NOVA

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-- $350,000-- 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 $1,000 in the next four or five years, but it's true.

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

A few years from now, 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 50 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 13 years, $3 billion and hundreds of scientists. (applause) When the first draft was finished in 2000, 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 20,000 genes on 23 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 23andMe, 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 99.9% identical. But by analyzing the DNA in your saliva, 23andMe 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 600-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 60% 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 23andMe.

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-2 diabetes.

COLLINS

And that got me motivated. I am 27 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." 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-4, on chromosome 19, 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-4 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. 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. 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 50% 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-1 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 2008, 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 20s.

ELTON

If I had made those decisions at 27, 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-1, 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. 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 200 actionable genes, including one that boosts your chance of colon cancer by age 45. So what can you do about that? Well, if you start colonoscopies at 25 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 45 days and cost $7,500. 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? Now, nearly two years later, Nick is paying Jacob a visit. Ask the question, how many PhDs does it take to assemble Green Lantern? 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? In Boston, genomics is also being used in the battle against better-known conditions, like cystic fibrosis, or CF. Michael McCarrick, age 29, 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. 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 torture 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 bullet.

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 1980s, this was like looking for a needle in the haystack in the dark with thick gloves on. And one day, in the spring of 1989, 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 7. Because the mutation is recessive, only those who inherit a copy from both parents get the disease. While we now know 1,800 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 1989, 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. In reality, a clinical breakthrough would take another 20 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 600,000 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. Since taking the drug, Paul has gained 12 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 $294,000 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 50-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 90-plus percent of the time. To have that turn around and have it be 90-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." But that doesn't mean the war 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. 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. At present, patients like Tom are getting between two and 18 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. The hope is by studying cancer genes, we'll come up with a cocktail 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 300 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. 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 180 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 180 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 14-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 10

30,

11

00 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. 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 15 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... 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. 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. 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. Th This NOVA program is available on DVD. To order, visit shopPBS.org, or call 1-800-PLAY-PBS. NOVA is also available for download on iTunes. Captioned by Media Access Group at WGBH access.wgbh.org