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.
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 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.
The 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 rotten fruit
with the aim of sabotaging American agriculture.
First you'd have to figure out which gene controls
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 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