Evolution - What Darwin Never Knew - NOVA PBS Documentary

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One question:

"Why is there such a
stunning diversity of life?"

One answer:

"Evolution:

"Charles Darwin's brilliant theory that
explains how species adapt and change."

It's been called
the best idea anyone ever had.

But there's one big problem:
How does it actually work?

Now, extraordinary science is
answering that question.

It is uncovering the hidden
mechanisms inside creatures' bodies

that can explain
astonishing transformations,

like how birds can
evolve from dinosaurs...

why a fish was
once your ancestor...

and above all,
what makes us human.

Right now on NOVA, you'll
find out what Darwin never knew.

Major funding for "NOVA"
is provided by the following:
STEPHEN GREEN LEE, Exxon Mobil,
Pacific Life, and people like you.

The Tree of Life on earth
is one of stunning diversity.
NARRATOR:

9.000 species of birds.

350,000 kinds of beetles.

28,000 types of fish.

Two million
living species and counting.

And we
are just one of them.

But why is there such an
amazing variety of animals?
(birds calling)

Why are there so
many types of fish?

So many different
species of beetle?

How did this extraordinary
profusion of life on earth come about?

Today, we celebrate the man who
would ultimately answer that question.

Charles Darwin.

He was born 200 years ago and it is 150
years since he published the work that has

become the bedrock of our
understanding of life on earth.

What Darwin wanted
to understand was

how you get this extraordinary
diversity of life on earth.

He was spot on.

He really nailed it.

Darwin's theory of evolution; his account
of why species adapt and change;

Darwin's theory of evolution; his account
of why species adapt and change;

has been called the best
idea anyone ever had.

But even Darwin admitted that
his work was incomplete.

Vast questions
were still unanswered.

And the biggest question
was: How?

How did evolution
take place?

He didn't know any of
the mechanics of that process.

He didn't understand
the physical forces

that would actually change the way
species appeared.

that would actually change the way
species appeared.

But today, we can answer
the questions that Darwin could not.

We can look under
the hood of evolution

and see exactly how this mysterious process
gives rise to such astounding diversity.

What's incredible about this time from

a scientific perspective is, we're going
to be able to understand that diversity.

And that just adds to the excitement.

It doesn't demystify it.

It makes it all the more magical.
CLIFF TABIN :

And this is the magic
and mystery of evolution.

NARRATOR:
And this is the magic
and mystery of evolution.

NARRATOR:

Over eons of time,
a single species gives rise to many.

An ancient fish evolves to become

the ancestor of all four- limbed
animals, even us.

And one species, our own,
develops a large

and uniquely complex brain,
enabling us to dominate the planet.

This is the search for the answers
to what Darwin never knew.

(CHILDREN CHATTERING):

Darwin began his love affair
with nature when he was a child,
(CHILDREN CHATTERING):

just like many of his
modern followers, including
(CHILDREN CHATTERING):

evolutionary biologist,
Sean Carroll.
(CHILDREN CHATTERING):

I developed my interest in animals
the same way I think most biologists did,
SEAN CARROLL:

which was either going out
in the backyard or going to zoos.
SEAN CARROLL:

SEAN CARROLL:

And anytime I got a chance, I'd flip
over logs and look for salamanders and
SEAN CARROLL:

snakes and frogs and things like this.
SEAN CARROLL:

And I was just fascinated with
their patterns and behavior.
SEAN CARROLL:

NARRATOR:

So it was with
the young Charles Darwin.
NARRATOR:

Young Charles liked to
traipse around the outdoors.
SEAN CARROLL:

SEAN CARROLL:

He loved to collect beetles and things.
SEAN CARROLL:

He was a completely ordinary kid.
SEAN CARROLL:

And he didn't like school.
SEAN CARROLL:

SEAN CARROLL:

In fact, he was such a poor student that
his father, a rather successful physician
SEAN CARROLL:

and a pretty imposing figure, was
worried about Darwin's direction in life.
In fact, he was such a poor student that
his father, a rather successful physician
SEAN CARROLL:

SEAN CARROLL:
and a pretty imposing figure, was
worried about Darwin's direction in life.

So his father packed him off to Edinburgh,
NARRATOR:

the finest medical school in Europe,
to become a doctor.
NARRATOR:

But young Charles was just too squeamish.

And he was really horrified by medical school.
SEAN CARROLL:

He witnessed an operation on a child
and this is in the era before anesthetics.
SEAN CARROLL:

And he just fled the operating theater
vowing never to return.
SEAN CARROLL:

Next, his father sent him to Cambridge,
to study for the clergy.
NARRATOR:

He didn't succeed at that either,
but he did find his direction in life,

reviving his childhood interest in nature.

Darwin starts on his path to his divinity
degree and he starts to mature as a student.
SEAN CARROLL:

SEAN CARROLL:

He becomes more serious about some subjects,
particularly natural history, and he learns
SEAN CARROLL:

a lot more about botany and
about geology and these things.
SEAN CARROLL:

He's becoming a pretty
solid field scientist.
SEAN CARROLL:

His reputation as a naturalist
gained him a spectacular invitation.
NARRATOR:

NARRATOR:

Charles was offered a place on the
British Navy ship the HMS Beagle,
SEAN CARROLL:

whose mission was to survey
the waters around South America.
SEAN CARROLL:

SEAN CARROLL:

Now, the captain of the Beagle wanted a well
educated, scientific person aboard,
SEAN CARROLL:

and a dinner companion,
somebody to share conversation with.
SEAN CARROLL:

And Darwin fit the bill perfectly.
SEAN CARROLL:

And so, Charles Darwin set off
on a fateful voyage
NARRATOR:

that would revolutionize our
understanding of life's great diversity.
NARRATOR:

The voyage of the Beagle
took nearly five years.

It wove its way from the Cape Verde
islands and along the coast of Brazil.

It was in Argentina that he made
his first important discovery.

Early on in the voyage,
Darwin found some amazing fossils.
SEAN CARROLL:

He dug up some skulls, some jaws,
SEAN CARROLL:

some backbones of what
turned out to be giant mammals.
SEAN CARROLL:

SEAN CARROLL:

Now, these were clearly extinct and
Darwin began to ponder, .
SEAN CARROLL:

what was the relationship of those fossils
to the living animals of South America.
SEAN CARROLL:

But one port of call on Darwin's voyage
proved more important than all the others.
NARRATOR:

The Galapagos.

This cluster of 13 isolated islands

lies 600 miles off the coast
of Ecuador in the Pacific Ocean.

These islands are home to unusual
animals found nowhere else on earth.

Penguins that live at the equator
and swim in warm water,

instead of the frigid seas of the South Pole.

Giant tortoises that weigh up to 600 pounds.

Iguanas, huge lizards that swim and dive in the sea.

Everywhere else, they dwell only on land.

(BARKING)

Traveling for the first time
in the Galapagos,

Sean Carroll is seeing the same
creatures that so intrigued Darwin.

Of all animals, I think these
marine iguanas
SEAN CARROLL:

are the greatest symbol of the Galapagos,
what I most wanted to see here.
SEAN CARROLL:

are the greatest symbol of the Galapagos,
what I most wanted to see here.

And to see them in their native habitat,

blending against that black rock,
just as Darwin described it...

It's an absolute thrill.

It's a hideous looking creature,
of a dirty black color,
DARWIN (dramatized):

stupid and sluggish in its movements.
DARWIN (dramatized):

DARWIN (dramatized):

They're as black as the porous
rocks over which they crawl.
DARWIN (dramatized):

NARRATOR:

Darwin meticulously described
the iguanas in his diary.
NARRATOR:

But he was far from the
scientific authority he would become.

The Darwin that arrived here was not
the great theorist that we know today.
SEAN CARROLL:

He was a 26-year-old collector,
collecting really, almost at random,
SEAN CARROLL:

any kind of plants,
any kind of animals, any kinds of rocks.
SEAN CARROLL:

He didn't even know the meaning of
what he was collecting until much later.
SEAN CARROLL:

He was also fascinated
by the giant tortoises,
NARRATOR:

which allowed him to ride on their
backs as they slowly lumbered around.
NARRATOR:

I frequently got on their backs and then,

DARWIN:
I frequently got on their backs and then,

upon giving a few raps on the hinder part
of the shell, they would rise up and walk away.
DARWIN:

But I found it very difficult
to keep my balance.
DARWIN:

Darwin measured the
creatures' extreme slowness.
NARRATOR:

NARRATOR:

About four miles a day, he calculated.
NARRATOR:

About four miles a day, he calculated.

But the local people knew
something else about the tortoises.

They could tell which island
SEAN CARROL (whispering):

any tortoise came from
just by looking at its shell.
SEAN CARROL (whispering):

Their shells differed depending
on which island they lived on.

NARRATOR:
Their shells differed depending
on which island they lived on.

Their shells differed depending
on which island they lived on.

Some tortoises had shells
shaped like a dome.

Others had shells arcing over
their heads like a saddle.

Others differed subtly in color.

Or by how much the bottom
of the shell flared out.

Darwin had literally been sitting on a clue:

a way to understand the great diversity
of life, but he didn't yet realize it.

Instead, Darwin turned
his attention to birds.

(BIRDS CALLING)
Instead, Darwin turned
his attention to birds.

(BIRDS CALLING)

The islands were full of what seemed
to be a familiar assortment of species.

So, he stuffed his collecting bag with
what he thought were types of finches,

grosbeaks, wrens and blackbirds.

And then, after five weeks in
the Galapagos, Darwin and the Beagle

went to other ports in the Pacific
and finally set sail for home.

On board, he started to sort through

the vast number of specimens he had
collected on the five-year voyage.

But it was not until he returned to Britain
that he was able to make sense of them.

It began with a startling revelation.

All the different birds he had collected
actually were variations of a single type.

He learns that those
birds he had collected on
SEAN CARROLL:

the Galapagos actually represent
13 different species of finch.
SEAN CARROLL:

What misled Darwin was that
they looked radically different.
NARRATOR:

NARRATOR:

Some had wide, tough beaks.

Others had long slender ones.

And these differences depended on
which islands they lived on.

Now, why would that be?
SEAN CARROLL:

Why would there be slightly
different birds, slightly different
SEAN CARROLL:

species on different islands
all in one part of the world?
SEAN CARROLL:

Darwin now thought back
to the Galapagos tortoises.
NARRATOR:

They too differed from island to island.

His brain began racing.

Thoughts are starting to crystallize,
SEAN CARROLL:

take shape in his mind,
bit by bit, bit by bit.
SEAN CARROLL:

He starts this process he
describes as mental rioting.
SEAN CARROLL:

Just stream of consciousness where he's
jotting down note after note after note.
SEAN CARROLL:

Thoughts as they occur to him.
SEAN CARROLL:

SEAN CARROLL:

And finally, they converge on this one idea.
SEAN CARROLL:

What Darwin now realized was that somehow,
for some reason, species change.
NARRATOR:

Originally, there must have been just
one type of finch in the Galapagos,

but over time it had diversified
into many kinds, with different beak shapes.

The same for the tortoises.

One type of tortoise must have
turned into many kinds,

with different shells depending
on which island they lived on.

With this great insight,
Darwin entered dangerous new territory.

The standard view at the time was
that God had created every species.

And that what God had created
was perfect and could not change.

But Darwin said no.
SEAN CARROLL:

SEAN CARROLL:

Why would the Creator bother with
making slightly different finches
SEAN CARROLL:

for each of these different islands
that all looked alike?
SEAN CARROLL:

The prevailing view
just didn't make sense.
NARRATOR:

But this was only the beginning
of Darwin's revolution.

He turned his attention to the fossils
he had collected in South America.

One was of a giant sloth.

Another was of a huge
armadillo-like creature.

These animals were extinct, but little
sloths still existed in South America.

And so did smaller armadillos.

What could this mean?

It dawned on him that
they resembled each other.
SEAN CARROLL:

So, what he had found in the ground
SEAN CARROLL:

SEAN CARROLL:

were the buried ancestors of the
living animals of South America.
SEAN CARROLL:

So, again, here was more evidence
that species changed.
NARRATOR:

Somehow, these ancient giants
must have been transformed into

the smaller creatures we see today.

But what Darwin would later find out

took this idea of how species change
into a completely new league.

In Victorian times, scientists routinely
studied life-forms at the embryonic stage.

How these tiny forms develop
from just single cell

into an entire creature

has long been seen as one
of the wonders of nature.

Watching a developing embryo is truly
the most glorious miracle of nature.
MICHAEL LEVINE:

I mean, you know, no bologna.
MICHAEL LEVINE:

What Darwin learned from
studying the embryos amazed him.
NARRATOR:

In snake embryos, you could see tiny bumps.

The bony rudiments of legs.

But these would never
develop in the adult snake.

Darwin wondered, "Were snakes somehow
descended from animals with legs?"

He learned that whales, which have no
teeth as adults, had them as embryos.

Those teeth disappeared
before they were born.

To Darwin, it had to mean whales were
descended from creatures with teeth.

But human embryos provided
the most startling evidence.

Under the microscope, tiny slits
around the neck were clearly visible.

Exactly the same structures
were found in fish.

But in fish, they turned into gills.

In humans, they became
the bones of our inner ear.

Surely, this showed that humans
must be descended from fish.

It's an astonishing thought.

I don't know about
your ancestors, but mine,
OLIVIA JUDSON:

included priests and, you know,
the,the usual, the usual suspects.
OLIVIA JUDSON:

But, but the idea that all of us have,
OLIVIA JUDSON:

have fish in our family tree,
I think it's amazing.
OLIVIA JUDSON:

And so, Darwin arrived at an astonishing
conclusion, one that would become
NARRATOR:

central to his understanding
of the great diversity of life.

Darwin had this amazingly bold idea:
SEAN CARROL

The Tree Of Life :
That all species were connected.
SEAN CARROL

SEAN CARROL

And what it meant was,
if you go far enough back
SEAN CARROL

in our family tree of humans,
you'll come to fish.
SEAN CARROL

SEAN CARROL

If you go far enough back in the family
tree of birds, you'll come to dinosaurs.
SEAN CARROL

SEAN CARROL

So that creatures that don't look
anything at all like each other
SEAN CARROL

are actually deeply connected.
SEAN CARROL

SEAN CARROL

No one came close to having
this idea before Darwin.
SEAN CARROL

This seemed to be an explanation
for the vast diversity of animals.
NARRATOR:

Beginning with a common ancestor,
over time across generations,

species could change dramatically.

Some might add new body features.

Others might drop them.

Ultimately, one type of creature

could be transformed into
something utterly different.

It's a process Darwin called

"descent with modification."

But it all begged a question.

Why?

What was making creatures change?

Darwin needed clues.

And he found them in
a very surprising place.

Dogs.

Big, small, fat, tall.

The British have long
been obsessed by them.

It was a full-blown love affair
in Victorian England.

Even Her Majesty was dog crazy.

That love affair still continues today.

Especially among
scientists like Heidi Parker,

at the National Institutes of Health.

So, one of the most interesting
things about dogs,
HEIDI PARKER:

is the kind of variation that you have.

We have dogs the size of groundhogs
versus a dog like Zeppie,

the Leonberger, who can get
to be the size of a mule deer.

If we had that kind of size
variation in humans,

we would have people running
around the size of Barbie dolls.

In his day, Darwin knew this range
of sizes hadn't come about by chance.
NARRATOR:

Through a careful process
of selection, dog breeders

mix different dogs with different
physical traits to create new forms.

HEIDI PARKER:
Darwin was intrigued by what he was seeing
breeders doing with the domestic dog.

They could select for individual
traits like size or shape,
HEIDI PARKER:

HEIDI PARKER:

and they could
actually change their breed.
HEIDI PARKER:

The Whippet, for example,
had been developed to chase rabbits.
NARRATOR:

It was created by mixing
greyhounds for speed,

with terriers, used to
hunt small game.

And then it hit Darwin.

Was there a similar form of selection
going on in nature,

but without human interference?

Could natural selection explain
the great diversity of life?

It was brilliant.
SEAN CARROLL:

SEAN CARROLL:

He took something very familiar
and comfortable, for example,
SEAN CARROLL:

animal breeding, and explained that the
same sort of thing was going on in nature
SEAN CARROLL:

just at a little bit different pace
and with no human guide.
SEAN CARROLL:

But what could be
carrying out selection in the wild?
NARRATOR:

It was then that Darwin took a
completely fresh look at nature.

The Victorian view
of nature was sentimental.

Lambs lay down with lions.

But Darwin's travels on the Beagle,
led him to a different view.

For Darwin, nature was savage.

Every creature was locked in a
desperate struggle for survival,

ultimately ending in death.

The scale of death in nature
is absolutely horrendous.
OLIVIA JUDSON:

OLIVIA JUDSON:

And sometimes it's not just
that there's a lot of death,
OLIVIA JUDSON:

but it's very unpleasant death.
OLIVIA JUDSON:

But in all this brutal chaos,
Darwin saw a pattern.
NARRATOR:

Darwin showed that
nature was a battlefield,
SEAN CARROLL:

and that everything
was in competition.
SEAN CARROLL:

SEAN CARROLL:

And this brutal battle, this war of
nature as Darwin described it,
SEAN CARROLL:

was actually a creative process.
SEAN CARROLL:

The pattern that Darwin saw was
that the creatures that survived
NARRATOR:

were those best adapted to the
specific environments they lived in.

For instance, some could
handle extremes of climate.

Others were brilliantly
honed killing machines,

perfect for catching
the available prey.

Still others were perfect to evade
those who might be hunting them.

But how did this harsh view of nature
explain the finches on the Galapagos,

where Darwin observed that
the birds on different islands

had different beak shapes?

Somehow, those different beaks
must be helping the finches survive.

The finches of the Galapagos Islands
have beaks of many sizes and shapes.
CLIFF TABIN:

And there's a reason for that.
CLIFF TABIN:

They use their beaks as tools.
CLIFF TABIN:

CLIFF TABIN:

Now, if you think of the type of
tool you would want to crush
CLIFF TABIN:

a seed that's very tough,
but is the food that you really like,
CLIFF TABIN:

you'd want a beak like this, which is
the type of beak the ground finch has.
CLIFF TABIN:

On an island where the only food is
seeds that are hard to crack,
NARRATOR:

a short, powerful beak
will mean a finch will survive.

But on another island, the available
food isn't seeds but flowers.

If you wanted to get into narrow spaces
to get pollen and nectar
CLIFF TABIN:

CLIFF TABIN:

that are very hard to get at,
you wouldn't need a big,
CLIFF TABIN:

strong beak, you'd
need a probing beak.
CLIFF TABIN:

So, on a different island, where
you have a different food source,
NARRATOR:

you have a different beak shape.

And this pattern was
repeated across the Galapagos.

It seems that the finches' beaks had altered
to fit the diet of each particular island.

And that was how one original type
of finch had been transformed into many.

But how had these
changes come about?

Here, Darwin had another clue.

He could see
it in his own family.

As every parent knows, no two
children are ever exactly the same.

Charles looked different
from his brother, Erasmus,

even though they
shared the same parents.

Charles's children looked a
bit like him and his wife Emma.

But they too looked
different from each other.

That was something
he called variation.

He realized that not every
individual was the same,
SEAN CARROL:

SEAN CARROL:

stamped out like
a toy from a press.
SEAN CARROL:

But there is variation.
SEAN CARROL:

Darwin realized that variation must be the
starting point for change in nature.
NARRATOR:

In any generation, the animals in
a litter are never quite the same.

And in the wild,
such a tiny variation,

might make all the difference
between life and death.

Two penguins, for instance,
might differ a tiny bit

in the thickness of their blubber- a
big factor if you live in extreme cold.

In a harsh climate,
the environment will select

who will live and who will die.

And slowly, Darwin suggested,
over many, many generations,

these tiny variations
would allow the fit to get fitter

and the unfit would vanish.

These variations accumulate

and eventually,
new species branch off.

This is evolution
by natural selection.

It is one of the keys to how
new species are formed.

And so, in 1859,
after years of painstaking research,

Darwin finally published his masterwork,
"On the Origin of Species."

It is still impossible to
overstate its importance.

It was really a
quantum advance in understanding.
CLIFF TABIN:

It shook people up,
it changed the way people thought.
CLIFF TABIN:

Gone was the idea that all species
were created perfect and immutable,
NARRATOR:

taken as an article of faith.

In its place, Darwin provided
a proper scientific theory,

based on facts and observation.

It is much more than the presentation
of simply the idea of natural selection.
OLIVIA JUDSON:

OLIVIA JUDSON:

It is a, it's a vision of how
evolution by natural selection works.
OLIVIA JUDSON:

150 years later, his theory
has stood the test of time.
NARRATOR:

What's amazing is that
Darwin got so much right.
SEAN CARROLL:

SEAN CARROLL:

His ideas, largely stay intact today.
SEAN CARROLL:

But Darwin himself acknowledged
that there were holes in his theory.
NARRATOR:

He didn't actually
know how it worked.

What was happening inside a
creature's body that makes it change?

But now, at last, modern science
is providing the answers

through a hidden mechanism
that Darwin knew nothing about.

Arizona's Pinacarte Desert
is a harsh and brutal place.

Especially if you're
a rock pocket mouse.

They're the Snickers
bar of the desert.
MICHAEL NACHMAN:

They really are,
they're eaten by everything.

They're probably eaten by foxes
and coyotes and rattlesnakes, owls.

Weighing just half an ounce,
NARRATOR:

this mouse could never
fight off these large predators.

Its best hope for
survival is camouflage.

Not surprisingly, its fur matches
the color of the Pinacarte rocks.

But in some sections of the desert,
the environment is different.

Ancient volcanoes erupted
and now the desert

is a patchwork of
dark lava and light rock.

But of course, a light mouse on
a dark rock is easy pickings.

So, something has happened that
Darwin might have predicted.

The mice now living on the dark rocks
have evolved darker fur.

Those that stayed on
the light rocks remain light.

Michael Nachman was fascinated.

How had this happened?

To find out, he first
needed to catch some mice.

So, with Sean Carroll, he visits a line
of traps he set the previous night.

All of the dark ones have
a white underbelly and presumably,
MICHAEL NACHMAN:

there's no selection for
dark on the belly
MICHAEL NACHMAN:

because predators are going,
coming from above.
MICHAEL NACHMAN:

This much Darwin
could have done.
NARRATOR:

Find some mice and compare the color
of their fur to their environment.

But Nachman can now do something
that Darwin never could.

He can look inside the animal's DNA.

The study of DNA is one of the great
triumphs of modern science.

It has taken our understanding of how
creatures evolve and develop,

to a level that Darwin could
never have dreamed of.

The DNA molecule
is one of the real secrets of life.
SEAN CARROLL:

SEAN CARROLL:

It's a perfect system for storing
the vast amounts of information
SEAN CARROLL:

SEAN CARROLL:

that's necessary for building
all kinds of creatures.
SEAN CARROLL:

DNA consists of one long molecule
spiraling around in a double helix.
NARRATOR:

That helix is, in turn, made up
of four smaller molecules,

called by the letters
G, A, T and C.

DNA can be found in the cells
of every living thing on earth.

The thing about DNA
that I think is remarkable
OLIVIA JUDSON:

OLIVIA JUDSON:

is that the molecule
itself is so elegant.
OLIVIA JUDSON:

OLIVIA JUDSON:

With a small number of letters,
you can say almost infinite words.
OLIVIA JUDSON:

And that is the key.
NARRATOR:

DNA is a code and its double strand
contains all the information

to make living things
grow and develop.

Lined along each DNA molecule
are ranged special

sequences of this code
that form our genes.

Many genes get
translated into proteins.

And these proteins
make the stuff of our bodies.

One protein makes hair.

Another makes cartilage.

Others make muscle.

What makes DNA so amazing is
that it just contains four letters,
SEAN CARROLL:

but all sorts of combinations of those
four letters contains all the information
SEAN CARROLL:

for making all the creatures
that are on the planet.
SEAN CARROLL:

It's a gene that determines
whether our eyes are blue or not.
NARRATOR:

Another gives us freckles.

Another gives us dimples.

But DNA has one other vital quality.

It doesn't stay the same.

(BABY CRYING)

When a baby is conceived,
the fertilized egg receives
(BABY CRYING)

When a baby is conceived,
the fertilized egg receives

half its DNA from the mother
and half from the father,

creating wholly new combinations.

It's why we look a bit like our
parents, but also different.

Another way that DNA
can change is mutation.

Mutation is a critical ingredient
in the recipe for evolution.
SEAN CARROLL:

Without mutation, everything would stay
constant generation after generation.
SEAN CARROLL:

SEAN CARROLL:

Mutation generates variation,
differences between individuals.
SEAN CARROLL:

Mutations can happen
as our DNA copies itself
NARRATOR:

when our cells divide
and our bodies develop.

An "A" for instance, can be replaced
by a "G" or a "C" by a "T."

This can cause minute changes
that no one is even aware of.

But when mutations occur in the cells
we pass down to our children,

they can cause big changes.

Like turning a
light-colored mouse dark.

"Mutation" seems to mean that
something bad has happened.
SEAN CARROLL:

Well, mutations are neither good or bad.
SEAN CARROLL:

Whether they are favored,
or whether they are rejected,
SEAN CARROLL:

or whether they're just neutral,
SEAN CARROLL:

SEAN CARROLL:

depends upon the conditions
an organism finds itself.
SEAN CARROLL:

So for the pocket mouse, a mutation
that caused the mouse to turn black...
SEAN CARROLL:

SEAN CARROLL:

That is good if you're
living on black rock,
SEAN CARROLL:

SEAN CARROLL:

it's bad if you're living
out in the sandy desert.
SEAN CARROLL:

It was that mutation, the one that
turned a light-colored mouse dark,
NARRATOR:

that Michael Nachman
was hunting for.

Back in the lab, he began the
painstaking business of comparing

the genes of the two types of mice,
trying to pinpoint any differences.

Science is fun when you really
don't know what you're going to find.
MICHAEL NACHMAN:

One by one the genes in
the two mice proved identical.
NARRATOR:

But then, in one gene,
he found something.

There were four places where
the sequence of "A's," "T's,"

"C's" and "G's" were different..

When a mouse is born with these
mutations, its fur grows dark.

And that means it can survive on the
dark rocks when others would not.

Here was a clear example of evolution
and natural selection at work.

I think Darwin would have been
delighted to know that we can find
MICHAEL NACHMAN:

the genes that are responsible
for evolutionary change.

And this was just one of many
links that have been found
NARRATOR:

between genetic mutations and evolution.

Scientists can now pinpoint a range
of examples of evolution in action.

The Colobus monkey can see in color
because of a mutation in one gene.

It can now tell nutritious red leaves
from tough, old green ones.

A genetic glitch gave this Antarctic
fish a potent antifreeze in its blood.

So it can survive in the icy
waters when others cannot.

So powerful was this link between
genetic mutation and evolution,

that an idea took hold.

To understand how evolution works,

all you need to do is
compare creatures' genes.

One might think that you could
understand all of evolution simply by
SEAN CARROLL:

SEAN CARROLL:

mapping the genes of every creature.
SEAN CARROLL:

SEAN CARROLL:

Identify all the genes,
identify all the differences
SEAN CARROLL:

and you could explain
the differences between,
SEAN CARROLL:

SEAN CARROLL:

say, mouse and
monkeys and humans.
SEAN CARROLL:

So when the Human Genome
Project began in 1990,
NARRATOR:

the scientific world
was on tender hooks.

All three billion letters
of our DNA

were going to be
identified in order.

In parallel, the DNA of
some animals and plants

was also being sequenced.

Surely, this would be a quantum
leap in our understanding

of how different life-forms evolved.

With this came another idea:
That complex animals like us

would have many more
genes than simpler ones.

Here we are, the most complex and
sophisticated animal on the planet, right?
SEAN CARROLL:

You might think that would require
a whole lot more genetic information.
Here we are, the most complex and
sophisticated animal on the planet, right?
SEAN CARROLL:

SEAN CARROLL:
You might think that would require
a whole lot more genetic information.

The betting was on.
NARRATOR:

Just how big would our genome
be compared to other life-forms?

There were estimates that
humans would have between,
OLIVIA JUDSON:

let's say,80,000 and 120,000 genes.
OLIVIA JUDSON:

So when the final answer
came in 2003, it was a shocker.
NARRATOR:

23,000 genes -
the same number as a chicken...

less than an ear of corn.

I mean, people were freaked out by
the relatively small number of genes.
MICHAEL LEVINE:

MICHAEL LEVINE:

It's down to something
like22,000 or 23,000
MICHAEL LEVINE:

MICHAEL LEVINE:

protein-coding genes
in the human genome.
MICHAEL LEVINE:

MICHAEL LEVINE:

The simple nematode worm
has about that same number.
MICHAEL LEVINE:

And there are plants that have
considerably more genes
MICHAEL LEVINE:

MICHAEL LEVINE:

than the glorious human genome.
MICHAEL LEVINE:

The whole human genome project
has been a humbling experience,
OLIVIA JUDSON:

OLIVIA JUDSON:

as we've discovered that,
actually, it doesn't take
OLIVIA JUDSON:

OLIVIA JUDSON:

as many genes to make
a human as we had all hoped.
OLIVIA JUDSON:

And it wasn't just
that we had so few genes,
NARRATOR:

but many of our key genes were
identical to those of other animals.

Huge though,
the breakthrough had been,

the genetic revolution had
opened up a whole new set of puzzles.

As a solution to the mystery
of how evolution works,

genes and their mutations
were only part of the story.

There had to be something else more
subtle and more mysterious going on.

We have to explain then,
"How do you get all these differences
SEAN CARROLL:

SEAN CARROLL:

if you have really
similar sets of genes?"
SEAN CARROLL:

The quest to uncover what Darwin
never knew would have to start again.
NARRATOR:

The first tantalizing clues
would come from those life-forms

That Darwin himself
had studied: embryos.

Look at these embryos.

It is almost impossible to tell
just days after conception

which is the chicken,
the turtle, the bat, the human.

They look almost the same.

Only as they grow does it
become clear which is which.

Darwin wondered,
as scientists do today,

How could they start out so similar
and end up so different?

There is something profound about
what the embryo was telling us.
MICHAEL LEVINE:

MICHAEL LEVINE:

And we have rediscovered what
Darwin was talking about all along,
MICHAEL LEVINE:

MICHAEL LEVINE:

that the embryo's
where the action is.
MICHAEL LEVINE:

MICHAEL LEVINE:

In terms of animal diversity,
it is the platform for diversity.
MICHAEL LEVINE:

MICHAEL LEVINE:

it is the platform for diversity.
MICHAEL LEVINE:

What fascinates
modern biologists
NARRATOR:

is that all these different animals
don't just look the same,

they are using virtually the same
set of key genes to build their bodies.

The body plan genes determine
where the head goes,

where the limbs go,
and what form they take

whether they are
arms, legs or wings.

Another set of genes determines
an animal's body patterning:

the blotches,
the stripes and spots.

It is the same genes at
work in every creature

from the leopard to the
peacock to the fruit fly.

And yet they produce
radically different results.

This has led scientists
to a crucial insight

about how animal
bodies have evolved.

It's not the number
of genes that counts.

It's not the genes you have,
but how you use them
SEAN CARROLL

SEAN CARROLL

that generates the great
diversity of the animal kingdom.
SEAN CARROLL

Finding out just how these same genes
are used to create such amazing diversity
NARRATOR:

has been the work of Sean Carroll and
an unlikely hero of modern science.

The fruit fly.

As much as I'd like to study the
mammals of the African Savannah,
SEAN CARROLL:

SEAN CARROLL:

they make poor choices
for laboratory animals.
SEAN CARROLL:

They're large, expensive and
they reproduce very slowly.
SEAN CARROLL:

To get data, we have to find
the simplest examples
SEAN CARROLL:

to the phenomenon
we want to understand.
SEAN CARROLL:

But the humble fruit fly
does weird and wonderful things.
NARRATOR:

This fruit fly is dancing for sex.

A rapt female takes in the show.

She's particularly besotted by
the dark spots on the male's wings.

Watching it all is an equally
besotted Sean Carroll.

You might think them just be annoying,
but they're really charming.
SEAN CARROLL :

SEAN CARROLL :

And the males of this species does
a rather elaborate courtship dance,
SEAN CARROLL :

SEAN CARROLL :

where he displays these
spotted wings in front of the female.
SEAN CARROLL :

SEAN CARROLL :

To us, it's as magnificent
as what a peacock does.
SEAN CARROLL :

But in some species of fruit fly,
the males don't have wing spots.
NARRATOR:

There's another
fruit fly species
SEAN CARROLL:

that's different from the spotted
species in two important ways:
SEAN CARROLL:

SEAN CARROLL:

it doesn't have spots on its wings
and it does a lot less dancing.
SEAN CARROLL:

Here, then, is a classic
evolutionary puzzle.
NARRATOR:

Why does one type of fly
have spots and the other doesn't?

Sean Carroll wanted to know.

What is going on in their
genes that makes them different?

So we wanted to take apart
the genetic machinery
SEAN CARROLL:

SEAN CARROLL:

for making wing spots to understand
how those wing spots evolved.
SEAN CARROLL:

Carroll began the process of sifting
through the two types of flies' DNA.
NARRATOR:

He had one clue
to set him on his way.

He already knew the gene that
codes for the black wing spots.

He calls it the "paintbrush gene."

But surprisingly, when he compared
the genes of the two flies,

they both had that gene.

And yet, only one had spots.

When we look at
that gene in the two species,
SEAN CARROLL:

SEAN CARROLL:

really they both have
this paintbrush gene.
SEAN CARROLL:

SEAN CARROLL:

So the big difference is not
having the gene, it's how they use it.
SEAN CARROLL:

SEAN CARROLL:

One species uses it
in the wing to make spots.
SEAN CARROLL:

SEAN CARROLL:

The other one doesn't.
SEAN CARROLL:

So why did
the paintbrush gene
NARRATOR:

create spots in one type of fly,
but not in the other?

In search of answers,
Carroll turned to one of the least

understood regions of DNA:

the vast stretches that were
once known as "junk."

It has been called the
dark matter of the genome.

Mysterious.

Uncharted.

Strange.

The vast bulk of the double helix,
some 98% of it,

doesn't code for proteins,
which make the stuff of our bodies.

The genes which do,
comprise just two percent.

Even now, no one is sure what much of
this huge non-coding area actually does,

but it has long beckoned evolutionary
detectives, like Sean Carroll.

LAB SCIENTIST:
So, this is a bend.
SEAN CARROLL'S LAB:

SEAN CARROLL'S LAB:

CARROLL: That's the fragment to test?
LAB SCIENTIST: Yeah.
SEAN CARROLL'S LAB:

Carroll had already learned
that the paintbrush gene itself
NARRATOR:

was identical in the
two types of fly.

So he extended his
search through their DNA.

And in one place,
just outside the paintbrush gene,

he found an important clue.

A stretch of DNA that was different
in the fly with wing spots.

What could this mean?

So Carroll conducted
an experiment.

He decided to put that
mysterious stretch of DNA

that he had found in the spotted fly
in the unspotted fly.

To help him see if it had any effect, he
attached it to a gene from a jellyfish,

a gene that codes for a protein
that makes the jellyfish glow.

We cut the DNA
up into little pieces,
SEAN CARROLL:

SEAN CARROLL:

and we hook it up to a
protein that glows in the dark.
SEAN CARROLL:

SEAN CARROLL:

And then we inject that
into the unspotted fly.
SEAN CARROLL:

And then, something
remarkable happened.
NARRATOR:

When we looked at
those unspotted flies,
SEAN CARROLL:

SEAN CARROLL:

we see now their wings
are glowing in the dark with spots.
SEAN CARROLL:

Somehow that
mysterious stretch of DNA
NARRATOR:

had turned on the paintbrush
gene in the unspotted fly's wings.

Once spotless,
now it had luminous spots.

Bingo.
SEAN CARROLL:

SEAN CARROLL:

We'd found the piece
of DNA that mattered.
SEAN CARROLL:

Carroll had found something that
is revolutionizing our understanding
NARRATOR:

of how different animal
bodies have evolved.

A piece of DNA called a
"switch."

Switches are not genes.

They don't make stuff like
hair, cartilage or muscle.

But they turn on and off
the genes that do.

Switches are very
powerful parts of DNA,
SEAN CARROLL:

SEAN CARROLL:

because they allow
animals to use genes
SEAN CARROLL:

SEAN CARROLL:

in one place and not another,
at one time and not another.
SEAN CARROLL:

SEAN CARROLL:

And so, choreograph the spots and
stripes and blotches of animal bodies.
SEAN CARROLL:

In the case of the fruit fly,
it's a mutation-->
NARRATOR:

a change in just a few
letters of the DNA

that has caused the paintbrush
gene to be switched on.
a change in just a few
letters of the DNA

that has caused the paintbrush
gene to be switched on.

And so, a whole new species with
wing spots has been created.

But switches are now
explaining far more than that.

They are helping to solve many
perplexing evolutionary questions.

Like how one creature can become
another creature by losing its legs.

It all goes back to what Darwin
had seen in the snake embryo.

The rudiments of leg bumps.

This convinced him that a snake must have
evolved from some four-legged animal.

Over the years that same mysterious
process, the losing of legs,

has been seen in other creatures.

Like the whale.

Its front flippers have all the
bones of a land creature's arm,

even the fingers.

And further back in its body...

...it has the vestiges of a pelvis.

Clearly, it is descended from
an animal that walked on the land.

Lots of animals have evolved to
slither through the ground like snakes.
DAVID KINGSLEY:

DAVID KINGSLEY:

Other animals slither or swim
through the water like whales.
DAVID KINGSLEY:

DAVID KINGSLEY:

So if you need a streamlined body,
it's good to get rid of these things
DAVID KINGSLEY:

DAVID KINGSLEY:

that stick out
from the body, like limbs.
DAVID KINGSLEY:

Like the whale,
NARRATOR:

the manatee is another huge
mammal that lives in the sea.

And it, too,
has lost its hind legs.

How?

Darwin could never have
answered that question.

But now, thanks to our understanding
of how DNA is switched on and off,

and a very small fish,
we are getting a little closer.

In this lake in British Columbia,

there is a creature
that really shouldn't be here.

A stickleback.

Most sticklebacks
live in the ocean.

But some 10,000 years ago,

a few were left stranded in this lake,
cut off from the Pacific.

And over the years,
they have evolved.

The ocean stickleback has a pair of
fins on its belly that are like spikes.

They are for defense.

The spikes make the
stickleback hard to eat.

But the lake sticklebacks have
lost those spikes on their bellies.

And it's this that
intrigues researchers

David Kingsley and his
colleague, Dolph Schluter.

To understand what's behind it,
they first identified

the gene that makes
he stickleback's spikes.

It's one of those key body plan
genes and, not surprisingly,

they found it to be identical in both
the ocean and the lake stickleback.

The question was,
why hadn't in been turned on

in the lake stickleback,
which had lost its spikes?

Kingsley felt the answer
might lie in a switch.

We know these genetic switches exist,
but they're still very hard to find.
DAVID KINGSLEY:

We don't have a
genetic code that
DAVID KINGSLEY:

lets us read along
the DNA sequence and say,
DAVID KINGSLEY:

"There's a switch," to turn a gene
on in a particular place.
DAVID KINGSLEY:

But eventually, hunting
through the vast stretch of DNA
NARRATOR:

that does not code
for proteins, he found it.

A section of DNA that had
mutated in the lake stickleback.

These mutations meant
that the switch was broken.

It didn't turn on the
gene that makes spikes.

But this work may have implications
far beyond sticklebacks.

They are convinced that there is a link
between the stickleback losing its spikes

and other creatures,
like a manatee, losing their legs.

And they have two
tantalizing clues.

One: the same body plan gene that is
responsible for the stickleback spikes,

also plays a role in the
development of the hind limbs.

The second clue
is more tentative.

The lake stickleback
may have lost its spikes,

but evolution has left
behind some tiny remnants...

the traces of bones,
and they are lopsided

bigger on the left
than on the right.

We thought,
"Wouldn't it be amazing
DAVID KINGSLEY:

DAVID KINGSLEY:

"if in fact this classic unevenness
is "the signature of using
DAVID KINGSLEY:

DAVID KINGSLEY:

the same gene to control hind limb loss
in an incredibly different animal?"
DAVID KINGSLEY:

So Kingsley, and his team
went looking in manatees

searching for this
lopsided pattern.

And they found it.

In box after box of
manatee skeletons,

they saw pelvic bones that were bigger
on the left and smaller on the right.

Right now, Kingsley and his team are
looking for the same switch in the manatee

that caused the lake
stickleback to lose its spikes.

And if they find it, they will have
a powerful explanation

for something that
baffled Darwin

how creatures like manatees, wales
and snakes can evolve away their legs.

But all this begs
another question:

If switches can play
such a profound

role in the different shapes
and patterns of animal bodies

from wing spots,
to spikes to hind legs,

what is throwing those
switches in the first place?

Researchers would see the answer
in animals very familiar to Darwin:

Arkat Abzhanov and
Cliff Tabin have spent years

trying to find out exactly
how those Galapagos finches.

got their different beaks.

Their starting point was what they
had learned from Darwin himself.

Their beaks were vital
to the birds' survival.

On an island where
the main food was seeds,

finches had short, tough beaks
for cracking them open.

On an island where the
main food was from flowers,

birds had long pointy beaks for
sucking up nectar and pollen.

And they knew something else.

The finches are born with
their beaks fully formed.

So the answer to why
they had such different beaks,

must lie in something that happened
to them as embryos in the egg.

Something amazing is
happening inside those eggs.
CLIFF TABIN:

CLIFF TABIN:

Genes are turning
on and turning off.
CLIFF TABIN:

CLIFF TABIN:

And depending on exactly
how they turn on and off,
CLIFF TABIN:

CLIFF TABIN:

will determine what
type of finch is formed.
CLIFF TABIN:

To find out just
what was going on,
NARRATOR:

the researchers first had
to collect some eggs.

There she is.
TABIN and ABZHANOV (whispering):

TABIN and ABZHANOV (whispering):

She just came back. Yeah.
TABIN and ABZHANOV (whispering):

TABIN and ABZHANOV (whispering):

To lay eggs.
TABIN and ABZHANOV (whispering):

TABIN and ABZHANOV (whispering):

It's really likely that she
already has a clutch; great.
TABIN and ABZHANOV (whispering):

TABIN and ABZHANOV (whispering):

She's coming out.
TABIN and ABZHANOV (whispering):

Abzhanov checks a ground
finch nest and finds a single egg.
NARRATOR:

He won't remove it, because the
mother might abandon the nest.

Another nest already
has three eggs.

He takes one for his research, as he
knows the mother will lay a replacement.

The team collects
several eggs,

with embryos at different
stages of development.

That way they will be able to chart
exactly how the different beaks grow.

Back in the lab,
they can begin the process.

This cactus finch embryo
is well on the way

to its signature long,
pointy beak.

And this ground finch embryo
is growing a short, thick beak.

What we wanted to do was
try and understand the genes
CLIFF TABIN:

CLIFF TABIN:

that were involved in
making the beak the way it was
CLIFF TABIN:

CLIFF TABIN:

making a big,
broad thick beak
CLIFF TABIN:

CLIFF TABIN:

different from a long,
thin beak or a short, thin beak.
CLIFF TABIN:

They concentrated
on a group of genes
NARRATOR:

known to control the
growth of birds' faces.

As they looked,
they saw something intriguing.

One particular body plan gene
became active in the ground finch

with the short, thick beak,
on the fifth day of development.

But it didn't go to work
in the cactus finch,

with its long, slender beak
for another 24 hours.

This was a revelation.

The same genes were responsible
for the beaks in all types of finch.

Any differences were
in timing and intensity.

We've got it! We nailed it!
CLIFF TABIN:

CLIFF TABIN:

It's the same genes
in making a sharp,
CLIFF TABIN:

CLIFF TABIN:

pointy beak or a big,
broad-nut cracking beak.
CLIFF TABIN:

CLIFF TABIN:

What's essential,
what makes the difference,
CLIFF TABIN:

CLIFF TABIN:

and all the difference,
is how much you turn the gene on,
CLIFF TABIN:

CLIFF TABIN:

when you turn it on,
when you turn it off.
CLIFF TABIN:

And the revelations
didn't end there.
NARRATOR:

There was something
special about this gene.

Like all body plan genes, it doesn't
actually make the stuff of our bodies.

It didn't make the cartilage
for the finches' beaks.

It throws switches.

And the switches then turn on or
off the genes that do make the beak.

These are a
different type of gene.
SEAN CARROLL:

SEAN CARROLL:

They're genes that
boss other genes around.
SEAN CARROLL:

Scientists now realize that
not all genes are created equal.
NARRATOR:

Some make the
stuff of our bodies.

And switches are needed to turn
many of these "stuff" genes on and off.

The body plan genes are
what throw these switches,

which tell the stuff genes
what to do and when.

This subtle choreography
can have profound effects,

on how different
animal bodies are formed.

And this knowledge is
helping us solve,

perhaps the biggest
Darwinian puzzle of all:

the mystery of the
great transformations.

It all goes back to Darwin's
idea of the tree of life.

That all life-forms
are ultimately related.

And from the earliest common
ancestor over billions of years,

they have changed
and diversified,

so that creatures that started
out looking the same,

evolved to become
completely different.

And scientists have made
some amazing connections.

That dinosaurs share a
common ancestor with birds.

And that a fish must
have been the ancestor

of all four- limber
creatures, even us.

Of all his ideas, this was probably
Darwin's most astonishing.

It was one thing to
grasp how two species
SEAN CARROLL:

SEAN CARROLL:

of finch could become different,
how their beak shape could change.
SEAN CARROLL:

SEAN CARROLL:

That was a small step.
SEAN CARROLL:

But what about
the big differences?
SEAN CARROLL:

SEAN CARROLL:

The differences, say, between
the fish that swim in the sea
SEAN CARROLL:

SEAN CARROLL:

and the animals
that walk on land?
SEAN CARROLL:

SEAN CARROLL:

How did those
changes take place?
SEAN CARROLL:

Over the years, evidence for these
great transformations has been found.
NARRATOR:

For instance, just a year after Darwin
published On the Origin of Species

a fossil called
"archaeopteryx" was discovered.

It had features of both
birds and dinosaurs.

And Darwin had seen equally
persuasive evidence in embryos.

Those slits in the ear of
all land creatures, even humans.

In us, they become tiny
bones in the inner ear.

But in fish,
they become gills.

A tantalizing hint that land animals
must be descended from fish.

But the stumbling block
has always been how.

How could a fish develop
legs and walk on land?

Darwin had no idea.

But Neil Shubin was determined
to tackle that problem.

It captured
my imagination.
NEIL SHUBIN:

NEIL SHUBIN:

I mean, here's a fin and
on the other side was a limb.
NEIL SHUBIN:

NEIL SHUBIN:

And they looked
different in many ways.
NEIL SHUBIN:

NEIL SHUBIN:

And I thought, "Well, what a
first-class scientific problem
NEIL SHUBIN:

to devote my research to
NEIL SHUBIN:

NEIL SHUBIN:

And I've been devoting pretty much my
research to it ever since, over 20 years.
NEIL SHUBIN:

The first stage in Shubin's
quest was to find a fossil.
NARRATOR:

If Darwin were right,
somewhere out there,

there had to be
a transitional form,

a fossil that was part fish,
but had the beginning of legs.

But where to look?

He had one clue.

The fossil record shows
that creatures with legs

first appeared some
365 million years ago.

Before that,
they were only fish.

So, summer after summer, Shubin
set up camp on Ellesmere Island,

just a few hundred miles
from the North Pole.

It has exposed rock from
that crucial transitional time.

The scientist's own video shows
how remote and bleak the place was.

It's cold.
NEIL SHUBIN:

It's about freezing every
day over the summer.

Winds are high.

They can get up
to 50 miles an hour.

There are polar bears there.

We have to prepare
ourselves by carrying guns.

It's a beautiful place.
You've got to love it.

It's my summer home.

Each expedition was costly,
NARRATOR:

but after three of them there was
little to show for their efforts.

A fourth trip
seemed pointless.

I remember having a conversation
with my colleagues, saying
NEIL SHUBIN:

"Well, should we go?
Is this really a waste of money?
NEIL SHUBIN:

NEIL SHUBIN:

This was our do-or-die moment.
NEIL SHUBIN:

NEIL SHUBIN:

And we almost didn't go.
NEIL SHUBIN:

But they decided
to try one last time.
NARRATOR:

After three days, they still
hadn't found anything.

Then, just when no one
was expecting anything to happen...

A colleague was cracking rocks and
I was working about five feet from him.
NEIL SHUBIN:

NEIL SHUBIN:

And I hear, "Hey! Hey,
guys, what's this?"
NEIL SHUBIN:

NEIL SHUBIN:

Sticking out of the cliff
was the snout of fish.
NEIL SHUBIN:

NEIL SHUBIN:

And not just any fish,
a fish with a flat head.
NEIL SHUBIN:

NEIL SHUBIN:

By seeing a flat-headed fish in rocks
about 375 million years old...
NEIL SHUBIN:

NEIL SHUBIN:

we knew we had found
what we were looking for.
NEIL SHUBIN:

A flat snout with
upward staring eyes:
NARRATOR:

the signature of an animal that
pushes its head out of the water.

And for that, it would have needed
something like arms.

What we did at that moment
was all jump around high-fiving.
NEIL SHUBIN:

It was, uh, you know, there were only
six of us in the field that time,
NEIL SHUBIN:

NEIL SHUBIN:

so it was
quite a scene.
NEIL SHUBIN:

Back at home, Shubin and
his team got to work,
NARRATOR:

examining their
375-million-year-old fossil.

They named their new finding "Tiktaalik,"
an Inuit word for a freshwater fish.

Tiktaalik is a perfect
transitional form.

Much of its body
is that of a fish.

It's covered in scales.

But it also had
something very un-fish like...

an arm-like fin,
or perhaps a fin-like arm.

Tiktaalik had the bone structure that
is seen in the arms and legs

of every four
limbed animal.

One big bone at the top,
two bones underneath,

leading a cluster of bones
in the wrist and ankle.

It's the same pattern that is found
in everything from sheep,

to sheepdogs,
to Shubin himself.

You now have an animal that can
push itself up off the substrate,
NEIL SHUBIN:

NEIL SHUBIN:

either on the
water bottom or on land.
NEIL SHUBIN:

One obvious question
NARRATOR:

Was: Why had Tiktaalik
evolved this new structure?

One possible answer is suggested
by other fossils found near it.

There are large predatory fish
about ten to 15 feet long
NEIL SHUBIN:

NEIL SHUBIN:

living alongside Tiktaalik.
NEIL SHUBIN:

Tiktaalik was prey.
NARRATOR:

To survive, it had few choices.

You can get big, you can get armor
or you can get out of the way.
NEIL SHUBIN:

Shubin thinks Tiktaalik
got out of the way.
NARRATOR:

With those arm-like fins,

it could have dragged itself to
safety on land or in the shallows.

But this was only
half the answer.

What it doesn't show us is
the actual genetic mechanism,
NEIL SHUBIN:

NEIL SHUBIN:

the genetic recipe that builds a fin
into that which builds a limb.
NEIL SHUBIN:

At 375 million years old,
Tiktaalik's DNA had vanished long ago.
NARRATOR:

Shubin needed a next-of-kin,
a fish relative that was still alive.

What we needed
was a creature
NEIL SHUBIN:

NEIL SHUBIN:

was in the right part of
the evolutionary tree,
NEIL SHUBIN:

NEIL SHUBIN:

but also a fish that
has a very fleshy fin.
NEIL SHUBIN:

NEIL SHUBIN:

So the search was on.
NEIL SHUBIN:

A number of
fish fit the bill.
NARRATOR:

But Shubin favored
one in particular...

the paddle-fish.

The paddle-fish is
a really weird fish.
NEIL SHUBIN:

They developed
this really long snout.
The paddle-fish is
a really weird fish.
NEIL SHUBIN:

NEIL SHUBIN:
They developed
this really long snout.

NEIL SHUBIN:

And they're really voracious.
NEIL SHUBIN:

They eat each other.
And they're really voracious.
NEIL SHUBIN:

NEIL SHUBIN:
They eat each other.

NEIL SHUBIN:

So oftentimes you'll lose a lot of
your fish when they swim together,
NEIL SHUBIN:

NEIL SHUBIN:

because they'll
eat each other.
NEIL SHUBIN:

Living in the shallow waters of the
Mississippi, it's also a living fossil.
NARRATOR:

Scientists have spent years
working out the relationships

between different species of fish

and they know that the paddle-fish
is one of the last survivors

of the class to which
Tiktaalik once belonged.

But unlike Tiktaalik, the
paddle-fish is in plentiful supply.

Paddle-fish is a common
source for caviar.
NEIL SHUBIN:

NEIL SHUBIN:

So we'd get our paddle-fish
from caviar farms.
NEIL SHUBIN:

Intriguingly, even though
Tiktaalik is extinct,
NARRATOR:

the paddle-fish is actually
the more primitive form.

Its fins bear far less relation to
an arm or leg than Tiktaalik's.

And because
they are related,

the two kinds of fish
should share the same genes.

So Shubin began looking
at paddle-fish embryos,

hunting for the genes
that built its fins.

And soon he zeroed
in on one particular

group of body plan
genes called Hoax genes.

Hoax genes have been found
in all complex animals

from the velvet worm,
that dates back some 600 million years,

to the modern human.

And in all that time,

the letters of their DNA have
remained virtually unchanged.

They are aristocrats of
the gene community,

near the very top of
the chain of command.

They give orders that cascade
through a developing embryo...

activating entire networks
of switches and genes

that make the
parts of the body.

They are absolutely critical to the
shape and form of a developing creature.

These genes determine where the front
and the back of the animal's going to be;
SEAN CARROLL:

SEAN CARROLL:

the top, the bottom,
the left, right the inside,
SEAN CARROLL:

SEAN CARROLL:

the outside: where the
eyes are going to be,
SEAN CARROLL:

SEAN CARROLL:

where the legs are going to be,
where the gut's going to be
SEAN CARROLL:

SEAN CARROLL:

how many fingers
they're going to have.
SEAN CARROLL:

Shubin found that
Hoax genes had a key
NARRATOR:

NARRATOR:

role in the formation
of paddle-fish fins.
NARRATOR:

One set of Hoax genes orders the
first stage of fin development,

a sturdy piece of cartilage
that grows out from the torso.

Amazingly, in all four-limbed
animals, even us.

Exactly the same genes,
create the long upper arm bone.

In the paddle-fish,
another set of Hoax genes

command the next
stage of fin development.

Again, exactly the same genes control
the growth of our two forearm bones.

Finally, the same genes,
working in a different order,

make the array of
bones at the end of the fin.

The same sequence of the
same genes makes our fingers and toes.

This was a massive revelation.

Suddenly the origin of
creatures with arms and legs,

didn't seem such
a huge leap after all.

If the same genes
were at work in Tiktaalik,

then many of the genes
needed to make legs and arms

were already being carried
around by prehistoric fish.

All it needed was
a few mutations;

a few changes to the timing and order
of what was turned off and on,

and a fin could become a limb.

Oftentimes the origin of whole
new structures in evolution,
NEIL SHUBIN:

NEIL SHUBIN:

doesn't involve the origin of new
genes or whole new genetic recipes.
NEIL SHUBIN:

NEIL SHUBIN:

Old genes, old
genetic pathways,
NEIL SHUBIN:

NEIL SHUBIN:

can be reconfigured to make
marvelously wonderful new things.
NEIL SHUBIN:

So it is now possible to answer
what Darwin didn't know,
NARRATOR:

and explain how all four-legged
creatures could be descended from fish.

Around 375 million years ago, a creature
like Tiktaalik was under attack...

harried by predators.

But some random changes to the activity
of the Hoax genes led to its fins,

developing a
structure like a limb.

Tiktaalik could now haul itself
out of danger, onto dry land.

On land, it would have found
a world of plants and insects...

a world ripe for colonization...

a world perfect for
animals with arms and legs.

And so, over millions of years,

these new limbs evolved,
changed and diversified.

Some became
adapted for running.

Others for flying.

Some for digging.

Others for swinging.

And so four-limbed creatures took over the
world in a multitude of different ways.

And all because of some changes
to an ancient set of genes.

And this is the true wonder of where our
new understanding of DNA has led us to.

There are genes that
make the stuff of our bodies,

switches that turn
them off and on,

and still other genes that
give those switches orders.

Together in a complex cascade
of timing and intensity,

they combine to produce the amazing
diversity of life on this planet.

That truly is something
that Darwin never knew.

But can this new
science also explain

perhaps the most
fundamental question of all?

What makes us human?

The scope of human activity
is simply astounding.

What fascinated me were all
the crazy things that humans do.
KATIE POLLARD:

KATIE POLLARD:

You look around the world,
KATIE POLLARD:

KATIE POLLARD:

and if there is something bizarre and
interesting that you could be doing,
KATIE POLLARD:

KATIE POLLARD:

humans are up to it
somewhere in the world.
KATIE POLLARD:

KATIE POLLARD:

And when you look at all of this,
you just have to ask yourself,
KATIE POLLARD:

KATIE POLLARD:

what makes us special?
KATIE POLLARD:

KATIE POLLARD:

What is the basis
for this humanness?
KATIE POLLARD:

For all nature's wonders,
NARRATOR:

the achievements of the
human mind are truly unique.

We are the only species to think
about what others think about us,

to punish those who have
harmed others,

to create art...

music...

architecture...

to engage in science...

medicine...

the microchip.

Only we can destroy millions
at the push of a button.

Hardly surprising, then, that for
centuries we thought that humans

were different from all other species,
better, created in the image of God.

But then Darwin began to draw conclusions
from evidence like gill slits

in human embryos that showed that
we were descended from fish.

(PEOPLE AMAZED):

But it was when he drew
parallels with other close relatives,
(PEOPLE AMAZED):

But it was when he drew
parallels with other close relatives,

that he got into real trouble.

Shortly after Darwin
returned from his voyage,
SEAN CARROLL:

SEAN CARROLL:

in London, an orangutan
named Jenny went on exhibit.
SEAN CARROLL:

SEAN CARROLL:

And this was a huge sensation.
SEAN CARROLL:

SEAN CARROLL:

This was the first great
ape to be exhibited in captivity.
SEAN CARROLL:

SEAN CARROLL:

And Darwin was absolutely taken with
how she was sort of childlike in her ways.
SEAN CARROLL:

SEAN CARROLL:

And he saw a lot of human behavior
in the way this orangutan behaved.
SEAN CARROLL:

When Darwin suggested that human beings
must actually be descended from apes,
NARRATOR:

he was savaged.

He was accused of
attacking that core belief

that humankind had been created in the
image of God above all other creatures.

But today the idea that we share
a common ancestor with apes

is completely accepted in biology.

Instead, as a result of having sequenced
the genomes of both humans and apes,

we face a very different puzzle.

Katie Pollard is an
expert on chimp DNA.

Given all the obvious differences
between humans and chimps,
KATE POLLARD:

KATE POLLARD:

you might expect our
DNA to be really different.
KATE POLLARD:

KATE POLLARD:

But in fact, it's more
like 99% identical.
KATE POLLARD:

Just a one-percent difference in
the DNA of humans and chimps.
NARRATOR:

The mystery facing modern science is not
how can such different animals be related,

but how can such closely
related species be so different?

That really is something
that Darwin never knew,

but slowly, scientists are
starting to find the answers.

And one answer begins
with insights into the genetics

of a key human organ,
our hands.

The human hand is a marvel,

nimble and dexterous.

Nothing quite like it exists
anywhere else in nature.

It offers us a unique combination
of precision and power,

and much of that is down to
one particular digit, our thumb.

One of the features
of the human hand,
JIM NOONAM:

JIM NOONAM:

is our ability to touch all
four fingers with the thumb.
JIM NOONAM:

JIM NOONAM:

And that allows us to make grips
like this, gives us a lot of precision.
JIM NOONAM:

JIM NOONAM:

The power grip is the ability to put a
lot of strength into this sort of contact.
JIM NOONAM:

JIM NOONAM:

So if you're holding a ball,
you're basically pinching it,
JIM NOONAM:

JIM NOONAM:

and we can put a lot
of strength into that.
JIM NOONAM:

The better to
throw a fastball with.
NARRATOR:

Finding out why we have
such versatile hands

compared to our nearest relatives is
the task of Jim Noonan at Yale University.

He began sifting through
that vital one percent of DNA

that is different in
humans from chimps.

It's kind of one of the fundamental
questions in science:
JIM NOONAN:

Is, what makes us who we are?
It's kind of one of the fundamental
questions in science:
JIM NOONAN:

JIM NOONAN:
Is, what makes us who we are?

JIM NOONAN:

And that's really what
we're trying to get to;
JIM NOONAN:

JIM NOONAN:

what makes humans human.
JIM NOONAN:

It was slow work.
NARRATOR:

One percent may
not sound like much,

but it's still some 30 million of DNA's
chemical letters: A's, T's, C's and G's.

The genome's a big place.
JIM NOONAN:

JIM NOONAN:

And just by looking at sequence,
you really can't tell,
JIM NOONAN:

JIM NOONAN:

for the most part,
what is important and what isn't.
JIM NOONAN:

But eventually, in human DNA
he spotted something.
NARRATOR:

A sequence that was different in
13 places compared to chimp DNA.

The trouble was, he had no idea what
this piece of DNA actually did.

To find out, he inserted it into
the embryo of a mouse.

To make the effects of
the DNA easier to follow,

he attached it to another gene
that gives off a blue color.

That way he could see where the gene
became active in the embryo.

As the embryo developed, the piece of
DNA seemed to be active all over the place.

But most intriguingly, it was doing
something in the growing paw.

Well, I thought "Wow, this is really cool."
It was a really striking image.
JIM NOONAN:

What Noonan saw
was that the human DNA
NARRATOR:

became active in the mouse
embryo's thumb and big toe.

It seems that Noonan
may have found a switch

that helps form that
key human attribute:

our thumb, the part of our hand that
gives us so much power and precision.

It's that power and precision that
enables us to hold a paintbrush...

manipulate tools...

pilot a jet fighter,

record our thoughts.

All those things that
separate us from other apes.

Of course, having a
nimble hand is one thing,

but you have
to know how to use it.

And for that, you need to have
humankind's other signature organ:

our brain.

The human brain is vast,
three times bigger than a chimp's,

and is structured very differently.

How this extraordinary
organ evolved is central

to understanding why
we are the way we are.

It is something that Darwin
himself was at a loss to explain,

which is why many of his
critics remained unconvinced,

by his account
of human origins.

But now part of the answer to
why we have such a remarkable brain,

may have come from
a surprising source.

Hansell Stedman is a dedicated
athlete and a medical doctor.

He never imagined
he would come up with

an answer to a profound
evolutionary mystery.

He has devoted his career to trying
to cure muscular dystrophy;

a distressing and sometimes
fatal degenerative disease.

His quest is very personal.

My first exposure to muscular
dystrophy was inescapable;
HANSELL STEDMAN:

HANSELL STEDMAN:

my younger and my older brother
both born with muscular dystrophy.
HANSELL STEDMAN:

Muscular dystrophy
is a genetic disease.
NARRATOR:

Its sufferers have a
mutation in one gene,

that robs their muscles of
the ability to repair themselves.

Typical workout here on the rocks might
blow through a few thousand muscle cells,
HANSELL STEDMAN:

HANSELL STEDMAN:

but they'll regenerate overnight,
HANSELL STEDMAN:

HANSELL STEDMAN:

and if anything, be a little stronger
the next day I come in,
HANSELL STEDMAN:

HANSELL STEDMAN:

as a result of all of that.
HANSELL STEDMAN:

HANSELL STEDMAN:

Whereas, in muscular dystrophy,
HANSELL STEDMAN:

HANSELL STEDMAN:

the injury process
is greatly accelerated,
HANSELL STEDMAN:

HANSELL STEDMAN:

and the injury process outstrips
the body's ability to repair.
HANSELL STEDMAN:

In search of a cure,
NARRATOR:

Stedman is investigating
the hundreds of genes

that control the
development of muscles.

So when the Human Genome Project took off,
Stedman seized his chance.

When the horsepower of the entire
Human Genome Project kicked in,
HANSELL STEDMAN:

HANSELL STEDMAN:

we knew exactly
what to look for.
HANSELL STEDMAN:

Stedman was hunting for
any new muscle-making genes.
NARRATOR:

And so, as the human
genome was sequenced,

he began sifting through
the vast mountains of data.

Eventually he found
what he was looking for;

a previously unidentified
muscle-making gene.

But there was something
strange about this new gene.

It didn't look like any other
muscle-making genes.

Two letters were missing.

This gene should
cause a disease.

It became very clear early on that
if you have a mutation of this type,
HANSELL STEDMAN:

HANSELL STEDMAN:

you get some serious
muscle problem going on.
HANSELL STEDMAN:

Here was a puzzle.
NARRATOR:

Why would humans carry a
gene that was clearly damaged?

Perhaps it was simply
a mistake in the data.

Stedman decided to dig a little deeper
and look in another human subject.

In the department
of true confessions,
HANSELL STEDMAN:

HANSELL STEDMAN:

we do certain experiments
first on ourselves,
HANSELL STEDMAN:

HANSELL STEDMAN:

largely out of convenience.
HANSELL STEDMAN:

HANSELL STEDMAN:

You can swab your own cheek
and get working on some DNA.
HANSELL STEDMAN:

To his utter amazement, he found
the same damaged gene in himself.
NARRATOR:

I'm seeing this in my own DNA,
and it's suggesting that "Wait a minute.
HANSELL STEDMAN:

HANSELL STEDMAN:

"That means there's a muscle
disease here somewhere,
HANSELL STEDMAN:

HANSELL STEDMAN:

a muscle disease
that I'm unaware of."
HANSELL STEDMAN:

HANSELL STEDMAN:

And I thought it would
be worth checking this out
HANSELL STEDMAN:

HANSELL STEDMAN:

in some other
members of the lab.
HANSELL STEDMAN:

A few swabs later and...
NARRATOR:

Sure enough,
at the end of the day,
HANSELL STEDMAN:

HANSELL STEDMAN:

every single person had the same glitch
in their same DNA at the same place.
HANSELL STEDMAN:

Here then
was a real mystery.
NARRATOR:

It seemed that this particular muscle
-making gene was common in humans.

But when he identified
the same gene in apes,

it was just like any other
muscle-making gene.

Why was there
such a difference?

What did this gene enable one species
to do that the other could not?

Stedman began to research
the role of this gene in apes.

And he found it made one
particular kind of muscle;

the muscle for chewing.

In fact, the muscle used
to close the jaw.

In humans, that genetic
glitch meant that we chew

with just a fraction
of the force of an ape.

This in itself
was interesting,

but where Stedman went next was truly
intriguing and highly controversial.

He drew a direct connection between
the power of our jaw muscle

and the evolution
of the human brain.

Stedman's thinking
goes like this.

The skulls of apes and humans are made
of several independent bone plates.

They let our heads
get bigger as we grow.

The muscles for chewing
pull against these plates.

And in an ape,
these forces can be enormous.

In the gorilla, the muscle;
the size of a human thigh muscle;
HANSELL STEDMAN:

HANSELL STEDMAN:

lives here and has to go
through this large space
HANSELL STEDMAN:

HANSELL STEDMAN:

to power the jaw
moving back and forth.
HANSELL STEDMAN:

HANSELL STEDMAN:

We're not talking biceps,
triceps, we're talking quad here.
HANSELL STEDMAN:

HANSELL STEDMAN:

This is an
enormous muscle,
HANSELL STEDMAN:

HANSELL STEDMAN:

that has to come right through this hole
here to power the jaw-closing apparatus.
HANSELL STEDMAN:

Stedman contends
that all this muscle power
NARRATOR:

forces an ape's skull plates to
fuse together at an early stage,

and this puts limits on how
much the brain can grow.

In a chimpanzee,
gorilla, orangutan,
HANSELL STEDMAN:

HANSELL STEDMAN:

those growth plates
are pretty much shut down,
HANSELL STEDMAN:

HANSELL STEDMAN:

closed for business by
about three, four years of age.
HANSELL STEDMAN:

HANSELL STEDMAN:

In a human, they remain open
for growth to perhaps age 30.
HANSELL STEDMAN:

This, Stedman
believes, is the key.
NARRATOR:

A mutation in our jaw muscle
allows the human skull

to keep expanding
into adulthood,

creating a bigger
space for our brain.

And so our most important
organ is able to grow.

It's very cool to us
to think that some kind of
HANSELL STEDMAN:

HANSELL STEDMAN:

muscle-altering mutation might
have actually been a signature event
HANSELL STEDMAN:

HANSELL STEDMAN:

in the evolution of what
makes us distinct as a species.
HANSELL STEDMAN:

HANSELL STEDMAN:

It might have been an
absolute prerequisite
HANSELL STEDMAN:

HANSELL STEDMAN:

for us landing
where we are today.
HANSELL STEDMAN:

But having the space
for a big brain is one thing.
NARRATOR:

What is needed
to actually grow one?

That is the question that
Chris Walsh is trying to answer.

He's another scientist
who never expected

to be taking on what even
Darwin didn't know.

I never thought that
I'd be studying evolution.
CHRIS WALSH:

CHRIS WALSH:

I'm a neurologist interested in the
brain and kids with neurological problems.
CHRIS WALSH:

CHRIS WALSH:

How you doing, buddy?
Are you doing all right, huh?
CHRIS WALSH:

CHRIS WALSH:

You doing okay?
CHRIS WALSH:

CHRIS WALSH:

No one was more
surprised than us
CHRIS WALSH:

CHRIS WALSH:

to find that the study
of kids with disabilities
CHRIS WALSH:

CHRIS WALSH:

would lead us into these
fascinating evolutionary questions.
CHRIS WALSH:

CHRIS WALSH:

Is his breathing generally
okay during the day?
CHRIS WALSH:

CHRIS WALSH:

Sometimes when he gets startled,
it will go up fast, like...
CHRIS WALSH:

CHRIS WALSH:

(panting) ...but then he calms
himself right back down...
CHRIS WALSH:

Walsh is a specialist in a rare
disorder called microcephaly.
NARRATOR:

Children with microcephaly,

are born with brains that
can be half the normal size.

This disorder can be very devastating
for the kids that have it.
CHRIS WALSH:

CHRIS WALSH:

They typically will have s
severe mental retardation,
CHRIS WALSH:

CHRIS WALSH:

and so will not be able to achieve
normal language and normal schooling.
CHRIS WALSH:

CHRIS WALSH:

And so it's really an event
that defines the whole family.
CHRIS WALSH:

CHRIS WALSH:

It defines the lives
not only of the child,
CHRIS WALSH:

CHRIS WALSH:

but of the parents
of that child.
CHRIS WALSH:

CHRIS WALSH:

And these families are desperately
eager to try to understand,
CHRIS WALSH:

CHRIS WALSH:

at least what caused the
disorder in their kids.
CHRIS WALSH:

The purpose of Walsh's work
was initially to help families
NARRATOR:

that might be carrying
any defective genes,

causing microcephaly
to plan their lives.

We're able to offer those
families predictive testing,
CHRIS WALSH:

so that if they're planning
on having additional children,

we can tell them ahead of time whether
that child is likely to be affected or not.

First, Walsh had to decide
where to look in the vast genome
NARRATOR:

to find any possible
microcephaly-causing genes.

So he focused on one
particular area of DNA.

Other research suggested it contained
a gene involved in the condition.

That gene is known to control how and
when brain cells divide in animals,

such as
fruit flies and mice.

What this gene seems
to do is help control
CHRIS WALSH:

CHRIS WALSH:

the fundamental decision
that the brain has to make,
CHRIS WALSH:

CHRIS WALSH:

which is "When do
I stop making cells?
CHRIS WALSH:

CHRIS WALSH:

When is the
brain big enough?"
CHRIS WALSH:

Then his team began
searching for that same gene
NARRATOR:

in a family with a
history of the disease.

And sure enough,
they found something.

A gene that helps
direct brain growth.

And crucially,
it was defective.

Walsh decided to check this
finding in other patients.

Once we found this gene,
CHRIS WALSH:

CHRIS WALSH:

we sequenced it in our kids
with microcephaly disorder.
CHRIS WALSH:

CHRIS WALSH:

And we found that
one family after another,
CHRIS WALSH:

CHRIS WALSH:

had a disabling change in the gene that
completely removed its function.
CHRIS WALSH:

In total he has found some 21 different
mutations responsible for microcephaly.
NARRATOR:

Sometimes one of the DNA's chemical
letters is replaced with another letter.

Sometimes letters
are missing entirely.

But whatever the defect is, they all
stop the brain cells from dividing

at a very early
stage of development.

Walsh was now certain;
thanks to his microcephaly patients;

he had found a gene key to the
growth of the human brain.

Now he decided to
compare normal versions

of the gene found
in healthy humans

with the same gene in chimpanzees,
our closest relatives.

And what he found
was astonishing.

The gene in humans was radically
different from that found in chimps.

There had been a
large series of mutations.

It could be that
these mutations,

were a major factor in the
evolution of our huge brains.

And this discovery came about only
because of Walsh's work with his patients.

I think one of the
amazing things for us
CHRIS WALSH:

CHRIS WALSH:

was the extent to which
studying human disease
CHRIS WALSH:

CHRIS WALSH:

can unexpectedly enlighten us about
something like human evolution.
CHRIS WALSH:

But this is only the
beginning of our understanding
NARRATOR:

of the evolution of
the human brain.

It's an area of research that
is now attracting scientists

with a range of skills that
Darwin would have marveled at.

Katie Pollard is
a bio statistician.

Her life is spent
crunching numbers.

What I love about my work is
gee-king out on a computer
KATIE POLLARD:

and writing programs
and thinking about biology.

And that in doing this,

I'm actually working on something
that not just scientists care about,

but really every human being can
relate to and cares profoundly about,

and that's what
makes us human.

Pollard has constructed
an ambitious computer program.
NARRATOR:

It's designed to highlight DNA that is
similar in apes and other animals,

but which is very
different in humans.

That way, she hopes to identify
the key DNA that makes us, us.

Out of these 15 million letters that
make humans different from chimps,
KATIE POLLARD:

KATIE POLLARD:

we need to try to figure out
which ones were important.
KATIE POLLARD:

KATIE POLLARD:

And so we use a technique
which is to look for places
KATIE POLLARD:

KATIE POLLARD:

where human is
different from chimp,
KATIE POLLARD:

KATIE POLLARD:

but chimp looks almost
identical to the other animals.
KATIE POLLARD:

She too is looking for DNA
relating to the human brain.
NARRATOR:

The brain is one of the things that's
changed the most during human evolution,
KATIE POLLARD:

KATIE POLLARD:

both in terms of its
complexity and its size.
KATIE POLLARD:

KATIE POLLARD:

And so when we look to find the parts
or our genome that make us human,
KATIE POLLARD:

KATIE POLLARD:

we're particularly
interested in finding out
KATIE POLLARD:

KATIE POLLARD:

whether these are things
that are involved in the brain.
KATIE POLLARD:

It is a huge feat
of number crunching,
NARRATOR:

as Pollard loaded in DNA sequences
from both humans and chimps.

You basically take a bunch
of computer hard drives
KATIE POLLARD:

KATIE POLLARD:

and you stack
them up together.
KATIE POLLARD:

KATIE POLLARD:

We were able to take a task
that would have run for 35 years
KATIE POLLARD:

KATIE POLLARD:

on a desktop computer
and do it in one afternoon.
KATIE POLLARD:

And at the end
of that afternoon,
NARRATOR:

they had a whole
array of material,

charting the differences
between humans and chimps.

Importantly, many of those differences
were not in the actual genes.

They were in switches.

It turns out that the vast
majority are not genes.
KATIE POLLARD:

KATIE POLLARD:

Instead they're pieces of our DNA
that we can think of as switches;
KATIE POLLARD:

KATIE POLLARD:

they're pieces of DNA that turn
a nearby gene on or off...
KATIE POLLARD:

KATIE POLLARD:

that tell it where, in what cells
in our body, in what tissue,
KATIE POLLARD:

KATIE POLLARD:

at what time or at
what level to be operating.
KATIE POLLARD:

And there was something even more
intriguing about those switches.
NARRATOR:

A large number of them,
more than half,
KATIE POLLARD:

KATIE POLLARD:

were nearby a gene that
was involved in the brain.
KATIE POLLARD:

In Pollard's work, one particular
piece of DNA stood out.
NARRATOR:

It was a piece of DNA that is known
to be active in the development

of one of the key parts of the
human brain in the embryo...

the cortex.

The cortex is that wrinkled
outer layer of our brain.

It's vital for those defining
human capabilities like,

language, music
and mathematics.

When she looked at
that DNA in chimps

and compared it to
the same DNA in a chicken,

it was different
in just two letters.

But in humans it was
different by 18 letters.

A massive mutation.

This was about as great of a eureka
moment as you could have as a scientist.
KATIE POLLARD:

So here is another
intriguing piece of evidence,
NARRATOR:

suggesting how DNA can shape
our distinctive human qualities.

We now know that DNA
works in many different ways,

through genes that make
the stuff of our bodies,

through switches that turn
those genes on and off

and through sequences of DNA's
chemicals that throw those switches.

Taken together,
what this all adds up to,

is a way that we can at last understand
how small differences in DNA

can generate
enormous change.

Basically, you can make massive
changes just changing those switches.
KATIE POLLARD:

KATIE POLLARD:

So a small change,
a couple of DNA letters,
KATIE POLLARD:

KATIE POLLARD:

could have a
profound effect.
KATIE POLLARD:

And so that final
Darwinian puzzle;
NARRATOR:

how a human can be so
closely related to an ape,

and yet be so different;
is now slowly being answered.

150 years after Darwin first
put forward his grand theory,

to explain the great diversity of life,

the scientists who carry on his legacy
have advanced his work in wondrous ways.

I think if Darwin were here today,
he'd be absolutely stunned,
SEAN CARROLL:

SEAN CARROLL:

delighted, even moved to see
how much his theory has grown.
SEAN CARROLL:

What we now are able to understand on
the one hand would just blow him away.
CLIFF TABIN:

CLIFF TABIN:

But I also think it would give
him enormous satisfaction,
CLIFF TABIN:

CLIFF TABIN:

because ultimately
everything we've been learning,
CLIFF TABIN:

CLIFF TABIN:

validates the
things that he said.
CLIFF TABIN:

I think that Darwin
was a remarkable scientist
OLIVIA JUDSON:

OLIVIA JUDSON:

and absolutely
should be celebrated.
OLIVIA JUDSON:

OLIVIA JUDSON:

However, I do not think that he
was the end of evolution.
OLIVIA JUDSON:

OLIVIA JUDSON:

On the contrary,
I think he was the beginning.
OLIVIA JUDSON:

OLIVIA JUDSON:

He outlined the
major points,
OLIVIA JUDSON:

OLIVIA JUDSON:

but we have discovered more than
I think he would have imagined possible.
OLIVIA JUDSON:

As we celebrate the 200th
birthday of Charles Darwin
NARRATOR:

and the 150th anniversary
of his great work,

there is still much
more to understand

about how the endless
forms of nature have arisen.

And in rising to
that challenge,

it is likely that we will
continue to advance medicine

and come to a better understanding
of ourselves as well.

NOVA has a brand-new evolution
Web site with dozens of videos,

interviews, slide shows and the
latest in evolutionary science.

Bookmark it today and
let us know what you think.

Find it at pbs.org.