Nova (1974–…): Season 45, Episode 105 - NOVA Wonders: Can We Make Life? - full transcript
What do you wonder about?
The unknown.
What our place
in the universe is.
Artificial intelligence.
Hello.
Look at this, what's this?
Animals.
An egg.
Your brain.
Life on a faraway planet.
"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.
And making incredible
discoveries.
Trying to understand
their behavior, their life,
everything that goes on here.
Building an artificial
intelligence
is going to be the crowning
achievement of humanity.
We're three scientists
exploring the frontiers
of human knowledge.
I'm a neuroscientist
and I study
the biology of memory.
I'm a computer scientist
and I build technology
that can read human emotions.
And I'm a mathematician,
using big data to understand
our modern world.
And we're tackling
the biggest questions...
- Dark energy?
- Dark energy?
Of life...
There's all of these microbes,
and we just don't know
what they are.
And the cosmos.
♪♪
On this episode,
DNA is really just a chemical.
We're rewriting the code of life
like never before.
There's enough DNA
to make 30 copies
of every human genome
on the planet.
You can change every species
to almost anything you want.
Can this new genetic power
save lives?
Or even bring extinct creatures
back from the dead?
Could we bring a mammoth
back to life?
It's a revolution in biology.
This is rapid
man-made evolution.
- "NOVA Wonders"...
- "Can We Make Life?"
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.
For decades,
scientists have been
trying to master
this chemical cipher
that we call DNA.
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?
How much power
do we really have over life?
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"...
"Can We Make Life?"
♪♪
15,000 years ago,
the biggest thing on four legs
was this guy... the mammoth.
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.
From the paleontological record,
the best guess is that
there were many mammoths,
potentially hundreds
of thousands,
even to millions of mammoths.
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.
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.
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.
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.
Well, Dr. George Church...
But can this genetic magician
possibly resurrect
a long-dead woolly mammoth?
Every species on the planet
comes from a cell with a genome,
and that means
you can change it
to almost anything you want.
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...
The baby dinosaurs that hatched
were cute at first,
and then they weren't.
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.
They're very closely related
to the mammoths.
Even though they
don't look that way,
they're genetically
very similar.
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?
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.
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.
Here in a biochemical lab
at M.I.T...
We actually should
go back and reduce...
Kristala Jones-Prather
leads a team
that is also altering
the genes of microbes
to make proteins and chemicals
that are useful to us.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Lyme is a bacterial infection
that often starts with a rash
where a person has been bitten
by an infected tick.
You get rashes...
Most people can be cured
with antibiotics
that eliminate the rash,
fever, and joint pain
within a few days.
When we treated you,
you got better.
Yep.
And then the next day,
it had the ring around it.
But not everyone
recovers so quickly.
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.
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.
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.
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.
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.
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?
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.
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."
But people adore seeing deer
and don't want them removed.
Could it be
childhood memories of Bambi?
It is Bambi.
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.
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.
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.
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.
For Kevin Esvelt,
it's a risk people
should not have to take,
especially with their kids.
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!
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.
Kevin has a plan to
make the outdoors safe again.
The mice seem to be wary today.
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.
Enlisting mice
in the war against
tick-borne disease
would just be
an amazing proposition.
I'm counting 18 on the ears.
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.
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.
And M.I.T.'s Kevin Esvelt
wants to use CRISPR
to change the DNA of mice
and make them immune
to Lyme bacteria.
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."
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.
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.
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.
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?
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.
George Church is certainly
playing with evolution
by attempting to
de-extinct a woolly mammoth.
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.
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.
♪♪
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.
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.
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.
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.
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?
They could try and fertilize
the egg cell
of a captive Asian elephant
with woolly mammoth genes.
But this is difficult.
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.
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.
Could he possibly engineer
a living mammoth this way?
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?
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.
Although we may never see
a mammoth,
George's efforts to identify and
make more resilient animal genes
may have a hidden benefit.
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.
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.
This is the family we just met
this morning.
He's seven years old,
but wasn't diagnosed
until August.
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.
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?
Now at age nine,
Brandon still gets the love,
but A.L.D. is devastating
his mind and body.
All right.
He can do nothing
for himself anymore.
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.
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.
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.
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.
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.
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.
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.
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.
Children like 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.
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.
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.
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
and I didn't know how to react.
- 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.
Say hi, Brian.
Hi.
Sí!
It wasn't guaranteed
that having the bad gene
would give Brian the deadly form
of the disease.
But Lilliana was worried.
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..."
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?
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.
I got hit with a ton of bricks
after his MRI.
♪♪
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."
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.
Nice job.
♪♪
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.
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?
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.
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.
And for the therapy team,
this has been the experience
of a lifetime.
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.
We're extremely lucky.
There are some families
out there
that aren't as lucky
as our family.
He wore the black costume.
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.
Because of Brandon,
Brian was diagnosed early.
Brandon saved
his little brother.
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?
It is literally going to be
hundreds of diseases
that we'll now be able
to approach.
Very good, nice job.
The future of genetic therapy
is actually here.
♪♪
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?
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.
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'?"
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?
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.
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.
But our genetic knowledge
is increasing
and it certainly seems possible
that one day we will be able
to design our babies.
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.
But if we do go down this road,
where will it end?
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.
♪♪
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.
I worry every day
that I might be missing
something profound
about the consequences
of what we're developing.
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.
♪♪
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.
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...
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.
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.
Actually, no...
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.
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.
But Kevin's cautious,
open science approach
seems to be winning the day.
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?
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?
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.
♪♪
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.
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.
Despite all we can do,
there's still one thing
we can't do.
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.
♪♪
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?
♪♪
The unknown.
What our place
in the universe is.
Artificial intelligence.
Hello.
Look at this, what's this?
Animals.
An egg.
Your brain.
Life on a faraway planet.
"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.
And making incredible
discoveries.
Trying to understand
their behavior, their life,
everything that goes on here.
Building an artificial
intelligence
is going to be the crowning
achievement of humanity.
We're three scientists
exploring the frontiers
of human knowledge.
I'm a neuroscientist
and I study
the biology of memory.
I'm a computer scientist
and I build technology
that can read human emotions.
And I'm a mathematician,
using big data to understand
our modern world.
And we're tackling
the biggest questions...
- Dark energy?
- Dark energy?
Of life...
There's all of these microbes,
and we just don't know
what they are.
And the cosmos.
♪♪
On this episode,
DNA is really just a chemical.
We're rewriting the code of life
like never before.
There's enough DNA
to make 30 copies
of every human genome
on the planet.
You can change every species
to almost anything you want.
Can this new genetic power
save lives?
Or even bring extinct creatures
back from the dead?
Could we bring a mammoth
back to life?
It's a revolution in biology.
This is rapid
man-made evolution.
- "NOVA Wonders"...
- "Can We Make Life?"
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.
For decades,
scientists have been
trying to master
this chemical cipher
that we call DNA.
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?
How much power
do we really have over life?
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"...
"Can We Make Life?"
♪♪
15,000 years ago,
the biggest thing on four legs
was this guy... the mammoth.
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.
From the paleontological record,
the best guess is that
there were many mammoths,
potentially hundreds
of thousands,
even to millions of mammoths.
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.
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.
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.
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.
Well, Dr. George Church...
But can this genetic magician
possibly resurrect
a long-dead woolly mammoth?
Every species on the planet
comes from a cell with a genome,
and that means
you can change it
to almost anything you want.
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...
The baby dinosaurs that hatched
were cute at first,
and then they weren't.
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.
They're very closely related
to the mammoths.
Even though they
don't look that way,
they're genetically
very similar.
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?
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.
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.
Here in a biochemical lab
at M.I.T...
We actually should
go back and reduce...
Kristala Jones-Prather
leads a team
that is also altering
the genes of microbes
to make proteins and chemicals
that are useful to us.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Lyme is a bacterial infection
that often starts with a rash
where a person has been bitten
by an infected tick.
You get rashes...
Most people can be cured
with antibiotics
that eliminate the rash,
fever, and joint pain
within a few days.
When we treated you,
you got better.
Yep.
And then the next day,
it had the ring around it.
But not everyone
recovers so quickly.
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.
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.
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.
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.
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.
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?
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.
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."
But people adore seeing deer
and don't want them removed.
Could it be
childhood memories of Bambi?
It is Bambi.
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.
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.
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.
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.
For Kevin Esvelt,
it's a risk people
should not have to take,
especially with their kids.
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!
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.
Kevin has a plan to
make the outdoors safe again.
The mice seem to be wary today.
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.
Enlisting mice
in the war against
tick-borne disease
would just be
an amazing proposition.
I'm counting 18 on the ears.
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.
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.
And M.I.T.'s Kevin Esvelt
wants to use CRISPR
to change the DNA of mice
and make them immune
to Lyme bacteria.
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."
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.
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.
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.
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?
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.
George Church is certainly
playing with evolution
by attempting to
de-extinct a woolly mammoth.
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.
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.
♪♪
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.
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.
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.
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.
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?
They could try and fertilize
the egg cell
of a captive Asian elephant
with woolly mammoth genes.
But this is difficult.
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.
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.
Could he possibly engineer
a living mammoth this way?
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?
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.
Although we may never see
a mammoth,
George's efforts to identify and
make more resilient animal genes
may have a hidden benefit.
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.
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.
This is the family we just met
this morning.
He's seven years old,
but wasn't diagnosed
until August.
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.
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?
Now at age nine,
Brandon still gets the love,
but A.L.D. is devastating
his mind and body.
All right.
He can do nothing
for himself anymore.
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.
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.
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.
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.
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.
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.
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.
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.
Children like 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.
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.
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.
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
and I didn't know how to react.
- 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.
Say hi, Brian.
Hi.
Sí!
It wasn't guaranteed
that having the bad gene
would give Brian the deadly form
of the disease.
But Lilliana was worried.
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..."
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?
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.
I got hit with a ton of bricks
after his MRI.
♪♪
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."
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.
Nice job.
♪♪
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.
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?
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.
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.
And for the therapy team,
this has been the experience
of a lifetime.
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.
We're extremely lucky.
There are some families
out there
that aren't as lucky
as our family.
He wore the black costume.
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.
Because of Brandon,
Brian was diagnosed early.
Brandon saved
his little brother.
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?
It is literally going to be
hundreds of diseases
that we'll now be able
to approach.
Very good, nice job.
The future of genetic therapy
is actually here.
♪♪
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?
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.
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'?"
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?
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.
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.
But our genetic knowledge
is increasing
and it certainly seems possible
that one day we will be able
to design our babies.
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.
But if we do go down this road,
where will it end?
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.
♪♪
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.
I worry every day
that I might be missing
something profound
about the consequences
of what we're developing.
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.
♪♪
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.
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...
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.
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.
Actually, no...
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.
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.
But Kevin's cautious,
open science approach
seems to be winning the day.
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?
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?
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.
♪♪
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.
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.
Despite all we can do,
there's still one thing
we can't do.
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.
♪♪
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?
♪♪