All language subtitles for PBS.NOVA.Wonders.Series.1.Part.5.Can.We.Make.Life.720p.HDTV.x264.AAC.MVGroup.org.eng

you wonder aboutut?

MAN:
The unknown.

What our place
in the universe is.

Artificial intelligence.

Hello.

Look at this,
what's this?

Animals.

An egg.

Your brain.

RANA EL KALIOUBY:
Life on a faraway planet.

WILLIAMS:
"NOVA Wonders"-- investigating
the biggest mysteries.

We have no idea
what's going on there.

These planets in the middle

we think are
in the habitable zone.

WILLIAMS:
And making incredible
discoveries.

WOMAN:
Trying to understand

their behavior, their life,
everything that goes on here.

MAN:
Building an artificial
intelligence

is going to be the crowning
achievement of humanity.

WILLIAMS:
We're three scientists

exploring the frontiers
of human knowledge.

ANDRÉ FENTON:
I'm a neuroscientist

and I study
the biology of memory.

EL KALIOUBY:
I'm a computer scientist

and I build technology

that can read human emotions.

WILLIAMS:
And I'm a mathematician,

using big data to understand
our modern world.

And we're tacking
the biggest questions...

Dark energy?
ALL: Dark energy?

WILLIAMS:
Of life...

DAVID PRIDE:
There's all of these microbes,

and we just don't know
what they are.

WILLIAMS:
And the cosmos.

♪ ♪

WILLIAMS:
On this episode,

DNA is really just a chemical.

WILLIAMS:
We're rewriting the code of life
like never before.

DREW ENDY:
There's enough DNA

to make 30 copies
of every human genome

on the planet.

GEORGE CHURCH:
You can change every species

to almost anything you want.

WILLIAMS:
Can this new genetic power
save lives?

Or even bring extinct creatures
back from the dead?

BETH SHAPIRO:
Could we bring a mammoth
back to life?

(roaring)

WILLIAMS:
It's a revolution in biology.

WOMAN:
This is rapid
man-made evolution.

WILLIAMS:
"NOVA Wonders"--
"Can We Make Life?"

(babies crying)

IAMS:
The earth is brimming

with an unimaginable
variety of life,

a multitude of creatures

connected and intertwined
in countless ways.

They've evolved over
a billion years

driven by a very simple code.

EL KALIOUBY:
For decades,

scientists have been
trying to master

this chemical cipher
that we call DNA.

WILLIAMS:
Now, suddenly,

new tools
are allowing researchers

to manipulate the code of life

with incredible precision.

How powerful is this?

Could we change and mold life
at our command?

Could we bring extinct creatures
back from the dead?

(woolly mammoth growling,
roaring)

How much power
do we really have over life?

(giggles)

And are we ready
to use it wisely?

I'm André Fenton.

I'm Rana el Kaliouby.

I'm Talithia Williams.

And in this episode,
"NOVA Wonders"--

(tiger growls)

"Can We Make Life?"

♪ ♪

(crying)

15,000 years ago,

the biggest thing on four legs

was this guy-- the mammoth.

(mammoth growling)

These eight-ton giants

threw their weight around,
from the steppes of Europe

to the plains of North America,

until they vanished
from the face of the earth.

SHAPIRO:
From the paleontological record,

the best guess is that
there were many mammoths,

potentially hundreds
of thousands,

even to millions of mammoths.

WILLIAMS:
Evolutionary biologist
Beth Shapiro

deciphers the DNA--

the genetic code--
of ancient animals,

like the Ice Age mammoths
discovered here

in Hot Springs, South Dakota.

It's a absolutely unique site,
really amazing.

This is a ancient sinkhole

where lots of mammoths

would have wandered up
into a lake to have a drink

and once got stuck,
not been able to get out.

There are about 60 mammoths
that are in this site

in a pretty tightly condensed

little geographic area.

WILLIAMS:
These animals died at least
26,000 years ago,

before people
came to North America.

When human hunters
did show up,

mammoths wouldn't
stand a chance.

SHAPIRO:
People might have been

that proverbial straw that
breaks the camel's back.

These animals were in trouble

because the climate
was changing,

because there wasn't enough
habitat available to them,

just not enough to eat.

And then just at that really
worst moment, people turned up.

WILLIAMS:
Pretty soon, all the mammoths,

including the iconic
woolly mammoth

that loved colder climates,

would go extinct,
gone forever.

Or are they?

♪ ♪

If George Church has his way,

he will bring
the woolly mammoth

back from the dead
to roam the earth once again.

Kind of tall and woolly
like a mammoth himself,

George is one of the world's

most inventive
genetic scientists.

He once coded
his latest book in DNA

and brought it
on this piece of paper

to the Stephen Colbert show.

They took the book,
including the photographs...

Yes?

Zeroes and ones-- converted
to A, C, Gs and Ts.

Which is
the code of DNA,

Put a little drop that
contains some DNA in there.

That's right.

So this piece
of paper right there

contains 20 million
copies of this book.

That's right.

(laughter)

Well, Dr. George Church...

WILLIAMS:
But can this genetic magician

possibly resurrect
a long-dead woolly mammoth?

CHURCH:
Every species on the planet

comes from a cell with a genome,
and that means

you can change it
to almost anything you want.

WILLIAMS:
George is like

the fictional scientists
from "Jurassic Park."

They "de-extincted" dinosaurs

by implanting their DNA
into ostrich eggs.

Come on, little one,
come on...

WILLIAMS:
The baby dinosaurs that hatched
were cute at first,

and then they weren't.

(roaring)

Despite the movie's
dubious science,

George's de-extinction idea
is not very different,

And, fortunately,
his creatures are vegetarians.

George's real life plan
is to take mammoth genes

decoded from ancient remains

and implant them into the embryo
of a live Asian elephant.

CHURCH:
They're very closely related
to the mammoths.

Even though they
don't look that way,

they're genetically
very similar.

WILLIAMS:
And then he hopes

the Asian elephant's new baby
will come out woolier

and more mammoth-like
than this one.

At least, that's the plan.

Why would anyone think
they could reverse evolution

and bring an extinct creature
back to life?

(mammoth growls)

The answer lies deep inside

almost every living cell
in your body--

in your DNA.

One of the wonders of DNA
is how simple it is--

a double string
made of four chemicals

usually known by their initials:

A, T, C, and G.

Strings of these letters
form genes,

the coded instructions
that tell a cell

to build specific proteins.

Arrange the letters one way,
and you'll get keratin.

It's not just a hair treatment.

It's the main protein making up
our hair,

skin, and fingernails.

Switch the order of the letters,
and you could get ricin,

a protein made in the seeds
of a castor oil plant,

and to a human,
extremely poisonous.

DNA and the order
of its letters

are the instructions
that turn a fertilized egg

into a flounder,
a frog, or a fly.

The quest to use DNA
to control and manipulate life

began over 40 years ago

on creatures a whole lot
smaller than elephants

in an attempt
to treat a deadly disease.

In the 1970s, Herb Boyer

and Stanley Cohen
began using new DNA technology

to see if they could coax

common E. coli bacteria

into producing
human insulin protein.

People with diabetes
don't produce enough insulin

to help their bodies absorb
sugar and other nutrients

and will die
without injecting it.

Before the 1970s,
insulin was extracted

from cattle and pigs.

Unfortunately, insulin from
these animal sources

sometimes caused
severe allergic reactions.

But the Boyer team
was about to change that.

Their idea was to engineer
E. coli bacteria

by first cutting its
genetic material with enzymes

and then inserting
a synthetic version

of the human insulin-coding gene
into the gap.

Amazingly,
the altered bacteria

not only copied the human gene
whenever it divided,

they produced human insulin--

a lifesaver
for diabetics ever since.

ARTHUR CAPLAN:
I found it amazing

as a non-biologist that
you could trick a tiny microbe

into making something
that it doesn't naturally make

and reorient it
to make something that we want.

WILLIAMS:
Here in a biochemical lab
at M.I.T....

We actually should
go back and reduce...

WILLIAMS:
Kristala Jones-Prather

leads a team
that is also altering

the genes of microbes

to make proteins and chemicals
that are useful to us.

KRISTALA JONES-PRATHER:
You can actually look at

those individual cells
as little factories.

If you shrunk yourself down
to the size of a molecule,

you would just see lots and lots
of chemical reactions.

WILLIAMS:
But you need trillions
of organisms to produce

enough of these tiny chemicals
to be useful commercially.

So today, biotech companies

use giant fermenters
filled with microorganisms

to pump out
a slew of bio products,

all thanks to our ability
to manipulate DNA.

JONES-PRATHER:
The key observation

that really fueled
the entire biotech industry

was recognizing that DNA
is really just a chemical.

And the structure
is what matters,

and so it doesn't
matter if that DNA

came from a horse
or a mouse

or something you dug
off the bottom of your shoe,

the DNA is still just the DNA.

WILLIAMS:
Today, production facilities

not only make bio-products,

they make synthetic DNA
and can even process

the four basic chemicals

into an exact genetic sequence
you can order online.

You'd go to a website
for a company,

a DNA synthesis company,

and you'd submit to that website
this...

the sequence
of DNA you want.

NILLI OSTROV:
We can take the entire
gene sequence and copy,

and then put it
in an order sheet.

You can say T-A-A-T-A-C-G-A

C-T-C-A-C-T-A-T
A-G-G-G-A-G-A.

Give them a credit card number.

Order this DNA.

They'll print that DNA

and put it in an envelope
and mail it to you.

OSTROV:
We get the gene back

in a tube in about
a day or two.

It's DNA that is
made from scratch

by the machine.

This is a bottle
is full of the letter A.

Not the letter in the alphabet,
but the base of DNA.

There's ten grams
of stuff in here,

and it costs
about $250 for the bottle.

This is enough material
to make approximately 30 copies

of every human genome
on the planet.

EL KALIOUBY:
So think about what this means.

All the convenience
of online shopping.

Just like I can
custom order a car.

Do I want the silver?

Or the red?

Or build my own pizza.

Extra cheese...

Mushrooms.

Definitely not anchovies.

Perfect.

Along with all the stuff
you can buy online,

amazingly, you can
custom order actual DNA.

So now, with a credit card
and a computer,

not only can you build
your own jeans,

you can build your own genes.

WILLIAMS:
Our ability to build
and manipulate

the genes that control life

means we now have
the power to remake life.

And this young scientist
is trying to prove it

with one of the most
daring genetic experiments

on the planet.

Kevin Esvelt wants
to stop a growing menace

on Nantucket
and Martha's Vineyard,

beautiful island communities
off the coast of Massachusetts.

(gulls crying)

On the surface,
you wouldn't notice

anything especially scary
on Nantucket.

Tourists flock here,

and others live year-round

to enjoy the beauty, fun,

and comforts of island life.

What they don't come for,

but often get anyway,
is Lyme disease.

Devin, why don't
you come on down.

WILLIAMS:
Dr. Timothy Lepore

is a 30-year veteran

of treating Lyme disease
on Nantucket.

In the spring and summer
on Nantucket, if I see

somebody like that,
that's Lyme disease.

WILLIAMS:
Lyme is a bacterial infection

that often starts with a rash

where a person has been bitten
by an infected tick.

You get rashes...

WILLIAMS:
Most people can be cured

with antibiotics
that eliminate the rash,

fever, and joint pain
within a few days.

LEPORE:
When we treated you,
you got better.

Yep.

And then the next day,
it had the ring around it.

WILLIAMS:
But not everyone
recovers so quickly.

LEPORE:
People that have had

long-standing Lyme disease
may have some persistent issues.

If you wait, you can
have delayed symptoms

like complete heart block,

where your heart starts beating
20 to 30 times a minute,

or you can have a facial palsy

where it looks like one side
of your face is paralyzed.

Come on in.

KEVIN ESVELT:
Lyme is the single most common

infectious vector-borne disease
in the United States.

It's way more common than Zika.

It's way more common than
West Nile, anything like that.

The areas of Nantucket
and Martha's Vineyard

are number two and number three
when it comes to incidence

of tick-borne disease
in the United States.

WILLIAMS:
Kevin Esvelt is on a mission

to eradicate Lyme disease.

And for him,
these Massachusetts islands

are the perfect places to start.

This pocket of dense vegetation
is typical of Nantucket

and the rest of the Northeast.

Try to find
an easy way out.

WILLIAMS:
Sam Telford
is working with Kevin.

An expert on ticks
and tick-borne diseases,

Sam's diving into this brush
because he knows it's literally

crawling with ticks
for him to study.

Dragging a white furry cloth,

Sam is hoping to catch ticks

that think the cloth
is an animal.

SAM TELFORD:
Ticks are what
we call ambush predators.

They sit there
on a blade of grass

and they've got
their front legs sticking out,

and then as you walk by,

they'll latch on to something
they think is furry.

There is one here.

WILLIAMS:
This is a tick
in an early stage,

when it's very tiny.

No one who gets
Lyme disease

recalls that they
were bitten by a tick

simply because
of their small size.

How on earth are you going
to see something that small?

WILLIAMS:
Humans get Lyme disease
from ticks.

But ticks are not born
with Lyme bacteria.

They get it by feeding on
this innocent-looking critter--

the white-footed mouse

that carries Lyme bacteria
in its blood.

And another innocent-looking
creature, the deer,

is a crucial link in the chain
of transmission to us.

Baby ticks will
often feed on mice

that are close to the ground.

This is when they get
the Lyme bacteria.

As the ticks grow,
they will feed

on other mice,
deer, or people,

passing the Lyme bacteria
with each bite.

But only people get the disease.

A single deer is like
an all-you-can-eat buffet.

They live in the woods

and can't easily
scratch ticks off.

So female ticks
become engorged,

drop off, lay eggs,
and the cycle starts again.

ESVELT:
The typical deer has several
thousand ticks attached to it.

And the females will each
lay several thousand eggs.

So when you see a deer wandering
around through the woods,

you can think,
"That is the walking equivalent

of a million ticks
in the next generation."

WILLIAMS:
But people adore seeing deer

and don't want them removed.

Could it be
childhood memories of Bambi?

ESVELT:
It is Bambi.
(laughs)

We like seeing deer.

So, because there are
so many more deer

than there have ever
been before, historically,

there are many more ticks than
there have ever been before.

WILLIAMS:
Now, deer shed ticks
in our lawn clippings,

garden plots,

recreation areas,

and if they carry
the Lyme bacteria,

they can give it to us.

Here on Nantucket,

40% of residents
have caught Lyme disease.

And it's not
the only tick-borne disease

they have to worry about.

TELFORD:
There's an infection
called Nantucket fever

or human babesiosis,

which was first identified
here in 1969.

It's a malaria-like infection
and it actually kills people.

WILLIAMS:
There are four serious
tick-carried diseases

on the island,

with Lyme by far
the most common.

But it's not
just these tiny islands.

Mice, deer, and ticks

have spread Lyme disease
throughout the northeast U.S.

Almost anyone in the region
who ventures outdoors--

not just into the woods,
but in suburbs, too--

is putting themselves at risk.

(exclaims)

WILLIAMS:
For Kevin Esvelt,

it's a risk people
should not have to take,

especially with their kids.

ESVELT:
I'm from the west coast,

and there we have ticks,
but they're so rare

that I spent my childhood
running around through the woods

and never once
got bitten by a tick,

not once.

Come on, down the slide.

Whoa!

ESVELT:
I have two kids.

It's just terrible that we have
to be wary of them

just running in the woods.

So, the notion that you can
wander out here

through some of the worst areas,

and end up with
lots of ticks on you is just...

well, it's frankly horrifying.

All right, so I have
40 traps out in this site.

WILLIAMS:
Kevin has a plan to
make the outdoors safe again.

The mice seem
to be wary today.

WILLIAMS:
He believes he can
get rid of Lyme disease

by genetically altering the
white-footed mice

that carry it.

And if that goes well,
he hopes to edit their DNA

so they could
resist ticks entirely.

Oh, looks like
we've got one

to take back.

ESVELT:
Enlisting mice

in the war against
tick-borne disease

would just be
an amazing proposition.

I'm counting
18 on the ears.

WILLIAMS:
The number of ticks
is astounding,

especially on its ears.

And if this mouse has
the Lyme bacteria, all the ticks

will become infected and
can transmit the disease to us.

Kevin's plan is to make the mice
resistant to Lyme bacteria

with the help
of genetic engineering's

most exciting
and powerful tool-- CRISPR.

CRISPR stands for clustered

regularly interspaced

short palindromic repeats.

(crowd groans)

That's why it's just called
"CRISPR."

First discovered in bacteria,

CRISPRs are like
bacterial immune systems.

They have two key parts--

a destroyer protein,
like one called Cas9,

and a piece of RNA
that matches viruses

that previously
infected the bacteria.

If the same virus were
to invade again,

the RNA would recognize
the invader's DNA,

attach itself to its old enemy,

and its Cas partner would slice
the virus's DNA, destroying it.

A few years ago,
some researchers realized

they could use CRISPR

to edit the genome
of any living organism.

Here's the idea.

Say I have a stretch of DNA,

maybe a part of a gene
I'd like to change.

If I know the sequence
of letters there,

I can build a CRISPR
that carries a matching code.

Once inside the cell,
CRISPR will scan the DNA

until it finds that exact spot.

And when it does,
it slices the DNA right there.

Now I have a broken gene,
but it turns out

I can insert a new sequence
into the gap,

and that makes CRISPR
potentially

an extremely powerful tool.

CRISPR Cas engineering
is much faster,

it's much less expensive,
and it's much easier to make

those changes you want to make.

The really
significant revolution

with CRIPSR Cas9 is that,

as far as I can tell,
it pretty much works

in any organism
that you try it in.

WILLIAMS:
And M.I.T.'s Kevin Esvelt

wants to use CRISPR
to change the DNA of mice

and make them immune
to Lyme bacteria.

ESVELT:
The original idea
that sparked this

whole process
was very simple.

Hey.
Hi.

Animals like us,
and also mice,

when we get sick with something,

our immune systems
evolve an antibody,

often lots and
lots of antibodies,

that are really, really good

at telling the immune system
"This is the enemy, kill it."

WILLIAMS:
But these antibodies do not
get passed on to our children.

So we need vaccines

to give us antibodies
against certain diseases.

But there is no
human Lyme vaccine.

And even if there
was one for mice,

he couldn't just
line them up for shots.

So instead, Kevin wants
to give them a genetic vaccine.

Here's how that would work.

First, Kevin,
with the help of Sam Telford,

infects mice in the lab
with Lyme bacteria.

These mice quickly develop

robust, Lyme-resistant
antibodies.

Next, the team
deciphers the genetic code

that can create
those antibodies.

They make this antibody gene
in the lab.

And inject it,
along with CRISPR genes,

into the developing sperm cells
of Sam's lab mice.

There, CRISPR would
clear the way

for the new gene to slide
into the mouse's genome.

Now, if an engineered male
mates with a wild female,

roughly 50% of their babies,
boys and girls,

will inherit
the Lyme-resistant gene

and begin spreading it
to future generations of mice.

That is, if Kevin's plan works.

(ship horn sounds)

But before he can even try,

he'll need
Nantucket residents to approve

the release of genetically
modified mice,

something many people here
worry might backfire

like the disastrous
cane toad experiment.

♪ ♪

Cane toads were introduced
to Australia in the 1930s

to help kill off
sugar cane beetles.

But instead, they became
a biological wrecking ball.

A foreign species
with no natural predators,

they quickly overran
the country.

Poisonous to animals,
they've killed

countless pets
and native species,

disrupted key parts of
the country's ecosystem,

and they are now almost
impossible to get rid of.

The mice used
in Kevin's experiment

will be native, not foreign.

But some people worry

that genetically
modifying animals

could spell trouble.

LEPORE:
If you fool with Mother Nature,

very often it doesn't
turn out well.

So are we going to have
mice the size

of boxer dogs, I don't know.

WILLIAMS:
As Kevin releases

a wild mouse caught earlier,
he hopes

that someday the little creature
jumping away

will be resistant
to Lyme disease.

But to get that far,
he will need

the island's complete trust.

And the jury is still out.

♪ ♪

Will people's fear
of genetic engineering

prevent Kevin from using
this controversial science?

ELEONORE PAUWELS:
You know, this is a technology

too powerful for humankind
to refuse.

It's going to help us transform

not only our bodies
and our genes,

but can give us a chance

to actually play a role
in our own evolution.

WILLIAMS:
George Church is certainly
playing with evolution

by attempting to
de-extinct a woolly mammoth.

(growling, trumpeting)

But why does this gene giant
even want to do this?

George is one of those people
in science

who is just larger than life.

He just wants to be doing
those most exciting projects

at the cutting edge
of whatever it is.

Wow, that is the coolest dry ice
I have ever seen.

WILLIAMS:
George's lab is renowned
for stretching the limits

of genetic engineering,

from experiments using pigs

to grow human organs
for transplantation,

to using bacterial DNA
to encode and store data

and even digitize movies.

But the woolly mammoth would be
his greatest accomplishment yet.

Seeing a real mammoth again
would be amazing.

Or what about sabre tooth
tigers,

or giant dodo birds,

even flocks
of passenger pigeons?

Bringing back extinct creatures
wouldn't just be cool,

we could see how these
magnificent animals once lived

and maybe find out
how to save today's creatures

from going extinct.

Which is exactly what
George Church wants to do

for the Asian elephant.

♪ ♪

WILLIAMS:
George's plan is to combine
the genes of a woolly mammoth

with those of Asian elephants

because making them mammoth-like
might save them.

Hunted for their tusks
and chased from farmlands,

Asian elephant numbers
are shrinking.

But George has
a possible solution.

If you gave them access

to one of the largest ecosystems
on the planet,

which is the arctic tundra

where their very close relatives
used to roam,

that would probably
save the species.

WILLIAMS:
There's plenty of open, fertile
space in the tundra,

but it's too cold
for warm-weather elephants

to survive here.

So George's resurrection plan

begins with genetically
winterizing Asian elephants

to become more like woolly
mammoths, who loved the cold.

The team first identifies the
specific genes in modern animals

that code for things
like fat or thick hair.

Then they look
for their genetic counterparts

in decoded mammoth genomes.

Once they identify the mammoth's
"cold" genes,

they make them synthetically,

and insert them
into living cells

taken from an Asian elephant
to see if they work.

BOBBY DHADWAR:
What we're seeing here
is green cells--

these are elephant cells

that we've introduced
mammoth DNA into.

The brighter the green
that we're seeing

means the more DNA has taken up.

WILLIAMS:
In the lab, they've edited
about 35 functioning

woolly mammoth genes
into the Asian elephant genome.

This is a good start for making
a semi woolly mammoth.

But it's the next step that will
be the most challenging.

SHAPIRO:
There is a huge difference
obviously

between a cell growing in a dish
in a lab

and a baby mammoth
wandering around.

How do I take that cell
and turn that into

an actual living, breathing
organism?

(elephant trumpets)

WILLIAMS:
They could try and fertilize
the egg cell

of a captive Asian elephant

with woolly mammoth genes.

But this is difficult.

SHAPIRO:
It's very hard for them
to get pregnant in captivity.

The pregnancies often
don't go to term.

And this is probably
has to do with

the psychology of being
in captivity.

WILLIAMS:
And performing such an operation

on an endangered species
like this

may simply be
too great a risk.

♪ ♪

So George is studying mammals
like the platypus

and spiny anteater,
whose babies develop

outside a mother's body
in an egg.

SHAPIRO:
Could he possibly engineer
a living mammoth this way?

(cracking)

Can you imagine a baby woolly
mammoth hatching out of an egg?

Really?

Not even George has figured out
how to do this.

And what would this
sort of mammoth be like?

(trumpets)

CAPLAN:
I think you're going to get
a creature

that's sort of a pseudo mammoth,

not quite the same makeup.

So I think you're going to get
a sort of echo of the animal

that once was but not a replica.

So even if we could
get to the point

where we could transform
this elephant

to a living, breathing
baby mammoth,

a question that I have really is
should we?

We know that elephants
are very social creatures.

They live in herds
interacting with each other.

Unless we can get this down
in such a way

that we can do

many different individuals
at a time,

you're still just going to have
one generation to start with,

and that just seems
kind of unfair.

WILLIAMS:
Although we may never see
a mammoth,

George's efforts to identify and
make more resilient animal genes

may have a hidden benefit.

SHAPIRO:
This technology,

the ability to take genes
from the past,

put them into species
that are alive today,

has tremendous potential

as a new tool for conservation.

Many of the endangered species
and populations

have very little
genetic diversity

and that means that they have
very little ability

to adapt to rapid
climate change,

or if a disease comes in,

and wipes out most of
the individuals who are there.

We can use this technology
to help species

that are on the brink
of extinction today.

But what about us?

We've known for decades
that mistakes in our own DNA--

sometimes just the switching
of a letter or two--

can lead
to life-threatening problems.

For example:
an "A" instead of a "T"

on just one of our genes
causes sickle cell disease,

a lifelong blood disorder.

So, is it possible
to harness new technologies

to rewrite our own genetic code?

Could we use this power
to save lives?

♪ ♪

Doctors and researchers
have been trying to do this

for decades,
but with limited success.

Dr. David Williams
of Boston Children's Hospital

has participated in several
gene therapy trials

that invariably ended
in disappointment.

DAVID WILLIAMS:
We saw a real need for this
technology to be developed.

People were then disappointed--
including scientists--

when the hype
didn't get realized.

To make matters worse, in 1999,
18-year-old Jesse Gelsinger

entered a trial
for a genetic liver condition.

He only had a mild form
of the disease.

But, tragically, the gene
therapy ended up killing him.

♪ ♪

This set the field back
enormously

and it's taken a long time
for the field to recover

from those setbacks.

CHRISTINE DUNCAN:
This is the family we just met
this morning.

He's seven years old,

but wasn't diagnosed
until August.

WILLIAMS:
Today, Dave Williams heads
a new gene therapy trial

that aims to cure a devastating
childhood disease...

So he's had febrile seizures
since he was eight months old.

WILLIAMS:
...a heartbreaking killer

called cerebral
adrenoleukodystrophy, or A.L.D.,

and the stakes
couldn't be higher.

♪ ♪

Brian Rojas and his mother
Lillianna

are just about finished
trimming their Christmas tree.

But Brian's brother Brandon
cannot join them.

Three years ago,
the two boys were inseparable;

their family full of love
and joy.

Are you ready?

WILLIAMS:
Now at age nine,
Brandon still gets the love,

but A.L.D. is devastating
his mind and body.

All right.

WILLIAMS:
He can do nothing
for himself anymore.

WILLIAMS:
Adrenoleukodystrophy

is a genetic disease,

and it's what we call X-linked,

which means it occurs
mostly in boys.

And the typical history
that we hear from families

is that they have
a perfectly terrific young boy

who, at the age of five or six,

suddenly begins to have
developmental problems.

LILLIANA ROJAS:
Brandon started with drooling,

and we thought that it was
because he lost his front tooth

and we didn't think
anything else of it.

And little by little
he started losing his vision.

DUNCAN:
They may have change
in their vision.

They may have change
in their hearing.

They have change
in their ability to communicate

or speak with the family.

And it all ends up ultimately

with complete devastation
and death.

WILLIAMS:
Dr. Christy Duncan has watched
the inexorable decline

of many A.L.D. boys

because of a mutation on a gene
called ABCD-1

that affects micro-glial cells
in the brain.

DUNCAN:
These are cells in the brain
that are responsible

for maintaining
a healthy environment

around some of the neurons.

And so what you'll see over time

is inflammatory lesions
in the brain.

WILLIAMS:
On MRIs we can see these lesions
rapidly increase over time

as the disease
destroys the brain.

Unless you know there is A.L.D.
in your family,

the disease comes
as a complete shock.

HEATHER COOKSON:
It's heartbreaking to find out
that, unknowingly,

I passed this gene

and, ultimately, disease
to my children.

Heather Cookson's son Jerry
is 12,

older brother Ricky, 14.

Ricky was eight
when persistent headaches

convinced Heather to insist
he get an MRI.

HEATHER:
They found a lesion in
Ricky's brain during that MRI.

We just thought
it was headaches.

Never thought it was going to be

a life-changing disease
that he was going to have.

WILLIAMS:
Children like and Ricky
can often be saved

with a blood stem cell
transplant.

These cells originate
in bone marrow

and can become
all blood cell types.

But why new blood cells
stop the progress of A.L.D.

in the brain
is somewhat mysterious.

DUNCAN:
This is a disease
of brain cells.

These are not the same cells

and so it can be hard
to understand

why on earth that works.

WILLIAMS:
For his transplant to work,

Ricky needs
a good genetic match--

like his little brother Jerry.

But Jerry also carried
the faulty gene,

so could not donate.

Fortunately, Ricky found
an unrelated matching donor

and after the transplant
and chemotherapy,

he is now doing fine.

But by the time Brandon Rojas
was diagnosed,

his A.L.D. had progressed
too far

to even try a transplant.

And the news hit hard.

LILLIAN:
I couldn't accept the fact

that they said there's no cure.

We...
I-I-I couldn't accept that.

♪ ♪

And that's when my whole world
just fell down

(voice breaking):
and I didn't know how to react.

DUNCAN:
It's terrible.
It's a tragedy.

And the only--
even if you can call it--

sort of bright spot
of that tragedy--

his younger brother Brian
was identified

because of the older brothers'
disease.

LILLIANA:
Say hi, Brian.

Hi.

Sí!

WILLIAMS:
It wasn't guaranteed
that having the bad gene

would give Brian the deadly form
of the disease.

But Lilliana was worried.

LILLIANA:
We were hoping he was fine.

We thought, you know,

"Please, God,
don't let him have the same."

"He became a hero,
Dr. Steven..."

WILLIAMS:
But about a year later,
a small lesion appeared

on Brian's MRI.

Worse, there were no
matching donors

for an immediate transplant

and his A.L.D.
was progressing by the day.

So when a new gene therapy trial
opened up,

Lilliana jumped
at the opportunity.

One of the things
that the doctor said was,

"We can save him."

Do you want to go up there?

WILLIAMS:
Heather Cookson also learned
that her younger son Jerry--

like his older brother Ricky--

had developed A.L.D.

Follow my finger
with your eyes.

HEATHER:
I got hit with a ton of bricks

after his MRI.

♪ ♪

WILLIAMS:
But Jerry would soon join
Brian Rojas,

and 15 other boys,

in a gene trial that could
save their lives

And Jerry Cookson
was up for the challenge.

Oh, here?

Therapy begins by collecting
stem cells from the boys' blood,

then taking them to a clean room

where the genetic engineering
begins.

The doctors need to insert

a healthy version of the gene

into the boys' stem cells.

To do this,
they rely on a virus

that's incredibly adept
at invading cells--

H.I.V.

The lethal virus
has been altered

so it can't make anyone sick.

But it's still able
to enter cells

and do what virus's always do--

insert its DNA
into the host cell.

Only this time,
the DNA carries the healthy gene

that will hopefully stop
the spread of A.L.D.

These viruses sort of say
to the cell,

"these are your genes,
you start producing proteins

based on my genetic makeup."

WILLIAMS:
Researchers have been editing
with viruses for decades,

and they're still relying on
them for human gene therapy

while the newer CRISPR editing
is being perfected.

As their cells
are being engineered,

the boys undergo
intense chemotherapy,

to make room
in their bone marrow

for their new stem cells
to grow.

Then, it's time for reinfusion,
and hope for success.

NURSE:
Nice job.

♪ ♪

JERRY:
I started chemotherapy,
ten days after that,

on May 19th
I got my cells back into me.

And it's really kind of
anticlimactic

when you think about it.

WILLIAMS:
But Jerry could not feel what
was going on inside his body.

The new stem cells multiplied

and began circulating
in his blood stream.

As they reached his brain, some
changed into new glial cells--

now with the healthy gene.

But would this be enough to stop
the progress of the disease?

(cheering)

After three months Jerry Cookson
was released from the hospital

and is showing
no A.L.D. symptoms.

♪ ♪

Of the 17 boys
who entered the trial,

15 completed the therapy
and so far all are doing fine.

JERRY:
So I think it's kind of cool

that I'm like one in
like 16 or 17 people

that did this treatment.

And it's a new treatment
that could change

a lot of other people's lives.

He has been stable,
he's in school,

he plays soccer, he is perfect.

WILLIAMS:
And for the therapy team,

this has been the experience
of a lifetime.

DUNCAN:
I truly feel so incredibly lucky

to be at this end of it.

We're finally able to take
the fruits of years and years

of people's work
and treat these boys.

They are going to school
and they are living proof

of what science can do
and it is really remarkable.

HEATHER:
We're extremely lucky.

There are some families
out there

that aren't as lucky
as our family.

BRIAN (off-screen):
He wore the black costume.

WILLIAMS:
For the Rojas family, the end
of the trial is bittersweet.

Since Brian received
gene therapy,

he is healthy and seems to be
headed for a normal life,

while his brother Brandon
is slipping away.

But to Lilliana,
Brandon is a hero.

LILLIANA:
Because of Brandon,

Brian was diagnosed early.

Brandon saved
his little brother.

WILLIAMS:
A new gene therapy
decades in the making

saved Brian Rojas.

Could this be a sign
we've turned the corner

on gene therapy cures?

WILLIAMS:
It is literally going to be
hundreds of diseases

that we'll now be able
to approach.

LILLIANA:
Very good, nice job.

WILLIAMS:
The future of genetic therapy
is actually here.

♪ ♪

WILLIAMS:
For anyone touched
by genetic disease,

new breakthroughs
could not come quickly enough.

And many hope
genetic engineering

could go even further.

But if we can fix mistakes
in someone's DNA,

could we do that
even before they were born?

(heartbeat murmuring)

We have the ability to alter
the DNA inside human embryos,

and in the germline cells
that make them.

The big question is-- should we?

And why does even talking
about this so controversial.

(giggling)

CAPLAN:
I think the driving fear
of the germ line engineering,

fixing things across
generations,

is the slippery slope.

A lot of people would say,
"Yeah, okay.

"You want to go out and fix
Tay-Sachs disease

"that kills people?

"Hooray.

"You want to fix deafness?

"You want to get rid
of short stature?

"Where does that all end?

"Aren't we going to wind up
doing things like,

'I want my kid to be stronger,
smarter, faster'?"

WILLIAMS:
In other words, editing embryos
not to cure a disease,

but to enhance abilities
and make designer babies.

♪ ♪

There's been
experimental efforts

at curing genetic diseases
in embryos.

But the fear this could lead
to designer babies is so strong,

most countries prohibit it
entirely.

And the U.S. government
won't fund it.

But are these fears justified?

SHOUKHRAT MITALIPOV:
The complexity of how to make
designer babies

is such a big deal

we don't even know what genes

or how many genes would make

a child taller or smarter.

CAPLAN:
It's one thing to say,
"I'm going to repair

a single error that causes
a particular genetic disease."

It's another thing to say,
"I gotta insert 500 genes

in order to make
your memory enhanced."

The whole thing is hard to do.

WILLIAMS:
But our genetic knowledge
is increasing

and it certainly seems possible
that one day we will be able

to design our babies.

CAPLAN:
In a competitive market society

you see people showing up
at IVF clinics saying,

"You know,
we're having trouble conceiving,

"but as long as I'm here,

"could I get a 6-foot-7
Ukrainian mathematician donor

"because that's what we wanted;
red-headed, is that possible?"

Down the road long term
are we going to see

enhancement or improvement
anyway?

Yes.

WILLIAMS:
But if we do go down this road,
where will it end?

MARCY DARNOVSKY:
You know, when we start

doing really biologically
radical things,

we could see some terrible
health consequences develop

when the child is two years old,
20 years old,

or when that child has children
of his or her own.

We just don't know

what the unintended consequences
might be.

And that anybody
who would be contemplating

using a technology like this

should really ask themselves
whether it's worth the risk.

♪ ♪

WILLIAMS:
The power of genetic engineering
to sculpt ourselves

and the natural world
does bring a burden of risk.

And although Kevin Esvelt
is confident his engineered mice

will only reduce Lyme disease,

and not bring harm
to Nantucket's ecosystem,

he also knows

that absolute certainty
and genetic engineering

do not go together.

ESVELT:
I worry every day

that I might be missing
something profound

about the consequences
of what we're developing.

WILLIAMS:
At a town hall meeting,
Kevin assures residents

he will be taking
a go-slow approach.

Frankly,
what we're talking about here

is altering
the shared environment.

♪ ♪

WILLIAMS:
And that he could halt the
experiment if problems appeared.

Most importantly,
they would determine

if the mice would ever
get released here.

To be clear, this project
will only move forwards

if the community supports it
at every step of the way.

WILLIAMS:
He tells them he would
first perform a field test

on an isolated island
to check that the new gene

is working and the altered mice
are causing no problems.

Only then would he propose
releasing them on Nantucket.

Once we have those, then...

WILLIAMS:
But for his new gene to spread

throughout the mouse population,

he would need to release

a lot of engineered mice.

It might mean releasing, say,
100,000 mice on Nantucket.

WILLIAMS:
It would take that many

to spread the Lyme-resistant
gene effectively.

What happens
to the actual population,

the mouse population itself?

I mean that's just going to keep
growing, and growing,

and growing.

TELFORD:
Actually, no...

WILLIAMS:
Although residents are concerned
by the numbers,

Sam Telford assures them
the mice population

will stay in check.

Something is out there
that's regulating them.

Disease is regulating them.

There's a mite, a mange mite
that is regulating them.

WILLIAMS:
But even one GMO mouse
is still alarming for some.

The is rapid, rapid,
man-made evolution.

Some people think that
genetically modified organisms

should never be done.

They think that people
like Kevin are playing God.

We don't know what effect
it's going to have

15 years, 20 years, 25 years
down the line.

WILLIAMS:
But Kevin's cautious,
open science approach

seems to be winning the day.

ESVELT:
If you were to run
these kinds of experiments

the way science
is traditionally done--

behind closed doors--

you'd be denying people
a voice in decisions

intended to eventually affect
them.

Devon, why don't you
come on down?

WILLIAMS:
Islanders have given Kevin the
go ahead to engineer the mice.

But with a Nantucket release
years away,

there are no hard choices
for them to make... yet.

So how we doing?

Still, residents here
are so fed up with Lyme disease,

if the field test does go well,

Kevin's grand experiment
could go all the way.

And if he stops Lyme here,

what diseases would he
target next?

Could Kevin and other
researchers one day engineer

mosquitos to halt the spread
of deadly malaria?

ESVELT:
If we could just go in there
and change the mosquitoes

so they can't transmit malaria,

or better yet,

someday so that they
just don't want to bite people,

that would be the most elegant
solution to a problem.

♪ ♪

WILLIAMS:
Kevin Esvelt is walking
in the footsteps

of those early pioneers

who engineered bacteria
to make insulin for diabetics.

Today, we have the capacity

to alter the genomes
of every living thing.

So, the potential rewards--
and the risks--

of genetic engineering
have never been greater.

PAUWELS:
A few decades ago,

the changes we would impose
on biology

were very much incremental.

They were little steps.

But now we could
drastically accelerate

the engineering of our genes,

our bodies,
and even our ecosystems.

(moose bellowing)

WILLIAMS:
Despite all we can do,

there's still one thing
we can't do.

JONES-PRATHER:
We can't create life.

We can't create a cell
from scratch.

We can take an existing cell

and we can make so many changes
to it that it looks nothing

like what it started out as.

But we have to start
from something

that's already living

in order to end up with
something that's living.

♪ ♪

WILLIAMS:
So right now,
we can't make life,

but we can radically change it
in ways that will impact

our own evolution

and the future of the planet.

The question is:

will we use this power wisely?

♪ ♪

♪ ♪

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♪ ♪