Human Nature (2019) - full transcript

Dr. Bonner,
fellow prophets, and...

Ladies and gentlemen...

This summer,
I traveled through

northern Arizona
and southern Utah.

In this land,
the rivers have carved

great gorges,

and on the sheer cliffs
of these gorges,

one can read a billion years
of the history of the Earth.

On that immense scale

of what represents the passage of perhaps 100,000 years,

all of man's recorded history



took place as
an inch was deposited,

all of organized science,
a millimeter,

all we know of genetics,
a few tens of microns.

The dramatic advances
of the past few decades

have led to
the discovery of DNA

and to the decipherment of the universal hereditary code,

the age-old language
of the living cell.

And with this understanding

will come
the control of processes

that have known only
the mindless discipline

of natural selection
for 2 billion years.

And now the impact of science
will strike straight home,

for the biological world
includes us.

We will surely come to the time



when man will have
the power to alter,

specifically and consciously,
his very genes.

This will be a new event
in the universe.

The prospect is, to me,

awesome in its potential
for deliverance

or equally for disaster.

There we go.
Much better.

You want to squeeze my hand?

Relax your shoulders.

Relax your toes.

-Being in the hospital
isn't scary to me.

Having a certain new problem
isn't scary to me anymore

'cause it's happened
so many times.

I don't know.

My blood just does not
like me very much, I guess.

Your red cells are
supposed to be round

and have oxygen in them.

Mine are half-moon-shaped,
sickle-shaped,

which is why
it's called sickle cell,

so I don't get
the same amount of oxygen.

I always say, like,
oil change, you know?

You're draining the dirty out
and then put a clean in.

Yeah, so he just
needs a tune-up

every four to six weeks,
yeah, uh-huh.

Yeah.
That okay?

-Okay.
-Put this on.

Take deep breath and hold.

Mm.

Okay.

You okay, David?
Mm-hmm?

He used to tell me,
"Don't cry, Nonna.

Why are you crying?"

I said, you know,
"Love you, baby."

He goes,
"Don't worry about it."

He says, "If I lose my life,"
he goes,

"You'll see me again,"
and I thought,

"This child has more strength
and faith than I do."

-It's often called
the first molecular disease.

It's caused by a single change
in the DNA sequence.

It's the letter A
changed to a letter T.

-That's it?
-That's it.

-And that mutation causes
a kink in the protein

that prevents it
from folding properly.

If your folding structure
of a protein is disrupted,

now that protein
can't function.

It causes the red blood cell

to really collapse.

-It becomes very stiff,
and it can't squeeze through

and you're not able
to get red blood cells

to the tissues where
they can deliver oxygen,

and if you block the ability of
oxygen to get to those tissues,

those tissues won't work well
and they'll get damaged.

In Africa, the life expectancy

for somebody with
sickle cell disease

is on the order of
five to eight years of age.

In the U.S.,
it's the early to mid-40s.

What do you say to a kid
that their life is gonna be--

We avoid it.
We avoid that conver--

-it's not a--it's--
-Really?

It's not a conversation
we're good at having.

Makes me very nervous.

David can go from
crazy teenager,

joking, jumping around,

to a fetal position
on his knees.

-It's, like, pulsing.

"This hurts.

You're having
a sickle cell crisis."

I can have, like,
a little pain crisis

where it really doesn't count,

and then I can have
something really bad,

but I'm not just gonna
not play basketball.

You can't just
not play basketball.

This is David's
old red blood cells.

We're gonna save for research.

How do you sing?

It's a genetic disorder,

so in order to cure
a genetic disorder,

you literally have to
go in and fix the gene.

We just didn't have the tools

to make that single letter
change in a precise fashion.

-Even one letter?
-Especially one letter.

-Deoxyribonucleic acid,
or DNA for short,

is the material
that's the basis of life.

Each living thing
has its unique DNA

that determines what
that living thing will be:

plant or animal,
man or muskrat.

If we understood
the structure of genes,

the structure of chromosomes
and how genes work,

then we might better
be able to understand

and treat genetic diseases
which occur in humans.

The work that Paul Berg did,

that was probably
the beginning.

This dream of gene therapy

was born out of those
1970s experiments,

and we were still
very far away from it,

but you'll see people talking
about that hope right away.

The hope is that
the isolation of the gene

will lead to treatment
of people

with muscular dystrophy.

Scientists are
working on genetic cures

for diseases such as
Alzheimer's and Parkinson's.

A, T, A, G, C...

-The idea behind gene therapy
is really simple:

add in a copy
of the gene that works.

Then they'll make
the protein that works,

and then
they won't be sick anymore.

But the devil, as is often
the case, is in the details.

Right now,
we have the ability

to identify the gene,
to isolate it,

but the ability
to put it where we want it

is still a long ways away.

-If you put a gene
into a cell,

you cannot tell
exactly where that gene

is going to enter
the cell's chromosome.

-Conventional gene therapy

is an essentially
random process.

So imagine taking this
century-long narrative,

which is human DNA,

which is a very,
very long text,

and taking one paragraph

and just sticking it
somewhere random.

The change you are creating
is not a controlled one.

-There was a clinical trial
that was done in France.

This was for
really sick children.

I want to be clear.

This was for children who would have died otherwise.

Four of these children
developed cancer.

One of them died.

The gene went into
the wrong place

because it's a random process,
and, by chance,

it went into the wrong place,

and that random event
caused cancer.

You know, you always think
that what you know

is gonna get a little better
and a little better

and a little better
and soon will be there,

and what we knew how to do

wasn't getting
a whole lot better.

It was getting
a little bit better.

The technology
was just too clumsy

to actually use it
with human beings.

It became very,
very clear to us

that we are at the foot
of a very tall mountain

and we may not even have
the right mountaineering gear.

I worked at this company
called Sangamo Biosciences.

We decided to figure out a way

to change human genes
in a precise fashion.

You know, this would be like
word processors for your DNA.

This will get technical
but good technical.

DNA breaks all the time.

You go get a dental X-ray.

The technician points
this thing at your face...

And the X-rays
actually hit your DNA,

and they physically
create a break,

so the familiar double helix
of DNA physically goes...

The good news is,

the cell has its own machine
to fixing breaks.

Inside our cells,

there are two identical
DNA molecules

lying side by side,
literally side by side.

If one is broken,
it can say to its sister--

and that, in fact, is the
technical term--the sister.

"Hey, sis, I'm sorry.
I've had a break.

I'm wondering if I can copy the
missing genetic information."

And the sister goes, "Yeah."

Done.

"Chromosome broken

"awaits sounds
of strands pairing,

preserving the life's thread."

There's really a haiku about
homology directed repair.

Why is that useful?

So it's useful because

if you can cut a gene
inside a cell,

so if you can create a break
at a place of interest,

then you can change that gene.

You fool the cell,

give it a separate piece
of DNA that you have made,

a piece of DNA
which is identical

to the chromosome
that you are cutting

except for the change
that you wish to make.

And Mother Nature will
not know she's being fooled.

She will repair the break

using this piece of DNA
you provided as a template,

and so whatever change
you brought in

will then go into
the chromosome.

You can think of it like
a cursor in Microsoft Word.

In Word, if you have
a document where you edit,

first you have to
place the cursor there.

In DNA,
wherever you make a cut

is the equivalent of a cursor

in this word processor
of the genome.

That's where you can
type in a new word.

So if you wanted
to use that capability

to "engineer the genome,"

the challenge was to
introduce breaks in the DNA

at places where you wanted
to alter the code.

-How were we gonna do that?

We need something
that cuts only one gene

out of the, you know,
25,000 that we have.

-There were just such serious
blocks in the way.

So it looked like
it was gonna be a long road

and that's what changed

and that came
sort of overnight.

David's doctor told me,
"Just hold on.

There's something coming."

-When I first heard about it,

I was at a conference
in New York,

and it was a very strange
conference of futurists.

It was put on by a Russian guy

whose ambition
is to download his brain

and become an android
who lives forever.

In this future, people
will be young, beautiful.

They will have multiple bodies,
not only just one.

-But they had a lot
of good people there,

including an important
geneticist from Harvard,

George Church,
and I remember him saying,

"Remember this word: CRISPR."

It's like, you know,
in "The Graduate," plastics.

Remember the word CRISPR.

This is going to allow
human genome engineering

on a unprecedented scale.

-How old is CRISPR?

Oh, in terms
of millions of years?

-Yeah.
-Oh.

I mean,

probably...billions.

How you say even?

-Well, I'll tell you
the story that I know.

Microbial genome sequencing
started sometime in the 1990s.

What does that mean?

See--okay, so unraveling the
DNA code of organisms of life.

It's a relatively
recent part of biology,

and in the late 1990s, people
started to turn their attention

to the sequencing
of microbial genomes.

They're amazingly
highly evolved entities

that just chose a different
way of surviving in the world

than the cells that became us.

Clustered
regularly interspaced

short palindromic repeats.

-There really wasn't
much precedence

for anything like this
in the DNA of living things,

and when you see
something unusual,

you automatically assume
that it's interesting.

That's just how science works.

-CRISPR is actually clustered

regularly interspaced
palindromic repeats,

and so it's actually
named for the repeats.

But what was
really interesting

were these sequences
in between

that were completely
enigmatic.

-Spacers.

-And each spacer
was different.

Never seen anything
like this before.

Where the hell
come these sequences from?

I- have my own way of kind of

telling the story
in short form,

is, I show this article
from 2007, right,

five years before anybody
was talking about CRISPR,

and it's this headline
from a yogurt company saying,

"Holy grail is discovered."

And what was this
yogurt company's holy grail?

It was CRISPR.
It was CRISPR.

When did you get
your CRISPR license plate?

-The first one I got back
in the days in Wisconsin,

and when I first moved
to North Carolina...

One of the first things I did

was make sure
I still had my CRISPR rights

with my CRISPR mobile.

People were like,

"Have you heard about this
CRISPR thing?" And I'm like,

"Dude, like, I've heard of this
CRISPR thing for ten years.

Like, what the hell
are you talking about?"

-Danisco is a company
that sells microbes

to people who want
to make food.

A lot of foods are produced
using bacteria, and--

yogurt, for example.

Rodolphe was trying
to work out how to deal

with the problem
of his bacterial cultures

suddenly dying because
of viral infections.

Most people don't wake up
in the morning and think about

how bacteria defend themselves
against viruses.

It's just not on their...

sort of front and center
in people's agenda,

but it should be.

-Viruses are very simple
lean machines.

They have one job to do:

look for a host, take
the host over, and multiply.

That's it.

-The virus will
attach to the surface,

and then it will inject
its genetic material.

It hijacks the cell
and use the cell

just as a factory
of new viruses.

And then it's over.

It's over for the cell.

This is when people

call companies
like Danisco and say,

"You sold us a culture
that's not working.

We want our money back."

But there's a small subset
of the population

that survives
the viral attack.

We don't know why they make it,
but they make it.

They become resistant.

At that time,

we still don't know what
CRISPR is or what it does,

so there's no assumption
that CRISPR is involved.

Then what we do is, we take
the survivor that made it,

and then we check its DNA.

The DNA sequence had changed.

-And now it's immune.

-So now
scientists have a clue,

and, you know,
at this point, of course,

you've sort of put
your Sherlock Holmes hat on,

you take in your virtual pipe,
and you go,

"What are these clues
telling us?"

-We do the experiment
five different times,

and consistently, the bacteria acquired a spacer

that contains a sequence
from the virus

and became resistant.

So what if I take it away?

You lose the resistance.

Without that
little piece of DNA,

the microbial cell,
the bacterial cell, will die,

and if it had it,
it would survive.

Oh, that was like--
that was like,

"We got it."

-CRISPR is an immune system.

What an idea, a piece of
the genome of your predator

now stuck in your genome so you
can recognize it in the future.

That was really fantastic.

-At the time, you know,

it's useful
in manufacturing cultures

that are resistant to viruses,

and it's extremely valuable
to Danisco, you know?

But...

but we don't know what
the future holds...

We have no idea how useful
another's technology

is gonna be or pan out
in the end.

-I think I first
heard about it

when I had coffee
with Jill Banfield,

my colleague here at Berkeley,

at the Free Speech
Movement Cafe,

classic Berkeley cafe.

One thing they'll write
on my tombstone is,

"Told Jennifer Doudna
about CRISPR-Cas."

Like, that will
be the sum of my life.

-I love things that
not a lot of people

are paying attention to,

which certainly CRISPR was
in its early days.

Not anymore, but--
but, you know,

in the early days,
it was like that.

But then you always
ask yourself,

"Huh, is everybody else
just a lot smarter than me

and they've figured out
that this is a--you know,

a dead path and..."

So we've got the
antibody tethered to Cas9.

It's finding
the T cell-specific antigen.

-We're biochemists
in the lab.

We study the way
molecules work.

We try to isolate them from

all of the other pieces
and parts of the cell.

We love to ask,

"Well, what are the essential parts of this little machine?"

In nature, what
CRISPR systems are doing is,

they're giving bacteria
immunity to viruses,

so they're protecting them
from viruses.

-When an invader shows up,

the bacterium has a way
to store a small bit

of the invader's DNA
in its own DNA.

When the invader comes back,

the bacterium makes a copy,

like a little "Most Wanted"
poster of that spacer,

and gives it to
the marvelous machine

at the heart of CRISPR,

this extraordinary protein
that we call Cas9.

Cas9 is truly wondrous.

When Cas9 polices the
intercellular neighborhood

for invasions,
it literally carries a copy

of that "Most Wanted"
poster with it,

asking everyone that comes in, "Excuse me.

Do you contain an exact match

to this little 'Most Wanted'
poster that I'm carrying?

Yes? Then I'll cut you."

-The thing about Cas9
that struck me at the time

was that, you know,
fundamentally,

this thing was
a programmable protein

that finds and cuts DNA.

As a tool, right,
you could immediately see

a lot of uses
for something like that.

I will never forget

reading the last paragraph
of Jennifer Doudna's

and Emmanuelle Charpentier's
deservedly--

"immortal" is a strong word,
so I'm gonna use it carefully--

immortal science paper

in which they describe
that Cas9 can be directed.

Cas9 cuts DNA based on an
instruction that it carries,

and that instruction
is a molecule of RNA

that matches perfectly
the DNA of the invader.

-RNA, I think about it
as DNA's chemical cousin.

Like DNA, it has four letters,

and they can form pairs

with matching letters in DNA.

The letters in the RNA
allow Cas9

to find a unique DNA sequence.

Bacteria were programming
this thing all the time

with different viral sequences and then using it

to find and cut
and destroy those viruses.

But because it's using
these little RNA molecules,

those can easily be exchanged.

RNA molecules
are trivial to make

in a molecular biology lab
or order from a company.

And I can cut any DNA I want
just by changing this--

this little piece of RNA.

It was clearly a useful tool,

and I--initially I was thinking
about it that way, right?

'Cause, I mean, again,
I'm a biochemist, right?

I was thinking
about it as a tool.

I was thinking about
all the cool experiments

you could now do
with this tool, right?

I was thinking about that.

I wasn't thinking about,

oh, my gosh, I mean,
this is a tool that,

you know,
it fundamentally allows us

to change
our relationship with nature.

It actually allows us
to change human evolution

if we want to, right?

It's that--it's that profound.

In my left hand here,
I have purified Cas9 nuclease,

and in my right hand here,
I have a guide RNA,

and so CRISPR essentially
is the combination

of these two ingredients.

It's actually millions
of Cas9 molecules,

and this is millions
of RNA molecules.

I have to say it didn't
immediately hit me

until I started seeing the data

that this could be an
extraordinary transformation.

You know, it was real.

You can actually use CRISPR
in humans to change DNA.

You can actually do it.

Here's a copy
of a human gene.

You give it to Cas9 and
put it inside human cells.

It runs away, finds that DNA,
and cuts it.

-Before CRISPR, we were
getting 1% to 2% correction.

We're now up to
50% to 80% of the cells.

This could really work.

This could really
cure a patient.

-I think it's gonna help
a lot of people,

not just people
with sickle cell,

'cause I know they're working
on it for other things.

And I know so many
other people

that have--that have
things like this,

like--like my friend.

He...uh, had leukemia.

He actually--he didn't make it
out of the hospital.

If he had it
just a little bit later,

of course, he probably
could have been cured of that

'cause that's what
they're working on.

-CRISPR has,
really, the ability

to recognize and to target
any piece of DNA

in any type of cell
and organism.

It's really a universal tool.

It's often described as
a kind of Swiss Army Knife.

-We have
thousands of customers

who are working with CRISPR
in a wide variety

of organisms,
pretty much any organism

you can think of
from butterflies

to dogs to horses
to wheat to corn.

We have a design tool online.

Specify a gene that
you're looking to knock out.

You can specify
the types of edit

that you're looking to do.

You swipe your credit card,
and a few days later,

a couple tubes
of all the materials

that you need
show up at your door.

Obviously we like to validate
the researchers' authenticity

and credibility with regard
to their institution.

Meaning you're not
just shipping it off?

Correct.
We don't ship to just anyone.

That's correct.

-The analogy I like
is automobiles.

There were cars
before there were Model Ts,

but they were expensive and
they broke down all the time.

Ford comes out with
the Model T, and, suddenly,

it's cheap, and it's reliable.

Pretty soon,
everybody's got a car.

-CRISPR gives us the chance
to make precise,

targeted changes in the DNA
of any living organism.

It's a power
to change the biosphere.

That's what makes
CRISPR revolutionary.

Can you just sort of describe
where we are right now?

-Yeah, yeah, yeah.
-Oh.

-The field is called
xenotransplantation,

transplantation of an organ
from one species to the next.

These things have
actually been tried a lot,

and some of them
are pretty weird,

like people were--
were, you know,

in the early 1800s,
that kind of stuff,

they were trying
to transplant monkey testes

into men
to make them more virile.

So it's a--you know,
conceptually,

people have been trying this
for a long time,

but scientifically, this field
is probably about 20 years old.

Whether we like
to believe or not,

we are very similar
to the pig.

This pig, this pig, this pig,

all the organs in these pigs
have been modified

very, very slightly.

-They tried it 20 years ago.

Novartis had had a
billion-dollar investment in it

sort of gracefully retreated.

They did--they just didn't
have the technology.

Without the CRISPRs,
can't do it.

-Luhan Yang and her team,

they started as
a ragtag team of scientists

in my academic lab, and then
they went to a ragtag team

in the basement
of a startup incubator.

Nice to meet you, hey.

Happy Halloween...

You know, I dressed up today.
How are you?

Can you see anything?

Kind of.
Something, not everything...

-We have a revolution
going on.

We've never had
a revolution like this.

Closest we've come
is maybe the Internet

and computer revolution,

and that took us
kind of unaware.

We do a lot of iteration
of the pig production.

-How are the pigs
coming along?

So, uh...

This is Aldous Huxley,

a man haunted by
a vision of hell on Earth.

Mr. Huxley 27 years ago
wrote "Brave New World."

Today Mr. Huxley says that
his fictional world of horror

is probably just around
the corner for all of us.

-I first read
"Brave New World"

in a literature class
in high school,

and, yeah, it was startling,

and, yeah, it was provocative,

but I reread it recently,

and I was startled
by how a book written in 1932

could have the foresight
to predict

in vitro fertilization.

Now, of course,
it went beyond it.

It told a story
where human beings

were literally manufactured

to play specific roles
in society.

It was so sobering
to me because

CRISPR makes
that original worry

about engineering human
heredity actually feasible.

-We mustn't
be caught by surprise

by our own
advancing technology.

This has happened
again and again in history

where technology has advanced

and this changes
social conditions,

and suddenly,
people have found themselves

in a situation
which they didn't foresee

and doing all sorts of things
they didn't really want to do.

-There is no question
in my mind that

as this field advances,

people will be able to

order a change
in their genetic makeup

to create an outcome
of interest to them

in their metabolism,
in their appearance,

in principal, potentially,
in who they are as people,

personality changes.

And, again,
we have to be delicate

to not cross into
science fiction territory.

-We know that we could
engineer a single gene,

myostatin, in a way
that could potentially

make us all more muscular,

but should we make that
universally available?

They discovered that
there are people

who can go by
on four hours of sleep.

What would I give
for that mutation?

One gene, one change,

four hours of sleep,
no problem.

So should this be--
I don't know,

a job requirement for
air traffic controllers?

Do I want the world
to go there?

There are people
who feel no pain.

This was discovered
by studying

a 14-year-old boy in Pakistan

who felt no pain,
and guess what he did?

He performed street theater.

He died before
his 14th birthday.

He jumped, for money,
off a house roof.

He knew it would be painless.

The study of his DNA revealed
he has a mutation in one gene.

It makes a protein that
transmits the pain signal

from the periphery--
your finger, or your skin--

through the spine
to your brain.

You get rid of that gene,

you cannot transmit
the signal.
You feel no pain.

Why?

Well, I'll give you
a legitimate reason.

Pain due to cancer
is terrible,

especially
if it's terminal cancer

and we know a person
has months to live.

Why not get rid of that gene?

And I'm sure this will be.
I am surethis will be.

We will have gene editing
of that gene

to treat cancer pain.

Now,

do I want a scenario where
there are parts of the world

where special forces soldiers
are made immune to torture?

-I don't think my job
is that different

than what scientists do.

There's a lot of
kind of hunting around,

hunting and pecking, you know,

looking under things,

turning over stones,

and then eventually, you know,

you kind of get on
the scent of something,

and then that's
when the fun starts.

Before science gets published,

it circulates
among scientists.

The papers go out for review.

Someone passes it
to somebody else.

Like, they have
a certain circulation,

and so I'd gotten onto
the trail of these papers

coming out of China.

This was the first case
where someone had said about,

you know,
"I'm gonna use CRISPR,

and I'm gonna modify
a human embryo."

They had knocked out CCR5.

This is a receptor that,
if you don't have it,

you can't get infected
with HIV.

But think about what
they were proposing.

They said, "We're gonna make
someone who's immune to HIV."

Once I started
digging into it,

I found more examples
of people

that were thinking
along these lines.

John Zhang runs the
third or fourth biggest

fertility clinic
in the country,

and then he started a company
called Darwin Life.

He said that he was
enthusiastic about

the whole idea
of designer babies.

He basically said that,

"Of course.
That's the whole point."

There was a company
called OvaScience

that I discovered
a tape recording

that they had put on their own website of a investor meeting.

-We will be able to
correct mutations

before we generate your child.

It may not be 50 years,
actually.

It may only be 10,
the way things are going.

-I ended up having
several dreams

that were very intense
for me at the time,

where I walked into a room
and a colleague said,

"I want to introduce you
to someone,

"and I want you to tell them--
they want to--

they want to know
about CRISPR."

And I walked into this room,
and it was--

there was
a silhouette of a chair

with someone sitting
with their back to me,

and as they turned around,
I realized with horror

that it was Adolf Hitler,
you know?

And he leaned over,
and he said,

"So tell me all about
how Cas9 works."

I remember waking up
from that dream

and I was shaking.

And I thought, "Oh, my gosh.
I mean, what have I done?"

5 1/2 years ago,
it was recognized that

we could take the
CRISPR system out of bacteria

and move it first
into a test tube

and then into mammalian cells

and use it as a tool
for genome editing.

The Cas9 protein is gonna
make the cut in the DNA.

We are correcting
the sickle mutation

in blood cells.

So if it's a woman,
their eggs are not corrected.

If it's a man,
the sperm is not corrected.

That change will not get passed
along to future generations.

So they will be cured,

but their children might
get the disease as well.

Now we need to give the cell
another piece of DNA,

except instead of having
the T, it has an A.

So why not just do it
so that the disease gene

never gets passed along
to future generations?

And there's some people
out there who think

that's what we should do.

But we may be creating things

that we can't put back
into the bottle.

-When we engineer
gene changes

into my blood
or into my skin,

those gene changes die with me,

but the germ cells,
sperm, and eggs, embryos,

those cells
are very different.

They're part of what we call,
"the germ line."

If we engineer gene changes
into my sperm,

they're passed to my son.

They're passed to his son
and forever.

My colleagues and I wrote a fairly strongly worded piece

in "Nature" with the
fairly unequivocal title

"Do Not Edit
the Human Germ Line."

We proposed that there be
an unconditional moratorium:

Don't edit human embryos.

Don't use edited sperm and eggs to make human embryos,

just nothing.

We must understand that

when we authorize research
on human embryo editing,

we are enabling, ultimately,

human embryo editing
for human enhancement.

That's what we're doing.

We're putting the recipe
out into the world.

The debate that's being had

is whether society
should go in this direction.

Should you be allowed to make

a genetic change
into the next generation

that'll then go
on to other generations?

The gene pool,

like nature itself,
is kind of a common good.

I used to have a T-shirt,
and it had a little--

a guy that was kind of
a DNA spiral, right?

But he was the lifeguard
and he's blowing a whistle

and he says, "Hey, you,
get out of the gene pool!"

I loved that shirt.

-Baby shopping.

Imagine being able
to program the IQ of a baby.

Will we be sitting at computer
terminals like this one

punching up the traits
we would like in our children,

like the shape of their faces
or the color of their eyes?

Well, you know, the fear
that everybody focuses on most

is just this sort of
designer baby business.

-We're turning reproduction
into production.

We're turning children
into consumer products.

-Every time there's
a new technology,

we hear the same concerns.

If there's a market
for cloning,

there is no force on Earth

that will keep
buyer and seller apart.

Perhaps Saddam Hussein would
like to give birth to himself.

-With CRISPR,
even reputable magazines

could not resist
the temptation.

The little thing that says
"high IQ,"

as if we know
what intelligence is

let alone how to measure it
let alone how to design it.

Why do we keep
ignoring the fact

that we've seen
the same argument

every decade
for the last five decades?

And these nightmares,
they haven't come to pass.

We are capable
of really evil things,

but we don't need technology
to commit evil acts.

If the goal is genocide,
if the goal is eugenics,

if the goal is discrimination,

there will be another way
to do it and it will be found.

I kind of divide the world
into the bio-optimists

and the bio-pessimists.

-the final frontier.

-I grew up with the
original "Star Trek."

I have been a devoted follower

of all of the
"Star Treks" since then.

I've read pretty much
every "Star Trek" novel.

Don't get me started.

It is a vision of progress

and the potential of science
to make life better.

There are other people

who have read
the cautionary tales.

-A blade runner's job
is to hunt down replicants,

manufactured humans you can't
tell from the real thing.

-I don't think
the technologies

are inherently good or evil.

The technologies are tools.
They are power.

What you do with the power
determines if the result

is something that we applaud
or something that we deplore.

But it's not the tool
that determines the end point.

It's the user.

Now here are 23 representing
mother's chromosomes,

23 for father's.

Now we put them together.

-Our way of determining

the inheritance
of the next generation

is a lottery.

And it's a perfectly
good argument to say,

"I would rather determine it

than take a lottery."

Well, I think the right way
to say it is that

sex is for recreation

and science is for procreation.

50 years from now,
people may say, like,

"I can't believe
those barbaric people

in the early 21st century,

they were having kids this crazy, old-fashioned way.

They were just, like,
rolling the dice

with their kids' lives."

We've gone through
in vitro fertilization.

We've harvested the eggs.

It's not uncommon to produce

multiple viable embryos.

Which one do you choose?

One possibility is, "Yeah,
just--we'll just roll the dice.

We'll just--
I'll just point at one."

Another option would be

I run some
fancy genetic tests.

-Pre-implantation
genetic diagnosis

is the process of doing
genetic tests on an embryo.

When I talk
to most people about it,

they think
it's science fiction,

but it was first used
clinically in 1990.

With today's technology,
you've been limited

to looking at only
a handful of traits.

But soon, genome sequencing
will become cheap enough,

easy enough,
and accurate enough

that you'll be able
to learn everything

genetics can tell you.

-In the future,
let's imagine that CRISPR

gets really, really good.

Maybe you don't need
to produce lots of embryos.

Maybe you just produce one,

but you can make
whatever edits you want to it.

-So the carrier screening

that I was
talking about earlier

tends to focus on disorders
that show up early.

Everyone wants to have
a healthy, perfect baby.

I think that's
a universal truth.

You know,
"How can I make sure

"that my child
will be healthy?

"How can I make sure that,
you know,

"they're gonna have
some of these positive traits,

that they're gonna do well,
they're gonna learn well?"

Looking at this family history,
certainly I...

The opinion is that
information is good,

and almost everyone that talks
to me wants more information

and even wants more--
like, we'll give them

a whole bunch of information,
and they even want more.

-I know my grandmother
also had two...

-I actually first heard
about genetic counseling

from my mother.

Hemophilia A is the condition
that runs in my family.

It's a genetic
bleeding disorder.

There is a gene
on the X chromosome.

It encodes for a protein
called factor VIII.

When factor VIII
isn't working,

you can have a bleed
that will lead to death.

If I decide to have
children naturally

without
reproductive technology,

I am putting
that child at 25% risk

to have a really
severe disorder.

That responsibility
feels like it's on me.

It takes it from the universe's
decision to my decision.

Today, I'm unusual
because I know that

I'm a carrier of
a genetic condition,

but soon, everyone will know

genetic information
about themselves.

-What about the cost of it?

In the short term, there's
a disturbing possibility

that people with means

will be availing themselves
of this technology,

and people who don't
have those means will not.

So I kind of hope for a future

where government makes it
free for everybody.

You would have a generally
healthier population,

maybe longer lived population
on average,

maybe slightly smarter
population on average.

So if you have a smaller
fraction of your population

with Down syndrome,

the average intelligence
is a little bit higher,

and, you know,

society might run
a little bit more efficiently

if people are
a little bit smarter.

What is the bearing
of the laws of heredity

upon human affairs?

Eugenics provides the answer,
so far as this is known.

Eugenics seeks to apply
the known laws of heredity

so as to prevent
the degeneration of the race

and improve
its inborn qualities.

Well,
the concept of eugenics,

if you--if you go way back,

it really just means
good genes.

The idea is that the human
race could improve itself.

-It was, of course, hijacked,

and when people today
talk about eugenics,

they think specifically of
the Nazis of Nazi Germany,

of compulsory sterilization,
where, by force,

people were compelled
to be sterilized or killed

because the state
didn't like their genes.

There was shock last month
over the revelation

that the state of Virginia
sterilized thousands of persons

between 1922 and '72

in a program aimed at ridding
the state of so-called misfits.

What we're talking about here

where we're being paid
to do these genetic tests

by loving parents who want
to have a healthy child,

to equate that with Nazism is,

I think, just--not just stupid
but actually insane.

I've taken the liberty
of eradicating

any potentially
prejudicial conditions:

alcoholism and addictive
susceptibility,

propensity for violence,
obesity, et cetera.

We didn't want--
I-I mean, diseases, yes,

-but, uh...
-Right, we were just wondering

if--if it's good to just leave
a few things to chance.

You want to give your child
the best possible start.

Now, keep in mind, this child
is still you,

simply the best of you.

-My greatest fear in life,
honestly,

I--my two greatest fears,
going back to me

wanting to be a mom
at the age of five,

my first greatest fear is that
I wouldn't be able

to have a child,
and my second greatest fear

is that something would
be wrong with my child.

Okay, good job.
Not too much water.

Oh, careful, sweetie.

-With Ruthie,
I started seeing that

she kind of wasn't tracking.

When I would feed her,

her eyes would
slide back and forth.

Hi.

And then one day I went
to my friend's house,

and her baby looked me
right in the eyes

and I came home to Ethan
and I said,

"There's something wrong."

-We did genetic testing.

She inherited one mutated copy of this OCA2 gene from me

and one from Palmer.

I don't think I even
really understood

that people with albinism
had such impairment

of their vision.

-It's kind of like wrapping
Saran Wrap over your eyes

with Vaseline,
very, very hard for her to see.

Hi.

Now I just, like,
wanted to protect her.

Like, this isn't true.
This isn't happening.

It was horrible...

It was bad.

One, two, three, four.

Okay, where is he?
Where is he?

Whoa.

Hi.

She was really easy and happy.

-Whoo!

-And early on, I think
we wondered if she was

sort of, I don't know,

protected by the fact that
she couldn't see a lot.

Look, I have a flashlight!

-The world wasn't
as noisy to her.

-Blue.
-Light it. Light it.

-She was smart
and talkative.

Come here, Yoda.

-Super curious.

Oops...

-You don't know
what you don't know.

You don't know that even though
it's going to be different

than what you thought,
you don't know, you know,

maybe how much better
that's going to be.

I want to be a professional
basketball player,

but I don't think
that's gonna happen...

Can I hold him?

"Mission is simply one..."

-Well, I mean,
I've known about CRISPR

from the perspective
of being a doctor

probably since
the first publications

in whatever it was, 2012.

Oh, they come
to teach the natives.

-It really didn't intersect with our own world with Ruthie

until probably about
a year and a half ago

when I read something
on Twitter.

A scientist who I respect
a lot said he thought that

in one or two generations that all children would be born

with all of these genetic
abnormalities edited out.

-I know people
who have children

who have really
debilitating diseases

that make
their children suffer,

make their family suffer a lot,

so I totally understand

that desire to change that,

but the rest of it
scares me to death.

I don't know where
you draw the line

between not having albinism

and deciding your kid needs
to be an extra foot taller

so they can be a good oarsman
and go to Yale.

You know, where--
where is that line?

Who's going to draw that?

We're maybe a society
who is afraid of things

that are different or afraid
of people who are different,

afraid of people
who have needs.

I worry that when we're

manipulating
future generations,

those opinions are
going to be passed on.

-You know, we as a society
may think

that doing better on the SATs
is better than doing worse.

Being taller, being handsomer,
being more creative,

being more courageous,

those are traits that we would
want to potentially select for.

Should we go there?

Is there an inevitability
to going there?

You know, sometimes,
I'm invited to give a talk on,

like, kind of
futuristic science things,

and I've had tall, blonde

trophy wives come up to me

after the talk and say,
"Wow, that was incredible.

That was an incredibly
interesting talk,

but don't you think there's
a problem with all this?

Won't every parent
just select their kids

to be tall and blonde?"

The geeks all come up to me
and say, "Isn't this dangerous,

'cause all the parents
are gonna select

for the smartest kid
they can possibly get,"

'cause that's what
the geeks think is cool.

You know, probably if you were
talking to some NFL coaches,

they'd say,
"Oh, what--everyone's gonna--

everyone's gonna select
their kid to be 6'5"

and run a 4.2 40,"
you know?

So, um,

there will be a wide range
of what people think

is the right thing to
select for or engineer for,

and, actually, there's nothing
wrong with that, right?

Let a million flowers bloom.

On this estate
30 miles north of San Diego

is housed a sperm bank said
to be made up exclusively

of donations by Nobel
Prize-winning scientists.

The bank's founder will
consider for fertilization

only women
of high intelligence.

You don't know about
the Nobel sperm bank?

-Businessman inventor
Robert Graham

adds liquid nitrogen
once a week

to a lead-shielded
sperm repository

in an underground concrete
bunker in his backyard.

The more good genes
in the human gene pool,

the more good individuals
will come out of it.

We aren't even thinking
in terms of the super race.

-The so-called
genius sperm bank,

a sperm bank to provide women, for free,

with donor semen from men
that they viewed as geniuses.

We utilize
sources such as this:

"Who's Who
of Emerging Leaders."

-Very few women
actually went ahead

and took advantage
of this offer

to be given
superior sperm for free.

I did a tour of sperm banks
for the U.S. Congress.

I think I'm the only person
who's ever gone

on a congressionally financed
tour of California sperm banks.

Despite the fact that
the donors are described

taller, skinnier, you know,
better-looking or not,

people tended to pick somebody
who looked like their partner,

no matter how imperfect,

because the emotional
importance of the connection

outweighed any notion of

improvability
or perfectibility.

If I were trying
to have a child

and my partner was
light-skinned, short,

with eczema, I would
have had a child with a guy

who was light-skinned,
short, and prone to eczema.

-But what if you could
take that guy's sperm

and edit those
specific things out?

Could I change his sperm

so it's still him
but a better him?

-Exactly, yeah.
-Right?

Maybe, but every change
does come with risks

that you'll make changes
you didn't intend,

so I think it'd be
a long, long time

before you would
take that risk for anything

other than something
that was pretty significant.

But I might want
to take advantage

of editing something out
that would give my kid

a very strong chance
of developing a severe cancer,

even if it's 40 years
in the future.

Yeah.

So maybe that will happen.

This committee's gonna be
looking at both somatic

and germ line applications
of gene editing.

The committee
that I co-chaired

for the National Academy
of Sciences,

we were asked to look deeply
at whether or not

there was something
intrinsically unethical

about manipulating genes in a way that makes them heritable.

Significant degree
of uncertainty.

This should be
the goal of society,

to promote
a better life for all

and to ensure that
everybody can live a life

in dignity and freedom.

Can this be achieved
by germ line gene editing?

My view is no.

-The American
Medical Association,

bunch of European countries,
you know,

any number of organizations
all had positions,

like meddling in the germ line would be wrong.

It would be unethical.

But they all said those things

at a time when it couldn't be
done, so it was easy to say.

It was a gimme, right?

And then as soon as it comes
that you can do it,

then the positions change.

-Huntington's lurks in our DNA
like a time bomb.

It would really eliminate
a scourge in the world,

so I would say go for it.

-At the big
National Academy meeting,

there was not a good
representation of patients,

but the few who did speak
were definitely in favor.

I say, yes,
it is worth pursuing

in a safe and rational manner.

Definitely. Let's go.

Anything that will stop
my child from suffering,

I'm for.

You know, draw this
ethical line wherever you want,

but don't draw it
in front of my disease.

He was six days old.

-I remember one woman
told a story about a child

that she had and died
of an inheritable disease.

He had seizures every day.

We donated his body
for research.

If we have...

The skills and the knowledge

to fix these diseases,
then freaking do it.

The statement of task
demanded that we try to follow

the evidence
and follow the logic,

not that
we follow the politics.

We said, "We conclude it is not intrinsically evil."

It is, what we called
"ethically defensible,"

but we understood that this
was now a break from the past

in the thinking
on this topic, yes.

In Genesis 1,

we discovered the concept
of the Imago Dei,

being in the image
and likeness of God.

What does that mean
for this science

where we have the capacity
to edit in some things,

perhaps,
that we think are important?

Are we playing God?

-The balance of nature
is built of a series

of interrelationships
between living things

and between living things
and their environment.

Now, to these people,
apparently,

the balance of nature
was something that was

repealed as soon as
man came on the scene.

The babies that came out
of that are now adults,

and the adults are having
their own babies,

so it seems like
making that many edits

is completely compatible

with a happy, healthy pig.

I tell people they'll be

visually underwhelmed
by my lab.

It's just a bunch
of small rooms

with usually
very few people in them.

But in terms of what I see,

it's very exciting...

I've never really felt
that "mad scientist"

was realistic for
anybody that I knew,

including myself.

My lab has been accused
of taking science fiction

and turning it
into science fact.

I consider that
very high praise.

But turning science fiction
into science fact is not mad.

It actually can be
quite useful.

Aging reversal is
the term that I prefer.

You know, I'm 63 years old.

I feel like I just barely got
trained to do my job last year,

and so now you're gonna
pull the plug and recycle me?

That doesn't make sense.

We need to be cautious
in that, you know,

there's a--there's this
whole population problem,

so we could do that if we have
a place to put all those people.

Almost everything we do,

people just think
this is goofy,

this is not feasible,
it's science fiction.

But I think, originally,
people thought that

sequencing human genomes
inexpensively was a pipe dream.

-I can't not ask you
about mammoths

because there's a bunch
of them behind you.

Yeah, that should be up at
the top of the list of things

that seem quixotic
or misguided.

So in the Mammoth Project,

we read the ancient DNA,

decide which genes
we're going to resurrect,

put those into
the Asian elephant's cells,

and then we're
developing technology

that is not yet working
to make--

take those embryos
all the way to term.

Then we scale that up to
make a herd of these things,

maybe 80,000 of them,
to repopulate the tundra.

-Don't you see the danger,

John, inherent in what
you're doing here?

Genetic power is the
most awesome force

the planet's ever seen,
but you wield it

like a kid that's
found his dad's gun.

I don't think you're
giving us our due credit.

Our scientists have done things

which nobody's
ever done before.

Yeah, yeah,
but your scientists

were so preoccupied with
whether or not they could

they didn't stop to think
if they should.

Well,

I often try to avoid
talking about "Jurassic Park,"

but I'll--I'll give you this.

You know, "Jurassic Park"
was about hubris.

What species is this?

Uh, it's a velociraptor.

It's just the opposite

of what scientists
like George Church

and others that we work
with are thinking about.

When people say,
"Aren't you playing God?"

my real reaction is,

nobody is playing
in this field.

Nobody is toying with it

just to see if it can happen.

You know,
in order to even fathom

bringing back
an extinct species,

there's no end of engineering
that has to happen,

and it is all novel,
important, new science

that can be used
to protect any species,

endangered as well as extinct.

Once you realize the magnitude

of humans' impact
on the environment,

you know,
it's hard for me to say

that we can't
try to correct it.

We can't have
our head in the sand.

We have a responsibility
to use our human ingenuity

and our human skills
and our wherewithal.

Sometimes it's
leaving nature alone,

and sometimes it might be
intervening.

So the gene
we've edited controls

how the pores on the underside
of the leaves open and close.

In the nonedited plant,
these stomata or pores

will stay open during
the hot, dry conditions.

Water is lost, and then
these leaves lose water.

They wilt, and they roll.

In the edited plant,
those stomata pores

close sooner
under dry conditions

and the water is retained
inside the plant.

-We have been messing
with nature

ever since we came out
of the trees.

Most of the lifeforms we eat
are things we've made.

Corn used to be a grass.

Tomatoes used to be

tiny little berries
that were bitter.

Geneticists changed that.

Now, we didn't call them
geneticists.

We called them farmers.

-Do you think among these
people there was anyone

that would be fair to call
a scientist?

-Well, that's a really
interesting question.

I think there's lots
of different types

of scientists
that were involved.

The first people
who invented pottery

were really chemists,
in a way.

And certainly the people who
were inventing agriculture

and controlling plants
and animals,

they were biologists, you know,
botanists and biologists,

in our sense.

You know, you can see people
trying things out.

What is the best way
to grind grain

and how do you make bread?

You know,
that was invented here.

To work that out is really not
straightforward.

In this period of time,
something more modern-like

in terms of our relationship
with nature

was beginning to emerge.

As far as we understand it,
hunter-gatherers

had a relationship
of equality with nature

and had to look after nature,
and if you hunted an animal,

you would have to
give a gift to nature

to thank it for the animal
that you'd been given.

And then as people started

domesticating
plants and animals,

they started having
a new relationship

where they were dominating

and controlling
the natural world...

That made it something
that you could transform.

We definitely see

great advantages
in genetic engineering,

as agriculture, you know,
was a great advance.

Certainly it's the building
block of civilization

as we understand it.

But it definitely comes
with its negatives.

You could say that
the long-term consequences

were pollution
and environment degradation

and so on and so forth,

but you would have had
to be very farseeing,

you know,
9,000 years ago to realize that

that was what was gonna happen.

-These things
creep in slowly.

It's not like everybody
was hunting and gathering

and then next year,
somebody said,

"Oh, let's farm," right?

It happened slowly
and so it is disruptive

but it creeps up on people.

You don't realize
it's disruptive

until you look backward.

Often you don't realize

that you're in the middle
of a revolution until

after the revolution
has occurred.

All right, so I don't know
where we are right now.

It'll be interesting to see.

I hope I live long enough
to see it.

Do you think you want
to have kids?

I have too many siblings
for that.

The answer's probably
gonna change,

but for now, probably not, no.

-I'm not crazy.

They're saying
maybe one day with CRISPR,

they could go in and change

the gene in the embryo

so that the kid,
when it's born,

doesn't have sickle cell.

Hmm.

I guess that's kind of cool,
that they're thinking

that it can do
that in the future,

but I think that would be

up to the kid later.

What do you mean?

There's a lot of things that
I learned having sickle cell

just because I had it.

I learned patience
with everyone.

I learned, uh,

just to be positive.

So you don't wish that
you never had it?

I don't wish that
I never had it, no.

I don't think I'd be me
if I didn't have sickle cell.

-Sickle cell's
a really interesting,

unusual genetic disease.

If you've got two copies
of the sickle gene,

you're really sick,
and without modern medicine,

you die young.

If you've got two copies
of the normal gene,

you don't get
sickle cell at all.

It turns out, though,
that if you've got

one sickle gene
and one nonsickle gene,

you make cells
that are somewhat sickle?

You're not sick,

but the organism
that causes malaria

doesn't like
those red blood cells.

Having a sickle gene
is protective against

getting severe malaria,

so in the environment
where there's lots of malaria,

it's better to be
sickle cell trait

than not to be
sickle cell trait.

-And that's why you see
sickle cell anemia

in sub-Saharan Africa,

but you also see it
in the Mediterranean,

in Greece, and in Sardinia.

It's because they had
mosquitoes and malaria.

The relationship between
our genes and our environment

is incredibly complex.

"Thanks, little brothers..."

-And we don't
understand that.

-I think we have
to have humility.

Nature is one of the greatest
inventors of all time.

What we can do is a very, very

insignificant fraction of what
nature has already done.

Nature invented CRISPR.

-So now we're mixing
the cells with the CRISPR.

That's beautiful.

Once it's into the cell,

that starts
the editing process.

We can't see that.
We just know it happens.

-I don't know how, out of all
the genes that you have,

that it targets the one
that's doing sickle cell

and not the thing
that's making you grow hair.

Oh.

But it does, apparently.

Like, that's cool...

You have to appreciate
that this is a technology

that's only about
five years old,

but it's been deployed
incredibly rapidly.

We've never had
the ability to change

the fundamental
chemical nature

of who we are
in this way, right?

And now we do,
and what do we do with that?

It does make us
really think deeply

about what it means
to be human.

What do we value
about human society?

And I know for myself...

-The things that
make us most human

are some of the most
genetically complex,

which is kind of a relief.

Creativity...

-Emotionality.

Love.

Now, I want to be clear:

they all have
a biological basis.

They are all
written in our DNA.

But we are a very, very,
very long way away

from being able
to edit the person.

-You think that day
will come?

-I do,

but I'm hopeful that
we will mature as a species

before we get this incredible
technology to play with

for our own detriment.

I am hopeful for that, yes.

Is that hope based in fact?

We'll see.

How might we like
to change our genes?

Perhaps we would like to alter

the uneasy balance
of our emotions.

Could we be less warlike,

more self-confident,
more serene?

Perhaps.

-Ours is,
whether we like it or not,

an age of transition.

After 2 billion years,

this is, in a sense,
the end of the beginning.