Babies and Breakthroughs

00:00:56
Clip: A Delaware County baby, who is the world’s first patient to successfully be treated with a personalized gene therapy.

00:01:03
Kaylee Byers: A newborn named KJ.

00:01:05
Clip: KJ was treated with a customized gene editing therapy. KJ. KJ. KJ. KJ. KJ and his doctors have blazed a new trail that could help so many, thanks to highly personalized genetic treatment.

00:01:18
Kaylee Byers: Just days after he was born, doctors discovered KJ had a rare metabolic disorder, a CPS1 deficiency. This disorder meant toxic ammonia was building up in KJ’s blood, which can quickly damage the brain and other organs, and without treatment, it’s often fatal. Most babies in his position spend months in the NICU relying on strict diets and medication until they’re old enough for a liver transplant, a risky weight. But KJ’s doctors took a different approach. In record time, they created a CRISPR gene editing therapy built just for him, designed to correct his exact genetic variant, and it seems like it worked. Today, he’s home eating more protein, taking fewer meds, and living that good old baby life.

This story is a huge step for neonatal medicine, which brings us to today’s case, a look at how genomics is rewriting the playbook for diagnosing and treating our tiniest patients. Baby KJ’s story is an incredible moment of scientific innovation, but part of the reason he was able to get this novel treatment so quickly was because doctors could figure out what the problem was in the first place because.

00:02:28
Dr. Tara Wenger: We can’t start to treat rare disease or cure rare disease until we diagnose rare disease.

00:02:34
Kaylee Byers: And to tell us about some of these rattle-worthy breakthroughs is Dr. Tara Wenger.

Hi, Dr. Wenger, how are you?

00:02:41
Dr. Tara Wenger: Hi, it’s nice to meet you.

00:02:43
Kaylee Byers: It’s nice to meet you too.

00:02:44
Dr. Tara Wenger: I’ve been binge listening to Nice Genes! for the last couple of weeks.

00:02:47
Kaylee Byers: Oh, fun. So today, we’re talking about little babies, but can you start by introducing yourself and telling us about what you do?

00:02:55
Dr. Tara Wenger: I am a Professor of Pediatrics in the Division of Genetic Medicine at the University of Washington, and I am the Inpatient Medical Director for Inpatient Services at Seattle Children’s Hospital.

00:03:08
Kaylee Byers: Okay. So just to be clear, you and your team aren’t involved in baby KJ’s case, but you have been working at Seattle Children’s on doing some exciting work in the neonatal space. So can you tell us a little bit about that?

00:03:21
Dr. Tara Wenger: The projects that I have been working on really just pre-pandemic around 2020 was when we started to get into this work trying to understand how we could improve access to a genetic diagnosis for more kids. And it is very clear from the many children that we diagnose later in life that there may be missed opportunities to be able to make diagnoses earlier in life and potentially be able to implement therapies at an earlier stage.

So back in 2019, there was a larger study called the SeqFirst project, S-E-Q First. So I took over the arm of the study that was for neonates. It took place in the neonatal intensive care unit at Seattle Children’s Hospital, and we ran a trial from 2021 to 2022. And in that trial, we compared the conventional methods of identification of a genetic syndrome, generally that someone suspects there’s a genetic syndrome, and then they consult genetics and then we do testing and then hopefully end up in a diagnosis. We contrasted that where instead any child that was not fully explained by prematurity, infection, or trauma got a rapid genome. And so rapid genome is really the largest test that we can do clinically in order to try to make a diagnosis for children with rare disease. Prior to our study, around that time, it was really more conventional to reserve that until you had failed to find a diagnosis using conventional methods.

00:04:56
Kaylee Byers: Okay, before we go any further, a rapid genome test is basically a high speed scan of your DNA. Usually, it starts with something simple like a blood sample or saliva. And from that sample, scientists read through your genetic code, and in some cases your whole genome. They’re looking for tiny changes in your genetic sequence that could explain what’s going on in the body. The conventional or inclusion method for rapid genome testing only kicks in after every other option’s been tried and a genetic condition is suspected, and patients and doctors would need to make their case, sometimes to a committee before getting that test approved. The exclusion method that Dr. Wenger’s study tested flips that, using the rapid genome test right away for any baby in the NICU whose conditions can’t be explained. And when doctors tried it, what they found was remarkable.

00:05:53
Dr. Tara Wenger:  When we did that, we found that we made about nine times as many diagnoses using the exclusion-based approach. After that study in 2022, we made a change with Seattle Children’s Hospital. They agreed to make a policy change where we were able to implement that for the whole hospital. We started using exclusion-based criteria for offering this broadest biggest rapid genome sequencing test for all in-patients, not just babies and not just in the ICUs. And when we implemented this exclusion-based go big, go fast right away approach for testing, we found that for those patients who are not in ICUs, we brought down the length of time from their genetics consult to a diagnosis from about 10 months down to 13 days.

00:06:40
Kaylee Byers: Oh, wow. Okay.

00:06:41
Dr. Tara Wenger: We have now sustained that from 2022 to 2025, and overall in the hospital we’re making about seven to eight times as many genetic diagnoses per month compared to what we were in 2021.

00:06:54
Kaylee Byers: You’re talking about going from say 10 months to 13 days for a genomic consult or sequencing. What does this difference in timeline mean for kiddos and their families?

00:07:06
Dr. Tara Wenger: We have actually been very surprised at the number of children that it makes a substantial difference and we have been really humbled to learn that we are not that great at predicting which are the kids that are going to have a huge benefit. We’ve had several children that have either had really have had their life saved or have had a major change in their quality of life going forward because we were able to initiate precise therapies.

One of the things that we tested in the SeqFirst-neo paper was we were able to look at which of these kids are not getting genetics consults because there’s not a suspicion for a genetic syndrome. Those are kids we definitely would have missed, and then we can look at what happens when we initiate those therapies. We had children, for example, who had genetic evidence of having a severe immunodeficiency, but they hadn’t had a severe infection yet because they had just been born and so we didn’t need to wait until they had a severe infection. Immunology could initiate treatments to be able to mitigate the risk for them getting those infections. So being able to have the knowledge about what are the major things that could end their life or could cause severe disease or could impact their quality of life. When you know about it right up front, sometimes there are things that are treatable and we can cure. Other times, there are things that we just know about and so we can take precautions and make sure that we have those supports in place to be able to lead to the best possible outcomes.

00:08:40
Kaylee Byers: We’ve said it before, the medical system is often reactive. A broader, earlier approach to genetic screening can flag conditions in babies and children before symptoms ever show up so it can be an early detection tool, but rapid genome testing also plays a part in really urgent matters too. I want to introduce you to Meredith Thomas.

00:09:02
Meredith Thomas: Hi, my name is Meredith Thomas. I’m a mom of three, and my youngest is Solveig. It’s a Norwegian name. It means daughter of the sun, and I have a little sun tattoo.

00:09:15
Kaylee Byers: Little Solveig has cystic fibrosis, but they didn’t know that until much later after she was born.

00:09:21
Meredith Thomas: Upon her birth, something did feel off with her, but I had no language to say what that could be and I wrote it off like she’s just my third kid and she’s different in her own way. Like every newborn, she had her heel prick after she was born to test for the common genetic disorders and her cystic fibrosis levels were completely normal.

00:09:48
Kaylee Byers: A heel prick test is a quick little poke on a newborn’s heel to collect a few drops of blood checking for rare health conditions before symptoms even show up, and Solveig’s didn’t raise any flags.

00:10:00
Meredith Thomas: Fast-forward to when she hit around two to three months old. She developed a cough, and it did not go away for a month and it started getting worse and worse. At the same time, she slowed down gaining weight, she stopped. And when her symptoms really started hitting me that something was wrong, it was September, so it was right at the beginning of viral season. So when I presented my concerns to her pediatrician, he wrote it off and said, “It’s viral season. She’s probably just getting back to back viruses. Give her time, give her fluids and we’ll see how she does.”

00:10:45
Kaylee Byers: But Solveig was really struggling. She was fighting to breathe normally. Her ribs were retracting, her nostrils were flared. She was hungry for air, and things were getting worse.

00:10:56
Meredith Thomas: She had the whitest skin, she was so pale, and she started to get dark circles under her eyes and she became more and more lethargic, and she nursed constantly.

00:11:09
Kaylee Byers: Meredith knew it wasn’t just a kid cold. And after more pleading with her doctor, they ordered a chest x-ray.

00:11:17
Meredith Thomas: Unfortunately, nothing had big red flags with that chest x-ray.

00:11:20
Kaylee Byers: But again, everything came back fine.

00:11:23
Meredith Thomas: So I ended up reaching out to a different pediatrician at the same clinic and she said, “If you’re worried about her, yeah, bring her to the ER.” I did. We waited seven hours and they unfortunately just checked her glucose levels and they checked her vitals and we were sent home. And I remember my mom came home and both of us were just staring at her being like, “What is happening? This baby is so sick and we can’t get any help.”

00:11:57
Kaylee Byers: Still filled with worry, Meredith called a new pediatrician who recommended they go back to the ER. But first, she had an odd request.

00:12:05
Meredith Thomas: She said, “And I know this might sound funny, but can you lick her?” And I said, “What?”

00:12:12
Kaylee Byers: Ever heard of a lick test? I hadn’t, but cystic fibrosis affects a protein that helps balance salt in the body. Instead of keeping it in, the salt escapes through sweat. So while it’s far from a high-tech medical test, seeing if a baby is salty could be a sign of cystic fibrosis.

00:12:31
Meredith Thomas: My husband and I both licked her. I was like, “She tastes a little salty.” But I couldn’t tell if I was just hoping for something because I didn’t want to hear another, “Well, we just don’t know what’s going on.” My mother and I brought her to Children’s and it was a breath of fresh air that they were like, “Oh yeah, this baby’s very sick. We are going to admit her.” I had that, just a huge sense of relief.

00:12:56
Kaylee Byers: After the break, a test result that cracks this case wide open, but the clock’s ticking and Solveig’s health is slipping fast.

You are listening to Nice Genes, a podcast all about the fascinating world of genomics and the evolving science behind it, brought to you by Genome British Columbia. I’m your host, Dr. Kaylee Byers, and we want to get more people to listen to the genomic stories that are shaping our world. So if you like Nice Genes, hit follow on Apple Podcast or wherever you get your shows. If you’re interested in both the baby steps and huge leaps happening in genomics, help spread the love of science by sharing this episode with your friends.

Meredith was finally getting her daughter the care and attention she desperately needed. Doctors found that Solveig had several infections in her lungs and began trying to clear her airways. And so during that time, Solveig was being treated and consulted by many different departments in the hospital, including a visit from genetics.

00:13:55
Meredith Thomas: One of the days we were there, we were visited by the genetic team at Children’s. They came in the room, and they were so warm and friendly and they came in to say, “Yes, Solveig’s admitted here to address her acute symptoms, but we also learned that she is not growing and not hitting her milestones. We think it would be helpful to get her a rapid genome test.” So I was like, “Sure, yes, we would happily do that,” and we did the swabs and then we went on to just focusing on helping this very sick baby and my daughter recovered a bit. She still was very ill looking, but we got to a place where she was more stable and the hospital said, “Let’s discharge and we’ll go forward outpatient with trying to figure out why she’s not growing and not hitting her milestones.”

00:14:57
Kaylee Byers: Doctors gave the okay for Solveig to be discharged, but again, Meredith wasn’t totally convinced it was the right move.

00:15:04
Meredith Thomas: My husband and I remember that night, we were both just sitting there. Both of us were like, “This just doesn’t feel right, I don’t know why she’s home. We’ll hope for the best.” So fast-forward to the day after she was discharged, we got a phone call from the genetics team saying, “We got her results from her rapid genome test, it shows that she has cystic fibrosis.” And so I was both scared, what does this mean? I don’t know how bad this is, but also incredibly relieved because if there’s a name for what she has, then there could be treatment and a solution even if it’s a scary thing.

00:15:45
Kaylee Byers: But in the meantime, as the genetics team was looking at scheduling her first checkup, Solveig was declining, and Meredith didn’t think she could wait even a few days for the appointment so it was back to the hospital.

00:15:57
Meredith Thomas: Upon arrival, she was stable, but within an hour of being admitted, she completely crashed. They did a chest x-ray and they learned that she had a double pneumothorax, meaning she blew out both sets of her lungs. And I remember holding her at the time and she just was gasping for air and just seeing her seeing me lose my daughter, it was horrible. They called a code, they moved her to the biggest room in the ED. There was 30 people in the room and they gave her an IO, intraosseous IV line.

00:16:44
Kaylee Byers: While the doctors got to work treating Solveig’s lungs. Meredith watched until one of the doctors suggested she wait outside. Meredith waited and after what felt like ages, Solveig was stable.

00:16:55
Meredith Thomas: And she’s stable, we’re going to move her up to the ICU. And we had this hilarious nurse come out and give us the lowdown of what was going to happen, and it was such a weird time of he was cracking jokes and we were laughing, and it felt like such a weird time to laugh, but I think you’re trying to survive a really traumatic moment.

00:17:18
Kaylee Byers: Meredith and her husband spent the next two months in the ICU with Solveig treating a double pneumothorax and cystic fibrosis at the same time, which was already complex, and Solveig was also severely malnourished due to the cystic fibrosis. Then, on top of all of that, they learned she had an immune system disorder. Every day was complicated, full of ups, downs, visits from different doctors, but eventually, Solveig could go home, comfortably this time with a diagnosis, a treatment plan, and long-awaited answers to the questions they’d been carrying for so long. And Solveig began to flourish.

00:17:54
Meredith Thomas: And she’s a completely different kid now. She slowly adopted a personality. She didn’t have a personality, she just was a sick baby. Now, she has her medications and she has her team and she still has to get the infusions for her immune disorder, but she is Solveig.

00:18:14
Kaylee Byers: Solveig’s story is a powerful example of what genetic testing can do. Every traditional test said Solveig didn’t have an underlying condition, but something was clearly being missed. Dr. Wenger wasn’t one of Solveig’s doctors, but through her research, she knows the story well.

00:18:31
Dr. Tara Wenger: I really believe that she would not have survived, and we wouldn’t have known. We wouldn’t have known this was a missed genetic diagnosis. It wouldn’t have been something that we would’ve necessarily suspected was the case. And that’s been very impactful on all of us because we didn’t think we would miss a diagnosis like that. Cystic fibrosis is something that we just think we’re really good at catching, and it’s not a rare disease that we don’t know, it’s not something really out there. It’s something that’s really common, and yet we still miss it.

00:19:04
Kaylee Byers: It also makes you wonder, when tests miss something, it’s not just what’s overlooked, but also who gets overlooked. We know that in hospital settings, in all health settings, there are huge equity issues. Depending on who you are, your cultural background, where you live, your access to funds, all those things impact your ability to get a diagnosis for any disease or illness, right? And so have you seen any impacts of moving towards this kind of model in reducing those inequities?

00:19:33
Dr. Tara Wenger: The biggest thing that we saw that surprised us, it should not have surprised us, but it did surprise us. We found that in children who were receiving conventional care, there were racial disparities in terms of who had access to a precise genetic diagnosis. In the conventional care arm and in the SeqFirst arm, there were 17 babies each that had at least one parent that reported that they were Black. In our conventional care arm, we made zero precise genetic diagnoses, and in our SeqFirst arm, we made 11. Once we implemented this exclusion-based testing approach, since 2022, we have not had any detectable racial differences in the rates of genetic diagnosis. This is something that I think was consistent across the studies, and it shows a clear opportunity for being able to improve equity when you can use exclusion-based testing and you can do rapid testing, it’s multifactorial, but if you can use exclusion-based testing that you can eliminate these disparities in care. And I do think it’s important for us to understand the reasons, but I think it’s more important for us to fix the reasons and because we have this approach that mitigates it, I do think it’s important that we go back and understand what was at the root of these differences. But it’s even more important to change policies and implement change that can eliminate the differences going forward.

00:21:03
Kaylee Byers: And to do this study, I mean, families could opt in or they could not opt in.

00:21:08
Dr. Tara Wenger: Correct.

00:21:08
Kaylee Byers: And I’m thinking about that in terms of this data goes off to another company, it’s their whole genomic information. We’re still struggling with privacy around that.

00:21:18
Dr. Tara Wenger: Sure.

00:21:18
Kaylee Byers:  So can you talk a little bit about why someone might choose not to take this approach and also the potential privacy implications of having that amount of your data out there?

00:21:28
Dr. Tara Wenger: The first part, in terms of opting into the study, so the SeqFirst-neo study was a study that you can opt in or out of. It’s something that patients that might not have been offered clinical testing could access that testing through the study. But that said, it’s very important that there is an informed consent process.

Every one of the patients that is offered genome sequencing at Seattle Children’s Hospital sits down with a genetic counselor who talks to them extensively about what this testing means, what it means for privacy, whether or not they would want to opt in for secondary findings. So those would be things that are unrelated to the indication for testing but could impact their health later on. You could opt in with parents because this is trio-based testing. The parents can say, would they want to know if they had this secondary change?

In the United States, there are protections so that employers that are above a certain size can’t use genetic information to discriminate against their employees. But the Genetic Information Nondiscrimination Act does not apply to long-term care insurance or disability insurance, and it also does not apply to the government. And so some of our military families make different decisions about secondary findings than those who are not in the military. So we want to retain that autonomy that families get this testing only if they wish to do so. And with their preferences in mind, with respect to, do you want to include samples from both parents? Do you want to know about secondary findings for your child? Do you want to know about secondary findings for yourself? Do you want to be recontacted for research? It’s very different when you have this type of clinical genetic testing. There are a lot of protections around it. It’s not like these databases like Ancestry and 23andMe that can be accessed for other reasons. It’s not like that. And there’s misconceptions around that. Many parents when we do the testing, say, “Oh, well, I already did 23andMe, can you just ask them for my data?” No, this is not the same thing. There are many more protections on privacy. People can’t access this data.

00:23:35
Kaylee Byers: So in the US, there are protections to stop employers from using your genetic data, but not when it comes to things like disability or long-term care insurance. But here in Canada, it works a bit differently. In 2017, Canada passed the Genetic Non-Discrimination Act, and that’s made it illegal for anyone: employers, insurers, even landlords, to demand your genetic test results. So while the US approach has some gaps, Canada’s law is broader in scope with steep penalties for violations in both countries.

Though genomic testing isn’t treated like consumer DNA kits, it comes with strict privacy safeguards and detailed consent processes. What started as research on testing more newborns and infants for genetic conditions slowly grew, first to all pediatric patients, then to other parts of the hospital, and even to bigger questions about equity in healthcare, a small change in how we test can lead to massive shifts in our medical system and open the door for more baby breakthroughs like baby KJ for example. Could you also tell us a little bit about baby KJ?

00:24:40
Dr. Tara Wenger: Sure. This is not one of my patients. This is a patient who is at the Children’s Hospital of Philadelphia, and he had a type of biochemical disorder that was amenable to treatment with a new kind of gene therapy. So what they did was they were able to use CRISPR to be able to make his body produce enough of the thing that it couldn’t produce previously. I don’t think that we know yet is he cured, but he certainly has done much better than he would have. This is the first time that this type of technology has been used. It’s a specific case because we’re not there yet to be able to use this type of technology for the majority of patients. But it was really tremendous that Dr. Ahrens-Nicklas and colleagues were able to think of something so creative, something so innovative was able to be implemented.

00:25:36
Kaylee Byers: Not all heroes wear capes. Some of them wear lab coats or comfortable trousers. What’s something that you wish that every pediatrician or parent knew about the power of this kind of genomic testing?

00:25:51
Dr. Tara Wenger:  I think that there is a general lack of understanding about how genomic testing can benefit children. I find a lot of families that I talk with think that when you do genetic testing, it may give you an explanation but doesn’t necessarily change the care of the child or change anything going forward. And maybe 30 years ago, that may have been the case.

Historically, having a genetic diagnosis often meant terrible things happen. People are put in institutions. There’s a lot of historical wrongs that have happened, and I understand that that has consequences and people have mistrust of genetic testing and they don’t understand why it would be beneficial for their children to have a genetic diagnosis. It’s now 2025, and in 2025, we have a tremendous number of therapies, but we can’t get them to the children if we don’t know that the children have those diagnoses. I think that sometimes there’s an inclination of let’s just wait it out and we’ll see an ultimately it will become clear and maybe they’ll get a diagnosis later on. But if you have that knowledge right at the beginning, sometimes you can change that trajectory of that child’s life and you can get them access to therapies and you can connect them with parent groups who can learn from each other and have a community. There are these huge benefits of getting a genetic diagnosis. In addition to that, the more kids we know have rare disease, the more of them there are that we can learn from, and then trial therapies. And so I think we’re really at this time that we have a tremendous amount of evidence that we are able to cure a lot of rare diseases, or at least treat them and mitigate suffering, and there’s a huge benefit for families that wish to undergo testing.

00:27:45
Kaylee Byers: Dr. Wenger, thank you so much for coming on, and for all the work that you do.

00:27:50
Dr. Tara Wenger: Thank you so much. This has been really fun.

00:27:53
Kaylee Byers: An early genetic diagnosis can change a child’s life, open doors to treatments, support, and new possibilities. Families who’ve had to fight through uncertainty know that knowledge can mean everything.

00:28:05
Meredith Thomas: There’s so many people who are really good at their job. They’re trying really hard, they’re doing their best, and so many things are missed, and so many mistakes still happen. I would hope that there would be implementation of better tools so that parents don’t feel like they need to take on the burden of having to take on this role of hyper, hyper vigilance. It’s draining, I’m sure lots of parents can relate to medical dismissal or feeling like they need to push harder, and it’s exhausting so I have huge respect for a push in making genetic counseling and genetic tests more accessible. It makes a lot of sense that my daughter’s story would end up on a genetic podcast because the timing of her rapid genome test is what saved her life.

00:28:57
Kaylee Byers: Well, detectives, what we learned today is that when the usual leads run, cold genomic tools can help uncover the clues that our medical system might miss. Turning the NICU into the NIC who, what, where, when, and why.

Our guests for today were Meredith Thomas and Dr. Tara Wenger, Pediatrics Professor at the University of Washington and Associate Medical Director for Inpatient Genetic Services at Seattle Children’s Hospital.

You’ve been listening to Nice Genes, a podcast brought to you by Genome British Columbia. If you like this episode, go check out some of our previous ones. Wherever you listen from, share it with your friends and leave us a review. You can also DM the show on social media by going to @GenomeBC.

Hospitals are full of life-saving care, but on TV, they’re full of love triangles, rain-soaked goodbyes, and miracle recoveries right before the credits.

00:29:53
Dr. Krysta Coyle: I read a Reddit thread last night about all the mistakes people find in lab scenes, and I think we’re already winning when we have pipette tips on the pipettes.

00:30:02
Kaylee Byers: Join us next week as we look at how medical dramas shape the way we understand science. Thanks for listening, see you next time.