0:15

Pushkin, you're

0:25

listening to Brave New Planet, a podcast

0:28

about amazing new technologies that

0:30

could dramatically improve our world, or

0:33

if we don't make wise choices, could

0:35

leave us a lot worse off. Utopia

0:38

or dystopia. It's up to

0:40

us. On

0:48

October eighth, seventeen sixty nine, James

0:51

Cook, an explorer and captain

0:53

in the British Royal Navy, became

0:55

the first European to set foot on the

0:57

islands that are today known as New

0:59

Zealand. His arrival would

1:01

have dramatic consequences

1:04

for the Maori people that had inhabited

1:06

the land for hundreds of years. It

1:09

would also radically alter New Zealand's

1:11

ecology, because when Cook

1:14

disembarked, so too

1:16

did some of the rats that did hitchhike on

1:18

his ship. Previously

1:20

unknown to the Pacific Islands,

1:23

these rodents grew in population

1:25

over the centuries and wreaked havoc

1:27

on the environment. We're in the

1:29

middle of a rodent nami. You've

1:32

seen the headlines. Rats as big

1:34

as cats. Rats everywhere. It is

1:36

a problem too, everywhere

1:39

that you wouldn't believes.

1:41

Hey, we've probably got the most

1:44

rats that double the most rats with ever

1:46

head shocking actually jsay

1:48

shocking, and it's not just unpleasantness

1:51

that's the problem. The rats

1:53

and other invasive mammals have been

1:56

decimating New Zealand's birds. They

1:58

devoured tens of millions of

2:00

eggs and baby birds every year,

2:03

causing the extinction of one

2:05

quarter of the nation's unique

2:07

bird species. New Zealand

2:10

has long tried to get rid of these

2:12

invaders. The traditional answer

2:14

has been to spread rat poison all

2:16

over the islands, often by helicopters,

2:19

but rat poison is indiscriminate.

2:22

Native animals can also die from eating

2:25

it. Sometimes humans

2:27

accidentally consume it as well, and

2:30

it hasn't solved the problem.

2:34

Recently, scientists have proposed

2:36

a much more targeted solution. It's

2:39

called a gene drive, a

2:41

genetic engineering trick that guarantees

2:44

that when two animals mate, a

2:46

specific gene will be inherited

2:49

by one hundred percent of

2:51

their progeny. In time,

2:54

any gene, even a disadvantageous

2:57

gene, would spread through the

2:59

population. If New Zealand

3:02

were to release genetically engineered

3:04

rats with a gene drive, to dramatically

3:06

decrease the rat's fertility, while

3:09

the rat population would shrink,

3:12

In effect, evolution could

3:15

be directed to vote the rats

3:18

off the islands. And it's

3:20

not just rats. Gene drives

3:22

might be used against any invasive animal

3:25

or plant that uses sexual reproduction,

3:28

and they might also be used to save

3:30

species, for example, by helping

3:33

them survive the effects of climate change.

3:36

Most importantly, gene

3:38

drives might save millions

3:40

of lives by eliminating

3:43

or modifying the mosquito that's

3:45

primarily responsible for spreading

3:47

malaria throughout sub Saharan

3:49

Africa. Now, no

3:51

one has yet deployed gene drives

3:53

in the wild, but they've been shown

3:55

to work in the laboratory reshaping

3:59

nature. It's a heady concept.

4:02

Scientists are exhilarated by

4:04

the possibilities for improving the world. At

4:08

the same time they're wondering what

4:11

could possibly go wrong. Today's

4:16

big question. Should we use

4:18

gene drives to correct the past introduction

4:21

of invasive species, protect

4:23

species from the ravages of climate change,

4:26

and save humans from serious infectious

4:28

diseases or is

4:31

it too risky? Evolution

4:33

in ecology, after all, can be strangely

4:36

unpredictable. When might the

4:38

risks be justified? And

4:41

when you're proposing to release things into

4:43

nature, who needs

4:45

to say yes. My

4:53

name is Eric Lander. I'm a scientist who works

4:55

on ways to improve human health. I

4:57

helped lead the Human Genome Project, and

4:59

today I lead the Road Institute of MIT

5:02

and Harvard. In the twenty first

5:04

century, powerful technologies

5:06

have been appearing at a breathtaking pace,

5:09

related to the Internet, artificial intelligence,

5:11

genetic engineering, and more. They

5:14

have amazing potential upsides,

5:17

but we can't ignore the risks that come

5:19

with them. The decisions aren't just

5:21

up to scientists or politicians,

5:24

whether we like it or not, we all

5:26

of us are the stewards of a brave

5:28

New planet. This generation's

5:30

choices will shape the future as

5:32

never before. Coming

5:39

up on this episode of Brave New Planets,

5:44

we speak to scientists who played a key

5:46

role in inventing gene drives.

5:49

This is potentially a much more elegant

5:52

way of solving ecological problems

5:55

than poisons and bulldozers. We

5:57

talk with people trying to balance the benefits

6:00

and risks. Okay, so people

6:02

are looking at using genetic engineering to alter

6:04

wild species. This is really

6:07

exciting and at the same time I'm

6:09

literally in the same breath, I was also just

6:11

like, holy crap,

6:14

if this isn't used properly, this could be

6:17

really damaging to our planet. We

6:20

hear from a scientist in Burkina Fasso

6:22

who wants to use gene drives to get

6:25

rid of malaria. This is really

6:27

my dream and my hope that I

6:29

can come up with something that kind of really helps

6:31

not only Africa.

6:34

And a journalist from Kenya who's

6:36

pretty skeptical. It's very

6:38

nice to think that people really

6:40

care about the lives of Africans, But I think

6:43

the story is a lot more complex than that. Stay

6:45

tuned. Chapter

6:52

one snails the size

6:55

of baseballs. To

6:59

understand the reasons why people might want

7:01

to use gene drives, I talked with

7:03

someone who's thought a lot about them.

7:06

My name is doctor James Collins

7:08

go by Jim, a professor

7:10

in the School of Life Sciences at Arizona

7:13

State University. Jim is an evolutionary

7:15

ecollegist who co chaired a study on gene

7:17

drives for the US National Academy

7:20

of Sciences. For an evolutionary

7:22

ecologist, he has a bit of an unusual

7:24

upbringing. I grew up in New York

7:26

City, Queens and

7:29

always just had a love of plants

7:32

and animals. In New York City. In

7:34

New York City, Queens at the time

7:36

was different than Queens today.

7:39

I could go fishing. I could catch turtles

7:41

and snakes and frogs,

7:45

all kinds of insects, bring them

7:47

home to my very

7:49

tolerant parents. Jim knows

7:51

a lot about how ecosystems can be

7:53

disrupted by the introduction of new species,

7:56

from microbes to mammals. He

7:59

told me that Captain Cook was responsible

8:01

for more than just introducing rats

8:04

into New Zealand. Think about

8:06

Hawaiian birds where

8:08

they are endangered by avian

8:11

malaria, and that's

8:13

as a result of a

8:15

mosquito being introduced

8:18

by Captain Cook. Then

8:20

the colonists brought chickens, and they

8:22

brought avian malaria. The

8:24

mosquitoes begin to

8:26

feed on the chickens, acquire

8:29

the malaria, and then begin

8:31

to feed on native birds, transmit

8:33

the malaria to native birds, and

8:36

they are being diminished in terms

8:38

of population sizes, and even species. In

8:41

fact, Hawaii has become the bird

8:43

extinction capital of the world. Since

8:46

humans arrived ninety five,

8:49

one hundred and forty two birds species found

8:51

nowhere else in the world have

8:54

become extinct in Hawaii. Even

8:57

small scale introduction of a new species

8:59

can lead to massive problems. In

9:02

nineteen sixty six, a young

9:05

boy who was vacationing in Hawaii decided

9:07

to take a few of the giant land

9:10

snails that live there back

9:12

to his home in Miami to keep

9:14

them as pets in the family garden.

9:17

The snails, which can grow larger

9:19

than the size of baseballs, reproduced

9:22

quickly. They soon began to cause

9:24

economic damage to local farms, and

9:27

they also carried dangerous parasites

9:30

slithering along at quite literally

9:32

a snail's pace. They certainly don't

9:34

look menacing, but for the Florida Department

9:36

of Agriculture, this is a horror

9:38

movie. The problem with these things

9:41

They love just about anything that grows

9:43

in Florida. The eradication

9:45

effort, which used poisons, took

9:48

ten years and cost over a million

9:51

dollars, but despite all

9:53

the work, the snail population

9:55

eventually bounced back. In

9:57

twenty fourteen, the Florida

9:59

Department of Agriculture went door to door

10:02

searching for the snails. They

10:05

found a hundred and fifty thousands,

10:08

with two properties alone harboring

10:10

seven hundred of the critters. With

10:13

other invasive species, the measures

10:15

have been even more dramatic. In

10:17

the nineteen fifties, Australia

10:20

tried to exterminate an escalating

10:22

population of European rabbits

10:24

that had been introduced a century

10:26

earlier by an English settler. Their

10:29

solution was to release rabbits

10:31

carrying a deadly Mixoma virus.

10:34

It killed millions of rabbits across

10:37

Australia, but it didn't solve

10:39

the problem. There are

10:42

hundreds of invasive species that people

10:44

would like to be rid of, zebra muscles

10:46

in the Great Lakes, silver carp in the

10:48

Missouri River, kudzuweed,

10:50

and Georgia burmese pythons

10:53

in the Everglades. But the species

10:56

that cause the most harm to humans

10:58

aren't recent invaders. They're

11:01

indigenous mosquitoes that

11:03

spread malaria in Africa.

11:06

My name is Diane Worth. I'm on

11:08

the faculty at the Harvard chan School of

11:10

Public Health. I work on malaria.

11:13

Diane is also a colleague of mine at the

11:15

Broad Institute, and she studied

11:17

malaria for over thirty five

11:19

years. Malaria starts

11:22

as a fever and chills. It

11:24

has nondescript symptoms in the early

11:26

stages, but then as

11:29

the disease progresses, people

11:31

can go into a coma, they get very

11:33

sick, and it spreads

11:36

by mosquitoes. That's

11:38

right. The disease is transmitted

11:41

by the anopling mosquito in

11:43

Africa. That's Avelis

11:45

Gambia, a

11:47

mosquito that's very efficient at

11:49

transmitting malaria. The world

11:52

has tried to eradicate malaria once

11:54

before, in the middle of the last century, when

11:56

they had DDT and

11:58

chloroquin DDT to kill

12:00

mosquitos and chloroquin to treat

12:03

infected people, and that

12:05

effort did lead to some

12:07

successes. Malaria was eated from

12:10

Italy, from most of Southern Europe,

12:12

from the United States by

12:16

a combination of those techniques

12:18

and environmental activities,

12:21

including putting oil on the top of

12:23

water so it wouldn't be environmentally

12:26

allowed now, but was done in the Tennessee

12:28

Valley here in the United States in the

12:30

nineteen fifties. And that

12:33

effort failed in most

12:35

of the world, and in fact, that effort

12:37

really never included Sub Saharan

12:40

Africa, because the experts at

12:42

the time concluded that

12:44

in Sub Saharan Africa, transmission

12:47

was so intense that no effort

12:49

could bring it under control. How

12:51

are we doing in the elimination of malaria

12:53

today. I think what's happened

12:55

in the last decade is two things. One,

12:58

there's been an overall reduction

13:00

in the number of cases

13:02

of malaria through increased

13:05

distribution of bednets, better

13:08

diagnostics, better use of

13:11

treatment drugs. We've dropped

13:13

cases by forty percent worldwide

13:16

and deaths by about fifty percent

13:18

worldwide. The other part

13:20

of the story is really sub Saharan

13:23

Africa, where progress

13:26

has slowed and in many cases

13:29

reversed. For example, Nigeria

13:32

has twenty five percent of

13:35

all of the malaria in the world, and

13:38

ten countries make up

13:40

seventy percent of the burden

13:42

of malaria worldwide. All of these

13:44

countries in Africa, progress

13:47

using our standard tools

13:49

has stalled. In those countries. We're

13:52

going to need innovation in

13:55

order to actually

13:57

continue the downward trend and

14:00

in fact, in some cases reverse

14:02

what appears to be a rebound in the

14:04

number of cases. The mosquitoes

14:06

are rebounding in port because they've

14:08

evolved resistance to overcome

14:11

traditional methods of control. The

14:14

major insecticide that we use

14:16

to kill mosquitos. There's resistance

14:19

in almost all mosquito populations,

14:22

and so we anticipate that

14:25

the need to have new insecticides

14:28

is urgent, and without that we're unlikely

14:31

to reach to eradication girls, particularly

14:33

in sub Saharan Africa. So scientists

14:35

are constantly imagining new solutions

14:38

to save ecosystems and to

14:40

save human lives. Could

14:43

gene drives be the answer? Chapter

14:49

two selfish genes? Instead

14:52

of deploying poisons and viruses,

14:55

what if we could just genetically

14:57

reprogram pests to

14:59

slow or even stop their

15:01

reproduction. The strategy

15:04

may sound simple, but it has

15:06

a gaping hole. The logic

15:08

of natural selection means the disadvantageous

15:12

genes, ones that cause

15:14

an organism to produce fewer offspring,

15:17

should die out. Ah,

15:19

But there's a loophole in theory.

15:22

A gene could spread into population

15:25

even if it hurts an organism's reproduction,

15:28

if it could find a way to ensure

15:31

that it gets inherited by most

15:33

of the offspring. Could nature

15:36

actually do that? Nature

15:38

does such things often

15:41

again, evolutionary ecologist Jim

15:43

Collins well known example is a

15:46

driving y chromosome in some

15:48

species of mice, which converts

15:50

a population into all males, and of course

15:52

that population then would go extinct.

15:55

It's one of those very interesting

15:58

quirks of evolution in

16:00

which you wind up with populations

16:02

of all males basically blinking out of existence,

16:05

and so you get one group can be converted into

16:07

males, it goes extinct, but

16:10

there are other groups that still have males and females

16:12

and they'll continue on. When

16:14

we think of how genes are passed on, we

16:16

usually think about the laws of Mendelian

16:19

inheritance, first recognized

16:21

by Gregor Mendel, a friar and

16:24

scientist who studied pea plants

16:26

in the mid eighteen hundreds. Mendel

16:29

figured out that in sexually reproducing species,

16:32

each individual has two copies of each

16:34

gene, one from their mother, one

16:36

from their father. They pass on

16:38

one of those two copies to each child,

16:41

with the two copies each having a fifty

16:43

fifty chance of being passed on.

16:46

For example, imagine a gene that determines

16:49

the sex of an offspring. If

16:51

you have a sexually reproducing species that has

16:53

males and females in it, a baby

16:56

would be predicted to be a male

16:58

fifty percent of the time female fifty percent

17:00

of the time. But what if a gene naturally

17:03

evolved that could cheat,

17:05

could greedily stack the deck

17:07

so that it gets inherited sixty

17:10

eighty percent or even a hundred

17:12

percent of the time, biologists

17:15

referred to such selfish behavior as

17:17

a gene drive. Party

17:20

gene drive could do is changed

17:22

that ratio as far as any

17:24

particular genetic trade is concerned. So what

17:26

was the first time anybody noticed the existence

17:29

of a natural gene drive?

17:32

They were described the very late

17:34

eighteen hundreds, very early nineteen hundreds,

17:37

so it's been known for a long time.

17:39

Over the twentieth century, scientists

17:42

discovered a vast array of gene

17:44

drives in nature, but it was

17:46

only in the beginning of this century

17:48

that they began to seriously think about

17:51

how they might harness the power

17:53

of gene drives. Austin Burt

17:56

was the one who laid

17:59

out in principle the idea

18:01

that if there were a way

18:04

to control this

18:07

natural process, then indeed

18:09

you would have in your hands

18:12

something that could control the gene frequency

18:14

in populations. My name is

18:17

Austin Burt, and I'm a professor

18:19

of evolutionary genetics here at Imperial

18:21

College, London. Austin's an

18:23

expert in selfish genes, genes

18:26

that cheat mandilion inheritance.

18:29

Things that show gene drive or similar sorts of

18:31

behavior, and all the other sorts of

18:34

weird and wonderful genes out

18:36

there are able to spread through populations

18:38

not because they increase the survival

18:41

or reproduction of the organism, but because

18:43

they're distorting transmission to

18:45

their own advantage. He became very interested

18:48

in using gene drives for the

18:50

benefit of public health. So, for

18:52

example, in ades mosquitoes,

18:55

which is the factor

18:57

for a yellow fever and dany,

19:00

there is an actually occurring selfish element

19:03

on the Y chromosome, the male determining

19:05

part of the genome, that gets

19:08

into five percent or so of

19:10

the progeny, and so it has

19:12

the potential then to spread

19:15

through a population, and as it does so, distort

19:17

the sex ratio of the population to be more and more

19:20

male biased. That's worth reiterating.

19:22

A naturally occurring gene drive

19:24

in mosquitoes turn ninety

19:27

five percent of the male and

19:29

that caught people's attention. Because male mosquitoes

19:32

don't bite people, they don't transmit the disease, and

19:35

so the idea was that you might be able to use

19:37

that sort of elopment to control the diseases

19:40

spread by those mosquitoes diseases

19:42

like malaria. Unfortunately,

19:45

gene drives in animals tend to

19:47

use specialized tricks, many

19:50

of which still aren't fully understood.

19:52

The best gene drive to engineer would

19:55

be based on simple principles, and

19:58

you'd most likely find them in simple

20:00

organisms. As luck would

20:02

have it, That's what Austin studied.

20:06

My first grant was to study the selfish

20:09

genetic elements of yeasts.

20:13

The best known gene drive in yeast exploits

20:16

the fact that chromosomes come in pairs.

20:20

So here's the trick. The gene drive

20:22

occurs at a specific spot on

20:24

a specific chromosome, and

20:26

it encodes the instructions for

20:29

an enzyme called a homing endonuclease.

20:33

The sole purpose of that enzyme is

20:35

to make a cut at the exact

20:38

same spot on any other

20:40

copy of the chromosome that doesn't

20:43

already have the gene drive. When

20:45

a cell detects that cut, it

20:48

fills it in with the genetic information

20:51

from the matching spot on the uncut

20:53

chromosome, and presto chain

20:55

show the cell inserts

20:58

a copy of the gene drive into

21:00

that spot on the chromosome. When

21:05

I was reading about this, I thought, well, okay, so

21:08

if that was actually then

21:10

we could instead use that

21:13

same sort of approach to change them to recognize

21:15

mosquito sequences and then using

21:18

that to knock out a gene that's essential

21:20

for the survival or reproduction of the mosquito,

21:23

and so suppress the population that way.

21:26

In two thousand and three, Austin published

21:28

a paper in the Proceedings of the Royal

21:31

Society describing this

21:33

brilliant idea. In

21:35

principle, gene drives could be used to

21:37

suppress a population, say

21:40

decreasing the fertility of mosquitos,

21:43

or to alter a population, say

21:46

adding a gene that would prevent the

21:48

malaria parasite from growing

21:50

in the mosquito. But there

21:53

was one hitch, the homing

21:55

end. The nuclease in yeast recognizes

21:58

only one specific DNA

22:01

sequence. To

22:03

engineer new gene drives, you'd

22:05

need to be able to reprogram

22:07

them to recognize different sequences.

22:10

It was difficult to get the enzymes

22:13

to be recognized new sequences to recognize

22:16

mosquito sequences as opposed to E sequences,

22:18

It would take another ten years before

22:21

the solution emerged. It

22:23

turned out to involve another system

22:25

that accomplished the same thing in

22:27

a very different way. The

22:31

system was called Crisper.

22:38

Chapter three, A Shining,

22:40

Marvelous Future. Crisper

22:43

is a kind of immune system that bacteria

22:46

used to protect themselves against viruses.

22:49

Crisper uses an enzyme to cut

22:52

the virus's DNA. But what's

22:54

amazing is that the enzyme doesn't

22:56

have a fixed target. It's

22:58

programmable. The bacteria

23:01

create instructions based on past viral

23:03

infections. The Crisper enzyme

23:06

uses these instructions to search for matching

23:08

the A sequence and then cuts

23:11

it. It took twenty years

23:13

and dozens of scientists around the world

23:15

to understand exactly how Crisper

23:18

works, but once they did, scientists

23:20

figured out how to use its ability to target

23:22

DNA sequences to create a technology

23:25

to edit the genetic code inside

23:27

living cells, from yeast

23:30

to humans. Genome

23:32

editing has made a huge splash,

23:34

including the award of Nobel Prize

23:37

last month to two scientists for

23:39

their work on Crisper. Crisper

23:42

has so many potential applications.

23:45

Medical scientists realized

23:47

that it held the prospect of fixing mutations

23:50

in patients with severe diseases, and

23:53

Austin Bert realized that this

23:55

new technology could turn his

23:57

idea of gene drives from

23:59

dream into practical reality.

24:05

Austin had been working for the last

24:08

decade trying to engineer

24:11

existing gene drives from organisms

24:14

like yeast, and that was just a hideously

24:16

complicated and difficult endeavor that wasn't getting

24:18

all that far. Crisper was the perfect

24:20

tool for enabling gene drive.

24:23

This is biologist Kevin Esfeld,

24:25

who was the first person to propose a specific

24:27

design for a Crisper based

24:30

gene drive. I'm an assistant professor

24:32

at the MIT Media Lab, where I direct

24:34

the Sculpting Evolution Group, and

24:37

our job is to cultivate wisdom

24:39

through ecological and evolutionary engineering.

24:42

Kevin's interest in sculpting evolutions

24:44

started early when he read

24:46

Michael Crichton's nineteen ninety novel

24:49

Jurassic Park. The mere

24:51

notion that we might be able to resurrect dinosaurs

24:55

through genetic engineering was just

24:57

mind boggling. And even

24:59

more so, there's this notion at the park

25:02

was a synthetic ecosystem

25:05

built to host creatures

25:08

that live nowhere else us in the world. That's

25:11

an incredible idea that

25:13

we can potentially make

25:16

our own ecosystems. How old were

25:18

you when your address park? Oh, God,

25:20

probably eight or nine. At a very

25:22

young age, you might say, I knew what I wanted to do with

25:24

my life. I wanted to understand

25:27

how genetics made

25:29

organisms and ecosystems the way they are, and

25:31

I was interested in tinkering with them in order to

25:34

better understand the answer to that question. Kevin

25:36

remembers the moment when it dawned on him that

25:38

Crisper would make it practical

25:41

to engineer gene drives. He

25:43

immediately read all of Austin's

25:46

papers. The first day was purelation,

25:48

thinking about all the amazing things you could do. You were

25:50

thinking that applications already. One

25:52

is human health, things like malarias

25:55

just a semiasis dangey. It's

25:57

spread by mosquito, lime disease, tick born illness,

25:59

as mosquito, boorn illness, as parasites, you name

26:01

it. Number two is environmental

26:03

preservation, and then there's agriculture.

26:06

Because instead of spraying nasty

26:08

poisons on ours in order to get rid of the pests

26:10

that eat them, how about we program the pests to

26:12

dislike the taste. This is potentially

26:14

a much more elegant

26:17

way of solving ecological problems

26:19

than poisons and bulldozers. In

26:22

short, suppression gene drives

26:25

aimed at suppressing the population of a

26:27

dangerous or invasive species could

26:29

provide a general approach to conquer

26:32

terrible parasites and restore

26:34

natural environments. To say

26:36

that Kevin was excited would

26:39

be an understatement. The

26:41

possibilities of a shining, marvelous

26:44

future were just exploding all around me like fireworks.

26:47

Kevin published his proposal about how to

26:49

build a crisper based gene drive in

26:51

twenty fourteen. Within

26:53

a year, scientific papers began

26:55

reporting functioning gene drives,

26:58

first in yeast, then fruit flies,

27:00

and then in mosquitoes.

27:03

Beyond Kevin's favorite applications,

27:05

some people are thinking about gene drives

27:08

as a way to help nate sure adapt rapidly

27:10

to some of the devastating effects of climate

27:13

change. My name's Natalie Chefler.

27:15

I'm a molecular biologist, and I

27:17

recently founded an initiative called Editing

27:19

Nature, which tries to

27:21

integrate diverse worldviews and perspectives

27:24

to steer responsible development of genetic

27:26

technologies for the environment. Natalie

27:29

first became interested in gene drives because

27:31

she was frustrated with the methods that were

27:34

being used to get rid of specific

27:36

invasive species. In

27:38

Canada, where Natalie's from ash

27:41

trees were disappearing at a frightening

27:43

pace because they were being destroyed

27:46

by invasive beetles originally

27:49

from Asia. Ecologists

27:51

had started considering ways to get rid

27:53

of these beetles, and they pitched the idea

27:56

of importing Russian wasps to

27:59

prey on the Asian beetles.

28:02

I was like, are you kidding me? This doesn't make

28:04

Eddie sense and so and

28:06

so I just started thinking that there must be bio

28:09

tech options. That very year,

28:11

Kevin Esvelt and his group had published reports

28:14

on using crisper based gene drives to change

28:16

wild species. And that was sort of the

28:19

Aha moment where I thought, Okay,

28:21

so people are looking at using genetic engineering

28:23

to alter wild species. This is

28:26

really exciting because it could

28:28

provide a solution for these really huge

28:31

challenges that we're facing. Among

28:33

those challenges, Natalie points to what's

28:35

happening to coral reefs. So

28:38

we're seeing a huge decline in coral reef

28:40

health right now, in large part because

28:42

ocean temperatures are rising. Oceans

28:45

are becoming more acidic and

28:47

that's causing a lot of stress to the coral.

28:49

It's happening really quickly and

28:52

pretty extensively. White

28:54

of coral reefs matter. I

28:56

always see them as it was like the forests of the sea.

28:59

So they create huge amount of

29:01

habitat for many marine

29:03

fish. Many people's livelihoods

29:05

depend on the fish that depend on coral reef, and

29:08

so there's been estimates in the trillions

29:10

and trillions of dollars that would be lost if

29:12

the coral were to continue to decline at the rates

29:14

that they do, So losing all the

29:16

coral would be like losing all

29:19

the forests in a way. That's

29:21

somehow I think about it. In contrast

29:23

to suppression gene drives, Natalie

29:26

thinks that alteration gene

29:29

drives, ones that would

29:31

spread beneficial genes throughout a population,

29:34

could make some coals more resilient

29:36

to climate change. And there is research

29:39

starting to come out showing that certain mutations

29:42

and certain genes can be protective against things

29:44

like acidification or high temperatures,

29:46

or allow the coral to dat better. And

29:48

so the idea would be that you could use crisper

29:51

gene editing to rewrite

29:53

the genome of a coral to be able to express

29:55

these resiliency inducing genes. If

29:58

you were to introduce a gene drive

30:00

as well, then that would also allow you to release into

30:02

the wild, into the ocean and allow that

30:04

to spread. Chapter

30:08

four anopolies Gambii.

30:12

Of all the possible uses of gene drives,

30:15

none is more compelling than Austin Bird's

30:17

original idea of controlling

30:19

the spread of malaria. According

30:22

to the World's Health Organization, more

30:24

than four hundred thousand people

30:26

die from malaria each year. That's

30:29

close to one death every minute. Most

30:32

are children under five. Austin

30:35

Bird ended up creating Target Malaria,

30:38

a not for profit research collaboration

30:41

with a mission of developing and sharing genetic

30:43

technologies to help stop the spread

30:46

of malaria in Sub Saharan Africa.

30:49

Target Malaria is targeting several

30:51

mosquito species, including

30:53

Anaphly's gambii, the

30:55

mosquito responsible for most malaria

30:58

cases in Sub Saharan Africa,

31:00

which malaria expert Diane Worth

31:02

described earlier. Among

31:04

many possible designs, a simple

31:07

approach would be to create a pression

31:09

gene drive that causes mosquitos

31:12

to produce mostly male offspring.

31:15

The strategy is actually a two

31:17

fer. First, as Austin

31:19

Burt noted earlier, male mosquitoes

31:22

don't bite people, so they can't transmit

31:25

malaria. Second, the

31:27

lopsided sex ratio should cause of

31:29

the population to dramatically crash

31:32

and perhaps be eliminated in some areas.

31:35

Target Malaria is headquartered in the UK,

31:37

where Austin works, but it has

31:39

research teams in many places, including

31:42

Mali, Uganda and Burkina

31:44

Fossio. I spoke via Skype

31:47

with one of Target Malaria's lead researchers

31:49

in Burkina Fassio. My

31:52

name is on

31:55

A medical entomologist, Doctor

31:57

Abdulaye Diabate, was born

32:00

and raised in a rural area of southwest

32:02

Burkina Fassio, and he is intimately

32:05

familiar with the disease, the

32:07

leading cause of all There is absolutely

32:10

no doubt about that this is a really very big issue

32:12

for us, as myself as

32:14

a kid experienced several episodes

32:16

of malaria. All my brothers

32:18

and sisters cinematically, every single

32:21

one got malaria. If you don't have

32:23

a real treatment right

32:25

away, it can quickly need

32:27

to get and even remember

32:30

myself when I was still a kid long time

32:32

ago, I have stuck her, you

32:34

know, from malaria, and I could

32:36

really see from the eyes of my parents

32:38

that they were really very scared, but because they

32:40

knew that anytime they could lose me. Fortunately

32:43

I made it through. But as a parent

32:46

today I have the same experiencing of my kids.

32:49

Abdulas dedicated his life

32:51

to malaria prevention. He did his

32:53

PhD in France and postdoctoral

32:56

research at the US National Institutes

32:58

of Health before returning

33:00

to Burkina Fossil. I

33:02

felt really that I came to the US, you

33:04

know, to learn, and I have to come back

33:06

home, you know, to give back to my community and as

33:09

this is really my dream and my hope that

33:12

I can come up to be something that can really help

33:14

not only but the entire Africa

33:17

to make sure that we can get wead once

33:19

for all of malaria.

33:21

When he first returned home, the most promising

33:24

method of malaria eradication was

33:26

to target mosquitoes by

33:28

using insecticide treated

33:30

nets, and that tool

33:33

was pretty successful, at

33:35

least initially. We

33:37

were really really excited, you know when we saw

33:39

the data, because we had a really fantastic data

33:41

showing that because a clear impact on

33:43

a little transmission. But

33:46

soon researchers started to see problems

33:48

with the method we farted,

33:50

you know, to see insecitary. This sounds

33:52

you know, coming in and we wished a

33:54

point where most of those are no longer susceptible.

33:58

As he began desperately looking for new

34:00

tools, he came across the gene

34:02

drive proposal from Austin Bird and

34:04

Target Malaria and began working

34:06

with the team. My hope

34:08

really is that we are able, you know, to come

34:11

up with some really good intervention

34:13

tool that concident and then have a

34:15

really really good impact on malaria. Gooden

34:18

in Africa. Target

34:20

Malaria is still five to ten years away

34:22

from testing an actual gene drive in

34:24

the field, but the excitement

34:26

is palpable. Controlling

34:29

malaria in Africa saving

34:31

four hundred thousand lives a year would

34:33

be a big, big deal. A

34:36

gene drives clearly work in the lab,

34:39

So what are people waiting for? Why

34:41

aren't we just releasing gene drives

34:43

against mosquitoes and lots

34:45

of other targets as well? What

34:49

could possibly go wrong? Chapter

34:54

five? What could possibly go wrong?

34:58

In thinking about what could go wrong, many

35:00

scientists use terms like unintended

35:03

consequences, molecular

35:06

biologist Natalie Koefler, Well,

35:09

she puts it differently. Okay,

35:11

So people are looking at using genetic engineering

35:13

to alter wild species. This is

35:16

really exciting, huge challenges

35:18

that we're facing, and at the same time,

35:21

literally in the same breath, I was also just

35:23

like, holy crap,

35:26

if this isn't used properly, this could be

35:29

really damaging to our planet. To

35:31

prevent that, Natalie founded an organization

35:34

called the Editing Nature Initiative.

35:37

For his part, Kevin Esfeld

35:40

came to a similar realization, although

35:42

it took him just a little bit longer. Soon

35:45

after his day of euphoria, his

35:47

vision of a shining, marvelous

35:49

future with fireworks exploding,

35:52

Kevin says he fell into

35:54

utter despair, total

35:57

paranoia, of dark visions of

36:00

horrible, horrific misuse and weaponization.

36:03

What worries Kevin, Natalie and

36:05

others is the gene drives

36:07

actually might be so easy

36:09

to make and work so well

36:12

that things might get out of hand, Which

36:15

means if a crisper based gene

36:17

drive system will spread

36:19

in the wild, probably the most

36:21

populations of that species that are connected

36:23

by any kind of gene flow, then that means

36:25

that individual people could

36:28

potentially single handedly

36:30

edit entire species. Suppose

36:33

you release a gene drive and so the rat population

36:36

of a remote Pacific island. How

36:38

can you be sure that

36:40

it won't actually get off the island? And

36:43

the rodents got there in the first place, rights we

36:45

should have safely assume that they can also get off.

36:48

If one of those rodents stows away on a ship,

36:50

like the ones that stowed away on Captain Cook's

36:53

ship, It's possible that the gene

36:55

drive could eventually spread throughout the entire

36:57

species of black rats around

37:00

the world. Rats are

37:02

invasive species in some places,

37:05

but they're an important part of the ecosystem elsewhere.

37:08

So what happens if you unintentionally alter,

37:11

suppress, or in the worst case,

37:13

wipe out a species, I

37:16

asked evolutionary ecologist Jim Collins,

37:19

who co chaired the US National Academy

37:21

of Science study published in twenty

37:23

sixteen. You do not want

37:26

to be just reaching into ecosystems

37:28

and arbitrarily removing

37:30

species. Humanity has done

37:32

lots of that, and there

37:34

have been these unintended

37:37

consequences that are

37:39

not good. Can you give this a couple examples of

37:42

that. There are any number of instances in which

37:44

we've we've removed top predators, for

37:46

example, in ocean systems in which

37:48

top predators have been fished out, and

37:51

then you can wind up with the ecosystem

37:53

that is greatly

37:55

diminished. It's largely algae

37:58

and jellyfishes by the time you've taken off

38:00

the top predators in the system. What about

38:03

unintentionally wiping out the mosquito

38:05

species that carry malaria?

38:07

Could that disrupt den eco system?

38:10

Well, there are plenty of things that eat mosquitoes,

38:13

and so hypothetically,

38:16

yes, there could be effects. Do

38:18

we know exactly what they are yet? No.

38:22

Austin Bird, who founded Target

38:24

Malaria, has thought a lot about

38:26

the effects of suppressing mosquito populations.

38:29

He's asked, are mosquitoes

38:31

a keystone species on which other

38:33

organisms depend? According

38:36

to Austin, experts think not predators

38:39

that eat mosquitoes, who appear

38:41

to eat anyat flying insects. He's

38:44

also asked, if mosquitoes disappeared

38:47

from a region, would an insect

38:49

transmitting an even worse disease take

38:51

its place. Well,

38:53

it's hard to imagine, because mosquitoes

38:55

and malaria are amongst humanity's

38:57

worst scourges. Still,

39:00

Austin says we should take nothing

39:02

for granted, and mosquitoes

39:04

are a relatively easy case. You'd

39:07

have to answer the same question for

39:10

every possible use of gene

39:12

drives. But as Jim

39:14

Collins's National Academy report

39:16

notes, there's another problem. Beyond

39:19

unintended consequences, there's

39:21

the disturbing possibility that someone

39:24

might deliberately use gene drives

39:26

to cause harm. It

39:28

could be used maliciously. A

39:31

bad actor could decide

39:34

to try to develop a gene drive system

39:37

that might target some part

39:39

of the food supply in

39:41

a country. The individual could

39:44

decide to introduce traits,

39:46

undesirable traits, and other kinds of organisms

39:49

and cause lots of mischief. What would be the

39:51

most likely targets for it

39:54

Organisms that reproduce sexually, that

39:58

have a relatively short generation

40:00

time. You'd want this thing

40:02

to turn over pretty quickly, so

40:05

you're probably not going to use a gene drive

40:07

system for long lived

40:10

animals larger vertebrates,

40:12

let's say cattle, But for

40:15

smaller organisms

40:17

that turn over pretty quickly, maybe

40:19

poultry, you might be

40:22

able to think about using something like a gene

40:24

drive system. In short, Jim

40:26

says, a bad actor might

40:29

try to use gene drives as a bioweapon

40:32

to devastate agriculture in a country.

40:38

Chapter six, daisy chains.

40:42

As Kevin s Field thought more, he

40:44

stumbled across a big problem

40:46

with his initial design for gene drives. It

40:49

would be too risky even to run

40:52

field trials to test the technology.

40:55

Why because if

40:57

even a single organism escaped

41:00

from the test area, well, the gene drive

41:02

might invade the entire species.

41:05

The problem with the full power version

41:07

is it has everything it needs to copy it self

41:09

forever, in every generation. So Kevin

41:11

got to work designing gene drives

41:13

that couldn't spread forever self

41:16

exhausting gene drives. He

41:19

designs something he named a

41:21

daisy drive. Every link

41:23

in this daisy chain is the equivalent of like one

41:27

gallon of genetic fuel. And you

41:29

burn genetic fuel over generations,

41:31

and when you run out, it stops. Daisy

41:34

drives involve a chain of genetic

41:36

elements, say abcde,

41:40

each inserted into a different chromosome.

41:43

A copies B to make sure it's inherited

41:46

by all the offspring. B copies

41:48

C, see copies dance,

41:50

so on. But nothing's

41:53

driving A. It's

41:55

inherited by only half the offspring.

41:58

So when a is lost, there's

42:00

nothing copying B, so

42:03

it's eventually lost, and so on. When

42:05

you introduce a daisy chain into a

42:07

large population, it should

42:10

eventually peter out. And

42:12

Kevin has more tricks up his sleeve. He's

42:15

designed a gene drive that's engineered

42:17

not to spread beyond the geographical

42:19

area in which you released it. He

42:22

calls it a threshold drive.

42:25

It mimics one of the ways that reproductive

42:27

barriers arise in the wild by

42:30

using genetic rearrangements to

42:32

make interbreeding less efficient.

42:35

Kevin thinks of these tricks will make it

42:37

possible to do much safer field

42:40

trials. But still,

42:43

what if a drive spreads despite

42:45

these safety features. Well,

42:47

Kevin says, you can always create

42:49

a new gene drive to spread and overrite

42:52

the first one. He calls it a

42:55

restoration drive. Now

42:57

a lot of people say, wait a minute, you can't rely

42:59

on the same technology that just went wrong.

43:02

But hold on a second. If the problem

43:04

is what we did to the species, then

43:07

using another method that successfully

43:10

spread a change to the whole species to

43:12

successfully spread another change to the whole

43:14

species is perfectly valid

43:17

engineering. Even as Kevin

43:19

works to devise solutions daisy

43:21

drives threshold drives, restoration

43:24

drives. He knows he can't

43:26

imagine everything. I still

43:28

assume that evolution is cleverer than we

43:30

are. It's going to have some trick up at sleeve.

43:33

This is like you are fighting the

43:35

tide, or you're fighting a blind,

43:38

idiot alien god. To

43:40

use my preferred conception of what evolution really

43:42

is. It's like the story that

43:45

inspired Kevin to go into biotechnology.

43:48

Jurassic Park in the classic

43:50

nineteen ninety three film, Doctor Ian

43:52

Malcolm played by Jeff Goldblum,

43:55

is a mathematician who specializes

43:57

in chaos theory. Early

43:59

in the film, he presciently calls out

44:01

the park designers for the hubris

44:04

in thinking they can control the dinosaur

44:07

population. Know

44:09

they're all female. We control their chromosomes.

44:11

It's really not that difficult, John.

44:14

The kind of control your attempting is it's

44:17

not possible. As if there's one thing the history of evolution

44:20

has tossed that life will not be contained.

44:23

Life breaks free, It expands to new territories,

44:25

and it crashes through barriers painfully,

44:27

maybe even dangerously. But no,

44:31

there it is. You're

44:33

implying that a group composed entirely of

44:35

female animals, will breed.

44:38

No, I'm simply saying that life finds

44:42

a way, wife finds

44:44

a way. If Kevin

44:47

knows if we want the potential benefits

44:49

that gene drives offer, we

44:51

have to work hard to be sure that life

44:54

doesn't find a way. What

44:57

I'm worried about is the loss of public

44:59

trust when scientists accidentally

45:01

engineer a whole species. Whatever

45:04

they do can be undone except

45:07

for the fact that it would be

45:09

become very well known through the media that

45:11

scientists accidentally turned to species into

45:13

GMOs. So that's why you're very concerned

45:15

to get this right. You don't think

45:18

that this really will go wrong.

45:20

And you do have this ultimate safety

45:23

switch, which is send another gene drive

45:25

to go after the first gene drive. But

45:28

if we have to do that, we've already lost

45:31

public trust in the technology. So

45:34

we better never have to do that. Chapter

45:40

seven Skeptics. While

45:45

everyone is in favor of eradicating malaria,

45:48

which kills four hundred thousand people a

45:50

year, some people are

45:52

pretty skeptical about using

45:54

gene drives to do it. I

45:56

personally would not be in favor of gene

45:59

drives. This is Zarahmulu.

46:01

I'm a journalist and documentary filmmaker

46:04

from Kenya and I'm currently based in Montreal.

46:07

Zara has covered a wide range of time topics

46:09

that affect Africa, including an investigative

46:11

portrait of a multinational gold mine

46:13

in Tanzania. Recently,

46:16

she began collaborating with an organization

46:18

called the ETC Group. It's

46:21

a small organization that works

46:24

with civil society across

46:27

different parts of the world and they

46:30

do work on the impact of new technologies

46:32

on biodiversity and human rights and

46:34

agriculture, and so I came to learn

46:36

about gene drives through ETC Groups

46:39

through collaborating with them. In twenty

46:41

eighteen, Zara made a short film

46:43

and wrote an article casting doubt

46:45

on target Malaria's efforts in Burkina

46:48

Faso. For starters,

46:50

she challenges the motives of people

46:52

working on gene drives. The question

46:55

to ask, is our gene drives

46:57

really about public health and conservation

47:00

or other other interests and other other

47:03

ways that agribusiness companies can

47:05

make a profit from gene drives. Why

47:07

do we really need gene drives, what are they really for

47:09

and who is going to benefit ultimately

47:12

from the development of this technology. It's

47:14

very nice to think that people

47:17

really care about the lives of Africans. But I

47:19

think this story is a lot more complex than that.

47:21

Zara also argues that Africa

47:24

doesn't really need gene drives to

47:26

conquer malaria. I come from a

47:28

country where people contract malaria regularly.

47:30

People die in my country from malaria. We

47:32

do need to fight malaria, and it's a terrible

47:34

disease. No one's going to disagree with that. However,

47:38

it's also important to know that Paraguay

47:41

eliminated malaria recently, Tri Lanka eliminated

47:43

malaria. Algeria and Argentina

47:45

have just been declared malaria free, and

47:48

so there are ways in which countries

47:50

have successfully eradicated malaria without

47:52

having to employ very risky

47:54

technologies like gene drives. I

47:57

asked malaria expert Diane Worth

47:59

whether she thought malaria eradication

48:01

in those countries provided a useful

48:04

model for sub Saharan Africa.

48:06

She was skeptical. Algeria

48:09

it's a desert, mosquitoes need

48:11

water to breed. Paraguay

48:14

very small number of cases, probably

48:18

eliminated years ago, but finally

48:20

certified. Argentina same

48:22

story, relatively little malaria.

48:25

Ever, Sri Lanka is

48:27

an island they don't

48:29

have to deal with importation from

48:31

surrounding countries. They

48:33

have a very strong healthcare

48:35

system, so they're able to identify early

48:38

every case of malaria,

48:40

and they have a mosquito

48:42

vector that isn't very robust.

48:45

Diane argued that malaria in Sub

48:47

Saharan Africa represents a

48:50

very different challenge. They're

48:52

different mosquitos, there's different ecology,

48:55

there's different burden of disease in

48:57

the population. In many places

48:59

in Sub Saharan Africa, children

49:02

have malaria for half

49:04

the year and serve as reservoirs

49:06

for transmission. The mosquito

49:09

in Africa is a mosquito

49:11

that only bites humans. That means

49:13

that's the most effective transmitter

49:16

in most of Africa, and

49:18

so therefore detecting early,

49:21

preventing and getting

49:23

treatment for the disease represents

49:26

a challenge. Whatever you think about

49:28

the need for gene drives, Czara's

49:31

key issue is very important.

49:33

It's in the title of her film, A

49:36

question of consent Before

49:39

gene drives get released into the wild.

49:41

Who needs to say yes? Chapter

49:48

eight, charm l Shake to Nantucket.

49:52

What to do about gene drives is

49:54

a question that's been hotly debated

49:57

by the governing body for the Convention

49:59

on Biological Diversity in

50:01

international agreements among one hundred and ninety

50:04

six countries on preserving, sustaining

50:06

and sharing the benefits of biodiversity.

50:09

In December twenty eighteen, the

50:12

group met in Charmel Shaikh, Egypt.

50:14

Natalie Koefler, the founder

50:17

of Editing Nature, traveled to

50:19

Egypt to deliver a talk. At the meeting,

50:22

many representatives from Target Malaria were

50:24

present, and then many representatives

50:26

from several environmental groups, and those

50:28

include environmental justice advocacy

50:31

sort of technological white watchdogs groups

50:33

like ETC Group. The group

50:36

of the NGOs of the meeting, including

50:38

the ETC Group, called for a total

50:40

moratorium on gene drives, not

50:42

just undeploying them, but even studying

50:45

them in the laboratory. They

50:47

are calling for a moratorium on research,

50:50

so basically for all research to halt, which

50:53

I believe is just somewhat ridiculous.

50:55

I don't think there's a way you just stop people trying

50:58

to understand more. And if the point is that this

51:00

could be something that could be of great benefit, you would

51:02

want to be able to study it more and make sure you can understand

51:04

what those benefits or risks could be stopping

51:07

research. To me, seems your. The

51:10

Governing Body eventually rejected

51:12

the call for a moratorium.

51:15

Nonetheless, Zara Mulu saw the

51:17

meeting as a partial victory, pointing

51:19

to the closing statement by the Governing Body,

51:22

which she said requires organizations

51:25

seeking to release gene drive organisms

51:28

to obtain the quote free prior

51:30

and informed consent of

51:32

potentially affected communities. So

51:35

it has to be free, prior and informed consent

51:38

before these releases go ahead.

51:41

So who exactly do you ask for

51:43

consent? Elected officials?

51:46

Anyone who might potentially be affected?

51:49

How do you even know everyone who might

51:51

be affected? Well, Kevin

51:53

Esfeld has been wrestling with these issues and

51:55

a project he's working on to fight

51:57

lime disease in New England. Lime

52:00

disease is awful. Lime disease is disgusting.

52:02

I don't like ticks, so I figured, well,

52:05

what if we decide to prevent

52:07

lime disease caused by a bacteria.

52:11

Lime disease can lead to serious

52:13

long term symptoms, including

52:15

pain, severe headaches, and numbness.

52:18

Humans get lime disease from

52:21

being bitten by infected ticks.

52:23

And how do the ticks pick up the bacteria?

52:27

Most ticks get infected when they bite a white footed

52:29

mouse, so what if the white footed

52:31

mice were immune. Kevin's

52:34

big idea was to take the mice

52:36

that had developed antibodies against lime

52:38

disease, read out the genetic

52:40

instructions that encode those antibodies,

52:43

and use a gene drive to

52:46

spread those instructions throughout

52:48

the entire white footed mouse population

52:51

so that the mice get born

52:53

immune. For a

52:55

number of reasons, Kevin decided

52:57

the best place to test the idea

53:00

would be Nantucket and Martha's Vineyard,

53:02

former whaling communities turned summer

53:05

resorts in Massachusetts. First,

53:08

they have high rates of lime disease, about

53:11

half the people who grow up there

53:13

have had acute episodes. Second,

53:16

they're islands, so a gene drive

53:18

wouldn't spread as easily. And

53:20

third they had in place

53:23

a mechanism for consent. New

53:25

England has this tradition of town hall democracy,

53:27

in which communities actually get together and discuss

53:29

important problems. So Kevin reached

53:32

out to the boards of health on Nantucket

53:34

and Martha's Vineyard, and Nantucket

53:36

got back to us first and said, yeah,

53:39

come to our meeting. So we took the ferry

53:42

and I explained how we might

53:44

be able to do this. But if we were going to do it,

53:46

the community would need to tell us what to do. Are

53:49

they interested enough for us to bother and if

53:51

so, which option would they

53:53

prefer? What they say, this sounds

53:55

really interesting, We think you should begin research.

53:58

How many more meetings have you had after that first

54:00

meeting? Oh? Oh, well over a dozen

54:02

meetings on both islands. And

54:05

as this changed the way you think about the experiment,

54:07

it has so people who live there

54:09

know much more about the environment than I do,

54:12

or in collectively, more than any single

54:14

scientist does. They could notice something that

54:16

we haven't. And so if you want

54:18

to make this kind of project as safe as

54:20

possible, you invite everyone

54:22

to poke holes in your pet theory. Kevin

54:25

isn't actually proposing to start by

54:27

releasing gene drives on the whole

54:29

of Nantucket or Martha's Vineyard.

54:32

Instead, he's hoping to try it on

54:34

some very little islands nearby.

54:37

Fortunately, there are several owners

54:39

of islands who have volunteered their islands for this

54:41

project because they're tired of going out there over the

54:43

summer and getting bitten by ticks and having a take

54:45

doxy cycling these would be little islands,

54:48

uninhabited except for occasionally a few

54:50

summer residents, all of whom

54:52

have bought in. So what's your scenario

54:54

for releasing gene drive mice on

54:57

a little island. We're considering

54:59

the possibility of using a form of threshold

55:01

drive That might be the

55:04

very first field trial. Target

55:06

best case scenario would be three years

55:09

if it turns out the standard methods in

55:11

lab mice transfer pretty readily.

55:15

According to a recent update from Kevin,

55:18

most islanders are comfortable with the

55:20

idea of releasing genetically engineered

55:22

mice, provided that

55:25

all the DNA components

55:27

come from within the mouse species.

55:31

Many, though, are bothered by the idea

55:33

of mixing DNA from different

55:35

species, which would of course

55:37

rule out a crisper

55:39

based chain drive at least to start

55:46

Chapter nine, consent or

55:48

consensus. So

55:51

what to do about fighting malaria in West

55:53

Africa? The problem is far

55:55

more urgent than lyme disease, which is almost

55:57

never fatal, and the issues

56:00

around consent are far more complicated.

56:03

Again, Zaramolu is

56:05

highly critical of target Malaria's

56:07

process, which she views

56:09

as secretive. So I guess

56:11

a question PAPS for them is what constitutes

56:14

consent to them. What

56:16

have they done to ensure that the process

56:18

of free, prior and informed consent is

56:21

in place in Burkina Fasso following

56:23

the decision at the Convention on Biological

56:25

Diversity. When I spoke to people

56:27

in Burkina Fasso, they suddenly were not

56:29

informed. People need to be informed, not just at

56:32

the village level where these releases

56:34

are going to take place, but also in the cities.

56:36

Civil society needs to be informed. I

56:38

would say the whole country and even the whole

56:40

region needs to be informed because this is a very

56:42

risky technology whose consequences

56:45

are not known. In Czar's

56:47

film, she interviews about a dozen

56:49

people in the regional capital,

56:51

where Target Malaria's lab is located,

56:54

and in small communities where Target

56:56

malarias someday hopes to test gene

56:58

drives. The people interviewed

57:01

mostly say they haven't been told about

57:03

the research. Some say

57:05

they distrust GMOs, citing

57:08

Burkina Fasso's experiences with

57:10

genetically modified cotton, and

57:13

some worry the gene drives will have

57:15

side effects. According to one

57:17

woman interviewed quote it

57:19

will kill us. Sara

57:21

says Target Malaria hasn't accepted

57:24

the concept of informed consent.

57:27

Target Malaria talks about stakeholder engagement.

57:30

They talk about community engagement,

57:32

but they don't talk about consent. She

57:34

also says Target Malaria shouldn't be

57:36

the only group providing information

57:39

about gene drives because their advocates

57:41

for the new technology. Information

57:44

needs to be out there, information that's not just

57:46

from Target Malaria, but also independent

57:48

information from researchers, from

57:50

scientists. I asked Abdulaye

57:53

Diabate, the Burkina Faso

57:55

native and Target Malaria scientist,

57:57

about his organization's efforts.

58:00

It's extremely important that you have to work

58:03

in full competenty, you know, with the different community

58:06

and want communities not just about

58:08

the village is where you're doing the work. It's

58:11

you know, the religious authority,

58:13

in the media. We also even

58:16

with the civil society. So you have a willy to make

58:18

sure that you have worked clearly in all these

58:20

people. Abdula says

58:22

that he and his colleagues meet regularly with local

58:24

residents as well as citizens and

58:27

other parts of the country to

58:29

help people understanding drives. They've

58:31

developed a lexicon to

58:33

translate the scientific words into the

58:35

local languages. They've also

58:37

invited residents to visit the laboratory

58:40

to see how they feed the mosquitoes and explain

58:43

their experiments, and

58:45

he says they've put in place a

58:47

grievance mechanism anything,

58:50

that these people are religion, that in the villages,

58:53

I'm not happy about that they

58:55

have any customs. And now we come

58:58

and we see sit down with them and then

59:00

we can talk and and this is how really

59:02

you build for us, you know, with the villages.

59:06

Target Malaria has also worked with the Burkina

59:08

Fossil government, getting permission

59:10

from the National Biosafety Agency

59:13

for small scale releases of non

59:15

gene drive mosquitoes, and with

59:17

the African Union's Scientific arm

59:20

which issued a favorable report about

59:22

the potential for gene drives.

59:24

Still, Abdulay acknowledges

59:27

there will never be unanimity

59:29

about gene drives. It's

59:32

really excellutely difficult continual technology

59:34

to have everybody having, you know, the same

59:37

opinion. That being fair, it's clear

59:39

that the Buchina is really quite bad. So we're

59:41

almost about, you know, seventeen to eighteen

59:43

million people, so you cannot wish out to anyone

59:45

everybody. So we have done

59:48

what we could do. Faith to faith with

59:50

people and beyond that. Now we

59:52

have been working also with the media, either

59:55

through the TV or through

59:57

also the written paper, so to mixed

59:59

that the information and really help that that people

1:00:01

can you get the right information.

1:00:04

And then we open our door for anyone

1:00:06

who really have concerns about anything.

1:00:08

And I can say that we have rushed out

1:00:10

to a lot of people. Still

1:00:13

we still have a lot of work to do given

1:00:17

Target Malaria's engagement activities.

1:00:19

I asked Austin Byrd about Zara Mulu's

1:00:21

criticism that the group doesn't

1:00:23

talk about getting quote, informed

1:00:26

consent. Austin argued

1:00:28

that informed consent is the

1:00:30

right concept when you're performing a medical

1:00:33

procedure on an individual patient.

1:00:35

But he says public health interventions

1:00:38

are decided by communities and governments,

1:00:41

the practice is to work at the community level

1:00:43

to seek community acceptance or approval.

1:00:46

In fact, it turns out the statement by

1:00:49

the governing Body of the Convention on Biological

1:00:51

Diversity also endorsed

1:00:53

this approach. It called on

1:00:55

parties to seek either free,

1:00:58

prior and informed consent or

1:01:02

approval and involvement of local communities.

1:01:05

In other words, the international Statement

1:01:08

is open to both approaches. I

1:01:11

asked Natalie Koefler what she thought about

1:01:14

Target Malaria's efforts to inform the public.

1:01:17

They also run a really significant

1:01:19

public engagement initiative in the countries

1:01:22

that they're looking to release these mosquitoes and eventually,

1:01:25

and that would be Burkina, Fassa, Amali

1:01:27

and Uganda are sort of the three countries they're targeting.

1:01:30

Target Malaria also has significant

1:01:33

outreach with government

1:01:35

officials within the

1:01:38

African Union. I have to say

1:01:40

I'm impressed by the amount

1:01:42

of foresight they're using and the transparency

1:01:46

they are they are using. They're

1:01:48

going above and beyond what most technologists

1:01:50

have ever done in the past. While

1:01:53

Natalie applauded Target Malaria's efforts,

1:01:55

she agreed with Zaramolu on

1:01:57

one important point, namely

1:02:00

that communities can't just rely

1:02:02

on Target Malaria to provide

1:02:04

information or to lead the discussions.

1:02:07

It's concerning to me in a large,

1:02:10

well funded organization is

1:02:12

able to sort of lunilaterally steer

1:02:14

the technology's progress. So there

1:02:17

needs to be a third party, neutral body that

1:02:19

can help to mediate this sort of discussions

1:02:22

and deliberation and information that would be needed

1:02:24

to even come to any sort of decision. Who

1:02:26

is the independent third

1:02:29

party who's not either a

1:02:31

declared advocate trying to release

1:02:33

the gene drive or the declared

1:02:36

NGEO opponent. I mean, quite

1:02:38

frankly, that's the sort of organization that I'm in the process

1:02:40

of trying to create. These are really complicated

1:02:43

issues, and they really deserve time

1:02:46

and reflection, an engagement of

1:02:48

really diverse voices. Natalie

1:02:51

was the lead author of an unusual policy

1:02:53

article entitled Editing Nature

1:02:56

Local Roots of Global Governance,

1:02:58

published in November twenty eighteen and Science,

1:03:01

the leading American scientific journal. The

1:03:04

article calls for the creation of a

1:03:06

kind of honest broker organization

1:03:09

that can convene parties ranging

1:03:11

from local communities to technologists

1:03:14

and geo's and governments to

1:03:17

deliberate about proposed uses

1:03:19

of gene drives. We call for

1:03:21

the need to have really meaningful

1:03:23

locally based engagement around these technologies,

1:03:26

but then we also call for the need for some

1:03:28

sort of global coordinating body. The

1:03:30

articles a great model of scientists

1:03:33

scrappling with how society might come

1:03:35

together to make decisions about

1:03:37

whether and when to deploy a new

1:03:39

technology. It has sixteen

1:03:42

co authors, including Jim Collins,

1:03:45

who led the National Academy study

1:03:47

and Kevin Esfeld. I asked

1:03:49

Jim Collins how something like a global

1:03:51

coordinating body might work. For

1:03:54

example, who would choose the representatives

1:03:57

of the local communities. I

1:03:59

would be in favor of whatever governance

1:04:02

structure the local community uses

1:04:04

to pick its leadership or to pick representatives.

1:04:07

And yet you're an optimist that this be done.

1:04:09

I am an optimist that it can be done. And

1:04:11

furthermore, I think that we want to do it

1:04:13

now. You want to do it now. You want to work through these

1:04:16

problems now, so that you're thinking,

1:04:18

you've got the time. The technology has

1:04:20

not been perfected, so

1:04:22

we have a little bit of breathing room. So

1:04:25

this is the time to develop these sorts

1:04:27

of governance structures.

1:04:30

But scientists realize that achieving

1:04:32

consensus won't be easy. The

1:04:35

more people you have at the table, the harder it

1:04:37

is to find consensus. Sometimes it's a paradox.

1:04:40

I think about a lot because I'm hot,

1:04:42

like full on. I want as many diverse

1:04:45

voices at the table as we can have. I want historically

1:04:47

marginalized voices at the table. I even

1:04:49

want people speaking for nature at the table.

1:04:52

And this is going to make things

1:04:54

complicated, and so maybe we even have to think about

1:04:56

again differently. This isn't necessarily

1:04:58

a yes or no. This is more of sort of

1:05:00

an informing process that can help

1:05:03

steer, at least steer the technology in a way

1:05:05

that's reflective of a broader group of people inventing

1:05:08

why is ways to manage gene drives

1:05:11

may ultimately take as much creativity

1:05:13

as it took to invent gene drives

1:05:16

in the first place, and it may

1:05:18

take some time in that regard.

1:05:20

I want to note that at the Broad Institute, the

1:05:23

research institute I direct, we

1:05:25

ourselves have had to grapple with what

1:05:27

to do about gene drives. I

1:05:29

mentioned earlier that many scientists

1:05:31

had contributed to the development of Crisper,

1:05:34

the key technology underlying

1:05:36

modern gene drives. These

1:05:38

scientists include some of my colleagues

1:05:41

at the Broad and, as a result, the

1:05:43

Institute as a co owner of some of the

1:05:45

foundational patents on Crisper. We've

1:05:48

granted commercial licenses for the use of

1:05:50

Crisper for many purposes, but

1:05:53

the question arose, should we

1:05:55

let companies license our patents

1:05:57

on Crisper for use in gene

1:06:00

drives. After a lot

1:06:02

of discussion, we decided

1:06:04

not to do so. At least

1:06:06

not yet. We thought it would be

1:06:08

better to wait before granting licenses

1:06:10

to help buy time for society

1:06:12

to decide whether and how

1:06:15

to use the technology. Still,

1:06:21

the clock is ticking. As

1:06:24

I was finishing up this episode, I called

1:06:26

Austin Burt to confirm my recollection

1:06:28

the Target Malaria was on target

1:06:31

to release gene drive mosquitoes in about

1:06:33

five years. He corrected

1:06:36

me. He said Target Malaria

1:06:38

expected to be ready in five years to

1:06:40

submit an application asking

1:06:43

for permission. What would

1:06:45

happen next? He said, Well,

1:06:48

that would be up to society conclusion.

1:06:58

Choose your planet. So

1:07:02

there you have it. Gene drives.

1:07:05

They could help us restore ecosystems

1:07:07

disrupted by invasive species

1:07:09

or help critical native species

1:07:12

withstand climate change. Most

1:07:14

importantly, they might save millions

1:07:16

of lives by suppressing the mosquitoes

1:07:19

that spread deadly malaria.

1:07:21

But the great power of gene drives

1:07:24

to spread genetic changes throughout a population

1:07:27

might make them very hard to control.

1:07:30

They might spread beyond field tests

1:07:32

or intended targets. Can

1:07:34

tamer versions of gene drives,

1:07:37

daisy drives, threshold drives, restoration

1:07:39

drives, insure safety or

1:07:43

are we kidding ourselves? Whatever?

1:07:45

We do, will life find

1:07:48

a way. If

1:07:50

we refuse to consider gene drives

1:07:52

for any purpose, we'd be turning

1:07:54

our back on a powerful way to tackle

1:07:56

malaria. If we do

1:07:59

want to consider gene drives, communities

1:08:02

in Africa will need to answer some important

1:08:04

questions. Who should be engaged

1:08:06

and how, who should the

1:08:09

discussions, and who gets

1:08:12

to make the ultimate decision. But

1:08:14

it's not just Africa. Similar questions

1:08:16

will arise throughout the world, including

1:08:19

many places in the US, from

1:08:21

Martha's Vineyard to Maui. So

1:08:24

the question is what can you do a

1:08:27

lot? It turns out you

1:08:30

don't have to be an expert and you don't

1:08:32

have to do it alone. Invite

1:08:35

friends over virtually or

1:08:37

in person when it's saved for dinner

1:08:39

and debate about what we should do, or

1:08:42

organize a conversation for a book club

1:08:44

or a faith group or a campus event.

1:08:47

You can find lots of resources and ideas

1:08:49

at our website Brave New Planet

1:08:51

dot org. It's time

1:08:54

to choose our planet. The future

1:08:57

is up to us. Brave

1:09:10

New Planet is a co production of the Broad Institute

1:09:13

of mt and Harvard Pushkin Industries

1:09:15

in the Boston Globe, with support

1:09:17

from the Alfred P. Sloan Foundation. Our

1:09:19

show is produced by Rebecca Lee Douglas,

1:09:22

with Mary Doo theme song

1:09:24

composed by Ned Porter, mastering

1:09:26

and sound designed by James Garver, fact

1:09:29

checking by Joseph Fridman, and a Stitt

1:09:32

and Enchant. Special

1:09:34

Thanks to Christine Heenan and Rachel Roberts

1:09:36

at Clarendon Communications, to

1:09:38

Lee McGuire, Kristen Zarelli and Justine

1:09:41

Levin Allerhans at the Broad, to Milobelle

1:09:44

and Heather Faine at Pushkin, and

1:09:46

to Eli and Edy Brode who made

1:09:48

the Broad Institute possible. This

1:09:51

is brave new Planet. I'm Eric

1:09:53

Lander

1:10:09

ass