0:00

Hi everyone, I'm Emily Chang and this is Bloomberg

0:02

Studio. One point, Oh, imagine

0:05

the ability to cure genetic disease for

0:07

generations to come, to inoculate

0:09

the human race against the next COVID nineteen

0:12

before it becomes a pandemic, or

0:14

in a darker scenario, to choose the

0:16

color of your baby's skin. Doctor

0:19

Jennifer down A pioneered a technology

0:21

that may one day be able to do just that,

0:23

and it's one of the biggest scientific breakthroughs

0:26

of our lifetimes. It's called

0:28

Crisper, a bacterial defense

0:30

system that can edit genetic material.

0:33

It already shows promise in eradicating malaria

0:35

mosquitoes, appearing to cure patients

0:38

with sickle cell anemia, improving

0:40

cancer therapy, and diagnosing

0:42

COVID nineteen more quickly and

0:44

at the height of the pandemic. Dowd

0:47

n Up, along with Emmanuel Sharpetier,

0:50

won the Nobel Prize in Chemistry for

0:52

their Crisper innovations, But

0:55

there are major ethical questions looming.

0:57

How and when is it right to edit a gene?

1:00

Is Crisper playing god? One Chinese

1:02

scientist claims he's already edited the genes

1:04

of twin girls, giving them immunity to HIV

1:07

and sparking an international uproar.

1:10

Right or wrong, one thing is clear, Crisper

1:13

will change the human race forever. Joining

1:16

me on this edition of Bloomberg Studio at one point, Oh

1:18

biochemist and Crisper co invector,

1:21

Jennifer dowdne You

1:26

grew up in Hawaii, and I am so curious.

1:29

I grew up in Hawaii as well. How did your

1:31

upbringing shape your curiosity

1:33

about the natural world and the origins

1:36

of life? When

1:38

I think back on that time in my life,

1:40

it was kind of a wonderland. Um,

1:42

you know, well what it's like

1:44

in Hawaii. It's a very special place,

1:47

and I found myself just wondering, you

1:49

know, how is it that these plants

1:51

and animals have evolved to be

1:54

specialized for Hawaii And there are so

1:56

many examples of that in the natural

1:59

environments in the islands there. So I did

2:01

definitely think that was behind

2:03

my thinking about, you know, why it would be interesting

2:06

to become a scientist in the future. As

2:08

a budding scientist, you developed an early

2:10

fascination with RNA well

2:13

before it took center stage in the pandemic,

2:15

and also now a key player in

2:17

vaccines. What is it about RNA

2:19

that gripped your attention? When

2:22

I was an undergraduating college we

2:25

were, or at least I felt

2:27

like the the the

2:29

message we received was that RNA was

2:31

kind of the boring intermediary between

2:34

DNA, which encodes all genetic

2:37

information in cells, and

2:39

proteins that do the work in the cell,

2:42

and so those were kind of the important big

2:44

molecules in biology, and then there was this kind

2:46

of boring, uh intermediary

2:48

called RNA. However, when I got

2:50

to graduate school, I met the

2:53

the person who would become my future

2:55

advisor, Jack Shostak, and he

2:58

was fascinated by the possibility

3:01

that r and A in fact was

3:03

the original biological

3:06

molecule on Earth, that it was really

3:08

responsible for the evolution of

3:10

life as we know it here on Earth. And

3:12

that idea was so interesting and

3:15

so compelling to me that I,

3:17

you know, I I joined his lab and

3:19

I started studying R and A, and I sort of never left

3:21

it. Now, you spent most of your career

3:24

working at universities. You're joining us now from

3:26

Berkeley, where there's a lab named after

3:28

you, But you briefly ventured into the Corporate

3:30

Biotech World in two thousand nine and

3:32

worked at Shenentech for just two months.

3:35

Why was that so brief and what did

3:37

you learn? It was a

3:39

really important experience for me,

3:41

I have to say, even though short, because

3:43

at the time I was I had been running

3:46

my academic research lab for close

3:48

to fifteen years and I

3:50

was starting to question, you know, what

3:53

the impact of my work would really be was

3:55

I was I actually going to at

3:58

the end of my career feel that I had contributed

4:00

to solving real world problems?

4:03

And so that was a big motivation for

4:05

me to join the team at Genentech, a wonderful

4:08

company where I knew a number of the scientists

4:11

and some of the leadership team.

4:13

However, once I got to

4:15

the company, I quickly realized

4:17

that I just I really missed my

4:20

colleagues at Berkeley. I missed the

4:22

academic environment of you know, being

4:24

able to just think crazy ideas and you know,

4:26

run into people and the coffee line and chat

4:29

about experiments in a way

4:31

that would be very difficult to do in a company,

4:33

of course, because you have to be very focused

4:35

on UM, you know, the plans

4:39

and development UM pipeline

4:41

of the of the company. Fortunately, my

4:43

colleagues at Berkeley took me back and

4:46

I refocused my efforts

4:48

at the time on studying crisper,

4:51

which in the end was you know, turned

4:53

out to be a very productive line of

4:55

work. It's been called molecular scissors,

4:57

if you will. What is crisper

5:01

and what can it do? It turned

5:03

out that that crisper

5:05

is in fact a system in bacteria

5:08

that detects and cuts virus

5:10

genetic material, whether it's DNA or

5:13

RNA, and it was by studying how

5:15

that actually works, and we did this in collaboration

5:17

with Emmanuel Sharpontier's lab

5:20

um to study the function of a

5:22

protein known as crisper CAST nine.

5:25

That line of research led

5:27

to an understanding of the function of

5:29

this molecule that allowed us to harness

5:32

it as a tool for

5:34

genetic manipulation, namely for

5:37

altering DNA sequences in any

5:39

cell in a precise fashion,

5:41

in a programmable fashion. That

5:44

gives scientists now a very powerful

5:46

way to understand the function of

5:48

genes, but importantly also to change

5:50

the function of genes in a

5:53

targeted way. When did you realize

5:55

the power and usefulness

5:58

of this discovery, Well,

6:00

I would say almost right away. I mean, it's a relatively

6:03

simple technology that

6:05

can be easily adapted and adopted

6:07

to different applications, and so very quickly

6:10

after we published our work in

6:12

the summer of two thousand twelve, labs around

6:14

the world began to adapt Crisper

6:17

for various kinds of geno editing.

6:19

And it's just increased since then. The

6:21

pace of Crisper research the

6:23

application has been startling. It's

6:25

been incredible to watch. What are the

6:27

current use cases that inspire you the most

6:30

well. I always think about Victoria Gray,

6:33

who was the first patient with sickle

6:35

cell disease to be treated with Crisper

6:37

here in the US. Her story

6:39

is so inspiring. I mean, you know, she is

6:41

somebody who is benefiting right

6:43

now from the Crisper technology

6:46

to be able to live a normal

6:48

life without being impacted by

6:51

an otherwise quite devastating genetic

6:53

disease. And other patients are in

6:55

are similarly being impacted by

6:57

the Crisper technology. So

6:59

I think that's one area where

7:02

we will see increasing developments,

7:05

more and more clinical trials that are starting.

7:07

In fact, at the Innovative Generalmics

7:09

Institute that I started a few years ago

7:12

here in the Bay Area, we have just

7:14

received approval from the Food

7:16

and Drug Administration for our own

7:19

invasion Investigational New Drug or

7:21

i n d UH trial

7:23

for sickle cell disease. So you know, this

7:26

is really an extraordinary moment I think in

7:28

terms of thinking about cures for genetic

7:31

disorders. Once Crisper was confirmed as a

7:33

gene editing tool, leading researchers

7:35

raced to start their own companies,

7:38

and it turned into kind of a competitive free for all,

7:40

and the battle for the intellectual property

7:42

is still going on to determine who

7:46

can commercialize this technology. How do

7:48

you reflect on all of that. One thing important

7:50

to point out is that despite

7:52

the ongoing disputes over

7:55

patents, which by the way, isn't unique

7:57

to Crisper, I would I would argue that any any

7:59

really excited technology is going to have multiple

8:01

claims to it. In the case of

8:03

Crisper, because the technology

8:06

is relatively straightforward to deploy,

8:09

It's meant that the field has moved

8:12

quickly. As you mentioned, there are multiple companies.

8:14

There are multiple companies that are now publicly traded

8:16

and more coming down the pike UM

8:19

as well as all sorts of new companies

8:21

and UM and then established firms

8:24

that are adopting the technology as

8:26

well. So from a scientific perspective,

8:29

I think that's exactly what should be happening, right.

8:31

This is such an enabling technology

8:33

you wanted to see it deployed as widely

8:35

as possible. This

8:42

is my conversation with Jennifer downa biochemist

8:44

and Crisper co inventor. Coming

8:46

up, we dive deep into the morality and ethics

8:49

of gene editing and Dowton his reaction

8:51

to the world's first so called designer

8:54

babies, her thoughts on using

8:56

Crisper to edit the genes of human

8:58

embryos. I'm on only Chat

9:01

and this is Blue Brick Studio. At one point out at

9:19

what point in your research and discovery of Crisper

9:22

did you start becoming worried about the

9:24

ethical implications. Well,

9:27

quite early on, because it

9:29

was clear from you know, those very early

9:31

days that Cristopher was a broadly

9:34

enabling technology that you know, it

9:36

was useful and you know, worked in essentially

9:39

any cell type, and that meant that it

9:41

worked not only in fully developed

9:44

differentiated cells or tissues,

9:46

but it could also be used in embryos,

9:48

and in fact, that was one of the very early uses

9:50

in the research world was

9:53

to make you know, modified

9:55

mice at the you know, at the at

9:57

the embryo level, so those mice then

9:59

had genetic changes introduced

10:01

by Crisper that could be passed on to future

10:04

generations. And it didn't take too

10:06

much of a stretch to think about the

10:08

possibility that that could also be

10:10

done in human embryos, which of course, I

10:13

think comes along with with just very

10:16

profound ethical questions. I

10:18

think it was two thousand and fifteen we

10:20

organized the first meeting out here

10:22

in California on the topic

10:24

of human germline editing

10:27

human embryo editing with Crisper. That developed

10:29

into a much broader international

10:32

effort to understand the technology

10:34

and importantly to put in place criteria

10:37

that scientists globally should respect

10:40

in terms of applications of Crisper,

10:42

especially in the human germ line. Let's

10:44

talk a little bit more about the reasons, if, and when

10:47

to edit Jeanes is a profound and

10:50

complicated question. How do

10:52

you even begin to that? And to answer that question,

10:54

I think first of all, one has to ask,

10:57

are there situations where,

11:00

at least in principle, manipulating

11:02

the human germ lines in the embryo

11:04

would be the best, uh possible

11:07

way to deal with genetic

11:10

condition UM. And by

11:12

the way, I'm focused here on, you know, just

11:14

really strictly things that relate directly

11:17

to health, rather than changes

11:20

that might be you know, desirable

11:23

to somebody for some reason, but actually

11:25

have no benefit to

11:27

health. And right now we know that although

11:30

yes, it can be used in human

11:32

embryos and there are you know, multiple

11:34

scientific publications about that, we

11:37

also know that it's difficult to control

11:39

it and to make sure that editing

11:41

is happening exactly as the

11:44

scientists or experiment or might might

11:47

be desiring. And so that

11:49

to me is already a red flag

11:52

that you know, even if there were situations

11:54

where we said, g that might be the best

11:56

way to deal with the disease

11:59

UM, you know, the technology still needs to

12:01

be further developed before that would be

12:04

I think even a possible strategy.

12:07

Every new gene editing technology

12:09

has its sort of cultural shocker

12:11

moment. You had the first test

12:13

two baby Dolly the Sheep, and then of

12:15

course in the

12:18

so called Designer Babies, where twin

12:20

girls their genes were

12:23

allegedly edited by a Chinese

12:25

scientist Gan Quay. What

12:28

was your first thought when you heard that news,

12:32

Um, well,

12:34

uh, shocked for sure, definitely.

12:37

Um, you know, I guess it wasn't entirely

12:40

unexpected that someone would try

12:42

to do this. I had no idea that

12:45

it would happen as soon as it did. But

12:48

um, you know, it had been discussed at meetings,

12:50

of course, and that was in fact

12:52

the purpose of these prior uh

12:55

you know, conferences on the topic. So

12:58

it seemed you know, it certainly seemed possible

13:01

that someone would would do this. I didn't think someone

13:03

would would actually proceed, however, to

13:06

actually create a pregnancy with edited embryos

13:09

um as as was announced in

13:11

two thousand eighteen, and I think it really was

13:14

a wake up call to the international

13:16

community that we can't sit back and

13:18

just say, well, you know that

13:20

that's a problem for the future. No, no, this is

13:22

this is something we need to deal with right now,

13:25

and we need to take a strong stand. And I think

13:27

fortunately that's exactly what happened.

13:30

Are other scientists trying

13:32

these things elsewhere, we

13:34

really haven't heard about that kind

13:37

of manipulation going on in certainly

13:39

in any organized way. So

13:42

I just think that at

13:44

least I hope that the international

13:47

reaction, which was really negative

13:49

to you know, to this announcement

13:52

has has I think, at least for the time

13:54

being, really put a damper on anyone

13:57

that might be trying to do that kind of human

13:59

manipul elition for you know, fame,

14:02

for example. I do feel an ongoing

14:05

sense that we need to be really

14:08

proactive about this and not not

14:10

you know, not get complacent. And importantly

14:12

I I include in in

14:14

sort of ethical considerations also thinking

14:17

about widespread availability

14:20

and affordability of the technology,

14:22

because I think, you know, this is something that we

14:24

have to pay attention to. I mean just thinking back

14:26

to the example of Victoria Gray,

14:29

who I mentioned earlier, who has received

14:31

a Christopher treatment for her sickle cell disease.

14:33

Wonderful you know news about

14:36

that. However, her therapy currently

14:38

costs two million dollars, so

14:41

you know, that's just not going to be affordable

14:44

to most people around the globe that might

14:46

need this. So we're working hard to think about

14:48

ways that we can mitigate those costs. Wanting

14:51

to eliminate a genetic disease seems like

14:53

an important cause. Do you

14:55

think the case, the moral case

14:57

to eliminate a genetic disease is stronger

14:59

than the case not to. I

15:01

think we have to consider it, you know, on a

15:03

case by case basis. I mean, one could argue,

15:06

for example, like let's go back to sickle

15:08

cell disease that you know right now,

15:10

the therapy is designed

15:12

to be used in individuals, and

15:15

it doesn't make a germ line change,

15:17

right It's not a change that they would pass on

15:19

to children. It's just a change that affects

15:22

their body. And so in that

15:24

sense, it's like any any other type

15:26

of therapy or or drug that we might use

15:28

to treat disease UM.

15:30

Whereas you could imagine that

15:32

in a family that has a genetic

15:35

disease that is you know, is

15:38

sort of you know, spread across their family,

15:40

many people inheriting a gene that you

15:42

know predisposes them to disease,

15:45

and believe me, I hear from families

15:47

like that almost daily.

15:49

You could imagine that, you know, at some point in

15:51

the future, if the Crisper technology

15:54

were safe and robust, that

15:56

some families might make the decision to UM,

15:59

you know, to to remove that disease

16:01

causing mutation at the source so

16:04

that you know, future generations don't have to worry

16:06

about it and I think that's you know, that

16:08

that would make a lot of sense. But again, there's

16:10

a number of things that have to happen, I think before

16:12

that will be possible. Back in the seventies,

16:14

Test two babies were controversial, and now IVF

16:17

is widely acceptable, accepted

16:19

available. Do you think it

16:21

will be the same with crisper edited babies

16:24

over the coming decades. I

16:26

think sure, I think absolutely,

16:28

You know that because this is what happens, isn't

16:30

it is that you know, people um get

16:33

comfortable with an idea if it's

16:35

useful, you know, if it has proven and and

16:37

this is you know, this is still remains to be seen, like

16:39

if Christopher proves to be

16:42

useful um and and

16:44

and you know, kind of controllable in human

16:46

embryos, and that is still in the realm of

16:48

research. But if that were to happen, then

16:51

you know, I think it becomes a possibility

16:54

that in vitro fertilization clinics

16:56

offer that to their

16:58

clients, and and so then you know

17:01

who should make that decision? Should governments

17:03

be regulating that? Well, that doesn't actually doesn't

17:05

really happen for IVF clinics right now.

17:08

In fact, you know, there's as you probably know, there's you

17:10

know, different different regulations across different

17:12

states in the US, and of course in different countries is

17:14

different. And so I think, you know, the same

17:16

thing could possibly happen with Christopher, where

17:19

you know, it becomes a something

17:21

that you know, some clinics offered and parents will

17:23

have to decide do I want to do that or not. If

17:32

you're listening to my conversation with Crisper Cohen

17:35

mentor and Nobel Prize winner

17:37

Jennifer down Up up next amidst

17:39

an ongoing pandemic, how the biochemists

17:41

made a pivot in advance

17:43

Crisper as a diagnostic technology

17:46

for COVID nineteen and after winning

17:49

the Nobel Prize, Dowdnup

17:51

shares inspirational advice to girls

17:53

and women studying stem fields

17:55

everywhere. I'm emily changed. This

17:58

has boom Brick Studio one point out, stay with

18:00

us. The

18:17

ethical controversies around Crisper came

18:19

screeching to a halt when the pandemic hit.

18:22

What was going through your mind when the world

18:25

met COVID nineteen, Well,

18:28

I think, like like like

18:30

like many people, you know, it was quite

18:33

quite a shock. This was something that we really

18:35

had to face head on, and

18:37

that was actually, for me as a scientist, really a

18:39

motivation for pivoting the focus

18:41

of our work at least over the last year to

18:44

creating a clinical testing lab at

18:46

the Innovative Genomics Institute and

18:48

also to advancing crisper

18:51

as a diagnostic technology. You've

18:53

had this fascination with

18:55

RNA for so long and did

18:57

you ever think that your are

19:00

in a specialty would have a moment

19:02

like this the key to fighting a global

19:04

pandemic. Well,

19:07

uh no, I never thought that for sure.

19:09

And let me just point out, since you read up

19:11

ourn A, I think it's fascinating that, first

19:13

of all, the coronavirus, the stars

19:15

covie two virus that causes COVID

19:17

nineteen is an RNA virus.

19:20

So it's a piece of RNA that's

19:22

you know, been causing all this havoc.

19:24

And furthermore, many of us have received

19:27

vaccinations with r N

19:29

A right, so I received a

19:32

vaccination that is a messenger

19:34

RNA that carries a message into

19:36

human cells telling them make

19:38

antibodies against this virus

19:41

protein. And so that's been that's been also

19:43

very interesting, so RNA to fight RNA,

19:46

and then with Christopher, we have a third

19:48

type of RNA that potentially

19:51

could be useful I think primarily

19:53

in this case as a diagnostic

19:55

tool, a way to detect the coronavirus

19:58

RNA and report on his presence. Couldn't

20:00

Crisper one day also be used to edit our

20:02

genes to make us less susceptible

20:05

to viruses? Well maybe,

20:07

I mean there's definitely speculation about

20:09

that. You know, would it be possible to um

20:13

you know, I think about it sort of like genetic

20:15

vaccination in the sense that, you know, could we

20:17

educate our selves ahead of time to

20:19

be you know, sort of um

20:22

ready in case of virus shows

20:24

up? And it's you know, it's a tricky thing, right because you know,

20:26

you have to kind of know what to be ready for

20:28

and and so you know, there would have to

20:30

be some interplay there. But I think already

20:33

we're seeing opportunities to use Crisper

20:35

to edit immune cells. And then

20:37

this is being done in conjunction with cancer

20:40

immuno therapy for patients, for example.

20:42

So you could imagine taking that a step

20:44

further and saying, well, can we educate

20:46

our immune cells to be ready for a

20:49

virus? What do you say to the skeptics

20:51

who say that Crisper is playing God,

20:56

Well, I guess my my answer there is

20:58

that, um, you know, there are so

21:00

I mean, I don't even know how one defines

21:03

playing god because you know, there's so many

21:06

things, you know, ways that we manipulate

21:08

our environment. Now. For example, all the food

21:10

we eat is essentially engineered because

21:12

of you know, plant breeding that's

21:14

been going on for you know, thousands of years

21:17

really, and so when new technologies come along,

21:19

they enable new science. When new science

21:21

is done, they enable new technologies, etcetera.

21:24

And in the end, you know, that's

21:26

really what drives human advancement,

21:29

and it drives our economy in

21:31

many ways. So I

21:34

feel that overall this is all

21:36

positive. But you know, but you

21:39

know, scientists really need to be

21:41

engaged in, you know, accepting

21:43

that responsibility for what they're doing and

21:46

making sure that they're involved in the

21:48

discussions and the you know, decisions that have

21:50

to be made as technology advances. And that's certainly

21:53

true for Cristoper. Let's go ahead another

21:55

hundred years. If the next COVID nineteen

21:57

happens in another century, how

22:00

will things be different? How will we be more

22:02

prepared? Will our genes have already

22:04

been edited to prevent us from getting

22:06

the next big deadly disease. I

22:08

wonder, I guess. I I imagine

22:11

that certainly, within a hundred

22:13

years we will know so much more

22:16

about our own genomes. And you know,

22:18

the more we learn, honestly, the more complicated

22:21

it clearly is um but you

22:23

know, but so there's there, There will be plenty to keep

22:25

all of us busy. But but look,

22:27

I think in a hundred years we will know so

22:29

much more about our own genetics, including

22:32

the genetics of our immune systems

22:34

and our interactions with virus.

22:37

So my hope would certainly be that, you

22:39

know, if the next hundred year pandemic

22:42

comes along, that we will

22:44

be certainly much better prepared

22:46

to manage it than we were for this one.

22:49

So, in the middle of this global pandemic, in

22:51

October, news

22:53

came in that you won

22:56

the Nobel Prize for Crisper, which

22:59

you shared with a man, All Scharpentier, two

23:01

women winning the Nobel Prize.

23:04

Looking back on those days

23:07

when you were told girls don't do chemistry,

23:10

what do you have to say to inspire the girls

23:12

out there who might want to follow in

23:14

your footsteps? Well,

23:16

it's you know, just such a

23:19

kind of humbling experience for

23:21

me in a way, because I mean, who you know, I certainly

23:23

never, ever, in a million years would

23:26

have imagined that, you know, I would have won

23:28

the Nobel Prize. And um, I'm even sort

23:30

of shocked hearing myself say it right now. And

23:34

uh, you know, and I but here's an interesting

23:36

thing that's happened, and that is that I've

23:38

heard from many, many

23:41

girls and women since then,

23:43

some of whom I knew from my past

23:46

life, but some of many of whom I don't

23:48

know, who have reached out from all over

23:50

the world to um tell

23:52

me their stories, to tell me that our

23:55

work is inspiring to them. And

23:57

I really hope that that message gets

23:59

through very clearly to students,

24:02

especially to two women or other people

24:04

who feel maybe they have been um

24:07

excluded in some ways from or just

24:09

been underrepresented in the STEM

24:12

fields that you know, I certainly didn't

24:14

come. I'm not a likely person to have won

24:16

the Nobel in a way, you know, because I came from a you

24:18

know, a small town. Nobody in my family was

24:20

a scientist. I just kind of wanted to do science.

24:23

I thought it was cool, and and

24:25

that's the message I try to tell those students

24:27

you can do this well. Thank

24:29

you for paving the way for women and

24:32

for all of the girls who will come

24:34

after UM and congratulations,

24:37

Dr Jennifer Downutt, thank you so much for joining

24:39

us on this edition of Studio one Point. Oh. It's been

24:41

wonderful to have you. Bloombrook

24:56

Studio at one Point I was produced and edited by Kevin

24:58

Hines. Our executive producer is Alison

25:00

Weiss. Our managing editor is Daniel Culbertson,

25:03

with production assistants from Lauren Allis and

25:05

Mallory Abelhausen. I'm Emily

25:07

Chang, your host and executive producer.

25:09

This is Bloomberg