Cracking Your Genetic Code (1974)

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NARRATOR: This is no ordinary flash drive.

From a small company called Knome,

it contains a complete digital record

of a person's genetic code-- all six billion letters of it.

NATHANIEL PEARSON: Your DNA is what makes you unique.

It governed how you grew in the womb and how you look today.

And until now, only a few hundred people in the world

have had a chance to see their whole genome

and try to understand it.

NARRATOR: Few could afford the cost-- $,-- just three years ago.

But that's changing.

FRANCIS COLLINS: It's almost amazing to be able to say

that each of us will have the chance

to have our complete genome sequenced for less than $,

in the next four or five years, but it's true.

NARRATOR: The result could be a revolution in medicine:

using genetic information to diagnose and cure disease.

JOE BEERY: If you go back

and you look at some of the home movies that we took

and you see Alexis falling down,

and you look at her now and you think,

"It's unimaginable that she was actually that same child."

Whole genome sequencing really, really saved Alexis's life.

NARRATOR: But it could also lead

to wholesale invasions of privacy and an ethical quagmire.

JAY ADELSON: There's a lot of fear about, say,

insurance companies

or other professionals being able to access that data.

RUDI TANZI: And then the company geneticist says,

"He has an increased risk for cancer."

"Okay, just don't interview him.

He'll never know."

Do you want that?

Because that is a potential reality.

NARRATOR: Thousands of years ago,

the ancient Greeks were given some famous advice:

"Know thyself."

Today, when those words are a biotech company motto,

they present a new kind of challenge.

Just how well do you want to know yourself

in the age of personal genomics?

Up next on NOVA, "Cracking Your Genetic Code."

NARRATOR: MaA few years from now,is you may boot up your tablet

to find a life-changing report.

A report on your own personal genetic code,

on the thousands of genes that spell out

your body's instructions.

Deciphered, your genes will reveal your risks

for one disease after another--

those you may get yourself and may pass on to your children.

How will it feel to have this information?

You may find out sooner than you think.

GREGORY STOCK: We're entering an era

of unprecedented self-knowledge.

We are really beginning to understand

the living processes that constitute ourselves

where we can begin to intervene

to take control of our own future.

COLLINS: Genomics offers us the chance to look in the most precise way

at what the causes of illness are

and how to prevent and treat illnesses

with that information.

And we have that opportunity now in front of us.

NARRATOR: This could be your future.

A new kind of personalized medicine

based on your genetic code.

One that predicts risks,

so you can stop diseases before they appear,

if there's a way of stopping them.

TANZI: But what if you can't?

What if you have

a gene mutation that says,

"Doesn't matter how you live your life,

"doesn't matter what drugs you take.

You will get this disease and probably before years old."

CATHERINE ELTON: Not everybody can handle genetic testing.

And this information affects

the way you live the rest of your life

if you are going to get a disease.

NARRATOR: But while some sound notes of caution,

the science is rushing ahead

and is now taking on medical challenges

once thought impossible.

(laughing)

Consider Andrew Schmitz, a bubbly five-year-old

who has no idea his life hangs in the balance.

PAULA SCHMITZ: It started with high fevers and joint pains.

And then July he had his first stroke.

And then he had two in October

and one in November that required brain surgery.

And then his last one, number five, was a week ago.

NARRATOR: Andrew is at the center of a medical mystery.

His parents have consulted dozens of specialists,

but so far his symptoms defy diagnosis.

He gets steroids to calm his immune system

and has been on and off chemotherapy.

Nothing seems to work.

At Children's Hospital in Milwaukee,

Andrew's pediatrician, Dr. Sheetal Vora,

assesses his condition and the toll being taken

by the drugs used to treat him.

Can you look up all the way to the ceiling with your head?

VORA: It pains you because I've been there with this family

from the beginning and I've seen the ups and downs

and told them the brutal truth,

that you use all these medications,

but they also can have their harms as well.

Does the light bother you?

NARRATOR: Desperate for a diagnosis,

Dr. Vora has brought in geneticist Howard Jacob.

JACOB: Right now we don't know what is the cause of his disease.

It's possible that it's environmental.

It's possible he had some type of an infection.

In general, though, somebody else should have it.

Why doesn't anybody else have it in the family?

What about in the community?

So a more plausible explanation is that it's probably genetic.

So if it happens to fall into a gene...

NARRATOR: If Jacob is right, there's a chance that Andrew's condition

could finally be diagnosed,

opening up the possibility of a cure.

JACOB: So we will do everything we can

to sort through his genome and see what we can find in there.

NARRATOR: To fulfill this promise,

Jacob will be putting Andrew in a select group,

those who have had their genomes-- that is,

all the genetic material contained within their cells--

read out, letter by chemical letter,

six billion in all.

To start the process, a nurse draws Andrew's blood.

The next day, it arrives at Illumina,

one of a handful of companies

that reads, or sequences, genomes.

In the lab, the blood is processed

to extract its genetic material.

As proteins and fats are washed away,

delicate fibers clump together.

This is DNA, life's master molecule.

Next, the DNA is sheared into fragments,

making it easier to sequence.

It is such a complex task

that sequencing the first human genome took years,

$ billion and hundreds of scientists.

(applause)

When the first draft was finished in ,

it was hailed as one of humanity's great achievements.

ERIC LANDER: This is all the instructions there are,

telling you all the tricks cells use

to actually go from being a single cell

to a whole grownup individual.

All those recipes are written in exactly the same language.

NARRATOR: A language whose alphabet consists of four chemicals,

each known by its initial: A, T, C and G.

Strings of these chemical letters

spell out some , genes on pairs of chromosomes.

Genes code for proteins,

molecules that do most of the work in our cells

and help build parts of our body, from muscles to hair.

And in the world of genes and proteins, spelling counts.

If DNA is copied incorrectly or damaged, spelling errors,

known as variants or mutations, crop up.

PEARSON: Now, when you change the spelling of a gene,

sometimes it drastically changes

the way that a protein functions,

and those are the kinds of changes in the genome

that we really look to when we're trying to trace disease.

We're trying to figure out

what spelling variant in the genome

explains, for example, why this child is sick.

NARRATOR: And that's what Howard Jacob will search for.

Convinced that a misspelled gene underlies Andrew's condition,

he will comb through the boy's genome to find it.

But even if he does, it's still a gamble.

JACOB: The chances are pretty high that we're going to find something

that there's nothing we can do about it.

And that's where, I think, a lot of times people worry about,

well, if you can't change it, why do it?

And we believe that providing an answer to the family

does have merit to the family

even if we can't help his outcome.

And so here we've decided

that it's better to go look and potentially fail by looking

than to not have looked

and missed an opportunity to succeed.

NARRATOR: As advances in technology drive down the cost of DNA sequencing,

it's becoming accessible,

not just to the sick, but the curious.

And a handful of companies have arisen to meet the demand.

They don't offer whole genome sequencing yet,

more of an economy-class genome scan.

One of the best known is the Silicon Valley start-up

andMe, co-founded by Anne Wojcicki.

WOJCICKI: From day one when we started this company,

our goal has always been, "How do we make genetics accessible?"

And we started off with the genotyping technology

because it's a fabulously robust technology.

It's incredibly reliable.

And, most importantly, it's inexpensive.

NARRATOR: Human genomes are .% identical.

But by analyzing the DNA in your saliva,

andMe will show you a million sites in your genes

where the spelling sometimes differs between people.

These one-letter variants may predispose you

to certain traits and diseases.

A million letters may sound impressive,

but that's far less than one percent of your DNA.

JONATHAN ROTHBERG: Genotyping is not DNA sequencing.

Genotyping is identical to looking at a hundred words

in a -page novel

and believing you know everything about Tolstoy.

NARRATOR: Genotyping can explain odd traits,

such as why some people find Brussels sprouts bitter.

But when Jay Adelson wanted to know his chances

of getting the brain disorder known as Parkinson's disease,

he found the results far less clear.

ADELSON: There is something called an odds calculator.

And that odds calculator says I have roughly a % chance

of contracting Parkinson's disease.

And my father has it, but his parents and his grandparents,

no one had Parkinson's disease.

So, while it's a genetic trait that passes down,

it doesn't necessarily mean that I'm going to contract it.

And so I spent a lot of time

trying to understand what it meant.

Almost all the evidence we're going to get

will be not hard determining facts about our futures,

but it'll be probabilistic information.

It will tilt the odds a little bit one way or another.

ROBERT GREEN: And we're not very well prepared as a society

to sort of negotiate those risk elements.

And some people will overinterpret those risks,

and they will rush out and try to get diagnostic tests

or they'll try to get surveillance tests

to try to help them interpret

what this information means and what it doesn't mean.

NARRATOR: Given such concerns, critics argue that genetic information

should only come from a medical professional.

Anne Wojcicki disagrees.

WOJCICKI: As of today, we're the only company that allows you

to go direct to the website

and not require you to go through a physician.

And, again, I think this is really core to our belief

that this is your genetic information

and something that's fundamentally about you

and that you should have the right

to get access to that information.

NARRATOR: Even the head of the National Institutes of Health,

Francis Collins, decided to take the genomic plunge.

He submitted his DNA to three genotyping companies,

including andMe.

COLLINS: I was a little on the cynical side about,

"Yeah, yeah, yeah, these are early days,

and how do I know they even got the results right?"

But opening up that website

and beginning to look down the list of things

where I turned out to be at higher than average risk

got my attention.

NARRATOR: All three companies agreed

Collins was at a substantially increased risk

for getting type- diabetes.

COLLINS: And that got me motivated.

I am pounds lighter today than I was two years ago,

and I'm working out three times a week.

And the chance to have a little bit of a prediction

about your future, as imperfect as it is right now,

and it's very imperfect, could still be a teachable moment.

NARRATOR: But some of the results were contradictory.

Prostate cancer was the most glaring example.

One company said, "Higher than average risk."

One said, "About average,"

the other said, "Lower than average risk."

NARRATOR: So, what's going on?

According to neurogeneticist Rudy Tanzi,

companies often look at different parts of genes

and make predictions based on incomplete data.

These two-- these two or that one.

TANZI: Even when we have that full set of genes

where these variants increase your risk

and these variants protect you,

knowing how they work together or independently

to come up with a real number?

Good luck.

And remember, most of those variants

are going to work together with your lifestyle.

They're not guaranteeing anything.

It depends on how you eat, do you exercise?

DAVID ALTSHULER: I always think about,

is it possible that the person who's told

they're not at high risk will do less and maybe be harmed?

RONALD GREEN: "Oh, I don't have a cardiac problem genetically.

"Now I'm going to go out and eat rich foods

night and day," and so on.

So there are all sorts of decisions that result from that.

Information is always hard to handle.

NARRATOR: One example is a piece of genetic information

so potentially disturbing

that even a founder of modern gene science

refused to take a chance on running into it.

KEVIN DAVIES: James Watson,

the man who co-discovered the double helix of DNA,

one of the very first people in the world

to have his genome completely sequenced.

He said to the scientists who were doing the sequencing,

"There's one gene I don't wish to know anything about."

NARRATOR: Known as APOE-, on chromosome ,

it has been associated with late-onset Alzheimer's,

the leading cause of dementia in the elderly.

The variant increases one's risk three to tenfold.

TANZI: But what does that mean?

What does it mean to say, "You have a tenfold increased risk

over someone who doesn't have it"?

Can you then convert that

into an absolute lifetime risk type of number to say,

"Here's your percent chance of getting the disease"?

No.

Because you need to know what other genes work with APOE.

You need to understand

how lifestyle is working together with APOE.

NARRATOR: In fact, many people with APOE- never get Alzheimer's,

while others with the disease don't have the variant.

ROBERT GREEN: I think the real key here

is to disabuse people of the misunderstanding

that genetics is wholly deterministic.

In a few rare instances, there is a tight linkage

between a particular mutation and a disease.

But the vast majority of genetic information

is largely probabilistic.

NARRATOR: Yet some genes speak louder than others.

Although we get two copies of most genes,

one from each parent,

certain dominant genes confer a trait of their own.

♪ I'm going to eat lunch with Katie and my mom. ♪

NARRATOR: And certain dominant disease genes, although rare,

will eventually make you sick.

As a volunteer for the Huntington's disease society,

Katie Moser works with people in this rare category,

among them Meghan Sullivan.

Four years ago, Meghan was a high school student

with everything to look forward to.

But with college came a set of heartbreaking symptoms.

NARRATOR: The reason for Meghan's plummeting grades,

sudden movements and stumbling speech

is a snippet of genetic code that repeats many times

instead of a few, causing Huntington's disease.

The mutation creates an elongated protein in the brain,

which is as toxic to Meghan

as it was to Katie's grandfather,

who also had Huntington's.

And if he passed this gene to Katie's mother,

Katie had a % chance of carrying it herself.

For years she wondered if she should get tested.

TANZI: In the case of a gene mutation that guarantees the disease,

that's a real tough decision because there, there's no hope.

If you get the wrong answer,

it's somewhat of a death sentence.

MOSER: I decided to get tested for the gene

because I wanted to be able to plan my life--

financially, physically, emotionally.

And I wanted to know if someday I would start showing symptoms.

But my family did not want to know.

NARRATOR: Tests confirmed that Katie

will eventually get Huntington's disease.

But knowing has had repercussions--

dates who disappear,

relatives who won't speak to her

since they must now confront their own genetic status.

"The burden of knowing"

is what journalist Catherine Elton calls it.

ELTON: For this age of personalized genetic testing,

it's not personal.

People exist in families.

And by the nature of the fact that you have tested,

you are revealing this information

to people who may not want to know.

NARRATOR: Elton herself was offered a test

for mutations in the BRCA- gene,

linked with a high chance

of getting breast or ovarian cancer.

Her mother, her grandmother and her aunt

had their lives cut short by these diseases.

If Elton had the mutation, she could minimize her risks

by having her breasts and ovaries removed.

If she wanted children,

she would have to have them before surgery.

ELTON: I didn't want those results.

I didn't want to have that in the back of my mind

and maybe make me settle for the wrong guy

and rush into having kids before I was ready.

I mean, I think there is a real fine line

between avoiding death and ruining your life.

NARRATOR: But Elton, too, has paid for her decision.

In , while pregnant with her second child,

she was diagnosed with breast cancer.

Yet despite the ordeal of surgery and chemotherapy

and the risk the cancer might come back,

she's convinced she did the right thing

by not getting tested in her s.

ELTON: If I had made those decisions at ,

I can't even believe what I would have missed out on.

And as the technology becomes more accessible,

people just think, well, this is what you do.

But I happen to believe

that some of the costs of knowing our genetic destiny

can outweigh some of the benefits.

NARRATOR: While Catherine Elton sees genetic information

as potentially damaging,

others see her disease-causing variant, BRCA-,

as one of the first you can do something about--

a so-called "actionable gene."

These are genes where,

if you know the patient has a variant in that gene,

you can actually counsel them

on things that will improve their wellness.

NARRATOR: One of these variants causes deadly blood clots,

but needn't if you avoid long periods of immobility

or take blood thinners.

Another variant tells us we could fall victim,

even in our teens, to a heart attack.

PEARSON: As a healthy adult,

if you learned about one of those variants

and found out you carried it, how would that change your life?

Well, you might actually invest in defibrillator machines

for your home or your workplace.

You might change your vacation plans,

in terms of whether you want to do

really strenuous sports activities

or shock yourself by jumping into cold water.

NARRATOR: So far, scientists have found about actionable genes,

including one that boosts your chance of colon cancer

by age .

So what can you do about that?

Well, if you start colonoscopies at or so,

you can actually keep people free of the disease.

TANZI: If you look at a personalized medicine approach,

the mantra is early prediction, early detection.

You want to know pre-symptomatically

if you're in trouble so that you can start treatment

to nip the disease in the bud stage,

prevent it before it strikes.

COLLINS: And if you do get sick

and your doctor has to make a decision

about how to treat you,

there are going to be signals in your instruction book to say,

"Not that drug.

Use this one instead."

NARRATOR: Of course, personalized medicine only works

if we know the gene variant responsible for a condition.

Back at Milwaukee's Children's Hospital,

the search for the genetic cause

of Andrew's illness is beginning.

His decoded genome has arrived from Illumina.

Sequencing took days and cost $,.

The next challenge, and the major expense,

is figuring out what it all means.

To find Andrew's variants,

Jacob's team will compare his genome with thousands of others,

but mainly with the reference genome

sequenced by the human genome project.

DAVID DIMMOCK: So this here is the reference sequence.

JACOB: The computer's the first pass.

It basically goes through and asks a question

at each point across Andrew's DNA.

Are you the same or different from the reference?

And when we see a difference, we then ask a question,

"Is that difference meaningful?"

NARRATOR: Meaningful in that the variant must be unique to Andrew

and a possible cause of disease.

But as the list of suspects

shrinks from three million to a few thousand,

success proves elusive.

Meanwhile, Paula and Mike Schmitz keep Andrew's life

as normal as possible.

MIKE SCHMITZ: We had hoped that he would progress a little better

with his rehab, with his walking,

and it's hard to live every day

with the anxiety of not knowing what's next, you know.

And with Andrew, there's always something next.

But there is hope.

NARRATOR: One source of this hope is another Wisconsin boy.

From age two, Nicholas Volker struggled with a condition

that ate holes in his intestines.

When treatment after treatment failed,

Nick's doctors turned to Howard Jacob and gene testing.

That's for your birthday.

Shall we open it?

NARRATOR: Now, nearly two years later, Nick is paying Jacob a visit.

Ask the question,

how many PhDs does it take to assemble Green Lantern?

NARRATOR: Nick is the model for the success of this approach.

His illness was traced to a gene on chromosome X called XIAP,

linked with immune disorders.

A single letter was out of place:

a G that had mutated into an A.

I want to do the tank.

JACOB: You want to do the tank?

Yeah.

I was afraid you were going to say that.

We found one single letter change in this gene, XIAP,

which now was unique.

Nobody else has the same variation that Nick has.

And that's meaningful,

because that means that letter is so important,

anybody who would have had

this particular variation would die.

NARRATOR: This single variant caused Nick's symptoms.

But a transplant,

giving him a donor's immune system without the misspelling,

appears to have saved him.

What does the Green Lantern do?

NARRATOR: In Boston, genomics is also being used

in the battle against better-known conditions,

like cystic fibrosis, or CF.

Michael McCarrick, age , knows its ravages firsthand.

How I've experienced my decline has been sort of,

you know, in the beginning of my life I played a lot of sports,

and I had fun playing a lot of sports,

and then suddenly I couldn't run,

but I could walk long distances.

And now it's like walking itself is difficult.

NARRATOR: Like many CF patients his age,

Michael is facing end-stage lung disease.

AHMET ULUER: Where Michael is right now

and what he is dealing with

is the t*rture we don't like to watch our patients go through,

the struggle for that next breath.

NARRATOR: Michael may need a lung transplant.

But Dr. Uluer hopes a new, gene-based drug

will save him instead.

Called Kalydeco, it targets a mutation found

in four percent of CF patients.

McCARRICK: Every drug can have a side effect.

But I am hoping this one is free and clear.

Because who needs an extra problem?

So, hopefully it's a magic b*llet.

NARRATOR: The development of a drug for cystic fibrosis

is especially gratifying to Francis Collins.

Decades ago, Collins and a team of scientists,

using rudimentary technology,

set out to find the genetic defect behind the disease.

COLLINS: Back in the s,

this was like looking for a needle in the haystack

in the dark with thick gloves on.

And one day, in the spring of , the data came across

showing that individuals with cystic fibrosis

were missing just three letters of that code.

NARRATOR: Just three letters, that is,

from each copy of a gene called CFTR on chromosome .

Because the mutation is recessive,

only those who inherit a copy from both parents

get the disease.

While we now know , different mutations

in this gene can cause CF,

Collins' team found the main one,

truly his needle in the haystack.

When this was announced in August of ,

the excitement was palpable.

And I think many of us thought maybe this is the launch

of a therapeutic effort that could happen pretty quickly.

NARRATOR: In reality, a clinical breakthrough

would take another years of research

and hundreds of millions of dollars.

Some of the most successful work

has been done at Vertex Pharmaceuticals in San Diego,

where scientists are trying to fix

the defective protein made by the CF gene.

The normal protein creates an opening

for salts to move across cell membranes,

keeping them moist enough for tiny hairs called cilia

to beat and remove mucus.

FRED VAN GOOR: In CF, the cilia's not able

to clear out the bacteria and the mucus,

and this leads to the chronic cycle of infection.

So the first challenge was

to be able to find molecules

that help the protein work better.

NARRATOR: Drawing on a vast chemical library,

the research team employed a small army of robots

to test , compounds on cells taken from CF patients.

To date, two drugs have shown the most promise,

one of them Kalydeco.

When tested on CF cells, it helped the protein function,

allowing salts and fluids to flow across membranes.

Van Goor could watch the result:

cilia beating, clearing away mucus

while untreated cells languished.

VAN GOOR: It was an exciting moment

where we really felt we are on the right track:

designing drugs to fix a specific problem in a protein

caused by a mutation.

NARRATOR: Whether Kalydeco will work for Michael McCarrick,

whose lungs are severely damaged, remains unclear.

But younger patients like Paul Glynn

are seeing a world of difference.

It's a lot easier 'cause I'm not, like, coughing.

I can breathe easily.

And then my weight.

It's been going up.

NARRATOR: Since taking the drug, Paul has gained pounds,

enough to make the local football team.

For him, the hope is that CF

will become a manageable disease

and regular hospital visits a thing of the past.

Which may even make the drug cost-effective,

despite its price tag: as much as $, a year.

In Boston, meanwhile,

at Massachusetts General Hospital,

doctors are using new gene-based drugs

to target the most common disease of the genome: cancer.

Tom Garpestad is a -year-old building contractor.

He was stunned to learn he had the skin cancer called melanoma.

GARPESTAD: Melanoma is the cancer that doesn't act like cancer.

I had no symptoms,

no weight loss, no night sweats.

I felt perfectly fine up until the point

that my neck started bothering me.

That was the only time I had any symptoms.

NARRATOR: Scans revealed the cancer

had spread from his skin to his neck, lungs and liver.

KEITH FLAHERTY: Patients who have melanoma

that has spread to other parts of the body

from the primary skin site

have, from the time of initial diagnosis,

typically a year or less.

Tom had already had metastatic melanoma

for sufficiently long

that as he walked in the door to our clinic,

he was down to a month or two.

GARPESTAD: I talked to my brother, who's a doctor,

and he started telling me how severe melanoma is.

You know, the average life expectancy of somebody

with metastatic melanoma is nine months.

TODD GOLUB: Research labs weren't even working on it that hard

because it seemed to be completely intractable.

Nothing would ever work.

And this all changed almost overnight

with the sequencing of the melanoma genome.

LANDER: The idea of sequencing a cancer...

it's as big as the human genome.

Each cancer cell has an entire human genome in it,

just mutated in various ways.

And genomics told us there was a mutation in many melanomas

in a specific gene that goes by the funny name "BRAF."

And it led to the idea that if you could inhibit this BRAF,

you might be able to stop the melanomas.

NARRATOR: Luckily for Tom,

gene sequencing revealed he had the BRAF mutation.

He could now join a clinical trial

of a new drug designed to neutralize its effects.

GARPESTAD: The cancer was getting very aggressive.

And then they started me on the BRAF medicine,

and within a week, I could feel the tumors shrinking.

NARRATOR: The BRAF mutation results in a defective protein

that signals cells to divide uncontrollably.

The drug binds to this protein,

stopping both the signal and the cancer.

Unlike chemotherapy drugs,

this one kills only cancer cells, nothing else.

PET scans of patients reveal tumors that once riddled bodies

shrinking or vanishing within weeks.

FLAHERTY: We had a situation in a disease

that was never responsive to therapy

-plus percent of the time.

To have that turn around and have it be

-plus percent of the time that the treatment worked,

that's when we knew we had completely crossed

into uncharted territory.

NARRATOR: Only two months after lying near death in the hospital,

Tom was back to his old life.

I think that's too skimpy, because you've got...

You're gonna hand them right down.

People close to me, seeing me back on the job,

just getting out there and doing things again.

It was amazing.

And I was always, you know, thinking,

"Hey, how sick was I two months ago?

Look at me now."

NARRATOR: But that doesn't mean the w*r is over.

To Keith Flaherty's dismay,

scans show melanoma returning in many patients.

Cancer cells, like viruses and bacteria,

can evolve to resist drugs, even those that target genes.

But now, the ability to compare cancer genomes

before and after treatment

is allowing scientists to see how resistance develops.

LANDER: The goal is to use

the cancer genome itself to tell us how to defeat cancer,

tell us what's wrong in a cancer and where we should hit it,

tell us how it's becoming resistant

and how we can block it.

NARRATOR: With resistance, new mutations arise in melanoma tumors,

and once again defective proteins ignite the cancer.

So now Tom is taking a second drug,

which targets a mutation linked to these relapses.

Eight months after starting his treatment,

he awaits the results of a new set of scans.

The scans do show some re-growth,

but only in a limited area.

In all the other areas where we have seen signs before,

things look great.

NARRATOR: Afterwards, Tom takes in the news.

I probably wouldn't be alive right now, you know.

So I mean, I'll take... I'll take the eight months.

You know, I mean, it's still a miracle drug, I think.

NARRATOR: At present, patients like Tom

are getting between two and extra months of quality life

from the new treatment.

But genomics is also helping those

for whom there are no targeted drugs.

Thousands of breast cancer patients are taking a gene test

which tells them how aggressive their cancer is

and whether they need chemotherapy

or can safely skip it.

You're way down here.

And that says, "No role for chemotherapy."

Oh, that's wonderful.

NARRATOR: The hope is by studying cancer genes,

we'll come up with a c*ck of drugs

like those used to treat tuberculosis or HIV

to cure cancers or keep them in check.

GOLUB: The big difference, though,

is that now really for the first time

we can think about the right combinations of drugs

based on the genome,

based on the science of what's going on

inside the cancer cell.

LANDER: This is not a project for my life.

This is a project for my kids.

This is a project ultimately for their kids.

But if in the course of this century,

we have a complete roadmap of what a cancer knows how to do,

that will be a mind-boggling advance in medicine.

NARRATOR: Another extraordinary advance

would be to eliminate inherited diseases before birth.

We're already taking the first steps:

by fertilizing an egg and producing an eight-cell embryo.

You can pluck off one of those cells and analyze its genes.

Then you can screen that embryo for a host of diseases

using a technique called

pre-implantation genetic diagnosis, or PGD.

MARK HUGHES: When we first started performing this technology,

I think our biggest worry was,

"Are we going to create some kind of a birth defect

"that is maybe even worse than the disease

we're trying to avoid?"

And what we learned was that the embryo doesn't seem to mind.

NARRATOR: At the Genesis Genetics Institute,

Mark Hughes and his team are using PGD to test embryos

for mutations that can give rise to over diseases,

including Huntington's and cystic fibrosis.

Only embryos free of certain mutations

are implanted in the mother.

So this is the mutant gene,

this cluster of peaks.

And we have the normal gene over here

highlighted in pink.

Tens of thousands of healthy babies have been born to couples

who otherwise would have been afraid to have a child,

because the disease that they were at risk

of giving their child was so severe.

NARRATOR: PGD can also be used to test for traits like gender,

leading ethicists to ask

if designer babies are in our future.

GREEN: I think we are going to see people using genetics

to select traits.

Some of it is going to be relatively benign.

"I want a child with this hair color or eye color."

As to where our ability to really intervene

in our own living processes is really going to lead us,

we simply do not know.

And that is the promise and that is the threat of this period.

NARRATOR: Some fear PGD could even lead to a new kind of eugenics

and the sort of genetic elite depicted in the movie Gattaca.

Your extracted eggs, Marie,

have been fertilized with Antonio's sperm.

After screening we are left, as you see,

with two healthy boys

and two very healthy girls.

I have taken the liberty of eradicating

any potentially prejudicial conditions:

premature baldness, myopia,

alcoholism and addictive susceptibility,

propensity for violence, obesity...

NARRATOR: Fortunately, the traits a genetic elite would want--

intelligence, physical ability, even height--

are so complex, scientists assure us

we won't be selecting them in embryos anytime soon.

LANDER: Trying to predict height-- well, we already know

there's at least genes involved in height.

And each contributes a little bit.

It isn't going to be easy to go take some embryo

and sort out which of these are in which of these forms.

There's just no particularly good way to do that.

You really, really, really want to have a tall person,

go marry a tall spouse.

It's just more efficient.

NARRATOR: Even so, Gattaca raises real concerns.

GREEN: One of the negative implications of this new genetic knowledge

is that we're going to start thinking of ourselves

more in genetic terms than we ever have before.

Do I want to date that individual?

What's her genetics?

What's his genetics?

There's always been a tendency

to engage in deterministic genetics,

and I think scientists and medical people and educators

must make very clear the limits of that point of view.

PATRICIA WILLIAMS: We are deeply affected

by the kind of food we eat, the kind of air we breathe,

by the kind of good luck or bad luck that shapes our lives,

opportunities like education and money,

and by the real romance of simply falling in love

with an unlikely partner.

We narrow our vision if we focus or fetishize upon genetics.

NARRATOR: But as the cost of a sequenced genome falls,

new generations may not get far into the world without one.

ROTHBERG: And I envision a day when every child is born,

they prick that child's heel,

and that DNA from that child is decoded right at birth.

NARRATOR: For -year-old twins Noah and Alexis Beery,

sequencing at birth could have made a world of difference.

Today, it's hard to imagine that just two years ago,

Alexis was fighting for her life.

ALEXIS BEERY: The only really vivid memory that I have of that

is just seeing red, blue and white lights

just flashing everywhere.

That's definitely one of my, like, number one, kinda like,

nightmares that I still have.

JOE BEERY: After Alexis and Noah were born,

they didn't reach any of their milestones.

They didn't crawl on time, they didn't walk on time.

And we knew pretty early that something wasn't right.

NARRATOR: The twins were diagnosed with cerebral palsy.

Then at age five, Alexis got worse.

RETTA BEERY: She started losing more and more ability to walk during the day.

She started losing the ability to sit up

by :, : in the morning.

She could no longer swallow by that time.

And so that's not indicative of cerebral palsy.

NARRATOR: Retta began doing research.

One day, she came across a rare condition

that mimics cerebral palsy,

a condition that could be treated

with the brain chemical dopamine.

Dopamine is crucial to our bodies' ability to move.

And the morning after Alexis took it,

she woke up to a new world.

JOE BEERY: She was walking, she was talking,

she was using her arms, she was whistling.

NARRATOR: Noah also responded.

Yet the twins still had health issues,

especially Alexis.

We actually almost lost her on a couple of occasions.

We had paramedics coming into our house,

trying to get her breathing,

and we were back into that world of unknowns.

NARRATOR: Until, that is, Joe turned to his employer, a biotech company,

for help getting the twins' genomes sequenced.

I'm Retta Beery, hi.

JOE BEERY: We discovered through sequencing

that there was a second problem

associated with the rare mutation that they had.

NARRATOR: The mutation was suppressing yet another brain chemical.

Another drug solved that problem too.

BEERY: Whole genome sequencing really saved Noah and Alexis's life.

Had that happened at birth,

we would have had years less pain and suffering

and probably millions of dollars of cost.

NARRATOR: Yet sequencing at birth may have its downside.

GREEN: One of my concerns is the testing of children

raises many questions, including stigmatization.

"Oh, I'm not going to let Mary play soccer

because she's got this cardiac risk."

So we do have a problem of invasion of the child's privacy.

NARRATOR: And what about your privacy?

What if a company asks to use your DNA for research,

promising you'll remain anonymous?

WILLIAMS: Now the question is whether or not

that anonymized information is truly anonymized

just because they take your name

and your Social Security number off.

At some point in the future,

it may be that you don't need a Social Security number,

that you don't need to give your name,

because your genetic information will reveal you so precisely

that we'll have to develop a whole new definition

of what we mean by anonymity.

NARRATOR: And what if your DNA reveals you're at increased risk

for an incurable disease, say, Alzheimer's?

MURRAY: Can a company that sells long-term care insurance

ask you about that?

And can they use that result to either affect your premiums

or even deny you insurance entirely

because you're such a bad bet?

NARRATOR: In fact, in most states, the law already allows long-term care,

disability and life insurers

to discriminate based on genetics.

TANZI: I would not make one single base of my DNA sequence

available publicly in a million years.

There's too much risk.

You don't know what's going to happen

in the future with insurance.

And think about

your company going down the tubes

and now you have to get a new job.

And, yeah, employers can't discriminate,

but they happen to find out on your Facebook page under DNA,

click, there's the sequence.

NARRATOR: Everywhere you go, you leave a trail of genetic debris.

When you cut your hair...

enjoy a meal at a restaurant.

A crime that once seemed like science fiction

has become possible with cheap, fast DNA sequencing.

GREEN: It's been called genomic hacking.

That will be frightful.

It will be used to impugn people.

Somebody saying, "He should not or she should not

"be a candidate for the presidency

because she has the gene for depression."

If somebody wants access to your genome

for personal, romantic purposes,

for economic reasons,

for political reasons in the future,

if they want it they'll go after it.

NARRATOR: Yet when illness strikes,

privacy may seem a distant concern

and genomics your best hope.

In Milwaukee, after months of searching

through Andrew's genome,

finally there's a discovery.

This is a list of genes that we pulled out...

So yesterday at noon I got an e-mail from Liz saying,

"I found a very interesting gene."

He's got two protein-coding...

NARRATOR: Geneticist Elizabeth Worthey

has found something unusual in Andrew's genome.

WORTHEY: It says mutations in this gene have been linked...

JACOB: There's two rare variants,

one that's never been seen before

and one that's only been seen once, as far as we know.

The next question, then,

is does this gene look like it could explain

part of Andrew's clinical features?

And in this case, the answer's yes.

"Mutations in this gene have been linked with susceptibility

to recurrent viral infections," which he had.

JACOB: I will tell you

that this is where we get both excited as scientists

and nervous, then, as scientists,

because you think you've found it.

There's a big difference between thinking you've found it

to, "We've proved it."

NARRATOR: In fact, the suspect gene is soon ruled out

and the family learns the search must continue.

So don't worry.

Until we tell you that we've stopped looking,

we haven't stopped looking.

Well, we really appreciate it.

JACOB: I know you do.

NARRATOR: In a field this new, success and failure continually intermix.

In Michael McCarrick's case,

the drug targeting his cystic fibrosis mutation helped,

but his lungs were already so damaged,

he died waiting for a transplant.

Yet Paul Glynn,

who used to spend part of every fall in the hospital,

is healthier than ever.

Tom Garpestad is in a kind of limbo,

with some tumors shrinking, others growing.

GARPESTAD: Yeah, a little in my right ankle.

NARRATOR: As for the Beery twins,

their only regret is not getting sequenced sooner.

We have focused so much of our energies

on treating people with disease, often advanced disease,

and much less effort on trying to prevent that disease

in the first place.

If we are going to shift towards prevention,

your genome sequence may be

one of the most critical tools you could imagine.

NARRATOR: How can we balance the risks and benefits of this critical tool?

This will soon be a question for all of us

as we confront the ancient challenge "know thyself"

in the genome age.