Reshaping Nature Through Gene Drives

A new technology, called gene drives, has the power to spread any genetic instructions you wish across an entire animal or plant species in the wild. It might let us restore ecosystems ravaged by invasive species, or help species adapt to climate change. And, it might save millions of children from dying of malaria. But could altering nature in this way, and on this scale, have unintended consequences? And, when it comes reshaping ecosystems, who needs to say yes?

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Episode Transcript

Speaker 1 (00:15):
Pushkin, you're listening to Brave New Planet, a podcast about
amazing new technologies that could dramatically improve our world, or
if we don't make wise choices, could leave us a

(00:36):
lot worse off. Utopia or dystopia. It's up to us.
On October eighth, seventeen sixty nine, James Cook, an explorer
and captain in the British Royal Navy, became the first
European to set foot on the islands that are today

(00:58):
known as New Zealand. His arrival would have dramatic consequences
for the Maori people that had inhabited the land for
hundreds of years. It would also radically alter New Zealand's ecology,
because when Cook disembarked, so too did some of the
rats that did hitchhike on his ship. Previously unknown to

(01:21):
the Pacific Islands, these rodents grew in population over the
centuries and wreaked havoc on the environment. We're in the
middle of a rodent nami. You've seen the headlines. Rats
as big as cats. Rats everywhere. It is a problem too,
everywhere that you wouldn't believes. Hey, we've probably got the

(01:43):
most rats that double the most rats with ever head
shocking actually jsay shocking, and it's not just unpleasantness that's
the problem. The rats and other invasive mammals have been
decimating New Zealand's birds. They devoured tens of millions of
eggs and baby birds every year, causing the extinction of

(02:05):
one quarter of the nation's unique bird species. New Zealand
has long tried to get rid of these invaders. The
traditional answer has been to spread rat poison all over
the islands, often by helicopters, but rat poison is indiscriminate.
Native animals can also die from eating it. Sometimes humans

(02:27):
accidentally consume it as well, and it hasn't solved the problem. Recently,
scientists have proposed a much more targeted solution. It's called
a gene drive, a genetic engineering trick that guarantees that
when two animals mate, a specific gene will be inherited

(02:49):
by one hundred percent of their progeny. In time, any gene,
even a disadvantageous gene, would spread through the population. If
New Zealand were to release genetically engineered rats with a
gene drive, to dramatically decrease the rat's fertility, while the

(03:09):
rat population would shrink, In effect, evolution could be directed
to vote the rats off the islands. And it's not
just rats. Gene drives might be used against any invasive
animal or plant that uses sexual reproduction, and they might
also be used to save species, for example, by helping

(03:33):
them survive the effects of climate change. Most importantly, gene
drives might save millions of lives by eliminating or modifying
the mosquito that's primarily responsible for spreading malaria throughout sub
Saharan Africa. Now, no one has yet deployed gene drives

(03:53):
in the wild, but they've been shown to work in
the laboratory reshaping nature. It's a heady concept. Scientists are
exhilarated by the possibilities for improving the world. At the
same time they're wondering what could possibly go wrong. Today's

(04:16):
big question. Should we use gene drives to correct the
past introduction of invasive species, protect species from the ravages
of climate change, and save humans from serious infectious diseases
or is it too risky? Evolution in ecology, after all,
can be strangely unpredictable. When might the risks be justified?

(04:40):
And when you're proposing to release things into nature, who
needs to say yes. My name is Eric Lander. I'm
a scientist who works on ways to improve human health.
I helped lead the Human Genome Project, and today I

(05:00):
lead the Road Institute of MIT and Harvard. In the
twenty first century, powerful technologies have been appearing at a
breathtaking pace, related to the Internet, artificial intelligence, genetic engineering,
and more. They have amazing potential upsides, but we can't
ignore the risks that come with them. The decisions aren't

(05:21):
just up to scientists or politicians, whether we like it
or not, we all of us are the stewards of
a brave New planet. This generation's choices will shape the
future as never before. Coming up on this episode of
Brave New Planets, we speak to scientists who played a

(05:46):
key role in inventing gene drives. This is potentially a
much more elegant way of solving ecological problems than poisons
and bulldozers. We talk with people trying to balance the
benefits and risks. Okay, so people are looking at using
genetic engineering to alter wild species. This is really exciting

(06:08):
and at the same time I'm literally in the same breath,
I was also just like, holy crap, if this isn't
used properly, this could be really damaging to our planet.
We hear from a scientist in Burkina Fasso who wants
to use gene drives to get rid of malaria. This
is really my dream and my hope that I can

(06:29):
come up with something that kind of really helps not
only Africa. And a journalist from Kenya who's pretty skeptical.
It's very nice to think that people really care about
the lives of Africans, But I think the story is
a lot more complex than that. Stay tuned. Chapter one

(06:53):
snails the size of baseballs. To understand the reasons why
people might want to use gene drives, I talked with
someone who's thought a lot about them. My name is
doctor James Collins go by Jim, a professor in the
School of Life Sciences at Arizona State University. Jim is

(07:14):
an evolutionary ecollegist who co chaired a study on gene
drives for the US National Academy of Sciences. For an
evolutionary ecologist, he has a bit of an unusual upbringing.
I grew up in New York City, Queens and always
just had a love of plants and animals. In New
York City. In New York City, Queens at the time

(07:36):
was different than Queens today. I could go fishing. I
could catch turtles and snakes and frogs, all kinds of insects,
bring them home to my very tolerant parents. Jim knows
a lot about how ecosystems can be disrupted by the
introduction of new species, from microbes to mammals. He told

(07:59):
me that Captain Cook was responsible for more than just
introducing rats into New Zealand. Think about Hawaiian birds where
they are endangered by avian malaria, and that's as a
result of a mosquito being introduced by Captain Cook. Then

(08:20):
the colonists brought chickens, and they brought avian malaria. The
mosquitoes begin to feed on the chickens, acquire the malaria,
and then begin to feed on native birds, transmit the
malaria to native birds, and they are being diminished in
terms of population sizes, and even species. In fact, Hawaii

(08:42):
has become the bird extinction capital of the world. Since
humans arrived ninety five, one hundred and forty two birds
species found nowhere else in the world have become extinct
in Hawaii. Even small scale introduction of a new species
can lead to massive problems. In nineteen sixty six, a

(09:04):
young boy who was vacationing in Hawaii decided to take
a few of the giant land snails that live there
back to his home in Miami to keep them as
pets in the family garden. The snails, which can grow
larger than the size of baseballs, reproduced quickly. They soon
began to cause economic damage to local farms, and they

(09:27):
also carried dangerous parasites slithering along at quite literally a
snail's pace. They certainly don't look menacing, but for the
Florida Department of Agriculture, this is a horror movie. The
problem with these things They love just about anything that
grows in Florida. The eradication effort, which used poisons, took

(09:48):
ten years and cost over a million dollars, but despite
all the work, the snail population eventually bounced back. In
twenty fourteen, the Florida Department of Agriculture went door to
door searching for the snails. They found a hundred and
fifty thousands, with two properties alone harboring seven hundred of

(10:11):
the critters. With other invasive species, the measures have been
even more dramatic. In the nineteen fifties, Australia tried to
exterminate an escalating population of European rabbits that had been
introduced a century earlier by an English settler. Their solution
was to release rabbits carrying a deadly Mixoma virus. It

(10:35):
killed millions of rabbits across Australia, but it didn't solve
the problem. There are hundreds of invasive species that people
would like to be rid of, zebra muscles in the
Great Lakes, silver carp in the Missouri River, kudzuweed, and
Georgia burmese pythons in the Everglades. But the species that

(10:56):
cause the most harm to humans aren't recent invaders. They're
indigenous mosquitoes that spread malaria in Africa. My name is
Diane Worth. I'm on the faculty at the Harvard chan
School of Public Health. I work on malaria. Diane is
also a colleague of mine at the Broad Institute, and

(11:16):
she studied malaria for over thirty five years. Malaria starts
as a fever and chills. It has nondescript symptoms in
the early stages, but then as the disease progresses, people
can go into a coma, they get very sick, and
it spreads by mosquitoes. That's right. The disease is transmitted

(11:41):
by the anopling mosquito in Africa. That's Avelis Gambia, a
mosquito that's very efficient at transmitting malaria. The world has
tried to eradicate malaria once before, in the middle of
the last century, when they had DDT and chloroquin DDT
to kill mosquitos and chloroquin to treat infected people, and

(12:05):
that effort did lead to some successes. Malaria was eated
from Italy, from most of Southern Europe, from the United
States by a combination of those techniques and environmental activities,
including putting oil on the top of water so it
wouldn't be environmentally allowed now, but was done in the

(12:28):
Tennessee Valley here in the United States in the nineteen fifties.
And that effort failed in most of the world, and
in fact, that effort really never included Sub Saharan Africa,
because the experts at the time concluded that in Sub
Saharan Africa, transmission was so intense that no effort could

(12:49):
bring it under control. How are we doing in the
elimination of malaria today. I think what's happened in the
last decade is two things. One, there's been an overall
reduction in the number of cases of malaria through increased
distribution of bednets, better diagnostics, better use of treatment drugs.

(13:12):
We've dropped cases by forty percent worldwide and deaths by
about fifty percent worldwide. The other part of the story
is really sub Saharan Africa, where progress has slowed and
in many cases reversed. For example, Nigeria has twenty five

(13:34):
percent of all of the malaria in the world, and
ten countries make up seventy percent of the burden of
malaria worldwide. All of these countries in Africa, progress using
our standard tools has stalled. In those countries. We're going
to need innovation in order to actually continue the downward

(13:58):
trend and in fact, in some cases reverse what appears
to be a rebound in the number of cases. The
mosquitoes are rebounding in port because they've evolved resistance to
overcome traditional methods of control. The major insecticide that we
use to kill mosquitos. There's resistance in almost all mosquito populations,

(14:22):
and so we anticipate that the need to have new
insecticides is urgent, and without that we're unlikely to reach
to eradication girls, particularly in sub Saharan Africa. So scientists
are constantly imagining new solutions to save ecosystems and to
save human lives. Could gene drives be the answer? Chapter

(14:49):
two selfish genes? Instead of deploying poisons and viruses, what
if we could just genetically reprogram pests to slow or
even stop their reproduction. The strategy may sound simple, but
it has a gaping hole. The logic of natural selection

(15:10):
means the disadvantageous genes, ones that cause an organism to
produce fewer offspring, should die out. Ah, But there's a
loophole in theory. A gene could spread into population even
if it hurts an organism's reproduction, if it could find
a way to ensure that it gets inherited by most

(15:33):
of the offspring. Could nature actually do that? Nature does
such things often again, evolutionary ecologist Jim Collins well known
example is a driving y chromosome in some species of mice,
which converts a population into all males, and of course
that population then would go extinct. It's one of those

(15:56):
very interesting quirks of evolution in which you wind up
with populations of all males basically blinking out of existence,
and so you get one group can be converted into males,
it goes extinct, but there are other groups that still
have males and females and they'll continue on. When we
think of how genes are passed on, we usually think

(16:17):
about the laws of Mendelian inheritance, first recognized by Gregor Mendel,
a friar and scientist who studied pea plants in the
mid eighteen hundreds. Mendel figured out that in sexually reproducing species,
each individual has two copies of each gene, one from
their mother, one from their father. They pass on one

(16:39):
of those two copies to each child, with the two
copies each having a fifty fifty chance of being passed on.
For example, imagine a gene that determines the sex of
an offspring. If you have a sexually reproducing species that
has males and females in it, a baby would be
predicted to be a male fifty percent of the time

(16:59):
female fifty percent of the time. But what if a
gene naturally evolved that could cheat, could greedily stack the
deck so that it gets inherited sixty eighty percent or
even a hundred percent of the time, biologists referred to
such selfish behavior as a gene drive. Party gene drive

(17:20):
could do is changed that ratio as far as any
particular genetic trade is concerned. So what was the first
time anybody noticed the existence of a natural gene drive?
They were described the very late eighteen hundreds, very early
nineteen hundreds, so it's been known for a long time.
Over the twentieth century, scientists discovered a vast array of

(17:44):
gene drives in nature, but it was only in the
beginning of this century that they began to seriously think
about how they might harness the power of gene drives.
Austin Burt was the one who laid out in principle
the idea that if there were a way to control

(18:06):
this natural process, then indeed you would have in your
hands something that could control the gene frequency in populations.
My name is Austin Burt, and I'm a professor of
evolutionary genetics here at Imperial College, London. Austin's an expert
in selfish genes, genes that cheat mandilion inheritance. Things that

(18:29):
show gene drive or similar sorts of behavior, and all
the other sorts of weird and wonderful genes out there
are able to spread through populations not because they increase
the survival or reproduction of the organism, but because they're
distorting transmission to their own advantage. He became very interested
in using gene drives for the benefit of public health. So,

(18:52):
for example, in ades mosquitoes, which is the factor for
a yellow fever and dany, there is an actually occurring
selfish element on the Y chromosome, the male determining part
of the genome, that gets into five percent or so
of the progeny, and so it has the potential then

(19:13):
to spread through a population, and as it does so,
distort the sex ratio of the population to be more
and more male biased. That's worth reiterating. A naturally occurring
gene drive in mosquitoes turn ninety five percent of the
male and that caught people's attention. Because male mosquitoes don't
bite people, they don't transmit the disease, and so the

(19:35):
idea was that you might be able to use that
sort of elopment to control the diseases spread by those
mosquitoes diseases like malaria. Unfortunately, gene drives in animals tend
to use specialized tricks, many of which still aren't fully understood.
The best gene drive to engineer would be based on

(19:56):
simple principles, and you'd most likely find them in simple organisms.
As luck would have it, That's what Austin studied. My
first grant was to study the selfish genetic elements of yeasts.
The best known gene drive in yeast exploits the fact

(20:17):
that chromosomes come in pairs. So here's the trick. The
gene drive occurs at a specific spot on a specific chromosome,
and it encodes the instructions for an enzyme called a
homing endonuclease. The sole purpose of that enzyme is to
make a cut at the exact same spot on any

(20:40):
other copy of the chromosome that doesn't already have the
gene drive. When a cell detects that cut, it fills
it in with the genetic information from the matching spot
on the uncut chromosome, and presto chain show the cell
inserts a copy of the gene drive into that spot

(21:01):
on the chromosome. When I was reading about this, I thought, well, okay,
so if that was actually then we could instead use
that same sort of approach to change them to recognize
mosquito sequences and then using that to knock out a
gene that's essential for the survival or reproduction of the mosquito,

(21:23):
and so suppress the population that way. In two thousand
and three, Austin published a paper in the Proceedings of
the Royal Society describing this brilliant idea. In principle, gene
drives could be used to suppress a population, say decreasing
the fertility of mosquitos, or to alter a population, say

(21:46):
adding a gene that would prevent the malaria parasite from
growing in the mosquito. But there was one hitch, the
homing end. The nuclease in yeast recognizes only one specific
DNA sequence. To engineer new gene drives, you'd need to
be able to reprogram them to recognize different sequences. It

(22:11):
was difficult to get the enzymes to be recognized new
sequences to recognize mosquito sequences as opposed to E sequences,
It would take another ten years before the solution emerged.
It turned out to involve another system that accomplished the
same thing in a very different way. The system was

(22:32):
called Crisper. Chapter three, A Shining, Marvelous Future. Crisper is
a kind of immune system that bacteria used to protect
themselves against viruses. Crisper uses an enzyme to cut the
virus's DNA. But what's amazing is that the enzyme doesn't

(22:56):
have a fixed target. It's programmable. The bacteria create instructions
based on past viral infections. The Crisper enzyme uses these
instructions to search for matching the A sequence and then
cuts it. It took twenty years and dozens of scientists
around the world to understand exactly how Crisper works, but

(23:19):
once they did, scientists figured out how to use its
ability to target DNA sequences to create a technology to
edit the genetic code inside living cells, from yeast to humans.
Genome editing has made a huge splash, including the award
of Nobel Prize last month to two scientists for their

(23:39):
work on Crisper. Crisper has so many potential applications. Medical
scientists realized that it held the prospect of fixing mutations
in patients with severe diseases, and Austin Bert realized that
this new technology could turn his idea of gene drives
from dream into practical reality. Austin had been working for

(24:07):
the last decade trying to engineer existing gene drives from
organisms like yeast, and that was just a hideously complicated
and difficult endeavor that wasn't getting all that far. Crisper
was the perfect tool for enabling gene drive. This is
biologist Kevin Esfeld, who was the first person to propose
a specific design for a Crisper based gene drive. I'm

(24:31):
an assistant professor at the MIT Media Lab, where I
direct the Sculpting Evolution Group, and our job is to
cultivate wisdom through ecological and evolutionary engineering. Kevin's interest in
sculpting evolutions started early when he read Michael Crichton's nineteen
ninety novel Jurassic Park. The mere notion that we might

(24:52):
be able to resurrect dinosaurs through genetic engineering was just
mind boggling. And even more so, there's this notion at
the park was a synthetic ecosystem built to host creatures
that live nowhere else us in the world. That's an
incredible idea that we can potentially make our own ecosystems.

(25:17):
How old were you when your address park? Oh, God,
probably eight or nine. At a very young age, you
might say, I knew what I wanted to do with
my life. I wanted to understand how genetics made organisms
and ecosystems the way they are, and I was interested
in tinkering with them in order to better understand the
answer to that question. Kevin remembers the moment when it

(25:37):
dawned on him that Crisper would make it practical to
engineer gene drives. He immediately read all of Austin's papers.
The first day was purelation, thinking about all the amazing
things you could do. You were thinking that applications already.
One is human health, things like malarias just a semiasis dangey.
It's spread by mosquito, lime disease, tick born illness, as mosquito,

(26:00):
boorn illness, as parasites, you name it. Number two is
environmental preservation, and then there's agriculture. Because instead of spraying
nasty poisons on ours in order to get rid of
the pests that eat them, how about we program the
pests to dislike the taste. This is potentially a much
more elegant way of solving ecological problems than poisons and bulldozers.

(26:22):
In short, suppression gene drives aimed at suppressing the population
of a dangerous or invasive species could provide a general
approach to conquer terrible parasites and restore natural environments. To
say that Kevin was excited would be an understatement. The
possibilities of a shining, marvelous future were just exploding all

(26:45):
around me like fireworks. Kevin published his proposal about how
to build a crisper based gene drive in twenty fourteen.
Within a year, scientific papers began reporting functioning gene drives,
first in yeast, then fruit flies, and then in mosquitoes.
Beyond Kevin's favorite applications, some people are thinking about gene

(27:07):
drives as a way to help nate sure adapt rapidly
to some of the devastating effects of climate change. My
name's Natalie Chefler. I'm a molecular biologist, and I recently
founded an initiative called Editing Nature, which tries to integrate
diverse worldviews and perspectives to steer responsible development of genetic
technologies for the environment. Natalie first became interested in gene

(27:30):
drives because she was frustrated with the methods that were
being used to get rid of specific invasive species. In Canada,
where Natalie's from ash trees were disappearing at a frightening
pace because they were being destroyed by invasive beetles originally
from Asia. Ecologists had started considering ways to get rid

(27:53):
of these beetles, and they pitched the idea of importing
Russian wasps to prey on the Asian beetles. I was like,
are you kidding me? This doesn't make Eddie sense and
so and so I just started thinking that there must
be bio tech options. That very year, Kevin Esvelt and
his group had published reports on using crisper based gene

(28:15):
drives to change wild species. And that was sort of
the Aha moment where I thought, Okay, so people are
looking at using genetic engineering to alter wild species. This
is really exciting because it could provide a solution for
these really huge challenges that we're facing. Among those challenges,
Natalie points to what's happening to coral reefs. So we're

(28:38):
seeing a huge decline in coral reef health right now,
in large part because ocean temperatures are rising. Oceans are
becoming more acidic and that's causing a lot of stress
to the coral. It's happening really quickly and pretty extensively.
White of coral reefs matter. I always see them as
it was like the forests of the sea. So they

(28:59):
create huge amount of habitat for many marine fish. Many
people's livelihoods depend on the fish that depend on coral reef,
and so there's been estimates in the trillions and trillions
of dollars that would be lost if the coral were
to continue to decline at the rates that they do,
So losing all the coral would be like losing all
the forests in a way. That's somehow I think about it.

(29:23):
In contrast to suppression gene drives, Natalie thinks that alteration
gene drives, ones that would spread beneficial genes throughout a population,
could make some coals more resilient to climate change. And
there is research starting to come out showing that certain
mutations and certain genes can be protective against things like

(29:44):
acidification or high temperatures, or allow the coral to dat better.
And so the idea would be that you could use
crisper gene editing to rewrite the genome of a coral
to be able to express these resiliency inducing genes. If
you were to introduce a gene drive as well, then
that would also allow you to release into the wild,
into the ocean and allow that to spread. Chapter four

(30:09):
anopolies Gambii. Of all the possible uses of gene drives,
none is more compelling than Austin Bird's original idea of
controlling the spread of malaria. According to the World's Health Organization,
more than four hundred thousand people die from malaria each year.
That's close to one death every minute. Most are children

(30:33):
under five. Austin Bird ended up creating Target Malaria, a
not for profit research collaboration with a mission of developing
and sharing genetic technologies to help stop the spread of
malaria in Sub Saharan Africa. Target Malaria is targeting several
mosquito species, including Anaphly's gambii, the mosquito responsible for most

(30:57):
malaria cases in Sub Saharan Africa, which malaria expert Diane
Worth described earlier. Among many possible designs, a simple approach
would be to create a pression gene drive that causes
mosquitos to produce mostly male offspring. The strategy is actually
a two fer. First, as Austin Burt noted earlier, male

(31:21):
mosquitoes don't bite people, so they can't transmit malaria. Second,
the lopsided sex ratio should cause of the population to
dramatically crash and perhaps be eliminated in some areas. Target
Malaria is headquartered in the UK, where Austin works, but
it has research teams in many places, including Mali, Uganda

(31:43):
and Burkina Fossio. I spoke via Skype with one of
Target Malaria's lead researchers in Burkina Fassio. My name is
on A medical entomologist, Doctor Abdulaye Diabate, was born and
raised in a rural area of southwest Burkina Fassio, and

(32:04):
he is intimately familiar with the disease, the leading cause
of all There is absolutely no doubt about that this
is a really very big issue for us, as myself
as a kid experienced several episodes of malaria. All my
brothers and sisters cinematically, every single one got malaria. If
you don't have a real treatment right away, it can

(32:27):
quickly need to get and even remember myself when I
was still a kid long time ago, I have stuck her,
you know, from malaria, and I could really see from
the eyes of my parents that they were really very scared,
but because they knew that anytime they could lose me.
Fortunately I made it through. But as a parent today
I have the same experiencing of my kids. Abdulas dedicated

(32:50):
his life to malaria prevention. He did his PhD in
France and postdoctoral research at the US National Institutes of
Health before returning to Burkina Fossil. I felt really that
I came to the US, you know, to learn, and
I have to come back home, you know, to give
back to my community and as this is really my
dream and my hope that I can come up to

(33:12):
be something that can really help not only but the
entire Africa to make sure that we can get wead
once for all of malaria. When he first returned home,
the most promising method of malaria eradication was to target
mosquitoes by using insecticide treated nets, and that tool was

(33:33):
pretty successful, at least initially. We were really really excited,
you know when we saw the data, because we had
a really fantastic data showing that because a clear impact
on a little transmission. But soon researchers started to see
problems with the method we farted, you know, to see insecitary.
This sounds you know, coming in and we wished a

(33:54):
point where most of those are no longer susceptible. As
he began desperately looking for new tools, he came across
the gene drive proposal from Austin Bird and Target Malaria
and began working with the team. My hope really is
that we are able, you know, to come up with
some really good intervention tool that concident and then have

(34:15):
a really really good impact on malaria. Gooden in Africa.
Target Malaria is still five to ten years away from
testing an actual gene drive in the field, but the
excitement is palpable. Controlling malaria in Africa saving four hundred
thousand lives a year would be a big, big deal.

(34:35):
A gene drives clearly work in the lab, So what
are people waiting for? Why aren't we just releasing gene
drives against mosquitoes and lots of other targets as well?
What could possibly go wrong? Chapter five? What could possibly

(34:55):
go wrong? In thinking about what could go wrong, many
scientists use terms like unintended consequences, molecular biologist Natalie Koefler, Well,
she puts it differently. Okay, So people are looking at
using genetic engineering to alter wild species. This is really exciting,

(35:17):
huge challenges that we're facing, and at the same time,
literally in the same breath, I was also just like,
holy crap, if this isn't used properly, this could be
really damaging to our planet. To prevent that, Natalie founded
an organization called the Editing Nature Initiative. For his part,

(35:38):
Kevin Esfeld came to a similar realization, although it took
him just a little bit longer. Soon after his day
of euphoria, his vision of a shining, marvelous future with
fireworks exploding, Kevin says he fell into utter despair, total paranoia,
of dark visions of horrible, horrific misuse and weaponization. What

(36:03):
worries Kevin, Natalie and others is the gene drives actually
might be so easy to make and work so well
that things might get out of hand, Which means if
a crisper based gene drive system will spread in the wild,
probably the most populations of that species that are connected

(36:23):
by any kind of gene flow, then that means that
individual people could potentially single handedly edit entire species. Suppose
you release a gene drive and so the rat population
of a remote Pacific island. How can you be sure
that it won't actually get off the island? And the
rodents got there in the first place, rights we should

(36:45):
have safely assume that they can also get off. If
one of those rodents stows away on a ship, like
the ones that stowed away on Captain Cook's ship, It's
possible that the gene drive could eventually spread throughout the
entire species of black rats around the world. Rats are
invasive species in some places, but they're an important part

(37:06):
of the ecosystem elsewhere. So what happens if you unintentionally alter, suppress,
or in the worst case, wipe out a species, I
asked evolutionary ecologist Jim Collins, who co chaired the US
National Academy of Science study published in twenty sixteen. You
do not want to be just reaching into ecosystems and

(37:28):
arbitrarily removing species. Humanity has done lots of that, and
there have been these unintended consequences that are not good.
Can you give this a couple examples of that. There
are any number of instances in which we've we've removed
top predators, for example, in ocean systems in which top

(37:49):
predators have been fished out, and then you can wind
up with the ecosystem that is greatly diminished. It's largely
algae and jellyfishes by the time you've taken off the
top predators in the system. What about unintentionally wiping out
the mosquito species that carry malaria? Could that disrupt den

(38:09):
eco system? Well, there are plenty of things that eat mosquitoes,
and so hypothetically, yes, there could be effects. Do we
know exactly what they are yet? No. Austin Bird, who
founded Target Malaria, has thought a lot about the effects
of suppressing mosquito populations. He's asked, are mosquitoes a keystone

(38:32):
species on which other organisms depend? According to Austin, experts
think not predators that eat mosquitoes, who appear to eat
anyat flying insects. He's also asked, if mosquitoes disappeared from
a region, would an insect transmitting an even worse disease
take its place. Well, it's hard to imagine, because mosquitoes

(38:55):
and malaria are amongst humanity's worst scourges. Still, Austin says
we should take nothing for granted, and mosquitoes are a
relatively easy case. You'd have to answer the same question
for every possible use of gene drives. But as Jim
Collins's National Academy report notes, there's another problem. Beyond unintended consequences,

(39:21):
there's the disturbing possibility that someone might deliberately use gene
drives to cause harm. It could be used maliciously. A
bad actor could decide to try to develop a gene
drive system that might target some part of the food
supply in a country. The individual could decide to introduce traits,

(39:46):
undesirable traits, and other kinds of organisms and cause lots
of mischief. What would be the most likely targets for
it Organisms that reproduce sexually, that have a relatively short
generation time. You'd want this thing to turn over pretty quickly,
so you're probably not going to use a gene drive

(40:07):
system for long lived animals larger vertebrates, let's say cattle,
But for smaller organisms that turn over pretty quickly, maybe poultry,
you might be able to think about using something like
a gene drive system. In short, Jim says, a bad

(40:27):
actor might try to use gene drives as a bioweapon
to devastate agriculture in a country. Chapter six, daisy chains.
As Kevin s Field thought more, he stumbled across a
big problem with his initial design for gene drives. It

(40:49):
would be too risky even to run field trials to
test the technology. Why because if even a single organism
escaped from the test area, well, the gene drive might
invade the entire species. The problem with the full power
version is it has everything it needs to copy it
self forever, in every generation. So Kevin got to work

(41:12):
designing gene drives that couldn't spread forever self exhausting gene drives.
He designs something he named a daisy drive. Every link
in this daisy chain is the equivalent of like one
gallon of genetic fuel. And you burn genetic fuel over generations,
and when you run out, it stops. Daisy drives involve

(41:35):
a chain of genetic elements, say abcde, each inserted into
a different chromosome. A copies B to make sure it's
inherited by all the offspring. B copies C, see copies dance,
so on. But nothing's driving A. It's inherited by only

(41:56):
half the offspring. So when a is lost, there's nothing
copying B, so it's eventually lost, and so on. When
you introduce a daisy chain into a large population, it
should eventually peter out. And Kevin has more tricks up
his sleeve. He's designed a gene drive that's engineered not

(42:17):
to spread beyond the geographical area in which you released it.
He calls it a threshold drive. It mimics one of
the ways that reproductive barriers arise in the wild by
using genetic rearrangements to make interbreeding less efficient. Kevin thinks
of these tricks will make it possible to do much

(42:39):
safer field trials. But still, what if a drive spreads
despite these safety features. Well, Kevin says, you can always
create a new gene drive to spread and overrite the
first one. He calls it a restoration drive. Now a
lot of people say, wait a minute, you can't rely

(42:59):
on the same technology that just went wrong. But hold
on a second. If the problem is what we did
to the species, then using another method that successfully spread
a change to the whole species to successfully spread another
change to the whole species is perfectly valid engineering. Even
as Kevin works to devise solutions daisy drives threshold drives,

(43:23):
restoration drives. He knows he can't imagine everything. I still
assume that evolution is cleverer than we are. It's going
to have some trick up at sleeve. This is like
you are fighting the tide, or you're fighting a blind,
idiot alien god. To use my preferred conception of what
evolution really is. It's like the story that inspired Kevin

(43:45):
to go into biotechnology. Jurassic Park in the classic nineteen
ninety three film, Doctor Ian Malcolm played by Jeff Goldblum,
is a mathematician who specializes in chaos theory. Early in
the film, he presciently calls out the park designers for
the hubris in thinking they can control the dinosaur population.

(44:09):
Know they're all female. We control their chromosomes. It's really
not that difficult, John. The kind of control your attempting
is it's not possible. As if there's one thing the
history of evolution has tossed that life will not be contained.
Life breaks free, It expands to new territories, and it
crashes through barriers painfully, maybe even dangerously. But no, there

(44:31):
it is. You're implying that a group composed entirely of
female animals, will breed. No, I'm simply saying that life
finds a way, wife finds a way. If Kevin knows
if we want the potential benefits that gene drives offer,

(44:51):
we have to work hard to be sure that life
doesn't find a way. What I'm worried about is the
loss of public trust when scientists accidentally engineer a whole species.
Whatever they do can be undone except for the fact
that it would be become very well known through the
media that scientists accidentally turned to species into GMOs. So

(45:14):
that's why you're very concerned to get this right. You
don't think that this really will go wrong. And you
do have this ultimate safety switch, which is send another
gene drive to go after the first gene drive. But
if we have to do that, we've already lost public
trust in the technology. So we better never have to

(45:35):
do that. Chapter seven Skeptics. While everyone is in favor
of eradicating malaria, which kills four hundred thousand people a year,
some people are pretty skeptical about using gene drives to

(45:55):
do it. I personally would not be in favor of
gene drives. This is Zarahmulu. I'm a journalist and documentary
filmmaker from Kenya and I'm currently based in Montreal. Zara
has covered a wide range of time topics that affect Africa,
including an investigative portrait of a multinational gold mine in Tanzania. Recently,

(46:16):
she began collaborating with an organization called the ETC Group.
It's a small organization that works with civil society across
different parts of the world and they do work on
the impact of new technologies on biodiversity and human rights
and agriculture, and so I came to learn about gene

(46:37):
drives through ETC Groups through collaborating with them. In twenty eighteen,
Zara made a short film and wrote an article casting
doubt on target Malaria's efforts in Burkina Faso. For starters,
she challenges the motives of people working on gene drives.
The question to ask, is our gene drives really about

(46:58):
public health and conservation or other other interests and other
other ways that agribusiness companies can make a profit from
gene drives. Why do we really need gene drives, what
are they really for and who is going to benefit
ultimately from the development of this technology. It's very nice
to think that people really care about the lives of Africans.

(47:18):
But I think this story is a lot more complex
than that. Zara also argues that Africa doesn't really need
gene drives to conquer malaria. I come from a country
where people contract malaria regularly. People die in my country
from malaria. We do need to fight malaria, and it's
a terrible disease. No one's going to disagree with that. However,
it's also important to know that Paraguay eliminated malaria recently,

(47:42):
Tri Lanka eliminated malaria. Algeria and Argentina have just been
declared malaria free, and so there are ways in which
countries have successfully eradicated malaria without having to employ very
risky technologies like gene drives. I asked malaria expert Diane
Worth whether she thought malaria eradication in those countries provided

(48:03):
a useful model for sub Saharan Africa. She was skeptical.
Algeria it's a desert, mosquitoes need water to breed. Paraguay
very small number of cases, probably eliminated years ago, but
finally certified. Argentina same story, relatively little malaria. Ever, Sri

(48:26):
Lanka is an island they don't have to deal with
importation from surrounding countries. They have a very strong healthcare system,
so they're able to identify early every case of malaria,
and they have a mosquito vector that isn't very robust.
Diane argued that malaria in Sub Saharan Africa represents a

(48:50):
very different challenge. They're different mosquitos, there's different ecology, there's
different burden of disease in the population. In many places
in Sub Saharan Africa, children have malaria for half the
year and serve as reservoirs for transmission. The mosquito in
Africa is a mosquito that only bites humans. That means

(49:13):
that's the most effective transmitter in most of Africa, and
so therefore detecting early, preventing and getting treatment for the
disease represents a challenge. Whatever you think about the need
for gene drives, Czara's key issue is very important. It's

(49:34):
in the title of her film, A question of consent
Before gene drives get released into the wild. Who needs
to say yes? Chapter eight, charm l Shake to Nantucket.
What to do about gene drives is a question that's

(49:55):
been hotly debated by the governing body for the Convention
on Biological Diversity in international agreements among one hundred and
ninety six countries on preserving, sustaining and sharing the benefits
of biodiversity. In December twenty eighteen, the group met in
Charmel Shaikh, Egypt. Natalie Koefler, the founder of Editing Nature,

(50:18):
traveled to Egypt to deliver a talk. At the meeting,
many representatives from Target Malaria were present, and then many
representatives from several environmental groups, and those include environmental justice
advocacy sort of technological white watchdogs groups like ETC Group.
The group of the NGOs of the meeting, including the
ETC Group, called for a total moratorium on gene drives,

(50:42):
not just undeploying them, but even studying them in the laboratory.
They are calling for a moratorium on research, so basically
for all research to halt, which I believe is just
somewhat ridiculous. I don't think there's a way you just
stop people trying to understand more. And if the point
is that this could be something that could be of
great benefit, you would want to be able to study

(51:03):
it more and make sure you can understand what those
benefits or risks could be stopping research. To me, seems your.
The Governing Body eventually rejected the call for a moratorium. Nonetheless,
Zara Mulu saw the meeting as a partial victory, pointing
to the closing statement by the Governing Body, which she
said requires organizations seeking to release gene drive organisms to

(51:28):
obtain the quote free prior and informed consent of potentially
affected communities. So it has to be free, prior and
informed consent before these releases go ahead. So who exactly
do you ask for consent? Elected officials? Anyone who might
potentially be affected? How do you even know everyone who

(51:50):
might be affected? Well, Kevin Esfeld has been wrestling with
these issues and a project he's working on to fight
lime disease in New England. Lime disease is awful. Lime
disease is disgusting. I don't like ticks, so I figured, well,
what if we decide to prevent lime disease caused by
a bacteria. Lime disease can lead to serious long term symptoms,

(52:15):
including pain, severe headaches, and numbness. Humans get lime disease
from being bitten by infected ticks. And how do the
ticks pick up the bacteria? Most ticks get infected when
they bite a white footed mouse, so what if the
white footed mice were immune. Kevin's big idea was to

(52:35):
take the mice that had developed antibodies against lime disease,
read out the genetic instructions that encode those antibodies, and
use a gene drive to spread those instructions throughout the
entire white footed mouse population so that the mice get
born immune. For a number of reasons, Kevin decided the

(52:58):
best place to test the idea would be Nantucket and
Martha's Vineyard, former whaling communities turned summer resorts in Massachusetts. First,
they have high rates of lime disease, about half the
people who grow up there have had acute episodes. Second,
they're islands, so a gene drive wouldn't spread as easily.

(53:20):
And third they had in place a mechanism for consent.
New England has this tradition of town hall democracy, in
which communities actually get together and discuss important problems. So
Kevin reached out to the boards of health on Nantucket
and Martha's Vineyard, and Nantucket got back to us first
and said, yeah, come to our meeting. So we took

(53:41):
the ferry and I explained how we might be able
to do this. But if we were going to do it,
the community would need to tell us what to do.
Are they interested enough for us to bother and if so,
which option would they prefer? What they say, this sounds
really interesting, We think you should begin research. How many
more meetings have you had after that first meeting? Oh? Oh,

(54:01):
well over a dozen meetings on both islands. And as
this changed the way you think about the experiment, it
has so people who live there know much more about
the environment than I do, or in collectively, more than
any single scientist does. They could notice something that we haven't.
And so if you want to make this kind of
project as safe as possible, you invite everyone to poke

(54:23):
holes in your pet theory. Kevin isn't actually proposing to
start by releasing gene drives on the whole of Nantucket
or Martha's Vineyard. Instead, he's hoping to try it on
some very little islands nearby. Fortunately, there are several owners
of islands who have volunteered their islands for this project
because they're tired of going out there over the summer

(54:44):
and getting bitten by ticks and having a take doxy
cycling these would be little islands, uninhabited except for occasionally
a few summer residents, all of whom have bought in.
So what's your scenario for releasing gene drive mice on
a little island. We're considering the possibility of using a
form of threshold drive That might be the very first

(55:04):
field trial. Target best case scenario would be three years
if it turns out the standard methods in lab mice
transfer pretty readily. According to a recent update from Kevin,
most islanders are comfortable with the idea of releasing genetically
engineered mice, provided that all the DNA components come from

(55:28):
within the mouse species. Many, though, are bothered by the
idea of mixing DNA from different species, which would of
course rule out a crisper based chain drive at least
to start Chapter nine, consent or consensus. So what to

(55:51):
do about fighting malaria in West Africa? The problem is
far more urgent than lyme disease, which is almost never fatal,
and the issues around consent are far more complicated. Again,
Zaramolu is highly critical of target Malaria's process, which she
views as secretive. So I guess a question PAPS for

(56:12):
them is what constitutes consent to them. What have they
done to ensure that the process of free, prior and
informed consent is in place in Burkina Fasso following the
decision at the Convention on Biological Diversity. When I spoke
to people in Burkina Fasso, they suddenly were not informed.
People need to be informed, not just at the village
level where these releases are going to take place, but

(56:35):
also in the cities. Civil society needs to be informed.
I would say the whole country and even the whole
region needs to be informed because this is a very
risky technology whose consequences are not known. In Czar's film,
she interviews about a dozen people in the regional capital,
where Target Malaria's lab is located, and in small communities

(56:55):
where Target malarias someday hopes to test gene drives. The
people interviewed mostly say they haven't been told about the research.
Some say they distrust GMOs, citing Burkina Fasso's experiences with
genetically modified cotton, and some worry the gene drives will
have side effects. According to one woman interviewed quote it

(57:19):
will kill us. Sara says Target Malaria hasn't accepted the
concept of informed consent. Target Malaria talks about stakeholder engagement.
They talk about community engagement, but they don't talk about consent.
She also says Target Malaria shouldn't be the only group
providing information about gene drives because their advocates for the

(57:42):
new technology. Information needs to be out there, information that's
not just from Target Malaria, but also independent information from researchers,
from scientists. I asked Abdulaye Diabate, the Burkina Faso native
and Target Malaria scientist, about his organization's efforts. It's extremely
important that you have to work in full competenty, you know,

(58:04):
with the different community and want communities not just about
the village is where you're doing the work. It's you know,
the religious authority, in the media. We also even with
the civil society. So you have a willy to make
sure that you have worked clearly in all these people.
Abdula says that he and his colleagues meet regularly with

(58:24):
local residents as well as citizens and other parts of
the country to help people understanding drives. They've developed a
lexicon to translate the scientific words into the local languages.
They've also invited residents to visit the laboratory to see
how they feed the mosquitoes and explain their experiments, and

(58:45):
he says they've put in place a grievance mechanism anything,
that these people are religion, that in the villages, I'm
not happy about that they have any customs. And now
we come and we see sit down with them and
then we can talk and and this is how really
you build for us, you know, with the villages. Target

(59:06):
Malaria has also worked with the Burkina Fossil government, getting
permission from the National Biosafety Agency for small scale releases
of non gene drive mosquitoes, and with the African Union's
Scientific arm which issued a favorable report about the potential
for gene drives. Still, Abdulay acknowledges there will never be

(59:28):
unanimity about gene drives. It's really excellutely difficult continual technology
to have everybody having, you know, the same opinion. That
being fair, it's clear that the Buchina is really quite bad.
So we're almost about, you know, seventeen to eighteen million people,
so you cannot wish out to anyone everybody. So we
have done what we could do. Faith to faith with

(59:50):
people and beyond that. Now we have been working also
with the media, either through the TV or through also
the written paper, so to mixed that the information and
really help that that people can you get the right information.
And then we open our door for anyone who really
have concerns about anything. And I can say that we
have rushed out to a lot of people. Still we

(01:00:14):
still have a lot of work to do given Target
Malaria's engagement activities. I asked Austin Byrd about Zara Mulu's
criticism that the group doesn't talk about getting quote, informed consent.
Austin argued that informed consent is the right concept when
you're performing a medical procedure on an individual patient. But

(01:00:36):
he says public health interventions are decided by communities and governments,
the practice is to work at the community level to
seek community acceptance or approval. In fact, it turns out
the statement by the governing Body of the Convention on
Biological Diversity also endorsed this approach. It called on parties

(01:00:56):
to seek either free, prior and informed consent or approval
and involvement of local communities. In other words, the international
Statement is open to both approaches. I asked Natalie Koefler
what she thought about Target Malaria's efforts to inform the public.

(01:01:17):
They also run a really significant public engagement initiative in
the countries that they're looking to release these mosquitoes and eventually,
and that would be Burkina, Fassa, Amali and Uganda are
sort of the three countries they're targeting. Target Malaria also
has significant outreach with government officials within the African Union.

(01:01:39):
I have to say I'm impressed by the amount of
foresight they're using and the transparency they are they are using.
They're going above and beyond what most technologists have ever
done in the past. While Natalie applauded Target Malaria's efforts,
she agreed with Zaramolu on one important point, namely that

(01:02:00):
communities can't just rely on Target Malaria to provide information
or to lead the discussions. It's concerning to me in
a large, well funded organization is able to sort of
lunilaterally steer the technology's progress. So there needs to be
a third party, neutral body that can help to mediate

(01:02:21):
this sort of discussions and deliberation and information that would
be needed to even come to any sort of decision.
Who is the independent third party who's not either a
declared advocate trying to release the gene drive or the
declared NGEO opponent. I mean, quite frankly, that's the sort
of organization that I'm in the process of trying to create.

(01:02:41):
These are really complicated issues, and they really deserve time
and reflection, an engagement of really diverse voices. Natalie was
the lead author of an unusual policy article entitled Editing
Nature Local Roots of Global Governance, published in November twenty
eighteen and Science, the leading American scientific journal. The article

(01:03:05):
calls for the creation of a kind of honest broker
organization that can convene parties ranging from local communities to
technologists and geo's and governments to deliberate about proposed uses
of gene drives. We call for the need to have
really meaningful locally based engagement around these technologies, but then

(01:03:26):
we also call for the need for some sort of
global coordinating body. The articles a great model of scientists
scrappling with how society might come together to make decisions
about whether and when to deploy a new technology. It
has sixteen co authors, including Jim Collins, who led the
National Academy study and Kevin Esfeld. I asked Jim Collins

(01:03:50):
how something like a global coordinating body might work. For example,
who would choose the representatives of the local communities. I
would be in favor of whatever governance structure the local
community uses to pick its leadership or to pick representatives.
And yet you're an optimist that this be done. I
am an optimist that it can be done. And furthermore,

(01:04:12):
I think that we want to do it now. You
want to do it now. You want to work through
these problems now, so that you're thinking, you've got the time.
The technology has not been perfected, so we have a
little bit of breathing room. So this is the time
to develop these sorts of governance structures. But scientists realize
that achieving consensus won't be easy. The more people you

(01:04:36):
have at the table, the harder it is to find consensus.
Sometimes it's a paradox. I think about a lot because
I'm hot, like full on. I want as many diverse
voices at the table as we can have. I want
historically marginalized voices at the table. I even want people
speaking for nature at the table. And this is going
to make things complicated, and so maybe we even have
to think about again differently. This isn't necessarily a yes

(01:04:59):
or no. This is more of sort of an informing
process that can help steer, at least steer the technology
in a way that's reflective of a broader group of
people inventing why is ways to manage gene drives may
ultimately take as much creativity as it took to invent
gene drives in the first place, and it may take
some time in that regard. I want to note that

(01:05:21):
at the Broad Institute, the research institute I direct, we
ourselves have had to grapple with what to do about
gene drives. I mentioned earlier that many scientists had contributed
to the development of Crisper, the key technology underlying modern
gene drives. These scientists include some of my colleagues at
the Broad and, as a result, the Institute as a

(01:05:44):
co owner of some of the foundational patents on Crisper.
We've granted commercial licenses for the use of Crisper for
many purposes, but the question arose, should we let companies
license our patents on Crisper for use in gene drives.
After a lot of discussion, we decided not to do so.

(01:06:05):
At least not yet. We thought it would be better
to wait before granting licenses to help buy time for
society to decide whether and how to use the technology. Still,
the clock is ticking. As I was finishing up this episode,

(01:06:26):
I called Austin Burt to confirm my recollection the Target
Malaria was on target to release gene drive mosquitoes in
about five years. He corrected me. He said Target Malaria
expected to be ready in five years to submit an
application asking for permission. What would happen next? He said, Well,

(01:06:48):
that would be up to society conclusion. Choose your planet.
So there you have it. Gene drives. They could help
us restore ecosystems disrupted by invasive species or help critical

(01:07:11):
native species withstand climate change. Most importantly, they might save
millions of lives by suppressing the mosquitoes that spread deadly malaria.
But the great power of gene drives to spread genetic
changes throughout a population might make them very hard to control.
They might spread beyond field tests or intended targets. Can

(01:07:34):
tamer versions of gene drives, daisy drives, threshold drives, restoration drives,
insure safety or are we kidding ourselves? Whatever? We do,
will life find a way. If we refuse to consider
gene drives for any purpose, we'd be turning our back

(01:07:55):
on a powerful way to tackle malaria. If we do
want to consider gene drives, communities in Africa will need
to answer some important questions. Who should be engaged and how,
who should the discussions, and who gets to make the
ultimate decision. But it's not just Africa. Similar questions will

(01:08:17):
arise throughout the world, including many places in the US,
from Martha's Vineyard to Maui. So the question is what
can you do a lot? It turns out you don't
have to be an expert and you don't have to
do it alone. Invite friends over virtually or in person

(01:08:37):
when it's saved for dinner and debate about what we
should do, or organize a conversation for a book club
or a faith group or a campus event. You can
find lots of resources and ideas at our website Brave
New Planet dot org. It's time to choose our planet.
The future is up to us. Brave New Planet is

(01:09:11):
a co production of the Broad Institute of mt and
Harvard Pushkin Industries in the Boston Globe, with support from
the Alfred P. Sloan Foundation. Our show is produced by
Rebecca Lee Douglas, with Mary Doo theme song composed by
Ned Porter, mastering and sound designed by James Garver, fact
checking by Joseph Fridman, and a Stitt and Enchant. Special

(01:09:34):
Thanks to Christine Heenan and Rachel Roberts at Clarendon Communications,
to Lee McGuire, Kristen Zarelli and Justine Levin Allerhans at
the Broad, to Milobelle and Heather Faine at Pushkin, and
to Eli and Edy Brode who made the Broad Institute possible.
This is brave new Planet. I'm Eric Lander ass