A Dose of Optimism
A Dose of Optimism is a podcast dedicated to exploring the world of healthcare innovation and the optimists driving meaningful change.
Hosted by Omkar Kulkarni, this show shines a light on bold ideas, transformative solutions, and the passionate individuals working every day to make healthcare better for children and their families.
Each episode dives into the real-world challenges facing the healthcare industry and highlights the people and organizations pushing the boundaries of what’s possible. From tackling mental health and food allergies to reimagining hospital care and harnessing Artificial Intelligence for better outcomes. Listeners will discover game-changing solutions, hear stories of creativity and resilience, and gain inspiration from leaders who believe in building a healthier, more hopeful future.
From medical professionals and entrepreneurs to patients and community advocates, the podcast brings together diverse voices united by a shared commitment to improving healthcare delivery. Whether you’re working inside the industry or simply curious about the innovations shaping tomorrow’s care, A Dose of Optimism offers insight, connection, and inspiration.
“The content, views, opinions, and information presented on this podcast do not reflect the views of Children’s Hospital Los Angeles or of the sponsors of the podcast. CHLA does not endorse the views, opinions and information presented on this podcast and CHLA specifically disclaims any legal liability or responsibility for the podcast’s content.”
A Dose of Optimism
Pigs, Texts & Sim
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Three very different innovations. Three very different settings. One shared direction: pediatric care moving closer to children and families.
Dr. John Cleveland, Associate Chief of Cardiothoracic Surgery at Children's Hospital Los Angeles, shares the science and the hope behind xenotransplantation, the use of genetically modified pig hearts as a bridge to human heart transplantation for infants dying on the waiting list. With baboon models now surviving over two years with pig hearts, and human trials potentially one to two years away, this may be the most significant breakthrough in pediatric cardiac care in a generation.
Dr. Katie Richardson, CEO of Lantern, describes a deceptively simple but genuinely valuable solution to one of pediatrics' oldest problems: parents don't get enough guidance between well visits. Lantern delivers free, expert-vetted, age-specific child development information directly to parents via text message (in English, Spanish, and Arabic) paired with hyperlocal resources linked to the family's zip code.
Dr. Todd Chang, Pediatric Emergency Medicine physician and simulation expert at Children's Hospital Los Angeles, explains why simulation matters more in pediatrics than almost anywhere else, because pediatric emergencies are rare, which means clinicians never get enough practice unless they simulate. He also shares a compelling vision for what AI and advanced technology could do for healthcare simulation, and for parent education, in the years ahead.
Episode Resources:
Children's Hospital Los Angeles: Heart Institute
Las Madrinas Simulation Center at CHLA
The Society for Simulation and Healthcare
Aaron Kornblith, MD, MS LinkedIn
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Connect with Dr. Katie Richardson:
Dr. Katie Richardson Instagram
Connect with Dr. Todd Chang:
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Children's Hospital L.A. Website
Children's Hospital L.A. Instagram
Children's Hospital L.A. LinkedIn
Welcome to the Dose of Optimism, where I talk to the optimists in healthcare. My name is Omkar Kulkarni, and I work at one of the world's best children's hospitals where I lead innovation. I started Kids X, which is a premier international startup accelerator for pediatric innovation. And over the years I've met thousands of startups, investors, and innovators. Every one of them has a story, and every one of them is optimistic about the problems they're solving. On this podcast, you'll meet amazing people who will share their stories and what makes them optimistic about the future of healthcare. A little note before we get into this episode. Alright, let's get started.
SPEAKER_02I always like talking about simulation. Thinking about people who are normally in the healthcare and healthcare innovation space, the concept of simulation may be a little bit new to them, right? For those of us who are in clinical training, simulation is a almost a daily thing. And there's lots of different definitions. The Society for Simulation and Healthcare has their own formal designation, which we're accredited to at the Las Medrina Simulation Center. But I like to think of it as it's a replica of a healthcare situation, whatever it may be. It may be a patient encounter. It may be simulating where the next big infectious disease will go. It may be simulating an entire system or system failure or system success. And the idea is that you use simulation to elucidate the difference between work as done. So work with the capital W, how we work, and work as imagined. We all think that we do really well, both in the clinical sphere at the bed side and research and education in the systems. But work as imagined, that's what I'm talking about, is almost always different than work as done. The slide that I like to use for visual people is work as imagined is the fully evolved Charizard, the giant uh dinosaur. And work as done is actually this tiny little like Pokemon, little Charmander. And what happens is really intelligent, well-meaning, excellent people, when they're under periods of stress or unusual circumstances, perform in a manner that's a little bit less than expected. I think people understand that to a degree, but when it happens to you or your child in healthcare, it doesn't feel so good.
SPEAKER_03Is it different in pediatrics than it is in other types of healthcare? Like simulation and how it's structured, the relevance, the importance.
SPEAKER_02I think the day-to-day operations is probably pretty similar, just the size of the mannequin, of course, is different when we're talking about mannequin-based simulation. But pediatric simulation is probably more important than other forms of adult-based medical simulation, partly because simulation is used to simulate really rare events. And pediatric crises, healthcare crises, both at the patient level and the system level, are really rare, super rare, way more rare than adults. So a couple of concrete examples. In the EMS world, the ambulance world, approximately 10% of all ambulance transports are minors, 18 and under in pediatrics, compared to 18 and over, which is the majority of what you're going to see in an ambulance. And then within that 10% of the pediatrics, about only 10% of those are actual critical care pediatrics. And the rest are reasonably okay kids who they just need a little bit of supervision, maybe one treatment of something, and then they could just drive to the nearest hospital. So if you think about all the experience that a regular paramedic has, only 1% of their transports is estimated to be critical pediatrics, which is different than the critical adult care, which they have way more experience. And so you're talking about a really rare high-stakes, low frequency event, which is some sort of pediatric resuscitation. And it could be a mental health crisis, it could be a physical health crisis, it could be any of those things.
SPEAKER_03Or is it more about learning new skills, leveraging simulation, because you may not actually see it until it actually happens for the first time?
SPEAKER_02It's both. So there's there's two ways to do simulation. One is the teaching method, where okay, you don't know the skills. This is what you're supposed to do. Let's practice it in this safe environment. And we ramp up the realism so it's actually like a dress rehearsal rather than a tabletop read. The alternative is what we call latent safety threats analysis, where we're not really teaching. We get a bunch of experts, but we put them in a very catastrophic scenario, something that is so rare they probably haven't seen yet. A mass casualty, God forbid, or a very specialized conjoint twin surgery that they've never done before. But people have done some sort of conjoint twin surgeries. And so we do a really realistic simulation to see what the experts would do in that team setting with a time restraint, and then what they end up doing, maybe the correct thing, or they discover things that are, oh wait, this isn't working. Maybe we should do something else. And we'd rather find out about things. So it's more of a discovery phase rather than a teaching phase if you use it in that direction. So you could do teaching, but you can also do discovery.
SPEAKER_03Now, given the rarity and the uniqueness of these scenarios, how do you find a scenario that is going to be relatable, translatable enough so that it can account for other things that they may see, but is designed in a way that is rich enough where you've got all the right inputs to make it seem realistic and whatever else, right? Because these are rare things. Yeah. And by nature, that makes it, I imagine, harder to create scenarios and create the simulations. How do you find that balance? I actually have a tech example for all of you techies.
SPEAKER_02And this is courtesy of Aaron Cornblith. He's a Pem physician over at UCSF. So I credit him with this knowledge that he provided to me. He interviewed folks from Waymo, currently the lead in the US at least, of autonomous vehicles. And one of the things that they had to do to make sure that there was enough safety was to actually make sure that the Waymo vehicles could operate under extremely rare catastrophes or things that normally don't happen, typically in a car accident, et cetera, or weather or whatever the inclement thing is. What they found was that if you just let a Waymo do its thing and collect data, there were not enough adverse events for it to train on. It just wasn't enough events, which is good, right? We don't want car crashes every day, at least for the single Waymo. And so they actually had to simulate and recreate some of the more catastrophic events. And some of them are bordering ludicrousness, like a multi-car pileup out of nowhere with no snow. And some of them are a lot more realistic, like, oh, this could easily happen tomorrow. And so the likelihood of it occurring in our lifetime, for example, was not a factor when Waymo created and all these different simulations for rare events, because they needed a level of safety for anything that it could a particular conceive, even if it was unlikely to happen in the next 30, 40 years. For them, simulation was vital because it was really about raising that bar of safety for the autonomous vehicle. For us in healthcare, it's raising the bar for safety and critical thinking and being extremely flexible when something unusual arrives, a disease we haven't seen, or a restraint that we haven't done before. For example, resuscitation and all of a sudden the power goes out. These combinations might occur, may never occur if we have great generators, but it's really thinking of these combinations and the rarities, they're going to be relevant at some point. And whatever the skills we develop for that scenario are pretty much transferable to other situations as well.
SPEAKER_03Taking the Waymo example a step further as an analogy, I imagine 20 years ago a sim center would have perhaps a camera on the corner, maybe some scribes, observe what someone's doing, you play back the video, and you discuss it. I imagine current or even future state, you can have perhaps a little a more far more cameras, maybe there's AI, maybe there's sensors on the people who are in the simulation to simulate various things. Perhaps you can customize the simulations given technology. Like, what's the role some emerging technologies playing in enhancing optimizing simulation centers today and in the next few years? Sure.
SPEAKER_02So there's several ways that technology is already improving and augmenting and changing uh simulations. One would be the modalities. So with the advent of 3D head-mounted virtual reality, augmented reality, those devices, there's a different level of realism that you can do that's electronic. And even during the pandemic, when we couldn't actually get everybody within six feet of each other for training, we could actually use these technologies to do simulations in locations that normally can't do it. So that's one the dissemination. Number two is improvement in fidelity. So there's a whole uh part of simulation is to make it as optimally realistic, not necessarily perfectly, but optimally realistic so that people can either learn or discover things. They can behave naturally. It's hard to behave naturally towards a patient if the patient looks like a $5 doll. It just doesn't work for nurses and physicians who are they're not really good, they're not actors, they're not trained in those acting arts necessarily. So having that level of fidelity for not just the what the patient looks like, but the patient context, the environment, the sounds, the noises, the smells, those actually improve the fidelity and make people react naturally. And that's what imprints on their learning anyway. So other technologies like 3D printing allows you to have more customized tactile feedback. For those of us who in the surgical and procedural arts, you need that level of feedback in order to actually really get into the simulation and really feel like this is real and then act accordingly. It's very different to train on how to insert a needle if it's very plasticky and you just don't it doesn't feel like well and your background's in trauma, right?
SPEAKER_03So are you i I imagine you can use these additional technological stimuli to simulate different factors that could occur in a trauma situation.
SPEAKER_02You and I live in Los Angeles near Hollywood. So the whole idea of making a set that looks and feels realistic is actually very important to the science and art of simulation. And we borrow a lot of the things that Hollywood has learned and developed for our work as well. So it is important. There's a minimum level of fidelity that you need. Otherwise, it's just you might as well pretend this pillow is a mannequin.
SPEAKER_03Flipping it a little bit, do you think there's a role that either simulation as a science and as a as a category has for patient education, right? For a parent who has to learn how to give insulin or has to check or draw blood regularly at home. I think I've seen CPR as probably the most common use case around simulation. That's more of a general use case. I'm curious if there's more pediatric use cases you can imagine.
SPEAKER_02Yeah. So CPR is a pretty easy textbook case of why you would do that. I think nobody would ever argue against CPR training with the mannequin, especially an infant one. But there is a role for the science of simulation. So not just here's a doll, push on the chest. I can give you a couple examples. The first one being CPR. We have a lot of children at our hospital, children's hospital Los Angeles, as well as in many hospitals around the world, where children with complex health needs are surviving and thriving. And therefore, we do need to actually think about them when we think about caring for them. We had a child with um some thoracic abnormalities, we'll just call it that, and who we needed to train CPR, but we actually needed to figure out how to do CPR when there's a thoracic abnormality. Because if you remember, normally you put your fingers or your thumb or your hand on the chest. But if the chest is not shaped the same, do you still do it? So we actually ended up using 3D printing to reconstruct the thorax with a compressible chest. Had a team meeting with our thoracic surgeons uh and everyone involved in the care and the people who were going to educate CPR, and really were able to use this customized mannequin using our simulation work in a 3D printing program to customize the CPR that was slightly different. And for the parents, and the child is, of course, too uh too young to know. So that was actually really interesting that we can actually start customizing simulation for uh what we need. And for patient and parent education, I think about the epi pens and any time that a parent needs to do an injection on a child, it's a whole different ball game. Even if you're a trained nurse who can do all the the syringes with you know their eyes closed with the best skills, doing it on your own child who's looking at you and crying is not easy. Right. And so that's the difference between somebody who's well trained and well-trained, but performing in a context that is really, really stressful. So we actually had the endeavor to do some projects where instead of the usual way where people take an orange because they have a rind and the pulp and practice doing injections and an orange, which works really well. The the idea was to actually place a simulated skin on the child, him or herself, usually around the thigh, is where an injection would go, and actually deliver an actual injection into the pad of the thigh, because that creates that context, even though the needle won't physically go into the child at that moment. We haven't done that uh yet, but these are the types of things that we can think of where we move the simulation of fidelity closer and closer, not all the way, closer and closer towards what it's like in real life, to really get that um fidelity going. So that's an idea that we have because we know that while almost all parents can handle an orange, they get paralyzed when it's time for their own child to receive it.
SPEAKER_03We've talked about the power of voice as an element of AI to be able to simulate conversation. So not necessarily anything procedural or action-oriented, but rather conversational. Uh, there are difficult conversations that providers have with parents, with children, with colleagues. There's lots of scenarios you can come up with. And it's a different form of simulation, but I could imagine a world where practicing any type of verbal conversation or communication with an AI could be an interesting future for simulation.
SPEAKER_02Yeah, you're right on. Yes, it's technically a different modality of simulation, but we still capture it as under the umbrella of healthcare simulation. It's a huge skill set of appropriate communication, sometimes called difficult communication, but we can label it a little bit more thoughtfully and say it's it's just it's complex empathic communication. All right. This could be de-escalation, like how to do de-escalation in intense areas. It can be giving bad news, and the news of could be as flavored as your child has cancer, or in a slightly different way, I'm worried that your child is being abused, and I need to talk to you about it as the parent who actually lives with the child, right, and all the implications of that. And so these are different conversations that we don't usually get training on outside of simulation. Typically, before AI, we used standardized actors, and they are really good. They're still the gold standard, right? Facial expressions, empathy, and they know how to break character if the mood or the tension gets too high because we still want it to be a worthwhile learning experience. And so those trained actors are really good for health care. They work in medical schools and nursing schools and other healthcare schools. But there is the rise of AI and the ability to do at least some level of communication, even if it's typed out, but at least voiced out, spoken in practicing these types of communication. And a lot of AI can be trained to rate the conversation either on empathy with validated empathy scales like the Jefferson Empathy Scale, for example, or other metrics that we ask the AI to do. And so there's a lot of active work on using AI to teach, assess, and to evaluate communication styles when the communication becomes a little bit more complex or high energy, high charge.
SPEAKER_03Dr. Chang, thanks for joining me today and talking about all the really important work you're doing around simulation and how it's helping train the next generation of clinicians as we navigate the future. Thanks so much, Amkar. This is really exciting. Well, Katie, thank you for joining us for the show.
SPEAKER_00Thank you so much for having me.
SPEAKER_03So, parenting is hard. And particularly for new parents or people that are taking care of children, it can be a lot going on at all points of the child's journey from the first days all the way through adulthood. How does Lantern help a parent with their journey?
SPEAKER_00The thing that's unique about Lantern, I believe, is we are delivering information for parents, not only aligned with their child's date of birth, like exact day of life, but also right to the palm of their hands. So this information comes via text messaging. And again, they can read it at their leisure. Each text comes with a link to additional information so they can read more when they have time, but it's bite-sized, so it's easily read and accessed in a short time when parents are always so busy. But again, it's about one to three messages a week and really aligns with things that our parents, parents are going through at that time of growth and development of their child.
SPEAKER_03What is the crux of what you're personally trying to solve?
SPEAKER_00Well, as a pediatrician, when I think about the fact that with most families, I have about 20 minutes in an exam room, right? So every well visit, short amount of time, not enough time to cover every topic that I would love to cover. So what Lantern does really is fills in those gaps, not only the things that maybe I didn't get to when they were in seeing me in the office, but also the things that they're gonna encounter between those well visits that many parents have questions about, common questions and things that come up for not only new parents, but parents that might be even more seasoned as well.
SPEAKER_03And do I text back or am I really receiving information through Lantern?
SPEAKER_00At this point, it is really just receiving information. Our hope with the next iteration of our product is not only the ability to search information and also text back, but right now this really is a one-way receiving of information from Lantern. And again, these are resources that are vetted and backed. Expert advice coming to the palm of your hand, right to your mobile phone.
SPEAKER_03It's like a helper's manual for parents.
SPEAKER_00Yes, our tagline is because kids don't come with instructions, right? That this is a very helpful way to get the information you need.
SPEAKER_03Now, do we have to pay for it? Do parents pay for this?
SPEAKER_00This is completely free for all families. In addition to the content, I want to point out, I agree with you, by the way, you and I are get both get very excited about healthcare, uh, innovation and technology. And so our future iterations will do exactly what you're talking about. But one of the things that I haven't mentioned that I think is also so helpful for families. So not only is it free, it's available in English, Spanish, and Arabic. And our hope soon will be to expand into more languages. But the third part about it, when you sign up for the program, we also ask for your zip code. And the reason for that is we partner with hospitals, health systems, nonprofits across the country, library systems, all kinds of other partners across the country to really put out information about free and low-cost events and resources, again, that are hyper-local, targeted to your zip code. So things that are happening in your area that those families can take advantage of as well. It could be library story times at your local library. It could be an immunization clinic that's happening at your local hospital. It could be a food pantry nearby that is easily accessible. So again, we partner with all kinds of organizations, but I'll give an example from Colorado. Rocky Mountain PBS, they every year have a free kids' fest, so free events that happen. And we put a message out in the Denver metro area to families, and they got 800 signups. In the first hour after our message went out. So people are paying attention and taking advantage of those fun things, free fun things to do for families in their area.
SPEAKER_03I think it's a great thing that you're doing. And I think it helps parents and people taking care of kids, understanding what they need to know in a modality that's not incredibly intrusive or time consuming. And it can activate people to go to events or participate in things in their community that are really beneficial to them. So, Dr. Richardson, thank you for all that you're doing and excited to see the next many phases of Lantern.
SPEAKER_00Thank you. So excited to be here.
SPEAKER_03Dr. Cleveland, thank you for joining us. Happy to be here. Thanks for having me on. I've been reading quite a bit about xenotransplantation and the work you're doing. Can you describe to us what that term means and why it's so important?
SPEAKER_01For a long time throughout history, humans have envisioned a time in which we could use animals and their organs to really fix a lot of our issues that we come up with from a health perspective, particularly since the advent of aloe transplantation, which we take organs from other humans to treat organ failure in other humans. Meaning that not enough humans pass away who have viable organs in order to be able to donate them to the individuals who need them. And so the transplant waiting list for every single solid organ has grown every single year. And there's really no end in site or solution in site in which we're going to combat the issue of supply and demand. The demand for organs is too high and supply is too low. So for historically, people have thought about animals as being a potential source of that. But as you can imagine, there are major immunological limitations that have his, you know, for in the past kept that from becoming a real reality.
SPEAKER_03In terms of pediatrics, is there an additional complexity associated with the traditional way we have transplanted a 65-year-old who dies? Are there organs perhaps not easily transplantable into an infant? Is that another challenge that the CARD system has?
SPEAKER_01Yeah. So I would say that that's probably our largest challenge uh within the pediatric side. You know, in order for there to be available pediatric organs, children have to die. And fortunately, that doesn't happen. Children don't have diseases that result in, you know, early loss of life. Uh, but it has resulted in a major issue being that infants who are waiting for heart transplantation. So infants would be defined as children less than one year of age. They have the highest weight list mortality rate of any individual of any age group for any solid organ at this point in time. And so what's happened now, you know, throughout history, we've sort of gotten better and better at treating heart disease in kids, and we've kept kids alive longer and longer, but eventually their hearts wear out. And so the transplant waiting list starts to grow because those children don't have hearts that they can continue to live with. And the transplant waiting list has increased almost 50% in the last 10 years. But because infants are so small and not able to use organs from anybody other than infants, their transplant rate has gone down by 50%. So we're we're adding more and more kids to the wait list, really without producing any true hope. So we put them on the wait list and they go on the wait list. And because it's heart disease, eventually their hearts give out and then they can't live long enough and then they die. We're just facing this crucial moment in time where we have to seek alternative solutions because the traditional pathways are clearly not going to provide the answers.
SPEAKER_03Is there hope with xenotransplantation? What does your research show us about the opportunities that may exist there, particularly for pediatrics?
SPEAKER_01Well, we started this work eight years ago. My dad actually started the work, and I told him at that point in time that he was crazy. My mentor, who's Dr. Vaughn Starnes, who works here at Children's Hospital, Los Angeles, uh, and recruited me here to work with him. His mentor uh was a man by the name of Norm Shumway. Norm Shumway is famous because he pioneered all the science behind human heart transplantation from one human to another and really made that success. And Norm Shumway is famous for saying xenotransplantation is the future and it always will be. And, you know, when my dad called me years ago and said, Hey, I just listened to a pioneer in xenotransplantation give this talk. Uh, I see a mechanism in which this could be super helpful to treat the kids who are dying on the wait list. What do you think about working on it together? And I said, I think that sounds pretty crazy. Fast forward about six months, he called me and he said, Hey, we did a couple of experiments in animals where we took a genetically modified pig heart and we put it into a non-human primate. So, you know, sort of the closest thing that we could find to human immune system and physiology. And these animals are alive six months later. What do you think about that? I said, I think we should work on this together. Uh, and so we went about obtaining an NIH grant and, you know, fast forward here to today, uh, we have animals that have been alive for over two years, having their life sustained by a genetically modified pig heart, with the intention that you would always use this as a temporary solution, but it it really would be transformative for the children on the waiting list to have functional hearts while they're waiting to find a human heart. And so that's sort of our vision that's that's really grown out of it. And we because of the potential that we've seen in an animal model.
SPEAKER_03So I'm trying to understand this a little bit more. So so far, what we've done is we've transplanted a pig heart into a did you say it was into a human or into into another animal?
SPEAKER_01So what we've done so far is you know, you never want to step forward with theoretical technology into human application. And obviously the FDA regulates that appropriately. And as a physician, under my Hippocratic oath of doing no harm, I wouldn't want to do that either. And so we've had to develop the best animal model that we could to replicate what we're looking to do, which is to take genetically modified pig hearts, put them into human babies who are on the transplant waiting list, uh, and allow it to buy them safe passage to a human heart. And so our animal model is taking genetically modified pig hearts, putting them into infant baboons, and then allowing that time to one, see what the longevity of these hearts, what they're capable of doing, how they function over time, and then how the immune system from the baboon reacts to the heart. So we can better plan for potential future studies and offerings in humans.
SPEAKER_03That's great. So you said the baboon has now been alive for two years with this genetically modified pig arc.
SPEAKER_01So that's that's our longest survivor. And for reference, the longest survivor of any animal model prior to that was about 260 days. And we subsequently have plenty of other animals who have lived 240, 250 days, some of which we've gone back and actually taken out the pig heart as a proof of concept and put back in a baboon heart to show that having a pig heart in for a prolonged period of time doesn't preclude you from being able to receive a heart from another member of your species. So, because that's really what our ultimate goal would be in a human infant population. The goal would always be to get back to the standard of care.
SPEAKER_03Now you started with the heart. Is there research around other organs from a either pig or baboon or another animal that is having similar promise?
SPEAKER_01When we started this work, every organ system was sort of at the same level in terms of its progress. They had studied kidney transplantation as well as eyelet cell transplantation, as well as liver transplantation and lung transplantation. And several of those have accelerated at a quicker rate. Uh, one in part by need, two in part because of funding, and three in part because of just the safety profile of offering it. And so the one that has come out to lead all the organ systems and age groups is xenotransplantation of kidneys in human adults who are not candidates for a human-to-human kidney transplant. And so there is an active clinical trial being carried out. Actually, two separate active clinical trials are being carried out to look at that, with I think a total of six patients so far in the United States having received those kidneys. Uh, and they're they're learning quite a bit. And I would say, thankfully, blazing a trail for us, because once you replace a heart, it's a pretty much full commitment. There's no going back. But the advantage that the kidney folks have is that they can do a kidney transplant. And if it eventually rejects or doesn't work out, they can always go back to dialysis. We don't have the same benefit within the heart transplantation realm. Uh, and subsequently, because of that, we're just walking really carefully forward and making sure the science is correct before we would ever move into human clinical tribes.
SPEAKER_03Wow. So we're already at a place where we are seeing xenotransplantation in adults with kidneys. And the hope is that we soon can safely do this work with some organs, kidneys, hearts, others with children.
SPEAKER_01It's one of the technologies and probably one of the few technologies that's more apt to be successful for children than it is to be successful in adults, primarily because as we are adults and go through our lives, we develop antibodies against pigs. And children are particularly our target population of children less than one year of age who are dying on the transplant waiting labs. They don't have anti-pig antibodies. We've gone through and we've studied our target population already and look at their blood and recognize that they don't have any pre-formed antibodies to these pigs, and their immune systems are much more capable of adapting to foreign antigens. And so, you know, for that reason, as an example, infants who receive a heart transplant, a standard heart transplant from another human, have better graft survival rates, overall survival rates in terms of their post-transplant course, and less rejection rates of their transplanted organ than any other age group, primarily a reflection of their immune system's ability to accommodate new things that are placed into the system.
SPEAKER_03That's a real advantage if we're able to do this, particularly with xenotransplantation with infants or young children, so they can ideally thrive with these new organs they receive. So the pig is the gold standard in this space in terms of the origin site of the organ? Great question.
SPEAKER_01Um, so pigs have been selected for uh a couple of reasons. One, they have a short gestation period of around three months. And so the pig organs can be produced relatively quickly. Their genomes are easier to manipulate than some others because we have the existing technology that allows us to do so, which is called CRISPR Cas9 gene editing technology. And for lack of a better explanation, it acts as a pair of scissors with paste where you can cut out portions of the existing pig genome and add in portions that you would like in order to produce a viable genetically altered organ that could evade the immune system of a human. And then the last piece is I would say just from an ethical and public perception standpoint, pigs are a generally well-accepted source of meat, you know, and for better or worse, people are certainly a lot more comfortable with the idea of utilizing organs for transplantation from pigs as opposed to, say, a non-human primate, um, you know, of which a great example would be back in 1983, not too far down the road from CHLA, Dr. Leonard Bailey transplanted a baboon heart into a baby. Worked initially, but um, but we were really at the forefront of transplantation at that period of time. And so they lacked a lot of the technology that would have been helpful to make something like that successful. And so, really, for that reason, pigs have become a preferred primary source of the companies as well as investigators seeking out to explore xenotransplantation once again in humans.
SPEAKER_03This is fascinating. I had no idea we were so close to such a milestone in human evolution to a certain degree or human growth and thriving. It's uh it's impressive, and it's very impressive that you are at the forefront of this work in pediatrics.
SPEAKER_01I've devoted my life that we face in the world of congenital heart care. A lot of the initial problems, you know, children used to die with very simple congenital heart diseases, uh, which happens to be the most common birth defect in the world. And I would say children around the world are still dying uh from simple congenital heart diseases. But here in the United States, we've altered the paradigm so drastically to the point where we're now having to try to come up with solutions to problems that they've created out of our own success. We're keeping kids alive who we never used to keep alive. And we owe it to their families and to those children themselves to continue to seek out the next iteration of answers that are going to make their quality of life better, but also to not lead them down blind alleys, alleys that end in a life that is not high quality and limited in its quantity because we don't have good transplantation solutions. And so I don't know xenotransplantation is going to be the final answer for those children and their families, but at this point in time, it at least offers hope that we that doesn't exist in this moment in time. Because what really initiated the work for both my dad and I is we just got tired of watching kids languish in the ICU and eventually die because a human heart couldn't be found. And we knew at the first moment when that child got sick, that was likely going to be the end. And it's it's just a terrible place to sit and watch the families hold on to hope that you know is founded in such a low percentage of being actually realized. At this moment in time, as a practitioner actively involved in the care of kids with congenital heart disease, I see no greater way to offer them hope than something as transformative, although it sounds crazy, as these genetically modified big organs and xenotransplantation.
SPEAKER_03We call this show a dose of optimism. I can't think of a better way to capture that sentiment than thinking about how this type of solution could help so many kids that are in the ICU or waiting unsuccessfully right now for a transplant at least have something. It may not be the perfect end solution, but it's it's something that can prolong and perhaps improve their life. My last question is how far do you think we are from seeing the first perhaps heart transplant in a child?
SPEAKER_01Well, I've been through different iterations and it's been a roller coaster along the way. We are in the process of validating what we do believe to be the right combination of genetic edits within the pig, the right immunosuppression regimen, and the right care protocol. And if those all check out in this current iteration of validation, I personally believe that we are within, you know, one to two years of seeing this applied in a hospital center because the need is so great and enough children are dying at this point in time. We really just don't have many other options other than to try.
SPEAKER_03Well, I look forward to that day. Dr. Cleveland, thank you so much for joining us and sharing your impressive work that you and your dad have done to really further the science and the hope of kids, hopefully around the world.
SPEAKER_01I appreciate the opportunity to share what we're doing. Yeah, I think it is important work. I think it's an opportunity to change paradigms, which we've gone comfortable on at this point in time. And I think that it's important to recognize how a place like CH Galais is targeting to make the lives of children better through research and advancement, uh, as opposed to just sort of getting comfortable uh in one specific place.
SPEAKER_03All right, thank you for joining us for your dose of optimism. Make sure to check out our show notes to get more information about our guests and the work they're doing. Visit our podcast page on the Kids X website to join our podcast community and to learn more about pediatric innovation. Thank you to our sponsors and to our presenting partner, Kids X. Please subscribe wherever you get your podcasts. And remember, it takes a village to make sure our kids grow into healthy adults. So volunteer at your local library, help out at the community center, and if you're so inspired, donate to your local children's hospital. Alright, see you next time. The content, views, opinions, and information presented on this podcast do not reflect the views of Children's Hospital Los Angeles or of the sponsors of the podcast.