Health - 60 Minutes Special Report: Could gene therapy cure sickle cell anemia?

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Could gene therapy cure sickle cell anemia?

An NIH clinical trial is ushering in a genetic revolution as an innovative type of gene therapy is used to attempt to cure sickle cell anemia. Dr. Jon LaPook reports

  • 2019Mar 10
  • CORRESPONDENTJonathan LaPook
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Last Updated Mar 10, 2019 8:07 PM EDT

Nearly 20 years ago, scientists stunned the world when they announced they had decoded the genes that make up a human being. They hoped to use that genetic blueprint to advance something called gene therapy which locates and fixes the genes responsible for different diseases.

Now, a clinical trial at the National Institutes of Health is doing exactly that in an attempt to cure sickle cell anemia, a devastating genetic disease that kills hundreds of thousands of people around the world every year.

For the past 15 months we've been following the scientists, and patients, who are ushering in a genetic revolution.


Dr. John Tisdale speaks with Jennelle Stephenson
Jennelle Stephenson: I'm excited.

Ray Stephenson Today is the big day.

It's the day after Christmas, 2017, and 27-year-old Jennelle Stephenson has come with her father and brother from Florida to the National Institutes of Health, just outside Washington, D.C.

Jennelle Stephenson: Good morning.

Dr. John Tisdale: Good morning.

She's one of a small group of patients to receive an infusion containing altered DNA.

Nurse: This is what they look like.

Jennelle Stephenson: Merry Christmas to me.

Brother: Best Christmas present ever.

Jennelle Stephenson: Yay.

The clear liquid in the bag contains Jennelle's stem cells that have been genetically modified.

Dr. John Tisdale: There are about 500 million in there.

Jennelle Stephenson: Oh, my goodness.

The hope is the new DNA in the cells will cure Jennelle of sickle cell anemia, a brutal disease that causes debilitating pain.

Dr. Jon LaPook: At its worst, on a scale of zero to 10, how bad was your pain?

Jennelle Stephenson: We can go beyond a 10. It's terrible, it's horrible.

Dr. Jon LaPook: Pain where?

Jennelle Stephenson: Everywhere. My back, my shoulders, elbows, arms, legs, even my cheekbones, just pain.

Dr. Jon LaPook: Can you actually describe it?

Jennelle Stephenson: It's a very sharp, like, stabbing, almost feels like bone-crushing pain. Feels like someone's kind of constricting your bones, and then releasing constantly.


Pain from sickle cell can occur anywhere blood circulates. That's because red blood cells, normally donut-shaped, bend into an inflexible sickle shape, causing them to pile up inside blood vessels. The resulting traffic jam prevents the normal delivery of oxygen throughout the body, leading to problems that include bone deterioration, strokes and organ failure.

The gene that causes sickle cell anemia evolved in places like sub-Saharan Africa because it protects people from malaria. There, millions have the disease, and it's estimated more than 50 percent of babies born with it die before the age of five.

In the United States, it affects a hundred thousand people, mostly African-Americans.

For Jennelle, having the disease as a child often meant spending Christmas in the hospital. As an adult, she struggled through pain to complete college, but keeping a job was tough because something as simple as walking up stairs could trigger "a pain crisis."

Dr. Jon LaPook: Do you have friends who've died from sickle cell?

Jennelle Stephenson: I do. Yes, younger than me.

Dr. Jon LaPook: And you've known this your whole life growing up?

Jennelle Stephenson: Right.

Dr. Jon LaPook: That you could potentially die early?

Jennelle Stephenson: Right. Yes.

Dr. Jon LaPook: Did you think you would die early?

Jennelle Stephenson: I did, actually. When I hit about 22, I was like, "You know, I'm-- for a sickle celler, I'm kind of middle-aged right now."

Dr. Jon LaPook: What are some of the things that you've always wanted to do that you couldn't do?

Jennelle Stephenson: Honestly, everybody laughs at me for this, I just want to run, to be honest.

Dr. Jon LaPook: Things that most people would take for granted.

Jennelle Stephenson: Just basic things.


One of the most cruel parts of the disease, Jennelle and other patients have told us, is being accused of faking pain to get narcotics, being labeled a "drug-seeker." During one trip to the emergency department, when she fell to the floor in pain, a doctor refused to help her.

Jennelle Stephenson: And I'm looking up at her, and I'm in tears, and, I'm like, "I'm doing the best that I can."

Dr. Jon LaPook: And you gotta be thinking….

Jennelle Stephenson: I just, sometimes I don't understand, I don't get it. Like... Sorry. I'm in so much pain, and you think I just want some morphine. And it just makes me sad that some people in the medical community just don't get it.

Dr. Francis Collins is director of the National Institutes of Health, the largest biomedical research agency in the world. He oversees a nearly 40 billion dollar budget that funds more than 400,000 researchers world-wide.

Dr. Collins was head of the Human Genome Project at the NIH in 2000 when he made a landmark announcement: after a decade of work, scientists had finally decoded the genes that make up a human being.

Dr. Jon LaPook: When did it all start for you?

Dr. Francis Collins: I got excited about genetics as a first-year medical student. A pediatric geneticist came to teach us about how genetics was relevant to medicine. And he brought patients to class and one of the first patients he brought was a young man with sickle cell disease who talked about the experience of sickle cell crises and how incredibly painful those are. And yet, it was all because of one single letter in the DNA that is misplaced, a "T" that should have been an "A." And that was profound. You could have all of that happen because of one letter that was misspelled.

The double helix of DNA is made up of billions of pieces of genetic information. What Dr. Collins is saying is, out of all that, it's just one error in the DNA code -- a "T" that should have been an "A" -- that causes sickle cell anemia. Fix that error, and you cure the disease.


Correspondent Dr. Jon LaPook walks with Dr. Francis Collins
But figuring out how to do that would take more than 20 years of research and a little serendipity.

Dr. Collins was playing in the NIH rock band in 2016 when his bass player -- hematologist Dr. John Tisdale -- started riffing on an idea.

Dr. John Tisdale: We'd finished setting up and went for a pizza before--

Dr. Francis Collins: I remember that.

Dr. John Tisdale: --before the gig. And at this point I pitched to Francis that it was really time that we do something definitive for sickle cell disease.

In the laboratory, Dr. Tisdale and his collaborators created a gene with the correct spelling. Then, to get that gene into the patient, they used something with a frightening reputation: HIV, the virus that causes AIDS. It turns out HIV is especially good at transferring DNA into cells.

Here's how it works. The corrected gene, seen here in yellow, is inserted into the HIV virus. Then, bone marrow stem cells are taken from of a patient with sickle cell anemia. In the laboratory those cells are combined with the virus carrying that new DNA.

Dr. John Tisdale: This virus will then find its way to one of those cells and drop off a copy or two of the correctly spelled gene. And then these cells will go back to the patient.

If the process works, the stem cells with the correct DNA will start producing healthy red blood cells.

Dr. Jon LaPook: I can hear people, our viewers out there, thinking, "Wait a second, how do you know you're not gonna get AIDS from the HIV virus?"

Dr. John Tisdale: The short answer is we cut out the bits that cause infection in HIV and we really replace that with the gene that's misspelled in sickle cell disease so that it transfers that instead of the infectious part.

"I believe that this looks like a cure. I gotta be careful. But from every angle that I know how to size this up, this looks like a cure."
Dr. Jon LaPook: The stakes here are enormous.

Dr. Francis Collins: Yes.

Dr. Jon LaPook: There's really very little safety net here, right?

Dr. Francis Collins: Make no mistake, we're talking about very cutting-edge research where the certainty about all the outcomes is not entirely there. We can look back at the history of gene therapy and see there have been some tragedies.

Dr. Jon LaPook: Deaths?

Dr. Francis Collins: Yes.

In 1999, 18-year-old Jesse Gelsinger received altered DNA to treat a different genetic disease. He died four days later from a massive immune response. And in another trial, two children developed cancer.

Jennelle Stephenson understands. This is a trial with huge risks and no guarantees.

Jennelle Stephenson: This is it.

When she arrived at the NIH clinical center in December 2017, Jennelle asked her brother, Ray, for some help.

Jennelle Stephenson: There goes Ray cutting my hair. Oh, snip.

She decided to cut off all her hair, rather than watch it fall out from the massive dose of chemotherapy needed to suppress her immune system so her body wouldn't reject the altered stem cells.

Jennelle Stephenson: I don't know how to feel right now. I'm a little emotional. But I'm OK, it will grow back.

A few days after the chemotherapy, Jennelle received the infusion of genetically modified cells.

Dr. John Tisdale: Is it going good now?

Nurse: Yes.

Jennelle Stephenson: It's just a waiting game.


But the wait was a painful one. Not only for Jennelle, but also for her father Ray. Who did what little he could as the effects of the chemotherapy kicked in, stripping Jennelle's throat and stomach of their protective layers.

Jennelle Stephenson: Oh, that hurts.

She was unable to speak for a week and lost 15 pounds. And because having a severely weakened immune system means even a mild cold can turn deadly, Jennelle had to stay in the hospital for nearly a month.

Last spring, she moved back to Florida and returned to the NIH for periodic check-ups.

Dr. John Tisdale: These are her red blood cells.

It didn't take long for Dr. Tisdale to notice something was happening.

Dr. Jon LaPook: This is Jennelle before any treatment?

Dr. John Tisdale: Right. All across her blood you can see these really abnormal shapes. This one in particular is shaped like a sickle.

Nine months later, this is what Dr. Tisdale saw: not a sickle cell in sight.

Dr. Jon LaPook: Was there ever a moment where you saw one of these normal-looking smears and thought, "Is this the right patient?"

Dr. John Tisdale: Oh, absolutely. When you're a scientist, you're skeptical all the time. So, first thing you do is look and make sure it's that patient, go grab another one, make sure it's the same. And we've done all that. And, indeed, her blood looks normal.

Jiu-Jitsu Teacher: Move. Switch your arms and move.

Remember, Jennelle used to struggle just to walk up a flight of stairs...

Jiu-Jitsu Teacher: And you fall.

...and a fall like this would have landed her in the hospital.

Jiu-Jitsu Teacher: Boom. Yeah. Good job. You did it. Bam.

Dr. Jon LaPook: Jennelle. You look amazing.

Jennelle Stephenson: Thank you.


Dr. Jon LaPook: I have to say, I was a little nervous when you were thrown and you went down on the mat.

Jennelle Stephenson: It was nothing. It was nothing. My body just felt strong.

Dr. Jon LaPook: Tell me about the adjustment that you need to make to go from the old you to the new you.

Jennelle Stephenson: My body it almost felt like it was, like, itching to do more. And I was like, "All right, well, let's go swimming today." "Let's go to the gym today." I'm like, all right, my body loves this. I kinda like it because my, I guess all my endorphins started pumping.

Dr. Jon LaPook: The endorphin high, something you had never experienced.

Jennelle Stephenson: Never experienced before. Yup.

Dr. Jon LaPook: What was going through your head as you were watching Jennelle being thrown down to the mat?

Ray Stephenson: I was just saying, "Thank you, Lord. Thank you for medical science. And thank you for giving her a new life."

Jennelle Stephenson: New life, indeed.

Eight other adults with sickle cell anemia have undergone the same gene therapy as Jennelle. So far, all are responding well. Dr. Francis Collins says it will take years to improve the treatment to make it more widely available.

Dr. Francis Collins: Here's another dream. There are 7,000 genetic diseases for which we know the precise DNA misspelling. Couldn't this same strategy, this same set of principles work for lots of those, maybe someday all of them?

Dr. Jon LaPook: You've been working on this for decades. You're at a moment which is significant.

Dr. Francis Collins: To lead the Human Genome Project and to put that foundation in place. And now, to see that emerging not just as hoped-for advances, but real data showing cures for people.

Dr. Jon LaPook: You just used the "curing" word. You're willing to say that?

Dr. Francis Collins: I believe that this looks like a cure. I gotta be careful. But from every angle that I know how to size this up, this looks like a cure.

Produced by Denise Schrier Cetta and Megan Kelty
 
Last edited:

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More on the trial aiming to cure sickle cell

60 Minutes reported on a gene therapy trial that may be a cure for patients living with the bone-crushing pain of sickle cell disease. Here's how to join

  • 2019Mar 10
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Below is a transcript of correspondent Dr. Jon LaPook's conversation with 60 Minutes Overtime's Ann Silvio about his story this week on a gene therapy trial that may be a cure for sickle cell anemia.

ANN SILVIO: Jon, you reported on a medical breakthrough on 60 Minutes this week. How significant is this for sickle cell anemia?

DR. JON LAPOOK: I think it's a big deal -- it's a proof of concept. It says, "We can actually do this." We can fiddle with the genes and we can cure somebody with sickle cell anemia.

DR. JON LAPOOK: Are you daring to say there's a cure for sickle cell anemia with this treatment?

DR. FRANCIS COLLINS: I am daring to say a cure for sickle cell disease may even be now at hand.

ANN SILVIO: Was there a voice in your head that was telling you, "Let him say the word "cure", I'm not gonna say it."

DR. JON LAPOOK: Oh, I would never have said the word "cure." We're people of science, but you don't want to jinx it, you know? Like, okay, if we don't say it-- but yeah, I think-- from everything that it looks like, it looks like a cure. And for me, it's especially emotional because from 1976 to 1986 -- ten years when I was seeing a lot of people who had sickle cell anemia. And I could tell you their names still, but I won't for HIPAA reasons. But one after the other, they died.

ANN SILVIO: You couldn't help them?

DR. JON LAPOOK: All you could do was give them pain medicine. So it was a very helpless feeling. So I was taught first, it was, like, the first month of medical school "Someday we're gonna have a cure for sickle cell anemia." That was 1976. And so for me to see that-- that patient, right in front of my eyes, who's cured.

ANN SILVIO: You're talking about Jennelle Stephenson?

DR. JON LAPOOK: Jennelle Stephenson


Jennelle Stephenson strolls with Dr. Jon LaPook
ANN SILVIO: So when you started reporting this story, did you know what the outcome was gonna be, that this would be successful?

DR. JON LAPOOK: Not at all, in fact I didn't know if it was gonna work. Jennelle hadn't gotten any treatment yet. Her whole life she's been a sick person.

JENNELLE STEPHENSON: It's a very sharp, like, stabbing, almost feels like bone-crushing pain.

DR. JON LAPOOK: She thought she was gonna die early. She had a lot of friends who died early.

DR. JON LAPOOK: You just seem so happy.

JENNELLE STEPHENSON: I am, I am, I really am.

ANN SILVIO: She's given up things though. I understand she's given up the choice to have children.

DR. JON LAPOOK: Right. That was part of the chemotherapy.

DR. JON LAPOOK: What was explained to you about the possible side effects?

JENNELLE STEPHENSON: That my reproductive system would have been kind of wiped out from the chemo--

DR. JON LAPOOK: Forever?

JENNELLE STEPHENSON: Yes. So-- yes. I just, I came to terms with it because, to be honest, I wouldn't want a kid with sickle cell anyway, it's a really rough disease, and I would never want to see an offspring go through it.

DR. JON LAPOOK: And she also risked her life to even go through this.


ANN SILVIO: 60 Minutes has aired stories about the dangers of altering genes-- messing with the human genome. Is that fear part of this story?

DR. JON LAPOOK: Yes. Because no matter how you're doing it-- I mean, you're fiddling with the genes of a human being. Once you put that gene into somebody, you can't un-put that gene into somebody, at least not now. In the future they talk about having a kill switch, so that if things go wrong you can somehow turn the gene off. But that's one of the big fears and there have been real calamities. Death from gene therapy in the past. Well, you talk to Jennelle, she knew all this.

DR. JON LAPOOK: This is fancy genetic tinkering. And it involves putting different kind of genes inside of you that you normally don't have.

JENNELLE STEPHENSON: Right.

DR. JON LAPOOK: Does that give you any pause?

JENNELLE STEPHENSON: I was terrified at first. I think they were using the HIV virus or something, just because it spreads so well.

DR. JON LAPOOK: Right, a weakened HIV virus.

JENNELLE STEPHENSON: Right. Of course. Of course.

DR. JON LAPOOK: That wouldn't give you HIV.

JENNELLE STEPHENSON: Of course. Of course.


ANN SILVIO: For anyone who was around during the HIV epidemic, you know, going back to the '80s--

DR. JON LAPOOK: March of 1981. My first patient with HIV. First bed on the left in the intensive care unit.

ANN SILVIO: So now you're doing a 60 Minutes story and HIV is really the secret weapon to curing disease--

DR. JON LAPOOK: It's amazing. Isn't that amazing.This is a great example of why you have to put money into basic research. Who would have known that figuring out how the HIV virus works would help you probably cure sickle cell anemia someday? We don't know what we're gonna use. We're building up all these tools, we're doing all this basic research. If I someday develop some disease, I'm gonna want a cure for that or a good treatment for it that day. Well, it takes ten, 20, 30 years maybe to come up with that. So, when I see Jennelle, encapsulated in Jennelle and in her success-- is so much.

JENNELLE STEPHENSON: These are the kind of things I've always wanted to do. Just an evening stroll. Nothing to it….

For more information about the NIH clinical trial:

The trial continues to enroll new patients with sickle cell anemia. To learn more about joining this trial and others at the NIH visit www.cc.nih.gov/recruit or call 1-800-411-1222.

The video above was produced by Ann Silvio and Lisa Orlando. It was edited by Lisa Orlando.
 
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