Cracking the Code Of Life ✪ PBS Nova Documentary HD

(Narrator) When I look at this, and these
are 3 billion

chemical letters. Instructions for a human

being, my eyes glaze over,

(laughing)

but when scientist, Eric Lander looks at

this, he sees stories.

(Eric) The genome is a storybook

that's been edited for a couple billion

years, and you couldn't take it

to bed like a 1,001 Arabian nights and

read a different story in the genome

every night.

(Narrator) This is the story of one of

the greatest scientific adventures ever.

And at the heart of it, is a small, very

powerful molecule, DNA.

For the past ten years, scientists

all over the world have been painstakingly

trying to read the tiny instructions

buried inside our DNA.

And now, finally, the human genome has

been decoded.

(Craig) We're at the moment the scientists

wait for. This is what we wanted to do.

We're now examining

and interpreting the genetic code.

(Francis) This is the ultimate

imaginable thing that one could do,

scientifically, is to go look at our

own instruction book, and then try

to figure out what it's telling us.

(Narrator) What it's telling us is so

surprising, and so strange, and so

unexpected.

(Narrator) 50% of the genes in a banana

are in us.
(Eric) How different are you from a banana

I feel like I can say this with

some authority, very different

from a banana.
(Eric) You may feel different from a

banana.

All the machinery for replicating your
DNA, all the machinery for controlling

the cell-cycle, the cell surface, for
making nutrients, all that's the same.

(Narrator) So what does any of this
information have to do

with you, or me? Perhaps more than we

could possibly imagine.

Which one of us will get cancer, or
arthritis, or Alzheimer's.

Will there be cures? Will parents in the
future, be able to determine their

children's genetic destinies.

(Eric) We've opened the box here

that's got a huge amount of valuable
information.

It is the key to understanding disease

and, in the long run, to curing disease.

But having opened it... we're also gonna

be very uncomfortable with that info

for some time to come.

(Narrator) Yes, some of the info

you're about to see will make you

very uncomfortable, on the other hand,
some of it, I

think you will find amazing and hopeful.

I'm Robert Krulwich, and tonight, we will

not only report the latest discoveries of

the Human Genome Project, you will meet

the people who made those discoveries

possible, and who competed furiously to

be first to be done. And as you watch

our program on the human genome,

We will be raising a number of issues,

genes and privacy, genes and corporate
profits,

genes and the odd similarity between you

and yeast. And we'd like to have your

thoughts on all these subjects, so please,

if you will, login to Nova's website. It's

located at PBS.org. It'll be there
after the

broadcast, so do it after the
broadcast,

where you can take a survey,
the results will

be immediately available and continually

updated. We'll be right back.

♪ (Intro music playing) ♪

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by the Park Foundation, dedicated
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and quality television.

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the Northwestern Mutual Foundation.

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(Woman) Scientific achievement is fueled

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(Man) Major funding for this program is

provided by, "The National Science
Foundation."

- America's investment in the future.

(Man) And by the Corporation For Public
Broadcasting

and by contributions to your PBS station

from viewers like you.

Thank you.

(Narrator) To begin, let's go back
4-and-some billion years ago

to wherever it was that the first speck of

life appeared on Earth.

Maybe on the warm surface of a bubble.

That speck did something that's gone on,
uninterrupted ever since.

It wrote a message. It was a chemical

message, that it passed to its children

and passed it on to its children, and

to its children, and so on.

The message has passed from the very first

organism, all the way down through time,
to you and me.

Like a continuous thread, through all

living things.

It's more elaborate, now, of course, but

that message is, very simply, is the

secret of life.

And here is that message, contained in

this stunning little constellation of

chemicals, we call, "DNA".

You've seen it in this form, the classic

"Double Helix", but since we're gonna be

spending a lot of time talking about

DNA, I wondered what it looks like when

it's raw, ya know, in real life?

So, I asked an expert.

Eric Lander - DNA has a reputation for

being such a mystical, highfalutin sort of

molecule. All this information, your

future, your heredity, it's actually goop.

See, this here is DNA.

(Narrator) Professor Eric Lander is a

geneticist at MIT's Whitehead Institute.

(Eric) It's very very long strands of

molecules. These double helices of DNA,
which, when you get them all

together, just look like little threads
of cotton.

(Narrator) And these strands were

literally pulled from cells. Blood
cells, maybe skin cells, of a human being.

Eric - Whoever contributed this DNA,

you can tell from this whether or not they

might be at early risk for Alzheimer's

disease. You can tell if they might be at

early risk for breast cancer.

And there's probably about 2,000 other

things you can tell, that we don't know

how to tell yet, but we'll be able

to tell. And it's, really, incredibly
unlikely that you could tell

all that from this.

But, that's DNA for you.

That, apparently, is the secret of life,

just hanging off there on the tube.

(Narrator) And already, DNA has told

us things that no one, no one had
expected.

It turns out that human beings have only

twice as many genes as a fruit fly.

Now how can that be?

We are such complex and magnificent
creatures, and fruit flies, well, uh,

they're fruit flies.

DNA also tells us that we are more closely
related to worms and to yeast than

most of us would ever have imagined.

But how do you read what's inside a
molecule?

Well, if it's DNA, if you turn it so you

can look at from just the right angle,

you will see, in the middle, what

look like steps in a ladder.

Each step is made up of two chemicals,

"Cytosine" and "Guanine", or
"Thymine" and "Adenine".

They come, always, in pairs called,
"Base-Pairs" either C and G, or T and A,

for short.

This is, step-by-step, a code.

Three-billion steps long; the formula for

a human being.

We're all familiar with this thing.

This shape is very familiar.

(Eric) Double Helix.
(Narrator) Double Helix.

First of all, I want to... this is my

version of a DNA molecule.

Is this, by the way, what it looks like?

(Eric) Well, ehm, give or take... a
cartoon version of it.

I mean, a little like that, yeah.

(Narrator) So there are, in almost every
cell in your body, if you look deep

enough, you will find this chain here?

Eric - Oh, yes, stuck in the nucleus of
your cell.

Narrator - Now how small is this?

In a real DNA molecule, the distance

between the two walls is how wide?

Eric - Oh, golly.

(Narrator) Look at this, he's asking for
help.

(laughing)

Eric -This distance is about
10 Angstroms.

(Narrator) That's one-billionth of a meter

when it's clumped up in a very particular
way.

Eric - Well, no, it's curled up sort of
like that, but, it's more than that.

You can't curl it up too much, bc
these little negative charge things

will repel each other. So, you fold it on
itself.

I'm gonna break your molecule..

Narrator - Yeah, don't break my molecule.

Eric - Ya know, ya got this
and then it's folded up like this

and then those are folded up on top

of each other. And, so, in fact, if you

were to stretch out all of the DNA, it

would run, oh I don't know, thousands

and thousands of feet.

Narrator - Okay.

The main thing about this, is

the ladder, the steps of this ladder.

Narrator - If I knew it was "A" and "T"
and "C" and "C" and "G" and "G" and "A"...

Eric - Oh, no, it's not "'G' and 'G', it's
'G' and 'C'. It's the grammar...

Narrator - If I could read each of the

individual ladders, I might find the

picture of... what?

Eric - Of your children.

This is what you pass to your children.

Ya know, people have known for 2,000
years that your kids look a lot

like you. Well, it's because you must pass

them something... Some instructions that

give them the eyes they have and hair

they have, and the nose shape they do.

The only way you pass it to them is in

these sentences. That's it.

(Narrator) And to show you the true power

of this molecule, we're gonna start with

one atom, deep inside.

We pull back and see it form its "A"'s and
"T"'s and "C"'s and "G"'s and the

classic double spiral....

And then starts the mysterious process

that creates a healthy new baby.

♪ (music playing) ♪

And the interesting thing is that every

human baby, every baby born, is 99.9%

identical in it's genetic code to every

other baby.

So, the tiniest differences in our genes

can be hugely important.

Can contribute to differences in height,

physique, maybe even talents, aptitudes,

and it also explain what can break...

What can make us sick.

Cracking the code of those minuscule

differences in DNA, that influence health

and illness, is what the Human Genome
Project is all about.

Since 1990, scientists all over the world

in university and government labs have

been involved in a massive effort to read

all three-billion A's, T's, G's, and C's

of human DNA.

They predicted it would take, at least

15 years. That was partly because, in the
early days of the project,

a scientist could spend years, an entire

career, trying to readjust a handful of

letters in the human genome.

It took 10 years to find the one genetic

mistake that causes Cystic Fibrosis.

Another 10 years to find the gene for

Huntington's Disease.

15 years to find one of the genes that

increase the risk for breast cancer.

One letter at a time, painfully slowly,

frustratingly prone to mistakes, and

false leads.

We asked Robert Waterston, a pioneer in

mapping DNA, to show us the way it

used to be done.

(Robert) The original ladders for DNA

sequence, we actually read by putting a

little letter next to the band that we

were calling and then writing those

down on a piece of paper, or into the

computer after that.

Uh, it's horrendous.

(Narrator) And we haven't mentioned the

hardest part. This part here, magnified
50 thousand times, is an actual

clump of DNA Chromosome -17.

If you look inside, you find, of course,

hundred of millions of A's, and C's, and
T's, and G's, but it turns out

that only about 1% of them are active

and important. These are the genes

that scientists are searching for.

So, somewhere in this dense chemical

forest, are genes involved in deafness,

Alzheimer's, cancer, cataracts, but where?

This is such a maze, scientists need a
map.

But at the old pace, that would take close

to forever.

And then came the revolution.

In the last 10 years the entire process

has been computerized, that costed

hundreds of millions of dollars.

But now, instead of decoding only a few

hundred letters by hand in a day...

together, these machines can do 1,000
every second.

And that has made all the difference.

(Man) This is something that is gonna

go in the textbooks. Everybody knows
that.

Everybody, when the Genome Project was

being born, was consciously aware of their

role in history.

(Narrator) Getting the letters out is, has
been described as, finding the

blueprint of a human being, finding

the manual for a human being,

finding the code of a human being.

What's your metaphor?

Eric - Oh, golly gee. I mean, you can have

very highfalutin metaphors for this kind

of stuff. This is basically a parts list.

Blueprints and all these fancy names...

it's just a parts list.

It's just a parts list with a lot of
parts.

If you take an airplane, a Boeing 777,

I think it has like a hundred-thousand

parts. If I gave you a parts list for the

Boeing 777, in one sense you'd know a

lot. You'd know a hundred-thousand

components that have gotta be there.

Screws and wires and rudders and things

like that. On the other hand, I bet you

wouldn't know how to put it together and

I bet you wouldn't know why it flies.

Well, we're in the same boat... We now

have a parts list. That's what The Human
Genome Project is about.

It's about getting the parts list.

If you want to understand the plane,

you have to have the parts list, but

that's not enough to understand why

it flies. But, of course, you'd be crazy

not to start with the parts list.

And one reason it’s so important
to understand all those parts is

to decode every letter of the genome,

Is because sometimes out of 3 billion base
pairs in our DNA, just one single letter

can make a difference.

Alice and Tim Lord are parents of
two-year-old Hayden,

Alice – good morning
Tim – hey pumpkin

(Tim) – the two things that I think of the
most about Hayden, which a lot of people .

got from him right from the beginning
was that he was always very funny

Alice - Make your very very very serious
face. I love you

(Tim) – he loved to smile and laugh,
he used to guffaw this was later when he

was a year old he just found the funniest
things hilarious he and I would just crack

each other up.

(Narrator) Hayden seemed to be developing
normally but Allison began to notice

that some things were not quite right.
Allison – I was very anxious all the time

with Hayden. I was certain things were
not the same. I would see friends

changing the diaper of their child
that was around the same age

and see the physical movement
and the legs movement and

Hayden didn’t do that

♪ (Singing “Happy Birthday”) ♪

Narrator – Doctors told them that Hayden
was just developing a bit slowly, but

by the time he turned a year old, it was
clear that something serious was wrong.

he never crawled, he never talked,
never ate with his fingers,

and he seemed to be going backwards, not
progressing.

(Tim) – I remember the last time he laughed.

I took a trip with him out to buy a suit
to a wedding that night

and we came back and it was really windy,
he just loves to fill the wind,

so we had a great time. We came back and
I brought them up on the couch and sat

next to him and he just kind of threw his
head back and laughed.

Like, oh, what a fun trip! Ya, know...

It was the last time he was able to
laugh, it’s really hard.

(Narrator) – it turned out that Hayden
had Tay-Sachs disease. A genetic

condition that slowly destroys
a baby’s brain

(Kolodny) – What happens is a baby appears
normal at birth,

and over the course of the first year,
begins to miss developmental milestones.

So at six months a child should be turning

over but is unable to sit up, to stand, to
walk, to talk.

(Narrator) – Tay-Sachs disease begins at
one infinitesimal spot on the DNA ladder

if just one letter goes wrong, say this
cluster of atoms is a picture of that

letter. A mistake here can come
down to just four atoms, that’s it.

But since genes create proteins,
that error creates a problem

in this protein, which is supposed to
dissolve fat in the brain. And now

the protein doesn’t work, so fat
builds up, swells the brain, and

destroys critical brain cells. And
all of this is the result of one

bad letter in that baby’s DNA.

Kolodny – in most cases it’s a single
base change as we say, a letter

difference.

(Narrator) – One defective letter out
of 3 billion. And no way to fix it.

Tay-Sachs is a relentlessly progressive
disease. In the years since his

diagnosis Hayden has gone blind, can’t
eat solid food, it’s harder for him to

swallow, he can’t move on his own,
and he has seizures as many as 10

times a day.

Kolodny – for children with classical
Tay-Sachs disease, there is only one

outcome. Children die by age 5 to 7.
Sometimes even before age 5.

(Narrator) – as it happens, Tim has an
identical twin brother. When Hayden

was diagnosed, that brother, Charlie
went to New York to be with him.

Charlie’s wife Blythe had had been
Allison’s roommate in college and

her best friend.

Blythe – Charlie called me on the phone
and told me to Hayden had Tay-Sachs

and explained I went to the computer and
looked it up and then just couldn’t

believe what I read.
(Blythe and Taylor talking)

(Narrator) – Blythe and Charlie had a
three-year-old daughter Taylor and a

baby girl named Cameron. Cameron
was happy and healthy except for one

small thing.
Blythe – on the NTSAD website it talks

about that typically between six and
eight months is when the signs start

coming. But one of the early signs is
that they startle easily and Hayden

had always had a heavy startle
response. We noticed that Cameron

had a comparable startle response.
Not as severe, but absolutely not

like Taylor had had.
(Narrator) – as soon as she saw

that early warning sign on the Tay-Sachs
website, Blythe went to get herself and

Cameron tested.
(Charlie) – it was another week until we

got the final results on Cameron’s
bloodwork. And then the Tuesday before

Thanksgiving, we went into our
pediatrician’s office we had the results

that Blythe was a carrier and Cameron
had Tay-Sachs

Blythe – all I said was “I’m sorry.”
(Narrator) – Tay-Sachs is a very rare

disease that usually occurs in specific
groups, like Ashkenazi Jews, but even

then the baby must inherit the gene
from both parents. So even though

there is a Tay-Sachs test, the Lords had
no reason to think they would be a risk.

And yet incredibly all four of them, Tim
and Charlie and both their wives, were

carriers. That was an unbelievably bad
role of the genetic dice.

Tim – Charlie and I are incredibly close
and have been all our lives. And when I

think about him and Blythe having to go
through this it seems really cruel

Charlie – I had already geared myself up
to be my brother’s rock. And I couldn’t

imagine having to help him and go
through it myself voice breaks

(Narrator) – for families like the Lords
and for everybody, the Human Genome

Project offers the chance to find out
early if we’re at risk for all kinds of

diseases.
Tim Lord - I would like to see a really

aggressive push to develop a test for
hundreds of genetic diseases, so that

parents could be
informed before they start to have

children as to the dangers that faced
them. I think it’s within our grasp, now

that we’ve mapped the human genenome,
the information is there for people to

begin to sort through
Tim – (talking to Hayden), “all right

pumpkin”
(Tim) – they are horrible horrible

diseases. If there is any way you could
be tested for a whole host of them and

not have them
affect the child, I think it’s something

that we have to focus on

(Narrator) – Hayden Lord died a few months
before his third birthday.

Narrator - what makes this story

especially hard to bear is we now know

that a loss that huge, and it was a

catastrophe by any measure, started

with a single error, a few atoms across,

buried inside a cell. Now, if something

so small could trigger such an enormous

result, is a perspective that is

incredibly frightening.

Except, that now geneticists have figured

out how to see many of these tiny errors

before they become catastrophes.

When you think about that, that's an

extraordinary thing, to spot a catastrophe

when it's still an insignificant dot in a
cell.

Which is the promise of the Human Genome
Project.

It is first and foremost, an early warning

system for a host of diseases, which

will give, hopefully, parents, doctors,
and scientists an advantage

that we have never had before. When you

can see trouble coming way way before

it starts you have a chance to stop it

or treat it... eventually, you might cure
it.

(Narrator) And that's why, when Congress

created the Human Genome Project in
1990, the challenge was

to get a complete list of our A's, T's,
C's, and G's as quickly as possible.

So, the business of making tests,

medicines, and cures could begin.

They figured it would take about 15 years

to decode a human being, and at the time,

that seemed reasonable.

Until this man: scientist, entrepreneur,

and speed-boat enthusiast, Craig Venter,

decided that he could do it faster, much
faster.

(Craig) It's like sailing. Once you have

two sailboats on the water going

approximately the same direction,

they're racing. And science works very

much the same way. If you have two labs

Craig - remotely working on the same
thing,

one tries to get there faster, better, or

higher quality... something different,
in part, because our society

recognizes only "First Place".

(Narrator) Back in 1990, Vinter was one

of many government scientists
painstakingly decoding

proteins and genes, his focus was one

protein in the brain.

Vinter - I took 10 years to get the
protein, and it took a whole year

to get 1,000 letters of genetic code.

(Narrator) For Venter, that was way too
slow.

Narrator - So, you're sitting there
thinking there must be

a better way when you were gazing out

the window.

Vinter - There HAD to be a better way.

(Narrator) And that's when he learned that

someone had invented a new machine
that could identify C's and T's and A's

and G's with remarkable speed.

And Craig Venter just loves machines that

go fast.

Vinter - I immediately contacted the

company to see if I could get one of the
first machines.

(Narrator) - And here's how they work:

Human DNA is chopped by robots into tiny

pieces. These pieces are copied over and

over again in bacteria and then tagged

with colored dyes.

A laser bounces light off of each snip of

DNA and the colors that it sees represent

individual letters in the genetic code.

And these computers can do this 24 hours

a day, everyday.

Venter - See, now you can see clearly the
peaks.

So, there's just a blue on coming up so

that's a "C" coming up. You could read

this and you could write this all down.

(Narrator) So, blue, yellow, red, red,
yellow...

Venter - So, that's C, G, T, T, A.

(Narrator) And, somehow all these little

pieces have to be put together again in
the right order. Venter's dream was to

have hundreds of new machines at his

fingertips, so he quit is government job

and formed a company he called,

"Celera Genomics". "Celera", from the

Latin word, "Celerity", meaning, "Speed".

And this is what he built.

Narrator - Oh my Lord. And you know what's

interesting is there's almost nobody here.

Vinter - Yeah. It's all automated.

(Narrator) So, who is this guy and why's

he such a bulldog for speed?

Craig Venter grew up in California,

left high school and spent a year as a

surfing bum on the beach by day and

a stock-boy at Sears by night. He was

inevitably drafted, went to Vietnam with

the Navy. That's him way over there on

the left. He was eventually assigned to a

Naval Hospital in Denang during the

Tet Offensive, when the Americans were

taking very heavy casualties.

At 21, he was in the triage unit, where

they decide who will live, and who will
die.

When you're young and you

Narrator - see a lot of people die, and

they could all be you, do feel like you

sort of owe them cures, cures that they'll

never get? Or am I over-romanticizing...

Vinter - Well, the motivation's become

complex, but that's certainly apart of it.

Also, I think surviving the year there
was...

(emotional pause)

So, it puts things in perspective that

I think, if you're not in that situation,

you could never truly have that
perspective.

Narrator - So, you hear ticking?

Vinter - Yeah... but also, I feel, that

I've had this tremendous gift for all

these years since I got back in 1968, and

I wanted to make sure I did something

with it.

(Narrator) In the spring of 1998, Venter

announced that he and his company were
gonna

sequence all three billion letters of the

human genome in two years.

Remember, the government said it

was gonna take 15.

(Venter) There was a lot of arrogance

that went with that program

Vinter - they were gonna do it at their

pace, and a lot of the scientists, ya
know, if they were really

being honest with you, would tell you that

they planned to retire doing this program.

You know, that's not what we think is the

right way to do science, especially

science that affects so many peoples'
lives.

Robert - Craig's a high-testosterone male.

Who has, who loves to be an iconoclast,
right?

He loves rattling peoples' cages. And he's

done that consistently in the genome
project.

(Narrator) Craig Venter's announcement

that his team would finish the

entire genome in just two years,
galvanized everybody working

on the public project. Now, they were

scrambling to keep up.

Man - There are some limitations,

we don't think we can this thing to go
any faster at the moment without

throwing a lot more robotics at it.
The arm physically takes 20 seconds

to move...

(Narrator) Francis Collins, the head of
the Human Genome Project, was

determined that Celera was not gonna
beat his teams to the prize. He made a

dramatic decision to try to cut five full
years off of the original plan.

Eric - The okay way to do it...

(Francis) When the major genome
centers met, and agreed to go for broke

here, I don't think there was anybody in

the room that was very confident we could

do that. I mean, you could sit down with

a piece of paper, and make projections,

if everything went really well, that might

get you there, but there were so many ways

this could have just run completely
off the track.

(Narrator) At MIT, they decided to try to

scale up their effort 15-fold.

And that meant a major change in their

usual academic pace.

(Woman) We basically had a goal since

Woman - march to get to a plate emitted
operation from womb-to-tomb all the

way through.

(Narrator) In the fall of 1999,
representatives from the five

major labs come to check out Eric
Lander's operation.

All the big honchos in the Human
Genome Project are here.

Scientists from Washington University

in St. Louis, Baylor College of Medicine

in Texas, the Department of Energy,

she's from the Sanger Center in England.

If they want to finish the genome before

Craig Venter, these folks have to figure

out how to outfit their labs with a lot of

new, and fancy, and unfamiliar equipment,

and they've got to do it fast.

Woman - So, we'll have to run some kind

of a conduit...

(Narrator) At MIT, a different crate is

arriving almost daily.

Man - It's like Christmas, everyone
unwrap something.

(Narrator) Just like a bad Christmas

present, assembly is required, and the

instruction are, of course, not always
clear.

(Man) Oh no, the magnet-plates stick
to each other?

Man - This is about, plus or minus three
feet.

(laughing)

(Eric Landers) Since one's on the cutting-
edge, I guess that they always call

Eric - it the "bleeding edge", right?
Nothing,

really, is working as you would expect.
All the stuff we're doing will be working

perfectly as soon as we're ready to junk
it.

(Man) Right, right.
(Narrator) The MIT crew is particularly

excited about their brand-new,

$300,000, state-of-the-art, DNA purifying
machine.

Man - Alright, maiden voyage, it didn't
ask me for a password, that's good.

On it goes.

Other man - Got the yellow light right
away.

(Man) That's okay...
(Narrator) I don't think the blinking

light is a good sign...

(Man) Looks like we have an air leak
somewhere.

Uh oh, look at this.

(Man) It's cracked.

(Eric Landers) It's sort of like flying a

very large plane and repairing it while

you're flying. And you're trying to figure

out what went wrong.

And you also realize that you're spending

10's of thousands of dollars an hour,

so you feel under a little pressure

to sort of work this out as quickly as
you can.

(Narrator) So, he calls the customer
service line.

And of course, he's put on hold...

(music playing)

So, he waits...

And he waits...

And he waits...

Anyway, it turns out the the $300,000

machine does have one tiny little valve

that is broke, and so it doesn't work.

(Man) Alright...

(Eric) You never know whether the problem

is due to some robot, some funky bit of
biochemistry, some

chemical that you've got that isn't really

working. And, so, it's incredibly
complicated.

Woman - So, we have a transformation,
where we transform a tenth of

our ligation...

Man - And add SDS to lice the phage.

Man - And all of our thermo-cyclers are
three to four well plates.

(Man) So, if you basically determine your

Man - (inaudible scientific jargon ... and

give them each a different run module...

(Francis) Try to ramp something up...
anything that's the slightest bit

cloogey suddenly becomes a major
bottleneck.

Man - We talked about doing a full-out

test today and we weren't quite feeling
good about doing that yet, so...

(Francis) There was a considerable sense

of white knuckles, because here we made

this promise, we were on the record here

saying we were gonna do this.

And things weren't working, the machines

were breaking down.

Woman - This is like... November?

Francis - And it's gotta work now. The
time is running out.

Man - This is one of it's three inaugural
runs and

(Man) it seems to be flawless, so far.

(Narrator) It took awhile, but the
government teams finally hit

their stride.

(Francis) But the fall of that year was

really, sort of, the determining time.

The Center's really proved their mettle.

And every one of them began to catch

this rising curve, and ride it and we
began to see data

appearing at prodigious rates.

Man - Do all...

(Francis) By early 2000's, a thousand

base pairs-per-second were rolling out of

this combined enterprise, seven days a
week, 24 hours a day,

1,000 base pairs a second.

Then it really starts to go.

(Narrator) And those thousands of base
pairs poured out of

university labs directly onto the
internet.

(music playing)

(Narrator) Updated every night, it's

available for anyone, and everybody.

Including, by the way, the competition.

Man - Customers love our data...

(Narrator) Celera admits they got lots of

data directly from the government.

And Tony White, who runs the company

that owns Celera says, "Why not?"

Tony - That's publicly available data.

I'm a taxpayer, Celera's a taxpayer.

Ya know, why should we be excluded from

getting it? I mean, again, are they
creating it

to give to all mankind except Celera?

Is that the idea, it isn't about us

getting the data, it's about this
academic jealousy.

It's about the fact that our data, in

combination with theirs, give us a

perceived unfair advantage over this

so-called race.

Eric - If they wanna race us, that's
their business.

I suppose they may.

(Narrator) I suspect strongly that they
may.

Eric - Our job to get that data so that
everybody can go use it.

(Narrator) Since Celera was sequencing the

genome with private money, some critics

wondered why should the government put

so much cash into the exact same research?

(Eric) In the United States, we invested
in a National Highway system

in the 1950's. We got tremendous return

from building roads for free, and letting

everybody drive up and down them for

whatever purpose they wanted. We're

building a road up and down the
chromosomes... for free.

People can drive up and down those

chromosomes from whatever they need

to. They can make discoveries, they can

learn about medicine, they can learn

about history, whatever they want.

It is worth the public investment to

make those roads available.

(Narrator) Wait a second, what I really

want to know is if you're making a roadmap

of a human being, which human beings are

we mapping? I mean humans come in so many

varieties, so whose genes, exactly, are

we looking at?

Eric - Yeah, it's mostly a guy from
Buffalo and a woman from

Buffalo. That's because the laboratory--

Narrator - Whoa, whoa, wait... An
anonymous couple from

Buffalo?

Eric - No, they're not a couple. They've

never met. The laboratory was a

laboratory in Buffalo. So, they put an ad

in the Buffalo newspapers, and they got

random volunteers from Buffalo.

They got about 20 of them, and chose

at random the sample, and that sample,

and that sample, so nobody knows who

they are.

(Narrator) And what about Celera?

Whose DNA are they mapping?

They also got a bunch of volunteers,

around 20, and picked five lucky winners

Craig - We tried to have some diversity,

in terms of, if we had an African American

or somebody's self-proclaimed Chinese

history, two Caucasians, and a Hispanic.

So, some of the volunteers were here

on the staff...

Narrator - I have to ask, cause everybody

does, are you one of them?

Craig - I am one of the volunteers, yes.

Narrator - Do you know whether or
not you're one

of the winners?

I have a pretty good idea, yes, but I

can't disclose that, because it doesn't

matter.

Narrator - Well, if you're the head of

the company and you're watching the
decoding of muah. That has a little

Miss Piggy quality to it.

Craig - Well, any scientist that I know

would love to be looking at their own

genetic code. I mean, how could you not

want to in this field?

(Narrator) Well, I don't know, I don't

work in this field. But I do wonder, can

any small group, and could that guy

from Buffalo, could he really be a
stand-in

for all humankind?

Hasn't it been drummed into us since

birth that we're all... different? Each

and every one of us, completely unique.

We certainly look different.

People come in so many shapes, and

colors, and sizes... The DNA of these

humans has got to be significantly

different than the DNA of this human.
Right?

Eric - The genetic difference between any

two people is 1/10th of a percent.

Those two, and any people on this planet,

are 99.9% identical at the DNA level.

It's only one letter in a thousand
difference.

Narrator - And if I were to bring,

secretly into another room, a black man,

an Asian man, and a white man, and

show you only their genetic code,

could you tell which one was the white
one?

Eric - I could not.

What's going on? Well, it tells us that,

first, as a species, we are very very

closely related. Cause any two human

beings being 99.9% identical, means that

we are much more closely related than

any two chimpanzees in Africa.

(Narrator) Wait, wait, you mean if two

chimpanzees are swinging through the

forest, and you look at the genes of

chimp A, and you look at the genes

of chimp B...

Eric - Average difference between those

chimps, is 4 - 5 times more than the

average between two humans that you

could pluck off this planet.

(Narrator) Because we're such a young
species?

(Eric) That's right.

See, the thing is, we are the descendants

of a very small founding population.

Every human on this planet goes back

to a founding population of, perhaps,

10 or 20 thousand people in Africa.

About 100,000 years ago.

That little population didn't have a great

deal of genetic variation, and what

happened was, it was successful; it

multiplied all over the world, but in that

time, relatively little new genetic

variation is built up. So, we have today

on our planet, about the same genetic

variation that we walked out of Africa

with.

(Narrator) So, people are incredibly

similar to each other. But not only that,

it turns out that we also share many

genes with, well, everything.

50% of the genes of a banana are different
from us?

Eric - How different are you from a
banana?

Narrator - I feel, and I feel like can say

this with some authority, very different

from a banana.

Eric - You may feel different from -
Narrator - I eat a banana but I-

Eric - Look, you've got cells, you've

gotta make those cells divide. So, all

the machinery for replicating your DNA,

all the machinery for controlling the

cell-cycle, the cell's surface, for making

nutrients, all that's the same in you and

a banana.

(Eric) Deep down, the fundamental
mechanisms of

life were worked out only once on this
planet.

And they've gotten reused in every
organism.

The closer and closer you get to a

cell, the more you see a bag with

stuff in it and a nucleus and most of

those basic functions are the same.

Evolution doesn't go reinvent something

when it doesn't have to.

(music playing)

Take baker's yeast, baker's yeast, we're

related to one-and-a-half billion years

ago. But even even after one-and-a-half

billion years of evolutionary separation,

the parts are still interchangeable for

lots of these genes.

Narrator - Now, does that mean,
I want to understand,

does that mean when you look through

those things, that all the C's, A's, T's,

T's, and the G's, are you seeing the same

exact same letter sequences in the

exact same alignment? When you look at

the yeast and you look at the person, is

it the same?

Eric - Sometimes it's eerie. The gene

sequence is nearly identical. There are

some genes, like Ubiquitin, that's 97%

identical between humans and yeast,

even after a billion years of evolution.

Narrator - Well, with a name like that,|
it's gotta be...

Eric - Well, yeah, but you gotta

understand that deep down we are very

much partaking of that same bag of tricks

that evolution's been using to make

organisms all over this planet.

(Narrator) It seems incredible, but all

this information about evolution, about

our relationship to each other, and to all

living things, it's all right here in this

monotonous stream of letters. And as the

Human Genome Project progressed, and

hit high gear, the pace of discovery

quickened.

Once, they got fully automated, it wasn't

long until Lander, and Collins, and all

the other public project teams had reason

to celebrate.

Francis - I'm Francis Collins, the

Director of the National Human Genome

Research Institute, and we are happy to be

here together to have a party today.

(Narrator) By November of 1999, they had

reached a major milestone. In a five-way

award ceremony, hooked up by

satellite, the major university teams

announced they had finished a billion

base pairs of DNA. A third of the total

genome.

(corks popping)

(Eric) Have we got everybody?

Eric Lander - I would like to propose

a toast. A billion base pairs, all on the

public internet, available to anybody in

the world. It's an incredible achievement.

It hasn't been completely painless.
(laughing)

And, because, I know everybody in this

room is living and breathing and thinking

every single moment of the day about how

to make all this happen... how we can hit

full-scale. I want to be sure you realize

what a remarkable thing we pulled off.

I hope you also know that this is history.

Whatever else you do in your lives, you're

apart of history. We're apart of an

amazing effort on the part of the world to

produce. And it isn't gonna be like the

moon, where we just visit occasionally.

This is gonna be something that every

student, every doctor uses, everyday in

the next century, and the century after

that. It's something to tell your kids

about. Something to tell your

grand-kids about. It's something you

should all be tremendously proud of.

I'm tremendously proud of you.

A toast, to this remarkable group.

To the work we've done. To the work ahead.

Hear, hear.

Everyone - Hear, hear.

(Whistling)

(Narrator) Everybody here is hoping the

genome project will help cure disease.

And the sooner it's done, the better for

all of us.

(inaudible)

(Narrator) But there's something more than

idealism, more than even pride that's

driving this race to finish the genome.

And that's the knowledge that with every

day that passes, more and more pieces

of our genome are being turned into

private property by way of the U.S. Patent
Office.

(printing machine noises)

Woman - I said property.

(Narrrator) The office is inundated with

requests for patents for every imaginable

invention. From Star Wars action figures

to jet engines.

(paper shuffling sounds)

And here, along with all those gizmos, are

requests for patents for human genes.

Things that exist naturally in every one

of us. How is this possible?

(Todd) We regard genes as a patent-able

subject matter, as we regard almost any

chemical. We have issued patents on a

number of compounds and compositions

that are found in the human body.

For example, the gene that encodes insulin

has been patented, and that now has been

used to make almost all of the insulin

that is made. So, people's lives are being

saved today. Diabetics' lives are better.

As a matter of fact, if we ruled out every
chemical that's found in the human body

there'd be an awful lot of inventions that
would not be able to be protected.

(Narrator) Generally, to patent an

invention you've got to prove that it's

new and useful. But a few years ago

critics said that the patent office

wasn't being tough enough, so applicants

would say, "Well, here's a brand new

sequence of A's, C's, T's, and G's right

out of our machine's. That's new."

Now, "useful", wonder what they're gonna

be used for? Well, they were kind of vague

about use, says Eric Lander.

Eric - The sort of thing that people used

to do then was they would say that, "It

could be used as a probe to detect
itself."

It's a trivial use. I mean it's like

saying, "I could use this new protein as

packing peanuts to stuff in a box."

I mean, it's true-
Narrator - Well, wouldn't the patent

examiner say, "Well, that's not useful."
Eric - No, no, no, you see, you the patent

guidelines are very unclear. I don't
object to giving someone that limited time

of monopoly when they've really invented
a cure for a disease; some really

important therapy.
I do object to giving a monopoly when

somebody has simply described a couple

hundred letters of a gene, but has no idea

what use it could have in medicine...

cause what's happen is you've given away
that precious monopoly to someone who's

done just a little bit of work, and then
the people who come along and want to

do a lot of work to turn it into a
therapy, well... they've gotta go pay the

person who already owns it. I think it's
a bad deal for society.

(Narrator) It takes at least two years for

the patent office to process a single

application. So, right now, the patent

office says there are about 20,000 genetic

patents waiting for approval. All of them

are in limbo. This can cause problems for

drug companies who are trying to work

with genes to cure disease.

Narrator - I'm a company trying to do

work on this, this, and this rung of the

ladder.
Eric - Right

Narrator - Cause I think that I can maybe

develop a cure for cancer,
right here, for the sake

of arguing. But, of course, I have to

worry that somebody owns this space.

Eric - Oh, you have to worry a lot, that

this region here that you're working on
that might cure cancer, has already been

patented by somebody else. And that
patent filing is not public, and so you're

living with the shadow that all of your

work may go for naught.

Narrator - Because one day the phone

rings and says, "Sorry, you can't work
here. Get off my territory."

Eric - That's right.
Narrator - Or, you can work here, but I'm

gonna charge you $100,000 a week.
Or, you can work here and I'll charge you

a nickel, but I want 50% of whatever you
discover.

Eric - And the problem there is, it's even
worse, because many companies don't start

the work whenever there's a cloud over

who owns that. If there's uncertainty,

companies would rather be working

some place where they don't have
uncertainty.

And, therefore, I think, work doesn't get

done, because of the confusion over who

owns stuff.

(Narrator) Supporters of patents say they

are a crucial incentive for drug
companies.

Drug research is phenomenally expensive

but if a company can monopolize a big

discovery with a patent, it can make

hundreds of millions of dollars.

Research scientists suddenly find

themselves in an unfamiliar world, ruled

by big money.

(Sheldon) Every scientist that does
is research

now being looked upon as a generator of

wealth. Even if that person is not

interested in it. If they sequence some

DNA, that could be patent-able material.

So, whether the scientist likes it or not,

he or she becomes an entrepreneur just

by virtue of doing science.

(Narrator) Craig Venter is first a
scientist

but he has made the leap from academia

into the business world.

Narrator - Let me talk about the business

of this. Do you consider yourself a

business man?

Craig - No, in fact, I still, sort of

bristle at the term for some reason.

But my philosophy is, we would not get
medical

breakthroughs in this country, at all, if

it wasn't done in a business setting.

We would not have new therapies if we

didn't have a biotech and pharmaceutical

industry.

Narrator - But are they... if you bristle

at the word "businessman", that might be

because in some part of your soul, you may

think that the business of science and the

business of business are fundamentally

incompatible for one simple reason:

that the business has to sell something

and the science has to learn, or teach,

something.

Craig - I think I bristle at it because

it's used as an attack. It's used as a

criticism. In this case, if the science is

not spectacular, if the medicine is not

spectacular, there will be no profits.

(Narrator) Venter was given $300,000,000

to set up Celera, and his investors are

expecting something in return.

But how can they profit from the genome?

At the moment, the company is banking on

pure computer power.

This is Celera's master control.

24 hours a day, technicians monitor all

the company's major operations, including

the hundreds of sequencers that are

constantly decoding our genes.

And they oversee Celera's main source of

income: a massive website, where, for a

fee, you can explore several genomes,

including those of fruit flies, mice, and,

of course, humans. What all this

adds up to is something like a big

browser. A user-friendly interface between

you and your genes.

Tony White - Our business is to sell

products that enable research. That's

essentially what we do. So, we're used to

selling the picks and the shovels to the

miners. Tools to interpret the human

genome and other related species.

Or, merely more products along the

same genre, they just happen to be less

tangible than a machine.

(Narrator) So, Celera's business plan is

to gather information from all kinds of

creatures, put it together, and sell their

findings to drug companies, or

universities, or whomever. But it's the

selling part, selling scientific

information, that makes some scientists

very uncomfortable.

Todd - This is a big change in the ethos

of the scientific community, which is,

supposedly, it was built upon the idea of

community values of the free and open

exchange of information. The fundamental

idea that when you learn something, you

publish it immediately, you share it with

others. Science grows by this community

interest of shared knowledge.

Tony - I think, why doesn't Pfeiffer give

away their drugs? They could help a lot

more people if they didn't charge for
them.

Man - At what point is "free" really free?

(Narrator) Tony White has absolutely no

problem with making money from the human
genome.

Tony - I hope we have a legal monopoly on

the information. I hope the product is so

good, and so valuable to people, that they

feel that it's necessary to come through

us to get it.

Anybody who wants to can build all the

tools that we're gonna build. Whether or

not they will choose to is a different

matter.

Narrator - Which is the better business
to be in, do you think? The landlord

business? Or this, "You subscribe and
I'll give you some information about

anything you want business."

Eric - They're both lousy businesses.
(Narrator laughing) Lousy?

Eric- They're lousy businesses by

comparison with the real business:
Make drugs.

Actually make molecules that cure people.

Narrator - curing people is the whole

point, right? But if there is one thing

that the Human Genome Project has

taught us, is that finding cures is a

whole lot harder than simply reading

letters of DNA.

(Narrator) Take for example, the case of

little Riley Demoush.

(baby sounds)

At two months, Riley appears to be

a perfectly healthy baby boy, but he's
not.

When Riley was just 13 days old, Kathy

got the call that every parent dreads.

Kathy - The pediatrician called on a

Thursday evening, and he said, "I need

to talk to you about the baby."

He said, "Are you sitting down?"

I'm like, "Yeah." And that really suprised

me. And he said, "Are you holding the

baby." Because he didn't want me to drop

the baby, obviously.

And he said, "The tests came through, and

Riley tested positive to cystic fibrosis."

And I was in shock.

(Narrator) As Kathy and her husband

would soon learn, Cystic Fibrosis, "CF"

for short, attacks several organs of the

body, but especially the lungs.

It's victims suffer from chronic

respiratory infections, and half of all

CF patients die before the age of 30.

David Waltz - To think that we can still

be hopeful that their child will grow up

to have a normal, healthy, happy, and long

life. But at the present time, I don't

have any guarantees about that.

Kathy - Someone had asked me, "Are you

prepared to bury your son at such a young

age, whether it's four or 40?" And he was

seventeen days old when that happened

and I said, "I've had him for seventeen

days, and I wouldn't trade those seventeen
days."

(Narrator) Finding the genetic defect

that causes CF was big news back in 1989.

News woman - Medical researchers say

they have discovered the gene which is

responsible for Cystic Fibrosis; the most

common inherited fatal disease in this
country.

Robert Dresing - We're going to cure this

disease...

(Narrator) A lot of people expected the

cure to arrive any day... it didn't.

Francis Collins, now head of the gov's

Genome Project, led one of the teams that

discovered the CF gene.

Francis - We still have not seen this

disease cured or even particularly

benefitted by all of this wonderful

molecular biology. CF is still treated

pretty much the way it was 10 years ago,

but that is going to change.

(Narrator) The original hope was that

babies like Riley could be cured by gene

therapy. Medicine that would provide a

good working copy of a broken gene, but

attempts at gene therapy have hardly ever

worked. They remain highly controversial,

so if there's gonna be an effective

treatment for Riley, instead of fixing his

genes, we're gonna take a look -- and this

is new territory -- at his proteins.

Narrator - What do proteins do?

Venter - When you look at yourself in the

mirror, you don't see DNA, you don't see

RNA... you see proteins and the result of

protein-action. That's what we are

physically composed of.

Narrator - So it's not a Rodgers and
Hammerstein thing

where one guy does the tune and the other

guy does the lyrics, this is a case where

the genes create the proteins and the

proteins create us.

Craig - That's right, we are the

accumulation of our proteins and our

protein activities.

(Narrator) A protein starts out as a long

chain of different chemicals, amino acids.

But, unlike genes, proteins won't work in

a straight line.

Francis - Genes are effectively
one-dimensional.

If you write down the sequence of A,C,G,
and T,

that's kinda what you need to know about

that gene. But proteins are 3-dimensional.

They have to be, because we're
3-dimensional and

we're made of those proteins, otherwise

we'd all sort of be linear, unimaginably

weird creatures.

(Narrator) Here's part of the protein.

Think of them as tangles of ribbon.

They come in any number of different

shapes. They can look like this, or like

this, or like this. The varieties are

endless. But, when it's created, every

protein is told, "Here is your shape."

and that shape defines what it does,

tells all the other proteins what it does,

and that's how they recognize each other

when they hook up and do business.

In the protein world, your shape is your

destiny.

Francis - They have needs and reasons to

want to be snuggled up against each

other in a particular way. And actually,

a particular amino acid sequence will

almost always fold in a precise way.

Narrator - Should I think origami-like?

When you're stretching, folding, and--

Francis - It's elegant, very complicated,

and we still do not have the ability to

precisely predict how that's going to

work, but obviously it does work.

(Narrator) Except, of course, if something

does go wrong, and that's what happened

to baby Riley.

Riley has a tiny error in his DNA, just

three letters out of three billion are

missing, but because of that error he has

a faulty gene, and that faulty gene

creates a faulty or misshapen protein.

And just the slightest little changes in

shape and "Boom" the consequences are

huge, because it is now misshapen and

a key protein that is found in the lung

cells can't do it's job. So, let's take a

look at some real lung cells, we'll travel

in. This is the lining, or the membrane

of a lung cell, and here's how the protein

is supposed to work. The top of your

screen is the outside of a cell, the

bottom the inside of the cell, of course,

and our healthy protein is providing a,

kind of chute so that salt can enter and

leave the cell. Those little green bubbles

that's salt and. as you see here, the salt

is getting through. But if the protein is

not the right shape, then it's not allowed

into the membrane; it can't do its job.

And, without that protein, as you see here

salt gets trapped inside the cell and that

triggers a whole chain of reactions that

makes the cell surface sticky and covered

with thick mucus.

Woman - The first two positions that are

done sitting up are probably a little more

difficult to do...

(Narrator) The mucus has to be dislodged

physically. Riley's family is learning to

loosen the mucus that may develop in

his lungs and fight infections with

antibiotics.

(Woman) You sort of wanna do it with

a cupped hand.

(Father) Trying to get at the top of the

lungs?
Woman - Yep, you wanna be like right here-

(Narrator) But what the doctors and the
scientists would love to do is, if they

can't fix baby Riley's genes, then maybe
there's someway to treat Riley's misshapen

protein and restore the original shape.

Because if you could just get them shaped

right, the protein should become instantly

recognizable to other proteins and get

back to business.

But, look at these things. How would we

ever learn to properly fold wildly

multi-dimensional proteins? It may

be doable, but it won't be easy.

Eric Lander - The Genome Project was

a piece of cake compared to most other

things, because genetic information is

linear. It goes in a simple line up and

down the chromosome. Once you start

talking about the 3-dimensional shapes

into which protein change can fold, and

how they can stick to each other in many

different ways to do things. Or the ways

in which cells can interact, like wiring

up in your brain... you're not in a

one-dimensional problem anymore. You're

not in Kansas anymore.

(Narrator) As the scientists head into

the world of proteins, they're looking

very closely at patients like Tony Ramos.

Tony has cystic fibrosis, but it's not the

typical case. CF almost always develops in

early childhood. Tony didn't have any

symptoms until she was 15.

Tony - I started having a cough, and then

we kept thinking I was catching a lot of

colds and my step-mother thought,

"Well, that's not right." So, I started

going to doctors, trying to figure it out.

And went through a lot of tests because
I don't fit the profile. Tuberculosis,

walking pneumonia, ya know, test after
test.

(Narrator) At the time of diagnosis,

Tony's family was told she might not

survive beyond her twenty-first birthday.

She's now in her mid-forties. But her CF

is worsening. 2 or 3 times a year she does

have to be admitted to the hospital to

clean out her lungs.

Tony - Ya know, they were always doing

some little funky study to help the cause,
because we're not the normal, ya know

there's not a whole lot of us. I know that

they don't know why, and it's the big

question mark, and hopefully research

will keep going and figure it out.

(Narrator) Here's the question: Tony was
born with a mistake in the same gene as

baby Riley, and yet for some reason, when

Tony was a baby, she didn't get sick. Why?

And now that she is sick, she hasn't died.

Why? What does Tony have that the other

CF patients don't have?

Dr. Craig Gerrard believes the answer lies

in her genes; in her DNA.

Dr. Gerrard - Good morning.
Tony - Good morning.

Dr. Gerrard - So, do you think the change
in the antibiotics is helping you?

Tony - Yes, and I've dropped four pounds

overnight.
Dr. Gerrard - (laughing) That's a lot of

weight.
Tony - Yeah!

Dr. Gerrard - Okay, mind if I have a
listen?

(Dr. Gerrard) - No gene acts in isolation,

it is always acting as a part of a larger

picture. And therefore, the other genes,

which compensate.

(Narrator) Could it be that Tony has some

other genetic mutations, good mutations,

that are producing good proteins, that

kept her healthy for 15 years and are

keeping her alive right now?

(Dr. Gerrard) You sound a lot better than
you did when you came in. So, I think

you're on the mend. Okay, hang in there.
Tony - Thanks, bye.

Dr. Gerrard - In my opinion, there are

genes that are allowing her to have a

more beneficial course, if you will, than

another patient.

Woman - You sound good.

(Narrator) Dr. Gerrard is searching for

the special ingredient in Tony. If it

turns out she has one or two proteins that

are helping her, maybe we could bottle

them and use them to help all CF patients,

like little Riley.

(Woman) If there was ever an emergency,
and I didn't know how to do it, and I

couldn't get in touch with you--
(Narrator) No one can predict Riley's

future, or to what extent CF will affect
his life. But now that we are getting a

map of our genes, we'll be able to take

the next big step. Because, what genes

do, basically, is they make proteins.

Narrator - I get the sense that everybody

is getting out of the gene business, and
suddenly going into this new business

I hear about, called, "The Protein
Business."

There's even a new name, instead of
"The Genome" I'm hearing this other

name, "The Proteome".
Eric - The Proteome.

(Narrator) The Proteome.
Eric - Yes.

(Narrator) What is that?
Eric - Well, the genome is the collection

of all your genes and DNA. The proteome,
is the collection of all your proteins.

See, what's happening is, we're realizing
that if we wanted to understand life, we

had to start systematically at the bottom

and get all the building blocks. The first

building blocks are the DNA letters, from

them we can infer the genes. From the

genes we can infer the protein products

that they make, that do all the work of

the cell. Then we've gotta understand what

each of those proteins does, what its

shape is, how they interact with each

other, and how they make kind of circuits

and connections with each other. So,

in some sense, this is just the beginning

of a very comprehensive, systematic

program to understand all the components

and how they all connect with each other.

(Narrator) All the components and how they

connect. But how many components are

there? How many genes and how many

proteins do we have?

Eric - A real shock about the genome

sequence was that we have so many fewer

genes than we've been teaching our

students. The official textbook answer is

the human has a 100,000 genes. Everyone's

known that since the early 1980's, the

only problem is is it's not true. Turns

we only have 30,000 or so genes.

(Narrator) 30,000 genes, that's it? Not

everybody agrees with this number, but

that's about as many as a mouse. Even
a fruit-fly has 14,000 genes.

Eric - That's really bothersome to many

people that we only have about twice as

many genes as a fruit-fly, because we

really like to think of ourselves as a lot

more than twice as complex. Well, don't

you? I certainly like to think of myself

that way. And so, it raises two questions,

are we really more complex?

Narrator - You show me the fruit fly that
can compose like Mozart and then I'll--

Eric - Well, show me a human that can fly.

Right? So...
(Narrator) Ooo (laughing)

Eric - (laughing) We all have our talents,
right?

(Narrator) I suppose we do, but as it

happens, we have lots of genes that are

virtually identical in us and fruit flies.

But, happily, our genes seem to do more,

so, let's say that I am a fruit fly. One
of

my fruit fly genes may make one and two

slightly different proteins, but now I'm a

human and the very same gene in me

might make one, two, three, four different

proteins, and these four proteins could

combine and build even bigger and more
proteins.

Eric - It turns out, that the gene makes a

message, but the message can be spliced up

in different ways. And, so, a gene might

make three proteins or four proteins

and then that protein can get modified.

There could be other proteins that stick

some phosphate group on it or two

phosphates groups. And, in fact, all these

modifications to the proteins could make

them function differently. So, while you

might only have 30,000 genes, you could

have 100,000 distinct proteins, and when

you're done putting all of the different
modifications on them, there might be

a million of them.
(narrator clears throat)

Scary thought.

Narrator - So, starting with the same raw

ingredients, the fruit fly goes, "mmm,
spch, mmm, spch, mmm, spch."

but the human, by somehow or other, being

able to arrange all the parts in many

different ways, can produce melodies,
perhaps?

Eric - Yes, although we're not that good

at hearing the melodies yet. One of the

exciting things about reading the genome
sequence now, is we're getting a glimpse

at that complexity of the parts and how

it's a symphony, rather than a simple tune

but it's not that easy to just read
that sheet

music there and hear the symphony that's

coming out of it.

(Narrator) Okay, so it's not just the
number of genes, it's all the different

proteins they can make and the ways those
proteins interact, and to find out all of

those interactions and how they affect

health and disease, that's gonna keep

scientists very busy for the next few

decades. But, of course, before the

research can begin in earnest, they first

have to complete the parts list of all the

genes. And by the spring of 2000, both

sides, the public labs and Celera, they

were in hyper-drive. Each camp madly

trying to be first to reach the finish
line and get

all 3 billion letters.

(Gene Myers) The pace of things, and the

magnitude of things was really incredible.

I mean, I would remember coming in and

just having this gripping feeling in my

gut, just an intense, "Oh my God, am up to
this?"

Robert Cook-Degan - You know whoever has

this reference sequence to the human

genome out there in the world first...

they're going to be famous. They're gonna

be on the front page of The New York
Times,

and a lot more than that, for a long time.

And they're gonna be, ya know,
celebrities.

And, ya know, when that's going on, it's

not unreasonable that people are gonna

reach for that star and try to get there

before the other person.

(Tony White) I thought that the
really intense

Tony - competition of this world was
among business, where there is a profit

motive. I now find that we are pikers in
the business world, compared to the

academic competition that exists out
there.

And I'm beginning to understand why,
because their currency is publication.

Their currency is attribution. And their

next funding comes from their last
victory.

(Robert) I think we're all better off for
the fact that there is this competition.

What you want is a system that gets

people riled up and try to do something

faster, better, and cheaper than the next
guy.

(New Speaker, Male) The environment at

Celera was extremely intense and it
reminded me of finals week at Cal. Tech.

Man - And there's a tradition at Cal. Tech

that on the very first day of finals week,

the Ride of The Valkyries is played at
full blast.

And, so, I thought well, since every

week feels like it's finals week here, why

don't I play the ride and see what
happens?

So, we got a whole bunch of viking hats,

and we end up buying Nerf bows, because

we're Nordic Valkyrians. So, the next week

we're shooting each other, and we go,

"Ya know, there's something not right
about this." So, we decided the next week

that we would start doing raiding parties
and raid some of the other teams.

Unannounced to us, they had been preparing
themselves.

Man - Hey, you guys go to the back-stairs.

(Man) - They had little beanie caps, and

their own Nerf weapons and the war
started.

(shooting sounds)
(Ride of the Valkyries music playing)

(shooting sounds)

(laughing)

(shooting)

(Man) It's just a release. It's a way of

dealing with the pressure, I think.

(laughing)
(shooting)

(Man) We all ran like crazy for 5 or 10

minutes, and got a little physical
exercise.

And, had a few laughs and then we're

ready to really go after it.
(laughing)

(Narrator) The Wagner seems to be working.

Output at Celera continues at a relentless

pace. Venter insists that the urgency

stems not only from a desire to beat

the government project, but the firm

belief that what's coming out of these

machines, all the C's, T's, G's, and A's,

will have a profound impact on all our
lives.

(Venter) It's a new beginning in science.

And, until we get all that data, that

can't really take place.
Venter - I mean anyone who

has cancer, anybody who has a family

member with a serious disease, this data

and information offers some tremendous

hope that things could change in the
future.

Eric Lander - In the past, if you wanted
to explain Diabetes, you always had to

scratch your head and say, "Well, it might
be something else that we've never seen

before." But knowing that you have the
whole parts list, radically changes

biomedical research. Because you can't
wave hand and say it might be something

else. There is no "something else".

(Man) 1, 2, 3, 4, 5 C's in a row.

(Narrator) In the past,
Narrator - Finding genes that cause

disease was a painstakingly slow process,

but, with the completion of a list, it

should be much easier to make a direct

connection from disease to gene. But how?

Well, let's say I'm looking for a gene

that causes something, we'll make it

Male Pattern Baldness, how would I go

about that. Well, I'd want to get a bunch

of bald guys. So, here are three bald guys

and take their blood and look at their

DNA. Now, I'll take three guys with lots

of hair, and here's their DNA. And, what

if the bald guys all share a particular

spelling right here in this spot, which we

will call, "The Bald Spot", and at the

same spot, you notice the hairy guys have

a different spelling. So, is this the gene

that causes baldness? Maybe, but probably

not. This could be a coincidence. So, how

do I improve my chances of finding the

specific spelling difference that relates

to baldness? It would help if I knew that

the bald guys, and the hairy guys had

really similar DNA, except for the genes

I suspect may make them bald or hairy.

Where do I find guys who are very very

similar with a few exceptions? A family

right? If they were brothers, and fathers,

and sons, and cousins, for instance, who

share lots of genes...

(Narrator) So, let's say these three guys
are brothers. Astonishing similarities,

really, in the face, but notice that one
of them is hairy and two are bald.

Whatever is making this one different,

should stand out when you compare their

genes. And same for these guys. There's

a difference clearly in the photos, but

that difference may turn up in the genes.

Narrator - You can do the same thing for
any disease that you'd like. So, if I

could comb through the DNA of lots of
people who are related, and I find some

of them are sick and some of them are
healthy, I might have a much better

chance of figuring out which genes are
involved. But where do I do this?

(Narrator) Well, one place is a little

island nation in the North Atlantic,

Iceland. In many ways, Iceland is the

perfect place to look for genes that

cause diseases. It's got a tiny population

only about 280,000 people, and virtually

all of them are descended from the

original settlers: Vikings who came here

over 1,000 years ago.

(music playing)

(Kari) If you drive around this country,

you will have great difficulties finding

any evidence of a dynamic culture that

was here for all of these 1,100 years.

There are no great buildings, there are

no monuments.

(Narrator) But, one thing Iceland does

have is a fantastic written history,

including almost everybody's family tree.

And now, it's all in a giant database.

Just punch in a social security number and

there they are, all of your ancestors,

right back to the original Viking.

Thordur - So, what we have here is my

ancestor tree. I'm here at the bottom,

this is my father and mother. My
grandparents,

great-grandparents, and so on. We

can find an individual that was one of

the original settlers of Iceland. Here we

have, "Ketill Bjarnarson" called,

"Ketill "flatnefur", meaning he had a

flat nose. So, he may have broken it in

a fight or something. And we estimate

that he was born around the year 805.

(music playing)

(Narrator) Kari Stephanson is a Harvard

trained scientist who saw the potentional

gold mine that might be hidden in

Iceland's genetic history. He set up a

company called, "Decode Genetics" to

combine age-old family trees with

state-of-the-art DNA analysis and computer

technology, and systematically hunt down

the genes that cause disease.

Kari - Our idea was to try to bring

together as much data on healthcare

as possible. As much data on genetics

as possible, and the genealogy, and simply

use the information tools to help us to

discover new knowledge. To discover

new ways to diagnose, treat, prevent
diseases.

(Narrator) One of Decode's first projects

was to look for the genes that might
cause Osteoarthritis.

Ryn Hydr Magnus Dotre had the

debilitating disease most of her life.

Ryn - The first symptoms appeared when I

was 12, and by the age of 14 my knees

hurt very badly. No one really paid any

attention, that's just the way it was.

But, by the age of 39, I'd had enough, so

I went to a Doctor.

(Narrator) Mrs. Magnus was never alone in

her suffering, she is one of 17 children.

11 of them were so stricken with arthritis

that they had to have their hips replaced.

This was exactly the kind of family that

Decode was looking for. They got

Mrs. Magnus and other members of her

family to donate blood samples for DNA

analysis. And to find more of her

relatives, people she'd never met,

Decode just entered her social security

number into their giant database and there

they were. But which of these people have

Arthritis? To find out, Stephanson asked

the government of Iceland to give his

company exclusive access to the entire

country's medical records. In exchange,

Decode would pay a million dollars a year

plus a share of any profits. That way,

Decode could link everything in their

computers: DNA, health records, and

family trees.

Stephanson - This idea was probably more

debated than any other issue in the

history of the republic. On the eve of

that parliamentary vote, on the bill,

there was an opinion poll taken that

showed that 75% of those that took a

stand on the issue, supported the

passage of the bill, 25% were against it.

(Narrator) Among that 25% against were

most of Iceland's doctors.

(Tomas Zoega) I first thought that there

was something fundamentally wrong

in all of this. They do know everything

about you. Not only about your medical

history, about your medical past, but now

have your gene, the DNA. They know about

your future, about something about your

children, and something about your elders.

Bjorn Gundmarsson - We find ourselves

paralyzed, because there is really nothing

we can do. Because the one who takes the

responsibility is the management of the

Health Center. If they give away this

information from the medical records, they

get money. And everybody needs money.

Healthcare really needs money.

Narrator - So, what's really the problem

here? Well, let's take a hypothetical
example, I'm gonna make all this up. Let's

pretend these are medical records of an
average person, all we'll suppose that

right here I see a HIV test, and then over
here is medication for anxiety after what

appears to be a messy divorce, and over

here a parent who died of Alzheimer's.

Now, this is all stuff that could happen

to anybody, but do you want it all in

a central computer bank, and do you

want it linked in the same computer

to all of your relatives? And to your own

personal DNA file? And should anybody have

to go on a fishing expedition through

your medical history, and your DNA?

(Narrator) Well, it may frightening, but

it also might work. Decode claims it's

discovered several genes that may

contribute to Osteoarthritis. So, this

approach, combining family trees, medical

records, and DNA could lead to better

drugs, or to cures for a whole range of

diseases.

Stephanson - To have all of the data in

one place so you can use the modern

information equipment, to juxtapose the

pieces of data and hope that the pieces

fit. It's an absolutely fascinating

possibility.

(printing sounds)

(Narrator) Stephanson says no one's forced

to do this, and there are elaborate
privacy

protections in place. No names are used,

social security numbers are encoded. He

also argues that the DNA part of the

database is voluntary.

Stephanson - The healthcare database
only contains healthcare information.

We can cross reference it with DNA

information, but only from those

individuals who have been willing to give

us blood, allowing us to isolate DNA,

genotype it and cross referencing it with

the database. Only from those who have

deliberately taken that risk. It's not

imposed on anyone, and no one who is

scared of it, ya know who is really afraid

of it, should come and give us blood.

(Narrator) DNA databases are popping

up all over the world, including the US.

They all have rules for protecting privacy

but they still make ethicists nervous.

(George Annas) I like to use the analogy
of the DNA molecule to a "future diary".

There's a lot of information in the DNA

molecule. The reason I call it a "future
diary",

is because I think it's that private.

I don't think anybody should be able to

open up your future diary, except you.

(Narrator) One rather bleak vision of

where all of this could lead it presented

in the Hollywood film, "GATTACA".

This is a world where everybody's DNA,

everybody's future diary, is an open

book. Everyone who can afford to has

their children made to spec. But what

happens to the poor slob who's conceived

the old fashion way?

(Boy from GATTACA film) I'll never

understand what possessed my mother
to her faith in God's hands rather than

those of her local geneticists.
(baby crying)

Ten fingers, ten toes; that's all that

used to matter. Not now... now, only

seconds old, the exact time and cause of
(suction noise)

my death was already known.

(baby crying)

Nurse - Neurological condition: 60%

probability. ADD: 89% probability.

Heart disorder....: 99% probability.

Life expectancy: 30.2 years.
Father - 30 years...

(Narrator) 30.2 years. The nurse seems to

know precisely what is going to happen to

this baby, which is ridiculous, right?

Never happen. Or... is it possible that

one day we will be able to look, with

disturbing clarity, into our future?

10, 20, even 70 years ahead...

George - That is one possible future,

where this becomes so routine that, at

birth, everyone gets a profile that goes

right to their medical record, one copy

goes to the FBI, so we have an
identification

system for all possible crimes in the US.

One copy goes to your grade school,

to the high school, to the college, to the

employer, the military. Like a horrific

future, although, I have to say there are

many in the Biotech industry and the

medical professions that think that's

a terrific future.

(Narrator) In fact, a lot of the
technology

already exists now, today.

These guys in the funny suits are making

"gene chips". The little needles are

dropping tiny, nearly invisible, bits of

DNA onto glass slides. And where do the

DNA come from? From babies. Thousands

of them. Each chip can support 80,000 DNA
tests.

Mark Schena - So, a single chip, in

principle, will allow you to test, say,

1,000 babies for 80 different human

diseases. So, within a few minutes, you

can have a readout for thousands, or even

tens-of-thousands of babies in a single
experiment.

(Narrator) Already, babies are routinely

tested for a handful of diseases, but with

gene chips, everybody could be tested for

hundreds of conditions.

Mark - Knowing is great. Knowing early is

even better. And that's really what the
technology allows us to do.

(Narrator) Well, taking a test and knowing

is great for the baby, anybody really,

as long as there's something you can do

about it.

Narrator - But think about this, because

sometimes there may be a test, but it

might take 20 years, or 50 years, 50 years

to find a cure. So, you could take the

tests, and you could learn that there is

a disease coming your way, but you can't

do a thing about it. Do you still wanna

know? Or, you could take the test, but

the test won't say that you're going to

get the disease. It will simply say that

you may get a disease. And, as you know,

there is a big difference between

"you will" and "you may".

(women talking in distance)

(Narrator) Lisa Capos and Lori Segal are

sisters who shared the wrenching

experience of cancer in the family. Way

back, there was three sisters in 1979.

The youngest of the three, Melanie, was

diagnosed with ovarian cancer.

(Lisa) When my sister was diagnosed, my

response was disbelief. She was

Lisa - 30 years old, and I'd never known

anybody of that age to have ovarian
cancer.

(Narrator) Melanie fought her cancer

for four years, but died in 1983.

It seemed an isolated piece of bad luck,

but then, just about a year later, Lisa

discovered that she had breast cancer.

She was only 34, but the cancer hadn't

spread, so the long-term outlook seemed

optimistic.

Lisa - I actually had a radiation

therapist, who was, tops in the field.

Wrote many books on breast cancer, and

was very optimistic. And what I remember

him saying was that he and I would grow

old together.

(Narrator) And Lisa was fine for 12 years,

and then she found another lump in the

same breast.

Lisa - It was the worst fear come true.

The first time I could hold onto hope,

the second time nobody was talking

with me about living to be old.

(Narrator) When Lisa discovered her

second cancer in 1996, scientists were

just beginning to work out the link

between breast and ovarian cancers

that run in families.

Mary Claire King was one of the scientists

who discovered the changes, or mutations

in two specific genes make a woman's

risk of breast and ovarian cancer much

higher. The genes are called, "BRCA-1" and

"BRCA-2"

Mary - BRCA-1 and BRCA-2 are perfectly

healthy, normal genes that all of us have.

But in a few families, mutations in these

genes are inherited.

(Narrator) - So, in a normal gene, we're

gonna spell it out for you here, letter by

letter, this is the normal sequence

ending, "GTAGCAGT". Now, we're gonna make

a copy. Now, we're gonna lose two of the

letters, just two, and then see, watch

them shift over. You see that? This new

configuration is a mutation which can

often cause breast cancer.

Mary - In the United States and Western

Europe, and Canada, the risk of developing

breast cancer for women in the population

as a whole, is about 10% over the course

of her lifetime. With, of course, most of

that risk occurring later in her life.

For a woman with a mutation in BRCA-1 or

BRCA-2, the lifetime risk of breast cancer

is about 80%. It's very high.

(Narrator) Right around the time of Lisa's

second bout of breast cancer, a test for

BRCA mutations became available. Lisa and

her sister, Lori, decided to be tested.

(Lori) I do remember the day that I went

to find out the results.

Lori - Panic, terror. I mean, what was I

gonna find out? Talking about the blood

surging through your temples, I mean

I just remember sheer terror.

(Narrator) Turns out, Lori was fine, but

Lisa discovered that she does carry a

BRCA mutation. It is not easy waking

up every morning, wondering if today's

the day you may get sick.

(Doctor) Any questions about the results

from the biopsy from April?

Lisa - No questions about the results,

again it feels like often my life is

dodging bullets...

(Narrator) With the second cancer, Lisa

had her right breast completely removed.

And then another operation to take out her

ovaries.

(Nurse) Just make a tight fist until I'm
in.

(Narrator) She also has a high risk of
cancer in her left breast. BRCA mutations

are relatively rare, and only cause maybe

only 5 or 10% of all breast cancer.

But knowing that there's a BRCA mutation

in the family affects everybody.

(Man) The gene doesn't go away. The time

passed since the last cancer doesn't buy

you the safety.

Man - And, the consequences run through

the family. And, I suppose, that, for my

daughter, who yet has not shown any

significant impact of this. The knowledge

that there's a genetic component that she

can't deny. Will, I'm sure, color her life

in serious ways.

(Narrator) Lisa's son, Justin, is 21. Her

daughter, Alana is 18. There is a 50/50

chance that each of them has inherited

the BRCA mutation from Lisa. The only way

to know, would be to take a test.

And when should they do that? When is the

right time?

Alana - I actually never really thought
about it until biology this year, when my

teacher posed a hypothetical, supposedly,
question to people saying, "What would

you do? Can you imagine what you would
do if you were faced with a situation

where you knew that you might have this
disease that would be deadly, or cause

you to be sick? And you could do a test

to find out whether or not you had it."

And I was sitting there in class saying,

"Maybe it's not so hypothetical."

(Narrator) And then in her senior year of
highschool, Alana felt a lump in her own

breast.

(Alana) I did have the, "Oh, it can't be
happening to me. Not yet." kind of thing.

I mean, I have the reservation in the

back of my mind
Alana - that eventually it may very well

happen to me. And, if it does, I'll fight

it then. I'll deal with it then, but I

don't expect, or I definitely didn't

expect for this to be happening to me

when I was 17 years old.

(Narrator) Alana's lump was not cancer.

And for now, she doesn't want the test.

Because, if she knew that she had the bad

gene, she'd only have two options:

The choice of removing her breasts and

ovaries to try to reduce her risk. Or just

to be closely monitored, and wait.

Lisa - She's followed every year. Seems

a little young to, ya know, have her have

to face that. On the other hand, it also

feels like the belt-and-suspenders

technique, and we just have to do

everything we can do.

(Narrator) In the next 20 years, this

family's predicament will become more
and more common as more and more

genes are linked to more and more diseases
and more tests become available. But we

will all have to ask, "Do we want to
know?"

And, when we know, can we live with an

answer that says, "Maybe... but maybe
not?"

(Lisa) Driving home from work today, I was

tuned into public radio. And there was a

professor of astronomy talking about a

brand new telescope to look into the

galaxies. And they're calling it the

equivalent of The Human Genome Project.

And I was thinking, "Hmm, not quite the

equivalent of The Human Genome Project."

because it's without some of the ethical,

moral angst, real-people issues, where,

it's a bit of a roller-coaster ride

between, ya know, this is gonna hold

answers, and hope, and treatments,

and interventions, and cure versus - it's

not clear what this all means.

(Narrator) And if things aren't clear now,

what about the future when we may not

only cure disease but do so much more.

(Doctor) Your extracted eggs are, Marie,

have been fertilized with Antonio's sperm.

You have specified Hazel eyes, dark hair,

and fair skin. All that remains is to

select the most compatible candidate.

I've taken the liberty of eradicating any

potentially prejudicial condition.
Premature baldness, myopia, alcoholism,

obesity, and so...
Woman - We didn't want... I mean...

diseases, yes, but um..
Man - Right, we were just wondering

if, if it's good to just leave a few

things to chance.
Doctor - We want to give your child the

best possible start.

Keep in mind, this child is still you.

Simply the best of you. You could

conceive naturally a thousand times and

never get such a result.

(Francis) GATTACA really raised some

interesting points. The technology that's

being described there is, in fact, right

in front of us or almost in front of us.

Narrator - That seems to me almost

extremely likely to happen. Cause, what

parent wouldn't want.. ya know, to

introduce a child that wouldn't have,

at least, be where all the other kids

could be?

Francis - That's why this scenario is
chilling. It portrayed a society where

genetic determinism had basically run

wild. I think society, in general, has

smiled upon the use of genetics for

preventing terrible diseases. But, when

you begin to blur that boundary of making

your kids genetically different, in a way

that enhances their performance in some

way, that starts to make most of us
uneasy.

(Narrator) What if we lived in the world

of Star Trek Voyager? Talk about uneasy.

Actress - Computer, access Belana Toras'

medical file.

(Narrator) Lieutenant Toras is 50% human

and 50% Klingon.
Actress - Project a holographic image of

the baby.
(Narrator) She's also 100% pregnant.

Actress - Now extrapolate what the child's

facial features will look like at 12 years
old.

(Narrator) Like any caring parent, she

doesn't want her child to be teased. For

having a forehead that looks like... well,

like a tire tread.
Actress - Display the fetus genome.

Delete the following gene sequences.
(Narrator) But here's the twist...

She can do something about it.

Actress - Extrapolate what the child

would look like with those genetic
changes.

(Narrator) Hmm, she threw in some blonde
(music playing)

hair, too.

And is this limit? Or, could we go even

further?
Actress - Save changes.

Narrator - If you can eventually isolate

all of these things, can you then build a

creature that has never existed before?

For example, I would like the eyesight of

a hawk. And I'd like the hearing of a dog.

Otherwise, I'm quite content exactly how

I am. So, could I pluck the eyesight and

the hearing and patch it in?

Eric - Well, we don't know. We really

don't know how that engineering occurs

and how we can improve on it. It'd be

very much like getting a pile of parts to

a Boeing 777, and a whole pile of parts

to an Airbus, and saying, "Well, I'm gonna

mix and match some of these, so it'll

have some of the properties... I'll make
it a little fatter, but I also wanna make

it a little shorter." By the time you were
done, you'd think you'd made lots of

clever improvements, but the thing
wouldn't get off the ground. It's a very

complex machine, and going in with a

monkey wrench to change a piece, odds

are, most changes we would make today,

almost ALL changes we'd make today would
break the machine.

(Narrator) We may not be able to
genetically modify humans or klingons,

yet. But we do do it to plants and animals

everyday. Look at this stuff, tobacco

plants with a gene from a firefly. And

they use that same insect gene to create

glowing mice.

Narrator - So, it's theoretically possible

that we could create humans with other

advantages that borrowed from other

creatures?
Eric - That's right, but the humility of

science right now is to appreciate how
little we know about how you could

even begin to go about that. That is the

difference between 20th century and

21st century biology, is, it's now our job

in this century to figure out how the

parts fit together.
(music playing)

(Narrator) And just as the 20th century

was winding down, the race to finish the

genome was full throttle. The competitive

juices were flowing.

Venter - I am competitive, but, when the

social order doesn't allow you to make

progress, and it doesn't for most people,

I said, "To hell with the social order,

I'll find a new way to do it."

(Tony White) It changed the paradigm on

people, and people don't like that.

Tony - It was very offensive to these

people. "How dare they?" Ya know,

rain on our parade, this is our turf.

Eric - This was a challenge to the whole
idea of public generation of data. That's

what offended people, was that we really

felt deeply that these were data that had

to be available for everybody. And there

was an attempt to claim the public

imagination for the proposition that

these data were better done in some

private fashion and owned.

Tony - You wanna say, "Well, wait a
minute. Ya know, if you could do it in

two years, why weren't ya doing it in
two years? Why do we have to come

along to turn a 15 year project into a
two year project?"

Eric - I must say that The Human Genome
Project had a tremendous amount of

internal competition, even amongst the
academic groups. There's competition

amongst academic scientists, to be sure.

And more than anything, there's

competition against disease. There's a

strong sense that what we're trying

to find out is the most important

information that you could possibly get.

Tony - I don't know, I mean, I hope that
this will all go away.

(Narrator) In June of 2000, it kind of did

go away.
(orchestral music playing)

The contentious race to finish the genome

came to an end.
(Announcer) Ladies and gentlemen, the

President of the United States.

(Narrator) And the winner was...

Well, you probably heard, they decided

to call it a tie.

(Francis) I think both Craig and I were

really tired of the way in which the

representations had played out and wanted

to see that sort of put behind us. It was

probably not good for Celera, as a

business to have this image of being

sort of always in contention with the

public project. It certainly wasn't good

for the public project to be seen as

battling with the private sector
enterprise.

(Narrator) President Clinton, himself,

got the public guys and the Celera guys

to play nice, shake hands, and share

credit for sequencing the genome.
(clapping)

President Clinton - Nearly two centuries

ago, in this room, on this floor, Thomas

Jefferson and a trusted aid spread out a

magnificent map. The aid was Merryweather

Louis and the map was the product of his

courageous expedition across the American

frontier, all the way to the Pacific.

Today, the world is joining us here in the

East Room, to behold a map of even greater

significance. We are here to celebrate the

completion of the first survey of the

entire human genome. Without a doubt,

this is the most important, most

wondrous map ever produced by humankind.

(Narrator) And what does this map the

President is talking about, what does it

look like?

Narrator - When we look across the

landscape of our DNA for the 30,000 genes

that make up a human-being, what do we

see?

Eric - The genome is very lumpy.
Narrator - Very lumpy?

Eric - Very lumpy, very uneven. You might

think if we have 30,000 genes they're

distributed kind of uniformly across the

chromosomes. Not so.

(music playing)

(Eric) They're distributed like people are

distributed in America. They're all

bunched up in some places, and then you

have vast plains that don't have a lot of

people in them.
(car horn honking)

It's like that with the genes.

(music playing)

(Eric) There are really gene-dense regions

that might have 15 times the density of

genes. Sort of a New York City over here.

(music playing)

(Eric) And there are other regions that

might go for two-million letters, and

there's not a gene to be found in there.

Eric - The remarkable thing about our

genome, is how little "gene" there is

in it. We have three billion letters of

DNA, but only 1 to 1.5% of it is gene.

Narrator - 1.5%?

Eric - The rest of it, 99% of it, is
stuff.

Narrator - Stuff? This is the technical
term?

Eric - A technical term. More than half

of your total DNA is not really yours. It

consists of selfish DNA elements that

somehow got into our genomes about

a billion-and-a-half years ago, and have

been hopping around making copies of

themselves. To those selfish DNA elements,

we're merely a host for them.
Narrator - Wait a second...

Eric - They view the human being just as a

vehicle for transmitting themselves.
Narrator - Wait, wait, wait...

We have, in each and every one of our
cells that carry DNA, we have these

little... they're not beings, they're just

hitchhikers...
Eric - Yeah.

Hitchhiking hunks of DNA.

Narrator - And they've been in us for how
long?

Eric - About a billion or a half years
or so.

Narrator - And all they've done, as far as
you can say, is stay there and multiply?

Eric - Well, they move around.

Narrator - And what is that? What do

you call that? I mean, it's not an animal,

it's not a vegetable. It's just...

Eric - It's a gene that knows how to look

out for itself and nothing else.

Narrator - And it's just riding around
in us?

The majority of our genome is this stuff,

not us.
Narrator - Wow.

(music playing)

(Narrator) It is a little humbling to

think that we, the paragon of animals,

the architects of great civilizations,

are used as taxi cabs by a bunch of

freeloading parasites who could care

less about us, but, that's the mystery of

it all.
(lightning)

(music playing)

(Eric) - You come away from reading the

genome, recognizing that we are so

similar to every other living thing on

this planet.

(music playing)

(birds chirping)

(Eric) And every innovation in us... we

didn't really invent it. These were all

things inherited from our ancestors.

(music playing)

(Eric) This gives you a tremendous

respect for life. It gives you a respect

for the complexity of life, the innovation

of life. And the tremendous connectivity

amongst all life on the planet.

(music playing)

(Narrator) We are, in a very real sense,

ordinary creatures. Our parts are

interchangeable with all the other

animals, and even the plants around us.

And yet, we know that there's something

about us that is truly extraordinary.

What it is, we don't know, but what it

does is, it let's us ask questions and

investigate, and contemplate the

messages buried in a molecule shaped

like a twisted staircase. That's what we,

and maybe we alone, can do. We can wonder.

(music playing)

(Narrator) This program raises many

difficult questions, and we do want to

know what you think. So, please logon

to Nova's website and take our survey.

Also, you can see how scientists pinpoint

a gene, find out how sequencing works,

and more at PBS.org or AmericaOnline,

keyword: PBS.

(music playing)

(music playing)

(Announcer) To order this show or any

other Nova program for $19.95 plus

shipping and handling, call WGBH Boston

Video at 1-800-255-9424.

By inserting just one gene, our food can

grow bigger, resist disease, and feed the
world.

(Man) This is a mass genetic

experiment that's going on in our diet.

(Announcer) Harvest of Fear, a NOVA

frontline special report.

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(Announcer) NOVA is a production of WGBH
Boston.

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And by, the Corporation for Public
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