:59:59.999
As you might guess, this was not
a very popular strategy

99:59:59.999 --> 99:59:59.999
with the villagers.

99:59:59.999 --> 99:59:59.999
(Laughter)

99:59:59.999 --> 99:59:59.999
Then, last January, Anthony James
got an email


99:59:59.999 --> 99:59:59.999
from a biologist named 
Ethan Bier.

99:59:59.999 --> 99:59:59.999
Bier said that he and his grad student,
Valentino Gantz,


99:59:59.999 --> 99:59:59.999
had stumbled on a tool that could not only
guarentee

99:59:59.999 --> 99:59:59.999
that a particular gene trait
would not be inherited,

99:59:59.999 --> 99:59:59.999
but that it would spread
incredibly quickly.

99:59:59.999 --> 99:59:59.999
If they were right, it would basically
solve the problem


99:59:59.999 --> 99:59:59.999
that he and James had been
working on for 20 years.

99:59:59.999 --> 99:59:59.999
As a test, they engineered
two mosquitos

99:59:59.999 --> 99:59:59.999
to carry the anti-malaria gene

99:59:59.999 --> 99:59:59.999
and also this new tool,
a gene drive,

99:59:59.999 --> 99:59:59.999
which I'll explain in a minute.

99:59:59.999 --> 99:59:59.999
Finally, they set it up so that
any mosquitos

99:59:59.999 --> 99:59:59.999
that had inherited the
anti-malaria gene

99:59:59.999 --> 99:59:59.999
wouldn't have the usual white eyes,
but would instead have red eyes.

99:59:59.999 --> 99:59:59.999
That was pretty much just 
for convenience

99:59:59.999 --> 99:59:59.999
so they could tell just at a glance
which was which.

99:59:59.999 --> 99:59:59.999
So they took their two 
anti-malarial, red eye mosquitos

99:59:59.999 --> 99:59:59.999
and put them in a box with 30
ordinary white-eyed ones

99:59:59.999 --> 99:59:59.999
and let them breed.

99:59:59.999 --> 99:59:59.999
In two generations, 
those had produced 38,000 grandchildren.

99:59:59.999 --> 99:59:59.999
That is not the surprising part.

99:59:59.999 --> 99:59:59.999
This is the surprising part:

99:59:59.999 --> 99:59:59.999
given that you started with just
two red-eyed mosquitos

99:59:59.999 --> 99:59:59.999
and 30 white-eyed ones,

99:59:59.999 --> 99:59:59.999
you expect mostly white-eyed
descendents.

99:59:59.999 --> 99:59:59.999
Instead, when James opened the box,

99:59:59.999 --> 99:59:59.999
all 38,000 mosquitos had red eyes.

99:59:59.999 --> 99:59:59.999
When I asked Ethan Bier
about this moment,

99:59:59.999 --> 99:59:59.999
he became so excited, tht he was
literally shouting into the phone.

99:59:59.999 --> 99:59:59.999
That's because getting only
red-eyed mosquitos

99:59:59.999 --> 99:59:59.999
violates a rule that is the
absolute cornerstone of biology,

99:59:59.999 --> 99:59:59.999
Mendelian genetics.

99:59:59.999 --> 99:59:59.999
I'll keep this quick, but Mendelian genetics
says when a male and female mate,

99:59:59.999 --> 99:59:59.999
their baby inherits half of its
DNA from each parent.

99:59:59.999 --> 99:59:59.999
So if our original mosquito was aa
and our new mosquito is aB,

99:59:59.999 --> 99:59:59.999
where B is the anti-malarial gene,

99:59:59.999 --> 99:59:59.999
the babies should come out
in four permutations:

99:59:59.999 --> 99:59:59.999
aa, aB, aa and Ba.

99:59:59.999 --> 99:59:59.999
Instead, with the new gene drive,

99:59:59.999 --> 99:59:59.999
they all came out aB.

99:59:59.999 --> 99:59:59.999
Biologically, that shouldn't
even be possible.

99:59:59.999 --> 99:59:59.999
So what happened?

99:59:59.999 --> 99:59:59.999
The first thing that happened
was the arrival

99:59:59.999 --> 99:59:59.999
of a gene-editing tool
known as CRISPR in 2012.

99:59:59.999 --> 99:59:59.999
Many of you have probably heard
about CRISPR,

99:59:59.999 --> 99:59:59.999
so I'll just say briefly that CRISPR
is a tool that allows researchers

99:59:59.999 --> 99:59:59.999
to edit genes very precisely,
easily and quickly.

99:59:59.999 --> 99:59:59.999
It does this by harnessing a mechanism
that already existed in bacteria.

99:59:59.999 --> 99:59:59.999
Basically, there's a protein
that acts like a scissors

99:59:59.999 --> 99:59:59.999
and cuts the DNA,

99:59:59.999 --> 99:59:59.999
and there's an RNA molecule
that directs the scissors

99:59:59.999 --> 99:59:59.999
to any point on the genome you want.

99:59:59.999 --> 99:59:59.999
The result is basically a word processor
of genes.

99:59:59.999 --> 99:59:59.999
You can take an entire gene out,
put one in,

99:59:59.999 --> 99:59:59.999
or even edit just a single letter
within a gene.

99:59:59.999 --> 99:59:59.999
And you can do it in nearly any species.

99:59:59.999 --> 99:59:59.999
Okay, remember how I said 
that gene drives

99:59:59.999 --> 99:59:59.999
originally had two problems?

99:59:59.999 --> 99:59:59.999
The first is that it was hard
to engineer a mosquito

99:59:59.999 --> 99:59:59.999
to be malaria resistant.

99:59:59.999 --> 99:59:59.999
That's basically gone now,
thanks to CRISPR.

99:59:59.999 --> 99:59:59.999
But the other problem was 
logistical.

99:59:59.999 --> 99:59:59.999
How do you get your trait to spread?

99:59:59.999 --> 99:59:59.999
This is where it gets clever.

99:59:59.999 --> 99:59:59.999
A couple years ago, a biologist
at Harvard named Kevin Esvelt

99:59:59.999 --> 99:59:59.999
wondered what would happen
if you made it so that

99:59:59.999 --> 99:59:59.999
CRISPR inserted not only
your new gene,

99:59:59.999 --> 99:59:59.999
but also the machinery 
that does the cutting and pasting.

99:59:59.999 --> 99:59:59.999
In other words, what if CRISPR
also copy and pasted itself.

99:59:59.999 --> 99:59:59.999
You'd end up with a perpetual
motion machine for gene editing.

99:59:59.999 --> 99:59:59.999
And that's exactly what happened.

99:59:59.999 --> 99:59:59.999
This CRISPR gene drive
that Esvelt created

99:59:59.999 --> 99:59:59.999
not only guarantees that a trait 
will get passed on,

99:59:59.999 --> 99:59:59.999
but if its used in the germline cell,

99:59:59.999 --> 99:59:59.999
it will automatically copy and paste
your new gene

99:59:59.999 --> 99:59:59.999
into both chromosomes of every
single individual.

99:59:59.999 --> 99:59:59.999
It's like a global search and replace,

99:59:59.999 --> 99:59:59.999
or in science terms,

99:59:59.999 --> 99:59:59.999
it makes a heterozygous trait
homozygous.

99:59:59.999 --> 99:59:59.999
So, what does this mean?

99:59:59.999 --> 99:59:59.999
For one thing, it means we have
a very powerful,

99:59:59.999 --> 99:59:59.999
but also somewhat alarming new tool.

99:59:59.999 --> 99:59:59.999
Up until now, the fact that gene drives
didn't work very well

99:59:59.999 --> 99:59:59.999
was actually kind of a relief.

99:59:59.999 --> 99:59:59.999
Normally when we mess around
with an organisms's genes,

99:59:59.999 --> 99:59:59.999
we make that thing less evolutionarily fit.

99:59:59.999 --> 99:59:59.999
So biologists can make all the mutant
fruit flies they want

99:59:59.999 --> 99:59:59.999
without worrying about it.

99:59:59.999 --> 99:59:59.999
If some escape, natural selection
just takes care of it.

99:59:59.999 --> 99:59:59.999
What's remarkable and powerful
and frightening about gene drives

99:59:59.999 --> 99:59:59.999
is that that will no longer be true.

99:59:59.999 --> 99:59:59.999
Assuming that your trait does not
have a big evolutionary handicap,

99:59:59.999 --> 99:59:59.999
like a mosquito that can't fly,

99:59:59.999 --> 99:59:59.999
the CRISPR-based gene drive
will spread the change relentlessly

99:59:59.999 --> 99:59:59.999
until it is in every single individual
in the population.

99:59:59.999 --> 99:59:59.999
Now, it isn't easy to make
a gene drive that works that well,

99:59:59.999 --> 99:59:59.999
but James and Esvelt think
that we can.

99:59:59.999 --> 99:59:59.999
The good news is that this opens
the door to some remarkable things.

99:59:59.999 --> 99:59:59.999
If you put an anti-malarial gene drive
in just 1 percent

99:59:59.999 --> 99:59:59.999
of anopheles mosquitos,
the species that transmits malaria.

99:59:59.999 --> 99:59:59.999
Researchers estimate that it would
spread to the entire population

99:59:59.999 --> 99:59:59.999
in a year.

99:59:59.999 --> 99:59:59.999
So in a year, you could virtually 
eliminate malaria.

99:59:59.999 --> 99:59:59.999
In practice, we're still a few years out
from being able to do that,

99:59:59.999 --> 99:59:59.999
but sitll, a 1,000 children a day
die of malaria.

99:59:59.999 --> 99:59:59.999
In a year, that number could be
almost zero.

99:59:59.999 --> 99:59:59.999
The same goes for dengue fever,
chicken genuang (?), yellow fever.

99:59:59.999 --> 99:59:59.999
And it gets better.

99:59:59.999 --> 99:59:59.999
Say you want to get rid 
of an invasive species,

99:59:59.999 --> 99:59:59.999
like get Asian Carp out of
The Great Lakes.

99:59:59.999 --> 99:59:59.999
All you have to do is release 
a gene drive

99:59:59.999 --> 99:59:59.999
that makes the fish produce
only male offspring.

99:59:59.999 --> 99:59:59.999
In a few generations, there'll be
no females left, no more carp.

99:59:59.999 --> 99:59:59.999
In theory, this means that we 
could restore hundreds

99:59:59.999 --> 99:59:59.999
of native species that have been
pushed to the brink.

99:59:59.999 --> 99:59:59.999
Okay, that's the good news,

99:59:59.999 --> 99:59:59.999
this is the bad news.

99:59:59.999 --> 99:59:59.999
Gene drives are so effective,

99:59:59.999 --> 99:59:59.999
that even an accidental release 
could change an entire species,

99:59:59.999 --> 99:59:59.999
and often very quickly.

99:59:59.999 --> 99:59:59.999
Anthony James took the precautions.

99:59:59.999 --> 99:59:59.999
He breed his mosquitos in
a bio-containment lab

99:59:59.999 --> 99:59:59.999
and he also used a species
that's not native to the US

99:59:59.999 --> 99:59:59.999
so that even if some did escape,

99:59:59.999 --> 99:59:59.999
they'd just die off,

99:59:59.999 --> 99:59:59.999
there'd be nothing for them
to mate with.

99:59:59.999 --> 99:59:59.999
But it's also true that if 
a dozen Asian Carp

99:59:59.999 --> 99:59:59.999
with the all-male gene drive accidentally
got carried from The Great Lakes

99:59:59.999 --> 99:59:59.999
back to Asia,

99:59:59.999 --> 99:59:59.999
they could potentially wipe out 
the native Asian Carp population.

99:59:59.999 --> 99:59:59.999
And that's not so unlikely, given
how connected our world is.

99:59:59.999 --> 99:59:59.999
In fact, it's why we have 
an invasive species problem.

99:59:59.999 --> 99:59:59.999
And that's fish.

99:59:59.999 --> 99:59:59.999
Things like mosquitos and fruit flies,
there's literally no way to contain them.

99:59:59.999 --> 99:59:59.999
They cross borders and oceans
all the time.

99:59:59.999 --> 99:59:59.999
Okay, the other piece of bad news
is that

99:59:59.999 --> 99:59:59.999
a gene drive might not stay confined
to what we call the target species.

99:59:59.999 --> 99:59:59.999
That's because of gene flow,

99:59:59.999 --> 99:59:59.999
which is a fancy way of saying
that neighboring species

99:59:59.999 --> 99:59:59.999
sometimes inter-breed.

99:59:59.999 --> 99:59:59.999
If that happens, it's possible
a gene drive could cross over,

99:59:59.999 --> 99:59:59.999
like Asian Carp could infect
some other kind of Carp.

99:59:59.999 --> 99:59:59.999
That's not so bad if your drive
just promotes a trait, like eye color.

99:59:59.999 --> 99:59:59.999
In fact, there's a decent chance that
we'll see a wave

99:59:59.999 --> 99:59:59.999
of very weird fruit flies 
in the near future.

99:59:59.999 --> 99:59:59.999
But it could be a disaster
if your drive is deigned

99:59:59.999 --> 99:59:59.999
to eliminate the species entirely.

99:59:59.999 --> 99:59:59.999
The last worrisome thing is that
the technology to do this,

99:59:59.999 --> 99:59:59.999
to genetically engineer an organism
and include a gene drive

99:59:59.999 --> 99:59:59.999
is something basically any lab
in the world can do.

99:59:59.999 --> 99:59:59.999
An undergraduate can do it.

99:59:59.999 --> 99:59:59.999
A talented high schooler
with some equipment can do it.

99:59:59.999 --> 99:59:59.999
Now I'm guessing that this sounds 
terrifying.

99:59:59.999 --> 99:59:59.999
Interestingly though, nearly 
every scientist I talk to

99:59:59.999 --> 99:59:59.999
seems to think that gene drives
were not actually

99:59:59.999 --> 99:59:59.999
that frightening or dangerous.

99:59:59.999 --> 99:59:59.999
Partly because they believe that
scientists will be

99:59:59.999 --> 99:59:59.999
very cautious and responsible
about using them.

99:59:59.999 --> 99:59:59.999
(Laughter)

99:59:59.999 --> 99:59:59.999
So far, that's been true.

99:59:59.999 --> 99:59:59.999
The gene drives also have
some actual limitations.

99:59:59.999 --> 99:59:59.999
For one thing, they work in only
sexually reproducing species.

99:59:59.999 --> 99:59:59.999
So thank goodness, they can't be used
to engineer viruses or bacteria.

99:59:59.999 --> 99:59:59.999
Also, the trait spreads only with each
succesive genertion.

99:59:59.999 --> 99:59:59.999
So changing or eliminating a population
is practical only if that species

99:59:59.999 --> 99:59:59.999
has a fast reproductive cycle,


99:59:59.999 --> 99:59:59.999
like insects or maybe small vertebrates
like mice or fish.

99:59:59.999 --> 99:59:59.999
In elephants or people, it would
take centuries

99:59:59.999 --> 99:59:59.999
for a trait to spread widely enough
to matter.

99:59:59.999 --> 99:59:59.999
Also, even with CRISPR, it's not that easy
to engineer a truly devastating trait.

99:59:59.999 --> 99:59:59.999
Say you wanted to make a fruit fly


99:59:59.999 --> 99:59:59.999
that feeds on ordinary fruit instead
of rotten fruit

99:59:59.999 --> 99:59:59.999
with the aim of sabotaging 
American agriculture.

99:59:59.999 --> 99:59:59.999
First you'd have to figure out
which gene controls

99:59:59.999 --> 99:59:59.999
what the fly wants to eat,

99:59:59.999 --> 99:59:59.999
which is already a very long 
and complicated project.

99:59:59.999 --> 99:59:59.999
Then you'd have to alter those genes
to change the fly's behavior

99:59:59.999 --> 99:59:59.999
to whatever you'd want it to be,

99:59:59.999 --> 99:59:59.999
which is an even longer 
and complicated project.

99:59:59.999 --> 99:59:59.999
And it might not even work because
the genes that control behavior are complex.

99:59:59.999 --> 99:59:59.999
So if you're a terrorist and have 
to choose between

99:59:59.999 --> 99:59:59.999
starting a grueling basic research program

99:59:59.999 --> 99:59:59.999
that will require years 
of meticulous lab work

99:59:59.999 --> 99:59:59.999
and still might not pan out,

99:59:59.999 --> 99:59:59.999
or just blowing stuff up?

99:59:59.999 --> 99:59:59.999
You'll probably choose the later.

99:59:59.999 --> 99:59:59.999
This is especially true because
at least in theory,

99:59:59.999 --> 99:59:59.999
it should be pretty easy to build
what's called a reversal drive.

99:59:59.999 --> 99:59:59.999
That's one that basically overwrites
the change made by the first gene drive.

99:59:59.999 --> 99:59:59.999
So if you don't like the effects 
of a change,

99:59:59.999 --> 99:59:59.999
you can just release a second drive
that will cancel it out,

99:59:59.999 --> 99:59:59.999
at least in theory.

99:59:59.999 --> 99:59:59.999
Okay, so where does this leave us?

99:59:59.999 --> 99:59:59.999
We now have the ability to change
entire species at will.

99:59:59.999 --> 99:59:59.999
Should we?

99:59:59.999 --> 99:59:59.999
Are we gods now?

99:59:59.999 --> 99:59:59.999
I'm not sure I'd say that.

99:59:59.999 --> 99:59:59.999
But I would say this:

99:59:59.999 --> 99:59:59.999
First, some very smart people
are even now debating

99:59:59.999 --> 99:59:59.999
how to regulate gene drives.

99:59:59.999 --> 99:59:59.999
At the same time, some other
very smart people

99:59:59.999 --> 99:59:59.999
are working hard to create
safeguards,

99:59:59.999 --> 99:59:59.999
like gene drives that self regulate
or petter out after a few generations.

99:59:59.999 --> 99:59:59.999
But this technology still requires
a conversation.

99:59:59.999 --> 99:59:59.999
And given the nature of gene drives,

99:59:59.999 --> 99:59:59.999
that conversation has to be global.

99:59:59.999 --> 99:59:59.999
What if Kenya wants to use a drive
that Tanzania doesn't?

99:59:59.999 --> 99:59:59.999
Who decides whether to release
a gene drive that can fly?

99:59:59.999 --> 99:59:59.999
I don't have the answer to that question.

99:59:59.999 --> 99:59:59.999
All we can do going forward, I think,

99:59:59.999 --> 99:59:59.999
is talk honestly about 
the risks and benefits

99:59:59.999 --> 99:59:59.999
and take responsibility for our choices.

99:59:59.999 --> 99:59:59.999
By that I mean, not just the choice
to use a gene drive,

99:59:59.999 --> 99:59:59.999
but also the choice not to use one.

99:59:59.999 --> 99:59:59.999
Humans have a tendency to assume
that the safest option

99:59:59.999 --> 99:59:59.999
is to preserve the status quo.

99:59:59.999 --> 99:59:59.999
But that's not always the case.

99:59:59.999 --> 99:59:59.999
Gene drives have risks and those
need to be discussed,

99:59:59.999 --> 99:59:59.999
but malaria exists now and kills
1,000 people a day.

99:59:59.999 --> 99:59:59.999
To combat it, we spray pesticides
that do grave damage to other species,

99:59:59.999 --> 99:59:59.999
including amphibians and birds.

99:59:59.999 --> 99:59:59.999
So when you hear about gene drives
in the coming months,

99:59:59.999 --> 99:59:59.999
and trust me, you will be 
hearing about them,

99:59:59.999 --> 99:59:59.999
remember that.

99:59:59.999 --> 99:59:59.999
It can be frightening to act,

99:59:59.999 --> 99:59:59.999
but sometimes, not acting
is worse.

99:59:59.999 --> 99:59:59.999
(Applause)