The Current - How gene editing saved a baby’s life

Episode Date: May 21, 2025

“A triumph of science, a miracle of medicine” is how researcher Fyodor Urnov describes the gene-editing treatment that saved baby KJ Muldoon’s life. Now nine months old, KJ was born with a genetic condition called urea cycle disorder, which is fatal for many infants. Urnov was part of the research team supporting KJ's doctors, he tells us what gene-editing treatments could mean for others born with life-threatening conditions.

Okay, so I'm Tom Power. I host the award-winning interview show Cue, and it's not just about art. It's also a podcast that delves into conversations with artists as to why we create at all. Like you'll hear boy genius member Lucy Dacus open up about why she's dead dissatisfied with the way we talk about love. You'll hear Cate Blanchett describe what it's like to forget the sound of your own voice. And you'll hear how Coleman Domingo actually honed his acting skills in the circus. Listen to Cue with me, Tom Power, wherever you get your podcasts. This is a CBC Podcast. Hello, I'm Matt Galloway, and this is The Current Podcast. At a photo shoot at the Children's Hospital of Philadelphia, 9.5-month-old KJ Muldoon

is the center of attention. KJ has big blue eyes, rosy, chubby cheeks. He's also a medical pioneer. KJ was born with a genetic disease known as urea cycle disorder. It affects the body's ability to process protein and get rid of ammonia, and it can be fatal. But this winter, KJ became the first patient to be treated with personalized CRISPR gene editing therapy tailored just

for him. His parents, Nicole and Kyle Muldoon, said it was a difficult decision to give their son medicine that's never been given to anyone before, but they had faith in KJ. We thought it was important to give him a chance to show us what he could do. I just knew he was ready. Like he was ready to fight. He's proven us time and time again how stubborn and spunky he really is. KJ has had three infusions and while doctors are still cautious, the treatments seem to be working.

He's hitting milestones his parents never thought they'd see. He's rolling over, sitting up, eating avocados and waving. Nicole and Kyle said they're looking forward to bringing KJ home to be with his three siblings into a bright future. It's starting to be like the light at the end of the tunnel. Fairly soon, if all goes well, all six of us will be able to like be at home, sit on the couch, watch a movie. Like we're planning for him to come home. What I think about the most is him achieving things that were considered impossible. And the day he walks into like school with a book bag on and we like let him go at the door like you're gonna have to, I might have to take the day off that day.

In a moment we'll hear from a gene editing pioneer involved in this research but first I'm joined by Robin De Leonce. This breakthrough is personal for her. She's executive director of Connecting Families UCD Foundation. It's an organization for families affected by urea cycle disorders. The same kind of disorder that KJ was born with. Robin and her daughter both have a form of UCD and she's lost two infant sons to this disease. Robin, good morning. Good morning. Thank you for having me.

Thanks for being here. What went through your mind when you heard about this breakthrough with KJ? You know, it's, I'm so happy for this family, but I'm going to get emotional here. But it's sad for me. I wish that this was available to me, you know, for my boys. It's just an exciting time for UCD families to have these breakthroughs that are available to us. But yeah, I'm so happy that the baby's doing well and that these parents have a chance

to see their son thrive. I mean, you can't help but think about what you yourself have been through. And I appreciate you being willing to talk about this. How did you find out that you had UCD? I found out I had given birth to three healthy children and when I had given birth to my fourth, he just became sick immediately within 24 hours after he was born.

The doctors didn't know what was going on and he just slowly deteriorated and within three days he was gone. They asked us if we wanted an autopsy done and we said yes. We wanted to find out what happened and the autopsy was performed. His liver was sent to Baylor in the United States and about six weeks later, they came to me and told me that he had ornithine transcarbamylase deficiency, which is one of the UCDs.

They did testing on me also and told me that I was a carrier. You know, and it was just a devastating time for me and our family. We just couldn't understand where this came from. I had other family members tested. I was encouraged to have them tested, my other sons and my daughter and my parents and everybody was fine. So it was a spontaneous mutation that started with me.

As I mentioned, you've gone through this a couple of times in losing two infant sons to this disease and your daughter has the same disorder. How is she doing? My daughter's doing pretty good. She's 22 now. She has had a pretty rocky road throughout her life. We did have to homeschool her. Unfortunately, being in the public school setting, she caught

everything. And that's just one of the things that can happen with having a UCD is that a virus can trigger off you having hyperammonemia. And kids are germy. They catch everything and everything she caught would put her in the hospital. And so we had to, like I said, homeschool her. And it's, you know, that's the thing about having this illness is that you just never know when you're going to have a crisis. I mean, you could be doing everything right, following your diet, you know, and taking your ammonia scavenger medications, your supplements, and still have a crisis.

And so it's, you know, it's just like you have this cloud over you all the time. What do you think, just before I let you go, what do you think, and you got emotional in thinking about what this would have meant for you. What do you think this is going to mean for other families with UCD? That's part of your work in some ways, is to work with them. So when they hear about this, what do you think this will mean for them?

Oh, I know so many of them in our community are just thrilled about what's happening. We have more choices. I mean, there's other companies developing other therapies, you know, gene therapy things. And it's just an amazing time. I mean, I look back and when I wish this was available to me because when my son, my second son, did get his transplant, and unfortunately it didn't work, I mean, I watched him suffer so much.

He had just one setback after another for seven weeks after his transplant until he passed. And if this was available to me, I would have definitely been all over it. It's a remarkable story. And your involvement in speaking with other families, but also your own personal experience helps shape how important this is. Robin, it's good to talk to you about this. I appreciate it.

Thank you very much. Thank you for having me. Robin De Leon is the executive director of Connecting Families UCD Foundation. It was over 30 years ago that Clifford Olson first called me. Secret phone calls from Canada's most notorious serial killer. I knew I was killing the children, but I couldn't stop myself. Now it's time to unearth the tapes, because I believe there are still answers to be found.

I'm Arlene Bynum from CBC's Uncovered. Calls from a Killer, available now. Fedor Urnov was part of the research team supporting KJ's doctors. He's a professor of molecular and cell biology at the University of California, Berkeley, and director of technology and translation at the Innovative Genomic Institute.

The research institute was founded by Jennifer Doudna. She was awarded the Nobel Prize for Chemistry in 2020 for the development of CRISPR gene editing technology. Fyodor, good morning to you. Good morning. You call this a triumph of science and a modern medical miracle. How important is this case in terms

of what happened with Young KJ? Well, you know, the famous Canadian Leonard Cohen has this wonderful line in one of his songs where he goes, quote, There is a crack in everything. And that's how the light gets in. I think baby KJ's case is more than a crack. I think it's a door. Now, to be very clear, I was listening to your previous guests and frankly, I choked up as would anybody who would hear the story of a family living with one of these conditions and suffering so direly.

So the door has been open. Significance is the Food and Drug Administration has worked with the physicians at Children's Philadelphia, physician scientists at Penn Medicine, our team at UC Berkeley IGI and Danahur, the biotechnology company that made the CRISPR, and allowed for the first time this incredible team to build a medicine and administer a medicine to this kid before severe disability or heaven forbid death would set in. So we can now start walking through this door staying with the metaphor with you know with the doctor holding another child like this in their hands and another and another but honestly I was listening to Robin speak and the my my sense of joy,

frankly, my sense of pride for us as scientists, gratitude to the physicians, to the FDA is also infused, if you will, with a sense of purpose. We can't just sit here and look with fondness at baby KJ, which all of us are doing if you look at the kids picture. He's impossibly adorable But we can't look at this picture and go ah We just have to keep going faster and faster so that this door Becomes wider and wider and ultimately it becomes available to all children and families such as KJ's so that this available to all children and families, such as KJ's, so that this sort of triumph of science

and miracle of medicine, which is this gene editing on demand, becomes available to all. Can you just briefly explain, in a way that me, the average idiot, would understand, how this worked? How was CRISPR used to edit KJ's gene such that he's now able to do all the things that he's able to do. So the beautiful thing, and first of all, I love your self-deprecation. The beautiful thing is I can actually explain this in terms that my nine-year-old daughter would understand.

Actually, if I could explain this to her after this happened, like she said, Papa, what did you do here? So the child was born with a typo. You know, our DNA is very long. If you read our DNA one letter at a time, it'll take you a century to read the whole thing. KJ had a typo and as a result, his body could not process protein in his diet and he was being flooded by toxic ammonia. So I'm going to give you a bit of a sort of action movie style narrative of what happened next. So the first thing that happened is he was transferred to Children's Philadelphia to Rebecca Arens-Nicholas, who is a physician with deep expertise in how to basically keep children like this alive. Her colleague at Penn Medicine, Kieran Musunuru, and she collaborated on looking at the child's DNA sequence and they realized that they see

the typo and this CRISPR thing can fix it. Now, jump back to 2012. What is this CRISPR thing? So, Jennifer Doudna here at UC Berkeley won the Nobel Prize for discovering that CRISPR is a little molecular machine that bacteria use to work with DNA, and Jennifer invented a way to repurpose that machine to fix human DNA. 2016, a scientist at Harvard Broad, David Lu, invents sort of gene editing 2.0, which is it can repair specific little changes very precisely. So literally take one letter out, put one letter in. And so the pen medicine

scientists went, aha, here is this little CRISPR thing that we can use to fix the child's mutation. But you realize having a test tube at pen medicine in which there's a little CRISPR that can fix a mutation and injecting something into a baby, there is a giant gap. Sure. So then this extraordinary, I'm gonna call this sort of the fellowship of the CRISPR cure came together.

And step one was I was collaborating with Penn Medicine and CHOP on a different program. And we got on a call and we agreed that we'll work together to move as quickly as we can. And the number one challenge for us was in Canada, in the US, pretty much anywhere in the world, if you wanna inject something into a person, the local regulatory authority has to look at it

and say, yes, this is okay or no, this is not okay. So in the US, we are regulated by the Food and Drug Administration and we know their rules, right? You have to make this CRISPR thing very carefully. So fortunately, this is like, again, the child, you can't call him lucky because he was born with this disease, but Lady Luck smiled on him a number of times. And here we had an already a partnership with a huge company, it's called Danaher, and it has teams, one is in Corville, Iowa, called Integrated DNA Technologies, one in Fargo called Del Devoran.

And those teams, they can make the CRISPR to FDA grade. So we called Danaher and said, guess what? They said what? We said, there's a kid at CHOP and if you can make the CRISPR fast enough, the doctor thinks there's a chance. And to their tremendous credit, they got going same day. And to me, honestly, one of the joys of this moment, why is the sun shining a little bit brighter since last week, is the way all of these organizations came together to basically try to heal one kid. So bottom line took a few months to convince ourselves that this gene editor works, that it is probably going to be safe to make this CRISPR. Then believe it or not, scientists at Jackson Labs had to make

a mouse and you'll say why a mouse? It wasn't a simple mouse. It was a mouse that had KJ's mutation. It was made by Jackson Labs. And why was it done? Because we could inject the CRISPR into that mouse and show that at least at the level of a tiny mouse, that CRISPR works. That's what the FDA asked us to do. Okay, then we all held our breath.

Danaher made the CRISPR, sent it to Rebecca Arndt's Nicholas and on, it's an easy number to remember, February 25th, 2025, so 05, 02, sorry, 25, 02, 25. Dr. Rebecca Arntz-Nicholas injected this tiny teaspoon of CRISPR into baby KJ, and then we all held our breath and whatever metaphor, closed our eyes. Here we are. You said it was like an action movie.

I've been like sitting on the edge of my seat, kind of waiting to get to this point. I have to let you go, but I just, I find this fascinating. Part of it is your enthusiasm. You said, I haven't felt this good about science in a long time. Just, we have just a couple of seconds left. What is it like to be in this moment for you?

It's a sense of privilege that all of us scientists got to help a human being, and a tremendous sense of motivation that we cannot stop. We have to go fast with a sense of purpose so that the next child and the next child born in the US, in Canada, anywhere in the world, that they can get that magical teaspoon of crisper for them so that their families can take them home. This is a good news story. We've been looking for some good news these days, and I'm glad to speak with you about it. And as I said, the sense of pride that you have in this

and excitement kind of comes right through the radio. Fyodor, thank you very much. Thank you for having me. You've been listening to The Current Podcast. My name is Matt Galloway. Thanks for listening. I'll talk to you soon. For more CBC podcasts, go to cbc.ca slash podcasts.