[music] NARRATOR: It's the dawn of a new age in medicine.

EDWARD KAYE: For 20 years, all I would do is make a diagnosis, and then people would die.

Now we're actually able to tell a family that, you know, "We think we can help your child.

We can give them a better life."

NARRATOR: Every year more than a million babies are born worldwide with a disease caused by a single error in one of our many genes.

[medical device beeping] These are among the cruelest, and once the most hopeless diseases known to humankind, robbing patients of sight, movement, breath, life.

[dramatic music swells] But today, patients with these terrifying diseases have new allies: call them, "Gene Doctors."

They're leading a revolution by battling genetic disease at the source.

DENNIS NIELSON: It's probably the closest thing to a miracle that I've ever been involved with.

MOLLY TROXEL: I saw the moon.

RYAN TROXEL: Wow, Molly, you can see that?

NIELSON: She couldn't walk more than five minutes.

Now she does dance concerts.

ERIC GREEN: What we have now is incredible and revolutionary, but it's going to even get better.

That's the exciting part.

NARRATOR: Join the doctors who are on the brink of not just treating symptoms but replacing faulty genes or repairing the havoc they cause, forever changing the future of medicine and the lives of patients and their families.

JEAN BENNETT: It's definitely a very new world of therapies.

The promise is unbelievable.

[dramatic music swells] STUART SCHREIBER: It really is a special moment in time.

[dramatic music] NARRATOR: This program was made possible, [bells toll] [music] NARRATOR: Meet Sonia and Eric, aspiring young biomedical researchers.

They're on a quest to find a cure for one particular rare genetic disease.

Their motivation is both powerful and personal.

In March 2010, just months after her wedding, Sonia noticed that something had changed in her 52-year-old mother.

SONIA VALLABH: She couldn't finish a sentence without sort of trailing off.

That sort of inability to, like, speak in a clear way then got worse fast.

NARRATOR: Sonia memorialized the painful months that followed in paper collage.

[bird cawing] SONIA: There would be periods of intense anxiety, and if she stood up, she would fall.

Tests were run and a lot of things were proposed, but one by one these things failed to pan out.

[thunder] [wind] [thunder] By the middle of the summer, there was no rest.

It was sort of a constant uncomfortable movement.

ERIC MINIKEL: And she looked like she was in extreme pain every minute.

SONIA: By late fall, she was on life support.

And that was really hard.

[wind] On December 22nd, we decided to take her off of life support.

[wind] She passed away on the 23rd.

[wind] [music] NARRATOR: Heartbroken, Sonia had no idea that worse news lay ahead.

Her mother's illness was so rare, it took months after her death to identify it.

The illness is called Fatal Familial Insomnia.

Disrupted sleep is just one of many symptoms.

Patients suffer the death of neurons by the billions-- a wave of destruction across the brain, leading rapidly to dementia and death.

There is currently no treatment.

Its root cause is a genetic mutation.

And Sonia herself was at risk.

SONIA: It hit really hard.

That this, you know, really sad, hard, like, unexpected chapter of our life wasn't over, and that I was at risk.

ERIC: I felt like the floor had just fallen out from under me.

I just tried to curl up into a ball and make it go away.

[music] NARRATOR: Genes are composed of strings of smaller molecules, represented by four letters, that are encoded in DNA, which is stored within the nuclei of our cells.

A change in even one letter, in just one gene, can cause disease-- one letter among three billion.

And that was the case in Sonia's mother.

SONIA: It did seem incredible that this one change-- this one letter change, could be so dangerous.

NARRATOR: An error in DNA can derail a cell's ability to make a critical protein.

That's what genes are-- instructions for making proteins... ...which do essential tasks inside our cells like breaking things down... ...and building things up.

A DNA typo can result in a faulty protein or one that's missing entirely...

In either case, the result can be a devastating disease.

Sonia's mother's DNA had two copies of each of her genes-- that's normal.

For one critical gene, one copy was healthy and produced a healthy protein.

But the other had an error that produced a protein that becomes toxic to brain cells.

Sonia inherited one of her mother's two copies.

But which one--the normal or the flawed gene?

SONIA: 50/50 is very hard to wrap your head around.

And that limbo was terrible.

NARRATOR: Many people prefer not to know their fate.

But Sonia and Eric were determined to find out.

SONIA: We were always clear that we wanted the results.

NARRATOR: It would take eight excruciating weeks before they would learn what her DNA test had revealed.

SONIA: We met with the physician and the genetic counselor and were told, "The same change that was found in your mother was found in you."

And then--they sort of said, "We'll let you guys be alone."

[door closing and clicking shut] [music] NARRATOR: Sonia had been handed a death sentence.

But symptoms probably won't appear until her 50s.

So, she has a bit of time on her side but perhaps more importantly she has timing.

That's because she was diagnosed when new strategies for repairing broken genes-- or the devastation they cause-- are finally starting to work.

Ever since the discovery that genes were made of DNA, scientists dreamed of curing inherited diseases.

Many have sought ways to provide a correct copy of a gene to a patient who lacked one.

FREDA LEWIS-HALL: This is an idea that's been bandied around frankly for decades.

But the technology to actually make those changes real... ...has come slowly.

[scientists talking] [DNA machine whirring] NARRATOR: But gene therapy is finally arriving.

Hints that Molly Troxel was born with a problem came early.

LAURA TROXEL: When I was breastfeeding, she would look away from me to see a light somewhere else in the room.

And our first child never did that.

She had the nickname the light hog.

[laugh] RYAN TROXEL IN BACKGROUND: Stand up, Molly.

LAURA: And no matter where we were, she would find the light.

When we noticed that this activity kept up, that she would look at the lights, we went to see a specialist here in Omaha.

He had a great suspicion that it was genetic and that there was no cure.

RYAN IN BACKGROUND: Say bye, bye.

NARRATOR: Molly has a rare form of inherited blindness.

RYAN: You know, her and I just somehow our genes [laughs] ended up creatin' Molly, which is a great thing.

But, you know, with her havin' the eye disease, it's just a really rare thing as well.

Still tear up now thinking about it.

Just knowing that your daughter's not going to be able to see.

NARRATOR: Molly was declared 'legally blind' early in childhood.

What vision remained steadily deteriorated over the years.

MOLLY TROXEL: I used to run into mailboxes and things like that.

[bicycle bell] NARRATOR: And yet, here's Molly today.

MOLLY: I really try not to hit things, because I like to go fast.

And I am bad at slowing down.

I've gotten really better-- since the surgery.

NARRATOR: That surgery-- a breakthrough in gene therapy-- gave her a correct version of the faulty gene she was born with.

It might never have been possible without some unlikely allies.

[dog panting] JEAN BENNETT: If you watch my dogs they look like normal dogs.

Come on.

They're happy, they're waggin' their tail, they're moving all over the place, exploring things.

Let's go.

This is not the way they were when we first started working with them.

NARRATOR: For years, ophthalmologist Jean Bennett and her husband, eye surgeon Albert Maguire, have treated, and adopted, dogs with the canine version of Molly's disease.

Visually impaired dogs have played a key role in Bennett's long quest to find out whether inherited eye diseases can be treated by gene therapy.

BENNETT: The idea of gene therapy was really attractive because it was potentially a way of getting at the root of the disease, instead of fixing the complications of the disease or putting a Band-Aid on it.

LAB WORKER: Come on, come on... BENNETT: But of course, at that point in time, we didn't have any of the tools to be able to manipulate genes and put them into living cells.

LAB WORKER: ...come on, girl!

BENNETT: But as the field developed, people realized that we could use viruses as delivery vehicles.

We think of viruses as the enemy but they do some things really well... ...they deliver DNA to cells efficiently.

LEWIS-HALL: They come in and they hijack our cellular machinery, if you would, so that they can duplicate themselves.

And here we are now-- hijacking the hijacker to correct these gene mutations which is absolutely brilliant.

NARRATOR: This form of gene therapy simply changes the virus's payload, stripping away its disease-causing genes... ...and inserting a correct copy of the human gene that's flawed.

The next step is to inject billions of these viral delivery trucks, called vectors, near the cells that need the replacement gene.

The viruses take it from there, invading those cells and delivering the therapeutic gene.

By July 2000, Bennett and Maguire were ready for a test.

Maguire injected healthy replacement genes into the eyes of blind dogs.

Then, they waited.

[music] BENNETT: About two weeks after the first three dogs were injected, I got a call from one of the animal caretakers.

[music] "Jean..." LAB WORKER: Good girl!

Come on.

BENNETT: "These dogs are seeing.

They're watching us."

LAB WORKER: Good girl.

Good girl.

BENNETT: And universally, the reaction was, wow, that's amazing, we can make blind puppies see.

Wouldn't it be amazing to make blind children see?

[music] NARRATOR: Unaware of the dog studies, Molly and her family set out for the University of Iowa, for an appointment with Dr. Edwin Stone, a physician specializing in genetic eye diseases.

DR. EDWIN STONE: ...eye up there.

Over to the left.

LAURA: Poor Dr. Stone, I had a notebook full of questions and he took his time, and really made sure we understood, um, more about the disease.

STONE: Every single one of us carries at least ten or 12 if not 20 genes... ...that if they were matched up with a mutation in our spouse, could cause a problem.

NARRATOR: Molly's parents each have one good copy of a critical vision gene-- so their sight is fine.

But each also has a faulty copy.

Molly's bad luck was to inherit the faulty copy from her mother and the faulty copy from her father.

STONE: It's simply the chance occurrence of these two genes getting together that cause the disease.

NARRATOR: Molly's mutated genes affect cells in the back of her eye... called photoreceptors.

Within these cells are special molecules.

Their job is to capture light, the first step in vision.

After a capture, they become inactive and need to be reset.

But in patients like Molly, that resetting is disrupted.

And vision gradually fails.

Stone reviewed the medical options with Molly's parents.

STONE: What can we do?

What can we do today?

What can we do tomorrow?

NARRATOR: He had heard about Bennett's work with dogs.

STONE: I remember having conversations with the family about how gene therapy would work.

Theoretically, how would it work?

RYAN: Yeah, it did seem pretty far into the future.

I mean, you're talkin', you know, gene therapy kind of Star Trekky-like.

NARRATOR: The science fiction sounding reality of gene therapy has been a long time coming.

By the early 1990s, researchers like Stone had identified only a few of the flawed genes that cause diseases.

Then came the Human Genome Project with the goal of determining the DNA sequence of every human gene.

Knowing the normal letter sequences would let gene doctors identify changed sequences that cause disease.

Many felt that a medical revolution was at hand.

ROBERT BAZELL: A new kind of medicine promises to treat or prevent genetic diseases.

DR. LEON CHARASH: We are entering into the genetic age.

DR. RICHARD JOHNSTON: It's the best parts of a brave new world.

NARRATOR: Jean Bennett's restoring sight to blind dogs was a step into that new world.

But her triumph was overshadowed by shocking news from a human gene therapy trial.

ANN CURRY: The US Senate is looking into a medical procedure called Gene Therapy, a process where genes are injected into a patient to correct a serious health problem.

While the field shows great promise, it also has caused heartbreak for one father in Arizona.

PAUL GELSINGER: The concern should be making sure no unnecessary risks are taken, no lives filled with potential and promise are lost forever, no more fathers lose their sons.

NARRATOR: Jesse Gelsinger was a volunteer in a gene therapy trial.

He was mildly ill with a genetic disease of the liver.

Jean Bennett was working at the University of Pennsylvania where that clinical trial took place.

BENNETT: He had the infusion of the gene, and very shortly thereafter showed signs of a severe immune response.

NARRATOR: Gelsinger's body saw the viral vector as an enemy and mounted an intense attack that damaged his own organs.

BENNETT: He spiraled downhill very rapidly and died four days later.

The fallout from that was very close to home; just incredible sorrow and pain for this poor child, really-- 18-year-old and his family.

But also for the field.

The whole field-- came to a grinding halt.

Trials all over the place were shut down.

KATHERINE HIGH: There was a general sense, that this was a therapy that was not ready for primetime.

All the companies that had been involved in gene therapy were either turning away from it or they were failing.

NARRATOR: At the time, Katherine High was preparing tests of a different gene therapy at Children's Hospital of Philadelphia.

When the company that was supplying her gene-carrying virus left the business, she decided to search for a new and safer viral vector.

[music] In 2005, after five years of work, she felt ready to mount a new human trial.

Needing a collaborator with successful gene therapy experience, she crossed the street to the University of Pennsylvania.

BENNETT: I remember she walked into my office, sat down, and said, "Jean, how would you like to run a clinical trial?"

I was flabbergasted.

It was, I was so incredibly excited.

I could not believe my ears.

Hey, how's it going?

NARRATOR: Bennett had dreamed of moving from dogs to people.

She and High hoped this new study might help patients and get gene therapy moving forward again.

HIGH: At this point, of course, clinical trials in gene therapy are very heavily scrutinized.

Everything is always done exactly to the letter of the protocol.

BENNETT: We didn't want to make any stupid moves to basically grind the field to a halt again.

NARRATOR: As Bennett proceeded cautiously, her colleague Edwin Stone was hearing from an eager Molly Troxel.

Molly's vision was getting worse day by day.

But with limited places in the trial, she faced a long wait.

In fact, almost everyone with a genetic disease is playing a waiting game.

[wheelchair whipping around] Waiting has never been what Austin Leclaire does best.

AUSTIN LECLAIRE: If I want to do something, I'll generally figure out how to do it.

I like playing power soccer because it gives me the ability to play a sport.

Maybe not in the same way but I still get to be as competitive as everyone else.

COACH IN BACKGROUND: Still in!

Still in!

Set up!

Set up!

NARRATOR: Sixteen-year-old Austin and his thirteen-year-old brother Max face a lot of challenges.

COACH IN BACKGROUND: Should be 1, 2 goal, right here.

NARRATOR: For starters, there's mobility.

Max can still get himself around but Austin lost the ability to walk six years ago.

Health aide Patrick Claflin is there to help.

AUSTIN: He's my personal care assistant and part-time friend.

JENN McNARY: I was pregnant with Max when I first started thinking that something was really wrong with Austin.

He kept falling down stairs and he was getting concussions.

And then he broke his arm when he turned three.

And I was like, you know, something's wrong, he's really clumsy.

How'd you get that?

AUSTIN: From my bed.

McNARY: From your bed, did you fall off your bed?

The physical therapist watched him stand up, and she says, "We need to rule out muscular dystrophy because that--that looks a lot like what they showed me for muscular dystrophy.

What can you say?

AUSTIN: Hiyaa.

NARRATOR: Tests confirmed the worst: that both boys had the most severe form of Muscular Dystrophy-- called Duchenne.

McNARY: In general-- you start to get a diagnosis between three and five years old.

EDWARD KAYE: And as they get older and as they use their muscles they damage the muscle more and more every year.

AUSTIN: These are my braces.

[music] McNARY: Some stop walking around eight; but most everyone stops walking at least by 12.

McNARY: Hey, bud.

AUSTIN: Hi.

McNARY: What's the matter?

AUSTIN: My bus driver just kept talking, talking.

McNARY: Talking and talking...

Right around that same time, they start having cardiac involvement.

The heart's a muscle, too.

[music] By late teens, early twenties these kids die from respiratory failure primarily.

JERRY LEWIS: Strike back at this dread disease... NARRATOR: The horror of the disease was brought to public attention in the 1950s by the entertainer, Jerry Lewis.

JERRY LEWIS: It's precipitated by the fact that we have...

HOST: ...and we have Austin and Max, did I get that right?

NARRATOR: Fifty years later, the boys and their mother got a turn in front of the cameras.

HOST: Both of your boys have what is known as Duchenne.

McNARY: Yes, Duchenne muscular dystrophy, yes.

NARRATOR: Money raised by telethons, as well as federal funding, led to the 1986 discovery of a gene dubbed DMD, for Duchenne Muscular Dystrophy.

COACH IN GYM: Back up, back up!

Nice!

NARRATOR: In Duchenne, a defect in this gene results in the body's failure to make a critical muscle protein called dystrophin that strengthens and protects muscle fibers.

KAYE: It's a little bit like a shock absorber on a car.

You can go without the shock absorbers but eventually you'll completely destroy the car because it's hitting on the frame.

Same thing happens with the body.

NARRATOR: Because DMD is our largest known gene, a correct version won't fit in a viral delivery truck.

So, scientists developed a different strategy that doesn't target the gene itself.

Making a protein begins with transcribing the gene sequence into a messenger molecule.

If a gene has an error, so will that messenger.

McNary learned about efforts to target this messenger at a meeting of parents and scientists.

McNARY: I have no science background whatsoever and, you know, learning about oligonucleotides is not my idea of fun.

So I happened to go to the bar afterwards, which is [laugh] where all the researchers go and hang out with parents.

And I met this really dynamic guy and he pulls out a cocktail napkin... NARRATOR: And drew her a picture.

He showed her the way genes and their messengers come in sections.

DMD has 79.

In McNary's boys, one is missing.

McNARY: Your boys are missing number 52 and you see the pieces don't fit together correctly if you're missing 52, so boom, they make no dystrophin.

NARRATOR: But, he told her, by hiding 51 on the messenger, 50 and 53 can join.

That's exactly what a completely new type of drug does, allowing boys like Austin and Max to make a form of dystrophin-- it's not perfect but it's much better than none at all.

PATRICK CLAFLIN: Good?

AUSTIN: Yeah.

KAYE: Like if you have a shoelace that's broken.

You can tie it back together again, it's a little shorter, but it still works.

NARRATOR: For the last five years Max has been enrolled in a clinical trial of one of the first such drugs.

Austin later joined a different study of the same drug.

PATRICK: You should have seen it last night.

AUSTIN: It got stuck on my joy stick.

PATRICK: You gave everyone a free show--whoo-hoo!

AUSTIN: And they liked it, too.

NARRATOR: Every week, the boys receive an hour-long infusion.

AUSTIN: Oh, God.

NURSE: Is it cold?

NARRATOR: But that's not all the trial demands.

NURSE: Okay.

McNARY: I think I had no idea what was going to be asked of my kid.

These children have given their lives to science.

Max, he's had five open muscle biopsies where he has to be completely sedated and it's a long cut and large chunks of his muscle is taken out.

It's not a passive role.

You can't actually run a clinical trial unless you have kids that are really compliant.

If they don't walk their six-minute walk test to the best of their ability, well, then that drug fails.

NARRATOR: McNary's convinced this experimental drug is helping her boys.

McNARY: Austin stopped walking at 10 and a half.

Max, at 13 and a half, is able to walk throughout his entire day.

Before he got on the trial Max was falling all the time, all day long.

And then, you know, about six months into the trial he really wasn't falling at all.

And to this day, he doesn't fall.

NURSE: Okay.

Okay, everybody.

Can you see it?

McNARY: Austin's seeing benefit in ways that we didn't think were possible.

NURSE: It's what you are most times!

AUSTIN: Jackass?

[nurses laugh] McNARY: He's able to retrieve dropped objects, feed himself, lift a drink.

AUSTIN: Polar bear?

McNARY: He also feels better.

That's something that's missed in, in the clinical trial measurement.

MAX: My turn.

PATRICK: Jackass.

AUSTIN: Well, that's what I guessed.

PATRICK: Well, you got 7, that's pretty good.

AUSTIN: I mean the only downside is getting a needle once a week but I guess it's better than the alternative and like losing strength and not being able to do what I can do right now.

KAYE: You know, 20 years, all I would do is make a diagnosis, and then people would die, and I couldn't do anything.

And now we're actually able to make a diagnosis and tell a family, you know we think we can help your child, we can give them a better life.

[hair clippers buzzing] NARRATOR: The trials the boys are in will end soon.

PATRICK: Should we just leave it like that?

AUSTIN: No.

NARRATOR: Then their continued access to the treatment will depend on the answer to one question: has the trial proved the drug is effective?

With a Food and Drug Administration hearing coming in a few months, the boys' future hangs in the balance.

[ambulance sirens] It was September 11, 2001.

Across the country, people awoke to a national horror.

But Bay Area mother Wendy Vallejo was focused on a more personal crisis: her ten-month-old daughter Kimberly was desperately ill. WENDY VALLEJO: It started with some wheezing and her face was turning blue and purple.

Well, I was scared to see my kid having trouble breathing.

[music] NARRATOR: At the ER, Kimberly was stabilized, but not diagnosed.

WENDY: They couldn't give me an answer at all.

They were not sure what was happening to her.

[monitor beeping] NARRATOR: But then a visiting specialist examined her.

DR. DENNIS NIELSON: She'd been hospitalized for what people called bronchiolitis pneumonia.

And we went to see her and did the consult.

NARRATOR: Nielson felt Kimberly was still in acute danger.

He wanted her immediately transferred to his specialty clinic at the University of California, San Francisco.

But fear that the city might be attacked meant no ambulance was available to move her.

WENDY: But she was so sick, that he thought that if she wasn't transported to UCSF she could die.

NARRATOR: Nielson kept pushing... [dramatic music] Finally, an ambulance was provided.

At UCSF, tests confirmed Kimberly had cystic fibrosis, the most common fatal genetic disease in the U.S. NIELSON: We started treating her with everything that we knew how to do back then.

NARRATOR: Kimberly was in crisis because of a raging infection in her lungs-- in the lining of her airways.

Here, structures called cilia normally sweep out debris.

[intense music] But with cystic fibrosis, or CF, an abnormal coat of thick mucus builds up, preventing them from doing their job.

The mucus also provides a perfect breeding ground for a bacterial infection.

NIELSON: The airways are gradually destroyed by that chronic infection.

In the old days, the bad old days, all the kids that came in were sick.

And there was damage done that could never be repaired.

You know in the 1980s, I used to go to maybe half a dozen funerals a year, for kids, and yeah, that, that was hard.

NARRATOR: Kimberly spent a lot of time in hospitals as she grew up.

WENDY: For eleven years, we spent every Christmas in the hospital.

KIMBERLY: And some spring breaks too.

WENDY: There was times where she was like, "Mommy, I hate cystic fibrosis..." Why me?

NARRATOR: As Kimberly turned 12, Nielson started to consider the treatment of last resort.

NIELSON: We were within six months to a year of calling the transplant team... ...and talking seriously about a lung transplant.

[music] NARRATOR: The source of Kimberly's trouble is a protein that pokes through the surface of cells in her airway.

It has a flaw because of a mutated gene.

[music emphasized] The normal protein works as a channel, allowing charged molecules-- ions-- to flow in and out of the cell.

But in Kimberly and many other CF patients, this channel is stuck shut.

Mucus builds up outside because ions and water are trapped inside.

Identification in 1989 of the gene for this channel protein stirred optimism that a cure would follow quickly.

ARTHUR BEAUDET: The hope is that using gene therapy one could develop really definitive treatment for the lung disease.

ROBERT BEALL: Gene therapy was very, very in vogue around that time.

And we had meetings on gene therapy even before we found the gene, we were excited about the technology.

NARRATOR: But it was hard to find a viral vector that could deliver a replacement gene through built-up mucus.

So, unable to fix the gene itself, the CF Foundation turned its attention to the faulty channel protein, called CFTR.

BEALL: We had to understand more about that CFTR molecule, that protein, that channel.

And how we might be able to correct it.

NARRATOR: He committed 40 million dollars raised by the foundation to seek a completely new type of drug.

The first step was to expose the channel protein to a huge variety of molecules-- candidate drugs.

Over 200,000 were tested.

Only a small number stuck to the channel protein.

That's what any effective drug would have to do.

Next, for each good candidate, close variations were synthesized and tested.

The search was now for a safe one that best improved the channel's performance.

BEALL: It's a long process, lots of medicinal chemistry, and then clinical trials.

It took us from 1999 to 2012 to get our first product.

NARRATOR: Taken as a pill and delivered through the bloodstream, this drug attaches to the faulty channel changing its shape... ...and improving the flow of ions.

[music] That means less mucus build up... ...and fewer bacterial infections.

BEALL: The concept that you could take a protein and correct it with small molecules, oral drugs... ...was a milestone moment not only in the history of CF, but in all of genetic medicine.

NARRATOR: Nielson thought this breakthrough drug, called Kalydeco, could help Kimberly.

NIELSON: Deep breath.

NARRATOR: But there was a catch: CF, like many genetic diseases, can be caused by different mutations in the same gene.

Each might need its own treatment.

NIELSON: This new drug is approved for only one CF gene mutation.

BEALL: It was only 3% of our patients.

NIELSON: Kimberly didn't have that mutation.

But her mutation was in the same family as the CF mutation that had been approved.

NARRATOR: But was this a strong enough argument to get the family's health insurance to cover the $300,000 a year price?

NIELSON: What happened was she continued to struggle.

And I finally said, I don't care, I'll, I'm writing the prescription, you know, we'll fight this.

We'll go to the mat.

[music] NARRATOR: In the end, the insurer agreed to pay.

Kimberly got the drug.

NURSE: ...until we get the culture back... NARRATOR: But would it work well enough to keep her off the transplant list?

NURSE: I think so.

And you have an... WENDY: Yes.

KIMBERLY: Right away things started to change.

It felt amazing that this small pill would change everything that I had in my life.

[camera shutter clicks] MAN: Do you see the bridge?

FAMILY RESPONDS: No.

NIELSON: It was incredibly dramatic.

It's probably the closest thing to a miracle that I've ever been involved with.

MAN: Surprise, cheese!

[laughing] NIELSON: The last two years before we started the drug she spent 116 days in the hospital.

And since we started the drug she's not been in the hospital one day and that's now been over two years.

Now she couldn't walk more than five minutes without stopping to rest.

Now she does dance concerts.

She may never need that lung transplant, hopefully; means that she'll grow up, get married, have a family, she'll have a normal life.

[music] NARRATOR: And Christmas at home.

KIMBERLY: Where do we put that?

SISTER: Put it up here.

KIMBERLY: I'm gonna put mine over here.

NARRATOR: Recently, a CF medicine for a different mutation was approved by the FDA and other medicines for still more mutations are in clinical trials.

[music] Through years of waiting, Molly Troxel clung to the dream of saving her vision by joining a gene therapy trial.

LAURA: Molly was gung-ho.

She was going to do this, she wanted it.

I was afraid.

The hope was that she would have more vision but there's a possibility that it could make her vision worse.

NARRATOR: Eleven years after Jean Bennett gave sight to blind dogs... and five years after Bennett began preparing for human trials, Molly's family and friends threw her a party.

The next day she would head off to get replacement genes as a participant in Bennett's clinical trial.

MOLLY: I was really excited.

The wait was finally over.

NARRATOR: Six drops of liquid containing billions of gene-carrying viruses were injected into each of Molly's retinas.

[music] When the patch came off, at first it was hard to tell if anything was different.

But then... MOLLY: I saw the moon.

RYAN: Wow, Molly, you can see that?

For her to see the moon, and stars...

Things you would take for granted was just huge for us.

And now there's just no stopping her.

All of a sudden you know just eyes are beamin' and, "Wow, what is that, Mom?

You know."

LAURA: Good job, Molly.

NARRATOR: Molly's vision isn't perfect.

The therapeutic virus didn't invade all of her retinal cells.

Still, her sight is far better than it was.

RYAN: There is it, around the horn... LAURA: Even though to an outsider she still looks visually impaired, I'm so thankful that she can see better and if nothing else that it's stopped the progression of this disease.

RYAN & FAMILY: Nice, yeah!

LAURA: It's just amazing that this could even... be.

TROXEL FAMILY: Yay!

MOLLY: Thanks.

I was hoping for it was like perfection.

But that's hard to do.

But what I have now-- it's perfect.

[music] NARRATOR: In the three phases of this clinical trial more than forty patients have been treated.

MOLLY: Really?

NARRATOR: Each one improved.

[music] BENNETT: Each time I hear reports of how the intervention has improved somebody's life, it's a miracle to me.

It could be the first approved gene therapy in the United States.

NARRATOR: But Molly is extremely lucky.

She was treated long before her eyes were irreversibly damaged by her disease.

So she had the rare chance of having her vision partially restored.

STONE: It's absolutely the most favorable gene therapy target that there will ever be.

NARRATOR: For the big majority of other genetic eye diseases, future gene therapies will at best only stop further decline.

Still, for a patient facing blindness, that's no small promise.

For Austin and Max Leclaire, the brothers with muscular dystrophy, a day that could profoundly affect their future has arrived.

McNARY: Where do I register?

PERSON: The register table is... NARRATOR: Jenn McNary has brought her sons to an FDA advisory committee meeting where approval of the muscular dystrophy drug they've been taking will be considered.

Boys participating in the trial-- and their parents and doctors-- are here in force.

It's one of the largest crowds ever for such a meeting.

PARENT: We're asking that the agency utilize flexibility and the tools it has to approve... NARRATOR: Convinced that this drug is their best current hope, patients and their advocates make their case.

PHYSICIAN: ...freedom of ambulation is really life sustaining for a boy with Duchenne... KAYE: Patients are saying, we can't wait ten to 15 years for every new drug, which is currently what it takes now.

We need it faster.

AUSTIN: It's time to listen to the real experts.

So, to make that easier for you, we've brought them all here today.

Please use them.

[crowd cheers] SPOKESPERSON: Thank you very much.

Once again, please hold your applause... NARRATOR: But in a forum like this, anecdotal evidence rarely carries the day.

SPOKESPERSON: Thank you very much.

Will speaker number 17... JANET WOODCOCK: There's a lot of bias in these kind of personal observations.

And although we take them seriously as an expression of need and hope, then we need scientific data to decide whether or not a drug works.

KAYE: Today we've presented data that shows an unequivocal... NARRATOR: By late afternoon, committee members, independent experts outside the FDA, focus on the small size of the trial-- just twelve patients.

PANELIST: ...ambiguous, with regard to whether there's a threshold effect or not, but also... NARRATOR: At day's end, the panel votes on whether to accelerate the drug's approval.

PANELIST: Richard Hoffman, I voted yes... PANELIST: My name is Aaron Kesselheim, I voted no... NARRATOR: By a single vote... PANELIST: I voted no... NARRATOR: ...the panel votes against it.

PANELIST: I have concerns... NARRATOR: They want more data.

But this vote is just a recommendation.

WOODCOCK: ...whether Question 1A... NARRATOR: The drug's ultimate fate is in the hands of FDA official Janet Woodcock.

It's not a simple call.

WOODCOCK: We want to make sure that drugs that are on the market really are effective.

On the other hand, we don't want to have such a high bar that we leave a lot of drugs behind that could help people, especially for serious and life threatening diseases.

McNARY: I'll put Austin on the phone, okay.

NARRATOR: Months later, McNary and her boys are still waiting for Woodcock's decision-- and growing worried.

McNARY: Potentially, if they don't approve this drug it's this cascade of really unhappy events.

BOY ON PHONE: Do you want to come to my house for a party?

AUSTIN: Yeah, sure.

McNARY: But if the stock tanks, the company goes under, my kids are pulled off drug.

I mean it's really that simple.

BOY ON PHONE: Can I talk to your mom?

McNARY: The idea of taking my kids off a drug that's changing their lives-- it's really scary.

McNARY: Hey, Dillon.

NARRATOR: Like many of medicine's most challenging diseases, muscular dystrophy is caused by a single flawed gene.

Since a gene is like a page of text, what if gene doctors could fix disease-causing errors, letter by letter?

A new tool of extraordinary power called CRISPR promises just such precision.

JENNIFER DOUDNA: What CRISPR is, is a technology for changing the sequence of DNA in cells... in a precise fashion like a molecular scalpel.

We can design it in the laboratory so that it matches the sequence of, let's say, a mistake in the DNA, where we would like to trigger a change, to correct mutations that might otherwise cause disease.

It's going to enable a lot of science to be done that was impossible to do in the past.

And this is both at the level of research and applications.

NARRATOR: Heralded as revolutionary, CRISPR's power to cut at an exact place could take gene therapy to a new level.

But much work remains to be done.

FENG ZHANG: The human genome is like a book with three billion letters and if you want to go into that three billion letter novel and make a single correction of a typo that is remarkably challenging.

NARRATOR: When and if it's perfected, CRISPR could be used to actually cure many genetic diseases.

BENNETT: To be able to go into an individual patient and correct a specific DNA mutation, it, it's just a dream.

NARRATOR: A dream for some-- a nightmare for others.

One worry-- that CRISPR might be used to not only make sick people well, but also to give perfectly healthy people extra advantages.

Others worry about changes in human eggs and sperm that will be passed down to future generations.

KAYE: Now we're tinkering with the human gene, and we're making permanent corrections.

So we'd better be right and we'd better understand that we're not making things worse.

ERIC GREEN: Like a lot of technologies, there's two edges to that sword.

And one of them is very exciting, and you could see medical benefits.

But the other one gives pause to people in society.

And we want to be very careful not to see it used in ways that will make people feel uncomfortable.

NARRATOR: The first human trials of CRISPR-based therapies are just beginning.

So, for Sonia Vallabh, with her as yet incurable genetic brain disease, hope will have to come from some other form of therapy.

Right after her diagnosis, Sonia began to learn as much as she could about her disease.

SONIA: What I did every day is read articles and go to classes.

I introduced myself to the professors and I said, "Look, you know, I'm not a student here but this is-- this is why I'm interested in sitting in on your seminar.

Do you mind?"

Engaging with the science, it was the thing that helped.

NARRATOR: She quickly got hooked on the science.

So did her husband, Eric.

Neither had studied biology since high school.

SONIA: The first goal that we set after sort of being initiated into thinking about the science of this disease was, let's try to understand enough of this that we can follow the progress that's made over time.

NARRATOR: But that didn't satisfy for long.

Soon, they both decided to upend their careers and pursue science full-time.

Sonia put aside her law degree from Harvard, and Eric his MIT master's in city planning.

SONIA: There were things that felt very risky about leaving our careers behind, and it was scary, but... it was a lot less scary than doing nothing.

NARRATOR: Sonia's first step was the nightshift-- washing glassware in a lab.

ERIC: And she was going from, you know, having gone to law school and having a good consulting job to, you now, the very most entry-level technician job in a science lab.

But still, she had a job in science and that was a very intoxicating thing.

NARRATOR: Soon, Eric had a lab job of his own.

Three years after her diagnosis, the couple took another leap.

Both were accepted into Harvard Medical School's PhD research track.

They hoped to join the ranks of gene doctors.

They're now working with Stuart Schreiber of the Broad Institute of MIT and Harvard-- an expert on finding drugs that tame dangerous proteins like the one that threatens Sonia's life.

STUART SCHREIBER: They were crystal clear on what they wanted, which is, we're going to take out this disease.

That's the goal.

SONIA: ...obstacles to dragging two things together that are constrained... NARRATOR: They face a formidable challenge: getting a drug into the brain is difficult.

SCHREIBER: Lots to do.

SONIA: Absolutely.

SCHREIBER: They are unbelievably compelling and inspiring.

Their infectious enthusiasm and, you know, curiosity for science has sort of overtaken my life.

Really, truly remarkable people.

Two forces of nature.

SONIA: In some ways we are very impatient and we are on a timeline that's personal.

Already, a lot of things have fallen into place for us that I never expected to have.

The majority of our time is going into doing experiments.

And that has been like an amazing point to have reached.

[music] But right now, nothing is imminent.

It's all just, you know, cells in dishes and mice in cages.

Whether we're going to have some sort of drug candidate by the time I would want to be taking that kind of, that kind of thing, we don't know.

[music] These are really impressively hard problems.

[music] NARRATOR: Treating disease at its root is hard... but as those who've benefited from new therapies know... remarkable progress is possible.

GREEN: What we have now is incredible... ...and revolutionary, and actually has impact on medicine.

But it's going to even get better.

LEWIS-HALL: We can see things that we couldn't see before, understand things that we couldn't understand before, and do things that we couldn't do before.

SCHREIBER: It really is a special moment in time.

A lot of work to do, but a special moment in time.

SONIA: Even if you can't predict which avenue is going to be fruitful or how long it's going to take to have a treatment, what you can say for sure is that, over time, we learn more about these things.

And that, ultimately, moves us closer to being able to treat what we now call untreatable.

[music] "The Gene Doctors" is available on DVD.

To order, visit ShopPBS.org or call 1-800-PLAY-PBS.

This program is also available for download on iTunes