Episode Transcript
00:00:00
(Music up and under)
00:00:03
Host: Hello and welcome to this edition of Cook Children's Doc Talk. It's a very busy day here in the Child Life Zone at Cook Children's, so you may hear a little background noise. Research isn't new to Cook Children's, in fact, since its very beginnings to now, research has been one of the pillars of pediatric medicine, and today, there are over 400 active research projects focusing on childhood diseases and developing better therapies and treatment options, including some really profound medical breakthroughs. But in many ways, this research may be one of the best kept secrets in pediatrics, including the expansion of the research program and what it means for the medical world and, more importantly, for kids, teens, families and communities.
00:00:50
Host: Before we get started, let me introduce our guest, who is here to talk to us about the vision of pediatric research at Cook Children's. Dr. William Stigall, Vice President and Chief Research Officer at Cook Children's, is also a pediatric intensivist and bioethicist. Dr. Stigall earned a BA in business honors at the University of Texas at Austin, followed by earning his medical degree at UT Southwestern in Dallas, where he also completed his residency in pediatrics and a fellowship in pediatric critical care. He went on to complete an additional fellowship in pediatric cardiac critical care at St. Joseph's Hospital in Phoenix. As if that wasn't impressive enough, Dr. Stigall obtained a master's in philosophy from the University of Dallas during residency and fellowship. At Cook Children's he serves as an attending physician in the pediatric intensive care unit. Dr. Stigall has also served as physician advisor for the utilization review department and Medical Director of the Human Research Protection Program.
001:55
Host: In 2022 he assumed the role of Chief Research Officer following the retirement of the founding Chief Research Officer, Dr. James Marshall. Dr. Stigall is currently a faculty member of both TCU School of Medicine and the University of Dallas. He's published and spoken nationally on the philosophy of medicine, bioethics and mind body interaction, among other topics.
00:02:19
Host: Welcome, Dr. Stigall
00:02:21
Dr. William Stigall: Thank you.
00:02:22
Host: Dr. Stigall, let's begin with an overview of research at Cook Children's, where it started, where it is and where it's headed. What's the plan?
00:02:30
Dr. William Stigall: Cook Children's Research is a bit of a gem. We are getting better at understanding who we are and getting the word out on campus. We're getting better at getting the word out in the country, but we're still a bit under the cover.
So, Cook Children's Research starts about 20 years ago, and the whole story is a metaphor for where we're at now, where we're going. Cook Children’s is a large, free-standing children's hospital, it's one of the largest in the country. We may be the largest integrated health care system in the country. And if you do all that, then you're gonna see everything. You're gonna have lots of clients. Lots of clinical patients come in. You're gonna have a variety of patients. Rare disease won't be that rare when you're doing it at the scale we're doing. So, all of that was true 20 years ago as well.
So, to do the kind of clinical care we do, you have to do research, and the most obvious place for that to start is oncology. So, if you're gonna be a free-standing children's hospital, see everything, take care of all the people we take care of, you have to do oncology. And oncology is the most forward facing about research in pediatrics. Effectively, standard of care is research. So, Cook Children's Research, then, starts in oncology. So, we have these oncologists who are doing really amazing things. We are seeing all these patients. We start doing oncology trials. We started organizing that about 20 years ago into a centralized research office called the Research Administration Organization. It then blows up from there. So just like oncology requires research to do at the scale and the scope and the expertise that we have, other programs also need this same thing. So, neurology, endocrinology, hematology, all of these departments have the same sort of outward facing that they take care of everything. They have a really broad spectrum, but then they have a very deep spectrum as well, because they see rare diseases.
So fast forward all of that current state Cook Children's research, we have about 500 trials, studies open at any one time during a year. This is increasing every year. The majority of what we do is non-oncology work, but the biggest department of what we do is oncology. So, oncology is where we start. Oncology still has the most, but we actually do more research outside of oncology now than we do inside oncology. We have about 180 employees who are full time dedicated to research at Cook Children's. We have the full gamut of research. We do late phase clinical trials, so think all encompassing chemotherapy trials for leukemia, for example, we have the Children's Oncology Group, it's the largest consortium for children's oncology in the country. We're a member of COG. And then the other big player in children's oncology as a consortium is the St. Jude's network. We are actually the first non-St Jude's hospital as a partner to St. Jude's on their trials. So, we have this full gamut of late phase clinical trials, right? Then, late phase clinical trials are large trials that have been proven to be safe in early phases, and they're now being tested for efficacy in later phases. So, to prove something's safe, you just need smaller trials, smaller numbers, smaller time frames to prove something that's efficacious, and you need much bigger numbers. So late-phase clinical trials are the last part before a drug gets approved. It has to go through these trials. So, we do all that, then we have backed that down to now we're doing earlier and earlier phase clinical trials. Some of the trials we do are first in human trials, so first in the world for gene therapy, for genetic epilepsy. That's amazing.
Then we have another side of things. That's what we call sponsored trials, where an industry sponsor, a pharmaceutical company or a device manufacturer, they're wanting to try something out, and so we run their trial, then we have investigator-initiated work. In that world, that's where clinicians, scientists here, come up with the idea. And then we do those studies or trials. And then the last side of things we do now we're a non-academic medical center, meaning we don't have a pediatric residency, we don't have a partnership with a medical school that we were sharing, logos, that kind of thing. I'm sure we'll get into this in a little bit, but we're not a traditional academic medical center. But yet, now we have two arms that look a lot like an academic medical science wing in neurosciences and then in precision medicine.
00:06:47
Host: So, while not attached to an academic medical center, Cook Children's is very active in research and clinical trials, working with multiple universities on research, as well as other research organizations like, as you mentioned, COG and also NANT, for example. So does this provide for unique opportunities and, or advantages to improve care and advance outcomes for pediatric patients? And if so, how so?
00:07:11
Dr. William Stigall: Oh, absolutely. This is one of the things I'm most excited about with research at Cook Children's, is that we are not the same. When I first took over this position, I actually spent a decent amount of time looking for our peers, trying to find other institutions who are built like us. And the short version of that answer, that quest, is like, there's no one who's built like us, and I've looked quite a bit. We do have cousins. So, we don't have any brothers, but we do have some cousins out there who look somewhat similar. One of the metaphors I use is that the normal world out there, all the other pediatric hospital systems, the vast majority of them are attached to an academic medical center. And there are a couple that are not either fully attached or loosely attached, like us. No one exactly like us. So, I tell people that we're Australia, and I found a New Zealand. The advantage, I think, is at an academic medical center, this is in the literature, they've been talking about it for about it for about 30 years. It's called the three-legged stool problem. And the three-legged stool of an academic medical center is that you have to provide care, so you've got clinical responsibilities. Then as an academic medical center, you have trainees, so you have academic responsibilities. You have responsibilities to raise up the next generation of physicians, nurses, nurse practitioners, et cetera, et cetera. Then you have research responsibilities, because lots of times, most of your money comes to these research grants, right? So those are three related, but not necessarily the same priorities. And so, in the academic world, this three-legged stool is ... how they sort of work their way around this, is that, well, they're all important, right? And so, if one of those legs, that stool isn't as long as the other, you know, wonky build. So, this is a real problem for a traditional academic medical center. It's like, how do you do that? How do you prioritize clinical care, training and research?
So, the Cook Children's build, we're not a one-legged stool. I guess we're a cylinder. We have one base, and that base is clinical care. I love Cook Children's, the Promise is amazing to me. I mean, just everything for the child. That's a lodestar that can get you centered, and you know where you're headed if you just keep that in mind. So then, the Cook Children's build, then is everything for the child, which primarily, functionally means clinical care. We want to offer the best clinical care for a child, and that's why I actually came to Cook Children's in the first place, because I'm a pediatric intensivist, and this is one of the only places in the country that is this big, this bold, this deep, does all the things and has one mission, and that is the clinical care of that child. So then, research, see the previous question around, well, you're gonna do everything to the child for oncology, you have to do research. And then multiply that by 20 years, that inclined plane ends up all the research we do is child facing. That's really helpful. I tell people that we'll never have fruit flies on campus. At academic medical centers, you need fruit flies, and you need to be really, really interested in the electron transport chain and how mitochondria work, right? For its own sake, at Cook Children's, the research we're doing, okay, fine, if understanding the mitochondria is important for this kid, then we may be engaged in that kind of research, right?
That's super focusing. And I think whatever your political persuasion, the buffets that are happening right now with the NIH, with Department of Health and Human Services with funding of research, that's evidence that the system is a bit creaky. That there's inefficiencies in the system. That the system's got multiple priorities. It's incentivized in different ways, and I think that's what's happening. And we are totally built different. We're not at risk for getting off center on our mission, because it's everything for the child. That said, to do what we do, we need fruit flies.
When I first came up with this metaphor that we're gonna have fruit flies on campus, I was roaming the halls, and I went up to the neurology clinic, and there's a physician up there, Dr. Dave Shahani, and Dave is an amazing physician, super, super bright, and lots and lots of fun conversations with Dr. Shahani. So, I'm going up there, and I'm actually talking to one of our collaborating universities, and they're interested in studying some of our problems, right? So, we have kids with genetic diseases. These genetic diseases, when you send off their genome, many times, you'll find they've got a part of their genome that's abnormal. So, we know that that's abnormal. Then they have parts of their genome, which are called variants of unknown, significance, VUS, and so this is the real work of, okay, this doesn't look normal, but we don't know if it's abnormal. We don't know if it's a problem. And so, then you got to go work out. Well, that's nowhere near the kids’ symptoms, and so that's probably not relevant. Well, actually, that's in a protein that may be involved in something, right? So, you sort of have to sort of work out, does this variant matter?
So, one of the ways you do that is you go build fruit fly models. And so, there's universities then who are looking for clinical problems to solve, right? They're interested in genomes in general. They're interested in models of health and disease. And wouldn't it be great if they actually had, like, clinical problem to solve? I was talking to Dr. Shahani, and I was telling him that, you know, we're dealing with these other universities, and what we're probably end up doing there is looking at genetic sequences, and we got these variants, and then we'll tell them, hey, go look over here. And he goes, I need that today. So, as we started talking about it, he had a child he was taken care of, who had one of these variants, and the variant was unknown, and it was gonna affect some sort of protein that was probably involved in this child's seizures. And the problem was, he doesn't know if this variant makes the protein more active or less active, and if it's more active he would do one drug, and if it's less active he would do another drug. And so even as I made this thing up, we're never gonna have fruit flies on campus, which I still don't think we're still don't think we're gonna have fruit flies on campus. We'll leave that to universities to have fruit flies, but we need to be in touch with people who can do this kind of testing. That's one of the super exciting things that's coming is because we say, "everything for the child," now, we're in this world where we need advanced AI computational biology. Like we need to understand how to build out 3D structures of the genome of the proteins of the cells to understand, okay, what exactly is going on there so that we can treat this child. It's sort of a crazy world we're in, but it's super exciting, and Cook Children's is very well positioned for all of this.
00:13:19
Host: You've described research at Cook Children's as pioneering with innovation being a key value. Can you elaborate on that?
00:13:28
Dr. William Stigall: I'm from Houston and Austin, and I married a girl from Fort Worth, and I didn't realize Dallas Fort Worth, being from Houston and Austin, it was kind of one place. It was North Texas. So, then I come up here to medical school, and that was my first real time in Dallas. So, I went to UT Southwestern, did all my training over at Southwestern, and met my wife when I was in medical school, and she was over here in Fort Worth. And that's when I first was exposed to Fort Worth's, not Dallas, Dallas', not Fort Worth. So, if you look at the history of Dallas/Fort Worth, we really are built different. The city's logo is "Fort Worth, where the West begins." And that is an absolute truth. You can actually see it from space. So, if you look at it from space, the topography, the population, the world, looks different west of here than it does east of here. There's something like, twice as much rain falls 100 miles east as 100 miles west of Fort Worth. That's the 90th parallel. It goes all the way up the country. And the West really does begin here. So this pioneering spirit that started Fort Worth, it's still here. And I think that metaphor for me has been super helpful to understand why we look like we look, where we're positioned current state, and then, what's our value add? There's a real difference that we have, and I think at least some of it comes in the fact that, like, we really are still pioneers. We're still on the edge of the West.
00:16:14
Dr. William Stigall: Just one example of that from space. The reason why you can see it's not just the topography, it's the lights. So if you get like, a nighttime image the United States, you can see where Fort Worth is. It's at the start of the black. So east of us, it's. Lit up, and then west of us, it's pockets of lights. And so Fort Worth really does stand on this western face. And then that means that we take care of a bunch of children, right? But some of the children we take care of are six hours away, and they consider us home. I mean, six hours away in Boston is Philadelphia. These are just very different worlds. So I think that spirit is why people are attracted to Fort Worth generally, but I think it's also why you're attracted to Cook Children's is that when you come here, we are this giant outpost that we can do all the things, but we are right up on the edge, and we're gonna be taking all the things that come from everywhere, and we need to be prepared to take that, to care for those children. So I'm just gonna keep doubling and tripling down on this metaphor, because I think it really is ... in the pioneer world, you're not going to do research for research’s sake, right? You're not going to look up in the stars and just wonder and drive down lanes where it's not actually going to do you any good. In the pioneer world, everything you do needs to be productive. Everything you do needs to have a purpose. And that's everything for the child. That the research we're doing here is pioneering, it is innovative, it is radical, but it's so mission centric that it's going only to be used for the good of the child, not the good of publication, not the good of training, not the good of grant money from the federal government. Those are all great. We love grant money from the federal government. We love publication. Government. We love publications, but the primary mission is for the child, which then means you'll take some risks. You'll be innovative, if the risk benefit ratio works, and we're going to be super safe, and we're going to be super thoughtful, but we're built so that we can handle all those things, because we have this pioneering spirit, because we are so mission centric.
00:16:43
Host: It wasn't that long ago that getting proven research from bench to bedside took about 20 years. Today, the last I read, it's about seven years making treatment and positive outcomes much more rapid. Can you take us through how that opens up the possibilities for more advanced research and results here at Cook Children's?
00:17:02
Dr. William Stigall: I remember where I was when I heard that statistic in training. That was a very radical statistic. Scales fell from my eyes, you know, sort of how does that happen? So if you think about how it happened, why would it take 20 years? And what that statistic was, it takes 20 years from proving an intervention works to the state where over half of clinicians and patients got that proven intervention. And so you start walking that back. Well, why did it take so long? Well, maybe it was published in a paper journal that wasn't one of the top tier journals. So you can imagine how long it would just take to diffuse through people writing each other letters, people talking about it. And this 20 years ago thing is not that long ago. Literally, it's 20 years ago that statistic was still valid. And then you imagine what's happened last 20 years right? The Internet, we're much more connected. We're doing much more research at much more scale now than we were 20 years ago. So now that number is about seven. So seven years for it to sort of diffuse enough that over half of clinicians are doing it and over half of patients are getting it. That's a world of difference. 20 years is about two thirds or half of a career, if you sort of think about what's the longevity of a doctor or a nurse. And so what that could mean then is you could graduate medical school, nursing school and training, and then as long as you did the same thing at the same level, which was hopefully at, you know, a high level when you graduated, if you did no changes, then you're not really at a date right until about 20 years later, which means now you're at the average. And then by the time you retire, 40 years now, you've gotten to below average if you're just using the same things you did 40 years ago, right? It's not optimal, but it's not a terribly awful system, if you sort of think about all of the complexities, right? And it's not like we're throwing out everything every five years.
00:18:53
Dr. William Stigall: There's good stuff we learned 15 years ago, good stuff we learned 30 years ago that's still applicable right? Now, though, it's a much more rapid cycle, and so if you only do what you learned as best of class, you're the highest performer when you finish your training. Now you're average, you're 50th percentile in seven years, and then if you still don't change now, in another seven years, you're at the worst percentiles, right? So now you're just 15 years into your career, and you're one of the worst doctors. So that's all hypothetical, but you could imagine that's what that statistic really means, sort of at the population level. So then the answer is, you have to keep up. So that's one of the ways you keep up, is you do quality work, quality research, quality initiatives, and you take what's best practice and you apply it to your clinical practice. So that cycle, though, because it's moving so fast, because we're so big, because we're the edge of the West, because we're taking care of everybody, then Qi is not enough that we actually need to go solve problems that people haven't solved yet. And that's where research comes in. And, again, that's why I'm so excited about it, is that we have all of these possibilities. All this opportunity. And, then, now we live in this world ... the reason why that 20 has become a seven is all of the diffusion of information through the internet, all the diffusion of the information through artificial intelligence, all the diffusion of information now that we can build supercomputers that can model things like we never did before. So all that's now available, and we can then use all of that for the child in front of us.
00:20:25
Host: So what is Cook Children's mission, and what role does research play in fulfilling that mission? What challenges does that present, like maintaining the culture and balance that sort of academic side of things?
00:20:38
Dr. William Stigall: The Cook Children's mission is singular, right? It's everything for the child, and the Promise, knowing every child's life is sacred. That's a powerful pull, that we're planting a stake in the ground, that there's something really, really beautiful about what we're doing here, and because it's so powerful, then we're gonna do everything for it. So the mission is clear, and then now we have the opportunity, but we also have the challenge of, okay, if we're doing everything for the child? Now, everything is a lot bigger than it used to be 50 years ago, a lot bigger than used to be 100 years ago. And if we really are gonna do everything for the child, that means then we have to do research. But the “have to” is really “we get to” because we're built in such a way that we are so focused that we can do this safely. We can do this with the best of getting you what's next without harming you. But it's also this is the research role. This is why it's regulated.
00:21:35
Dr. William Stigall: This is why we have special ethics panels that oversee us. Is that it's risky, and we mitigate all those risks as much as possible. But when you're in a situation where you don't have a good option, then for sure, if you had great options that will completely solve your problem, you should do that. And then if there's a couple of choices you should make, then you should do the quality improvement to like, “Okay, we're gonna try this. We're gonna try that.” But if you're really in a situation where we don't know if this is a better option than not. That's where Cook Children's is really well set up, that we can do that safely. We can do that with oversight. We can do that cleanly, and then answer those questions while being focused on this child in front of us.
00:22:16
Host: As the research opportunities grow at Cook Children's, do you see an opportunity to attract some of the top, up and coming talent. And how can that compete with academia? And how does this give Cook Children's an edge in attracting some of the more brilliant minds who are currently active in pediatric research?
00:22:33
Dr. William Stigall: Not only do I see the opportunity, we've already done that. So, current state, Cook Children's is some of the best in the world at a couple of things. So probably the most forward facing of what we're doing here on the edge of research and clinical care is in our neurology program. So, in the neurosciences, we have built out a clinical trials machine. So we are doing late phase clinical trials. We're doing early phase clinical trials. We're doing first in human trials, gene therapy for genetic epilepsies. Then we've got a built-out investigator initiated side. We're doing very interesting things with registries, with studies, but also interventional trials that are homegrown, built out from Cook clinicians, Cook scientists. Then about five years ago now, we recruited a neuroscientist named Christos Papadelis. And Christos is an amazing, amazing scientist, one of the smartest people you'll ever meet. He's an electrical engineer, but he has this mind that can see the electrical engineering of the brain. And we recruited him down about five years ago, and it's just one success story after another.
00:23:36
Dr. William Stigall: We recently announced the neuroscience research expansion to where Christos went from having him being the lead investigator of a group and then having a bunch of other sub-investigators with him, post-doctoral students, PhD students, research assistants. Now we're giving Christos three wings of scientists. So we're expanding into movement disorders. We're expanding into behavioral disorders, and then we're going to get Christos more help in epilepsy, which is his focus. So Christos is a big deal. The colloquialism on academic medical centers is Christos is a whale. Christos is a big deal on any campus. And honestly, we're one of the best in the world right now at neuroimaging for difficult epilepsy.
So if you've got a hard-to-treat epilepsy, drug resistant epilepsy, genetic epilepsy, Cook Children's is one of the best places on the planet to go figure that out. And a lot of that has to do with Christos, but it mostly has to do with the relationship between our science or academic science program, Christos, and the investigator-initiated things we're doing, and the sponsored trial work we're doing. So it's the whole ecosystem. It is why we're so good there. So Christos came, and when Christos left his academic environment, there were some of his partners, peers, mentors, who said, See you later. Your career is over. You can imagine this is the whole Wild West metaphor. Probably there were people back east saying, “we'll never see you again.” “You're gonna go die on the west.” And then people came out here and they became cattle barons, or they came out here and they became oil barons. There is so much to do out here that if you've got the right mentality, you can really succeed. I think Christos would say this, that he is more successful here than he would have been there and he'd be successful anywhere. Christos is a brilliant scientist. He'll be successful anywhere but because of the resources we have, because of the mission we have, because he's so focused on this translational work to figure out electrical engineering for a child, we are very successful. He is very successful, and we're now expanding those things.
00:25:35
Dr. William Stigall: We recently hired another scientist, a neurogeneticist. His name is Dennis Lal. You will be hearing about Dennis here very quickly. Dennis is another whale. He is a neurogeneticist. He's doing work in AI that is just amazing, and it totally fits mission. And what he's doing with AI is really understanding what you have. So he uses AI, it's called deep phenotyping, or high-fidelity phenotyping. Your genotype is your genome. So what are the A's and T's and C's that you have in your DNA? Right? Your phenotype is what that genotype thing gets translated into, into all your proteins, all your cells, all your tissues, and that's who you kind of are, right? You're your phenotype. So linking phenotype and genotype. So your phenotype is that you have a seizure, your genotype is that you've got this genetic predisposition to seizures, right?
You could have seizures, though, because you have traumatic brain injury, has nothing to do with your genome. Figuring out phenotypes and genotypes is super important, and that's precision medicine. Effectively, that's what the world's heading towards. What Dennis Lal does, he's had this career of doing is really getting at both sides of that equation. Really understand the genotype, being able to understand all these variants. You’re substituting a C for a T at this point will change the architecture of the DNA, which will then change the architecture of the RNA, which changes the architecture of the protein. He can computationally understand that better than anybody. Then he's got this other side where he takes in all of these phenotypic data points. So how old are you? What kind of movement disorder Do you have? What's your blood levels of sodium, potassium, right? So all these biomarkers, and then in a really high-fidelity way, so super, super accurate, sensitive, specific ways of matching these genotypes and phenotypes. Multiply that times some crazy German IQ and Dennis Lal is a really, really interesting guy who's coming to campus, and we're gonna about to do stuff that's gonna be a lot of fun. And again, all directed towards the kid. We're gonna have to have really built out AI architecture to be able to do all this work, and it's gonna be directly pointed backwards towards this child.
The most clinical example I can give of that is, say you have some rare epilepsy, and we sort of think about these rare epilepsies. I'm not a neurologist, and when I sort of 100,000 foot would think about it, well, okay, that's a child with a seizure disorder. You gotta lump it in this bucket of seizure disorder, right? And so the neurologists are all scoffing right now at this intensivist that's just way too big a bucket to lump these kids in. And so when you start looking in smaller and smaller buckets of those children, you actually realize you can have the same disease, and it has a spectrum of phenotypic presence. And so we sort of know this, that there's high cholesterol and there's high cholesterol that gives you a stroke, right? And there's being a little bit overweight, and then there's being so overweight that it affects every organ system.
00:28:17
Dr. William Stigall: So there's a spectrum of disease, even in these rare diseases. Now, because they're rare, we don't have a giant population that can show us all these things, but they still have a distribution of disease. So wouldn't it be great to be able to tell a parent that they've got this disease, and in the next six months, this is what that actually progresses to. And so in the next six months, we're going to work on this and this and this to try to get you the best outcome you can right? Current state, because things are rare, we don't have that kind of discrimination of progression of disease like we do for normal development. And that's one of the things that Lal is being brought in to do. It's hard to really quantify how powerful that would be for a parent to know that, ”I hear you right now that you're concerned about eating.” This is now a phase where, based on our models, it looks like we're gonna have a problem with sleeping, and so we need to really work on sleeping. "That kind of anticipatory guidance would be gold for parents, right? And then we're not just gonna anticipate things. We're actually gonna intervene. We're gonna intervene. We're gonna go fix some stuff. And this whole ecosystem now is being built up that it's a really amazing time and place to be in pediatric research.
00:29:32
Host: So what's the advantage to kids for this process versus the academic process, say, in terms of back to the speed of bench to bedside.
00:29:40
Dr. William Stigall: In the academic world, you absolutely need to be doing research for research sake. You need to be doing discovery basic science research. The problem with discovery basic science research is it may not have any kind of clinical applicability, that there's going to be stuff you discover that's interesting but not relevant. If you start from the other side of that, is everything for the child, then you work backwards. We're going to do clinical trials that we know have safety and we have hints of efficacy. And then you work backwards, okay, we're going to make sure this thing is safe, because we have preclinical work that says this probably is going to do something. Then you keep working that backwards, where you build out what we now are doing with the neurosciences and precision health, precision medicine. Because it's so mission focused, mission centric, you have much less risk of getting out on side trails ... that the trail you're on is headed towards something for the child. As I've been thinking about our special sauce, one of the aspects of our special sauce is it's not ... it's not really children in the abstract. It's not really like kids as a thing. It's the child. It is the child in your care is our focus. And you can imagine thinking about children in the abstract and getting into a theory 'of.' And the less grounded you are in the practical realities of the world, the more errors you can make, the more side quests you can go down. And because we're so specific about, 'it has to be directly relevant,' we're going to be much more likely to make impact today on children that we take care of.
00:31:16
Dr. William Stigall: You absolutely have to have the basic science research. You have to have the research for the research sake. That's just not going to be here. The good news is, and the other sort of interesting thing about what we're up to is, we are surrounded by people, by institutions that are very interested in research for research sake, but they're now also recognizing the power of this mission, and even large institutions that are in the research for research sakes business, they want to become more relevant. And so we are partnering with a number of institutions. We're not an academic medical center, meaning we don't have a strict relationship with one medical center. It's because we have relationships with four. We have four big institutions that we partner with and that kind of platform status, I think, also focuses right back to the child and that we're able to leverage these giant institutions who have a lot of resources, a lot of expertise, and then point that expertise towards our problems, our challenges, our opportunities. So you do need fruit flies, and they need to be off campus and let the fruit fly experts do that, but we can then provide them the problem to solve, and while they're in this basic science mode and discovery mode that's on their dime, that's on their pathways, that's with their resources, and we're talking collaborating, And then when it's actionable, then, which shifts over here. And we will then scale up those trials, give these interventions to children that we take care of. And then you can see the virtuous circle that would happen. Right as we solve one problem, we're going to uncover others. And so let's redo that whole circle and get it back to, "Okay, we've noticed this in the world of neurology, in the world of endocrinology, the world of oncology, academics go run and work out the basic structures of those things." And then now we're building out these science wings in research at Cook Children's, which will translate those things. And then those are our bridges to late phase clinical trials, early phase clinical trials.
00: 33:16
Host: So that kind of bridges into this next question, which is, while not part of a single academia and therefore not a teaching hospital Cook Children's does have relationships, as you mentioned, with universities, and in fact, many of the physicians and researchers, including yourself, hold faculty positions at nationally recognized universities with the same opportunities to participate in and even lead groundbreaking research and delivering groundbreaking treatments. Can you maybe talk a little about these relationships and how Cook Children's is collaborating?
00:33:48
Dr. William Stigall: If I had more time in my day to be sort of self-reflective, I would probably have a better answer. But I don't know what I am. So I'm a pediatric cardiac intensivist. I am a career student. I'm in my master's program right now, I teach at a university. I never want to stop going to school, but I don't consider myself an academic. I'm a professor at a university in the philosophy department, but I don't consider myself a teacher. At my heart, I'm a clinician, but then I've got all these other things that don't completely look like being a clinician, but I don't really have time in my day to, like, sort of figure that out. So I just keep moving forward. I think that's also Cook Children's, that we say we're not an academic institution, but now we're actually graduating PhDs.
So Christos Papadelis has been the mentor for several PhDs. There are students who have their doctoral degree. He's got an appointment at the University of Texas in Arlington. He's got a big program over there, there are now PhDs who did their PhD work at Cook Children's and they did their postdoctoral work at Cook Children's. So we're not a teaching institution, except there's PhDs who call us home, and then we're not a training institution either, right? Except there's trainees in surgery, there's trainees in neurology, there are trainees. And by trainees, what we're talking about there is resident doctors, and there are, but they're not Cook Children's pediatric residents. It's this world we have where there's so much interesting things going on people want to be here. I know of one surgical subspecialty where the surgical fellows from the highest ranked fellowship in this world come to Cook Children's to be next to our orthopedic surgeons. That's amazing. But we're not a training institution. So what are we then? Well, I think it's because we're so mission focused that we have to have these things. But that's not what our primary mission is, although they're some of the best in the world.
00:35:35
Dr. William Stigall: We're a clinical enterprise that's totally focused on the child. It just so happens to be at our scale, scope, size, breadth, you have to have research. You're gonna want ... trainees are gonna wanna swim around. So what that then means in the research side is we have a partnership with the University of Texas at Arlington for Christos to have his academic home. He needs an academic appointment, and he needs an academic home for all of the academic programs he's got going. It's very much an academic exercise, but again, directed towards our children's problem sets. UTA is a really interesting place. It also sort of is under the radar. UTA is the second largest of the University of Texas System schools. There's 45,000 students over there, about 10- or 15,000 grad students, and some of their best work that's happening right now is in the neurosciences, and what I mean by that is Christos Papadelis, so they're doing all sorts of good things. Clearly, I'm biased. I love what Christos is up to, but Christos has now a whole wing of postdoctoral fellows that he's training up mentoring. He's got PhD students, he's got research assistants, he's got master's level students that he is training all up pointing them towards these clinical problems that he's solving for our neurology patients. Then UTA, because of the success of all of this, has now formed what's called the Pediatric Brain Health Institute. They have recognized how important all this work is, and they've recognized how powerful all this work is, to have this clinical partner giving them these clinical problem sets, and then they're now solving them with their academic focus. So the Pediatric Brain Health Institute is a really, really interesting concept.
The University of Texas Arlington is an R1 university, which is the highest tier of research universities in the United States, and they're pointing their neurosciences towards pediatric brain health. Again, if I had time to sort of bask in how cool all that was, I would know how many others there were out there. I suspect there's none. I think UTA is the only R1 university that's got a pediatric brain health institute built into it, and that's right down the street, and that's because of Cook Children's and what we're doing over here. The expansion that we've announced earlier last year for the neurosciences now gives Christos three wings of professors. We're gonna be ramping this up in the next five years to where we have people coming in who are not just being mentored by Christos, but then to have their own career trajectories. And so Christos will be running this. He's now our executive scientist of the neuroscience research program, and he'll have help in epilepsy. He'll have professor line in movement disorders and a professor line in behavior disorders. This is going to be amazing. The idea is that we accomplish as much in those areas that we've accomplished in epilepsy, and the direct benefits for the children we care for are going to be significant.
00:38:22
Dr. William Stigall: We've also just announced that Dennis Lal will also have a UTA side, so he is going to be wholly supported at Cook Children's. But he also will have three Professor lines, two of them in AI, and he'll have PhD students, research assistants, post-doctoral fellows, all working in his center. It's going to be called the pediatric precision health institute at the University of Texas Arlington. They're giving him oversight access to their Center for Healthcare Informatics. There's like 5,000 computer scientists, students that are at UTA and imagine that kind of horsepower directed towards a Cook Children's challenge, and he's also gonna have helping run the North Texas Genome Center at University of Texas Arlington. It's got two of the fastest genome sequencers in the world are at UTA.
We are in this bubbling ecosystem of really good things about to happen, and we haven't even talked about Texas A&M. So Texas A&M has also discovered Fort Worth. They're about capped out on their first building downtown. They're establishing a campus called Texas A&M Fort Worth. And they asked when they came into town, what do you need? One of the metaphors I use for describing when I first heard about a and m coming to town was that's a battleship that just rolled into port, and that is a large, large ship. I've been corrected that it's not really a battleship. It's like a ship of mercy. That's probably a better image. But whatever it is, it's a large vessel, and it's going into our port. And when large vessels dock, it's big waves, so even if they're friendly, stuff rumbles. So A&M's come to town. A&M has discovered us. We've discovered them, and we've got all kinds of interesting ideas that are bubbling up with the A&M system. A&M is a giant system. They have resources that are almost unmatched. They're in the top 10 of government funding. A lot of their research funding comes from the NIH, but a lot of it comes from other federal agencies. It's hard to describe how big A&M is, and now their most advanced, sort of forward-thinking campus is now plopped into town, and very much, Cook Children's is in their focus, and they're in ours. The small version of this is we need to have their medical students come in and do research training. So train them in the ways we do research at Cook Children's. There's plenty of opportunities. On the research side, we've also discovered that they've got basic researchers, translational researchers, which are very much interested in lots of things that we're doing. We're still in the dating phase where we're discovering, "Wow, I didn't know you liked that. That's interesting."
00:40:51
Dr. William Stigall: And so lots and lots of bubbling up. One of the things I'm most excited about is a biorepository. When you're doing all this research, wouldn't it be great to save some of this tissue, whatever it is, skin or intestine or lung or brain when you're doing all these procedures. Wouldn't it be great to be able to save some of that for later? Because technology advances and we may know stuff five years from now, we don't know now. And wouldn't it be great if we could save some of that to go test it again? We have the workings of a small biorepository here for a couple of different clinical trials, but nothing to the scale that we could really do given how big we are. So, we're talking to Texas A&M about those. Imagine an Aggie sized biorepository with a Cook Children's size program that helps feed that, matched with the oncology research we're doing, the endocrinology research we're doing, the precision medicine research we're doing, it could be an amazing thing. And again, it's this "little Cook Children's," "little old Fort Worth," except there's a million people in Fort Worth; except we're one of the largest integrated healthcare systems in the country for pediatrics. And I think it's just this pioneering spirit that we have. We've got this problem set that is vast, this opportunity that is just vast, and we are built for that. I really enjoy this because I don't get a lot of time to bask in how amazing all this is, because there's so much work to do. Most of the time my head's down, and we're just getting the work done. But I think we really are in a really, really special place.
00:42:15
Host I'm going to go back just a little bit. So, you've called to work here pioneering, and you've just given us a great example of that. And for me, I think about, going back to Dr Papadelis, the neuro research team has developed an AI tool that is life altering for a child with medicine resistant epilepsy. This tool can map the brain of a child to pinpoint exactly where the seizure is occurring, making a surgical treatment less risky and potentially being curative. So, these are the kinds of life changing results for kids that you're talking about, and not only in neuro research, but demonstrates the capabilities of Cook Children's across the spectrum of pediatric research. Is there anything more you wanted to add to that, based on what we just talked about that would impact kiddos, not only here in North Texas, but even maybe around the globe with our international program?
00:43:08
Dr. William Stigall: I'm a card-carrying nerd, and fully okay with that, I will attempt not to nerd out too much. The more I learn about what Christos is doing and how he does it, it is so amazing and so interesting, and so interesting, and then so impactful. Christos electrical engineer. That means he understands electricity and magnets better than almost anybody. He's our electrical engineer, and he is focused on the electrical systems in the brain. So, what Christos does is multimodal neuroimaging. What that means is like multimodal different ways of neuroimaging, so different ways of looking at the brain and the brain architecture. He uses a handful of techniques. He uses functional MRI. He uses eight high-definition EEG, so electrical encephalograms is where they put the electrodes on your head to look for seizures. Normally, you've got 20-30 of those electrodes on your head at any one time. Christos does HD EEG, high dense EEG. It can have 200, 250 of these signals. So, you get much more sensitive signals. Then he uses the MEG magnetoencephalogram.
This is for the other card-carrying nerds. You'll remember in physics that electricity runs in run direction and creates a magnetic field orthogonally to … that 90 degrees from it. So every time you have electrical signal, you have electrical signal, you actually have a magnetic signal as well. This is one of the ways alternators work. You can create electricity from magnets. So then you can actually measure things. So, you can imagine electrical signals in your brain. They're going to create these magnetic signals. That's what a MEG does. A magnetic encephalogram measures magnetic signals from the electrical work that's going on the brain. The last thing it does is called transcranial magnetic stimulation, TMS, which actually induces a magnetic field, and then see what happens electricity. So, you combine all that, all that stuff by itself is crazy complicated, and interpreting all those signals is its own thing. Christo says, "Well, that's, you know, yes, it's hard, and yes, it's complicated, but I want to do it four times over. I want to do all that together." And so, that's his special sauce, is he puts all of that together and then gets these different views of the one thing that's happening. So what he's done up to now, prior to the AI work, was raw computation, super smart dude, doing lots and lots of formulas, right, and trying to put all that together and figure out, "Okay, what does that signal mean compared to that signal?" And then when you do all that together, then that's one of the reasons why we're one of the best in the world right now at being able to tell where exactly your epilepsy comes from.
00:45:28
Dr. William Stigall: Some of this epilepsy you're well controlled with a single drug and we'll get you on the minimum dose possible, and the least interference with your life. And that's great. But then there's many children who have what's called drug resistant epilepsy, Multiple drugs, years of trying different drugs, lots and lots of seizures. And one of the outcomes for them is, okay, you need to go and just take out that part of the brain that is causing all those problems. And so, there's a couple ways of doing that. Surgery is one way of doing it. You literally open up the brain, and you take out the diseased portion of the brain that's causing all the seizures, because the seizures are so bad, because the treatments are so bad, you actually physically excise it. Another way of doing that is laser ablation, where you actually just take a laser and you heat it to where you kill that part, that's the disease part. Or you can do cryotherapy, where you're freezing it to death. So you can imagine, if you're taking those radical steps, then you would want to be exact where you're going to go. There's lots and lots of expensive architecture and real estate in your brain, and you want to know where exactly you're going, where exactly the seizure is coming from. The work Christos has done then, he's now shown that he is really, really accurate about being able to predict where those seizures are coming from. What he's now doing with AI is now leveraging artificial intelligence to help make these predictions, using all the data points that are coming in, looking for data that you can't see with the eye, that you can't see with your normal sort of computation, and then using that to predict where these seizures are coming from. The ability to offer a child a minimal intervention for a maximal response is amazing. You can imagine, if you're in that world of drug resistance to epilepsy, your child may seize 100 times a day, and the decision a parent would have to go through to say, "You know what, it's worth doing surgery to stop that, because the seizures are so bad, the number of drugs they're on is so life altering." Then if you were able to get this hope, we're some of the best in the world at preventing taking out things that don't need to be taken out. That's so hope-filled.
00:47:44
Host: That's amazing. That's one of the great things that I'm always every time we do these is like, as you mentioned, it's like the focus is always ultimately on that child and being able to relate to this is what a parent's going through. This is what the child is going through to really connect with that, which then drives everything that we do, including the research. I think in a different way, there's a clinical side to it, but there's a very human side to it.
00:48:10
Dr. William Stigall: Absolutely, I think that's the mission centric approach. And the academic world has that. I mean, the reason why you're an academic scientist working on this is because you do have some clinical problem you want to solve, but it's just you're torn in a couple directions, and that is great. America's research and science is the best in the world for a good reason, but what we're doing is this really, really special version of all that. And I think the time and space and place we're in, we're in a different world than we were 30 years ago. And there's a reason why all this is bubbling up and is so successful current-state, and why the vision is even bigger and broader, is because all these things have kind of converged, that we're exactly where we need to be. And the beauty of that is that our patients are gonna be the most benefited from this,
00:49:00
Host: And not just here in the area, but ultimately, I think I do see this as an international impact.
00:49:07
Dr. William Stigall: Absolutely an example of that is outside the neuro world on a GI world, because we're so big, we have such a broad base. There was a drug that was approved last year, the year before, for eosinophilic esophagitis. So this is an allergic inflammation of your esophagus. And you can imagine having inflammation in your esophagus can be a real problem. So children who have this failure to thrive, they can't eat, they have pain. It's got a whole spectrum where some of it's not that hard to treat. You put them on an anti-inflammatory diet or an anti-inflammatory medicine. But you can imagine there are going to be children who have very resistant disease, right? So we were part of a trial for a drug, monoclonal antibody directed at eosinophilic esophagitis, and we were the largest enroller in the trial in the world. And so just play that out. What that means is one because it's a trial now we're giving drug to children who didn't have that drug available. It's not FDA. Approved, you can only get on this research study. So now we're giving our children access to drugs before it's approved, and we are giving access to more children than any other center in the world did. And because the trial was successful in large degree, because of what we did, then that drug is now approved, and now it's available to everybody. And so even though the child in Florida who's now on this drug didn't come to us to get it, it's in part because of us that they can get that drug. And then you just keep playing those stories out that we do have, we have people come from all over the planet, all over the country, to come here for our clinical care we're doing, but also coming here for the research we're doing. I'm really, really interested in scaling all of that up.
00:50:40
Host: So obviously you'll continue to grow the specialty areas of research. But in an earlier conversation you and I had, you pointed out that there's an interest in urgent and primary care research, as well, and community health. So, Cook Children's is well situated for since as a healthcare system, these are all areas that already exist for us. Can you be more specific about what that entails?
00:51:05
Dr. William Stigall: One of my roles is to bring some structure and some strategy around the organic growth we've had so, so much of what we're doing now is a direct reflection of demands that we had oncology patients, and so we had to build out an oncology research structure, we have this big, bold, broad neurology patient population, and so we have to build out these neurology research centers. One of the things we're doing is going to make these implicit choices we've made explicit, and that now includes creation of research centers and so full-on, get a strategy for neurology, endocrinology, oncology, precision medicine, cardiology, build those things out because they are clear system strategies. And now we're going to have a research strategy that goes along with those things. Still do everything. Still do the organic approach. As patients need solutions. We will be there, and we will establish those trials, those studies. One of the things that we've looked at is, what does the Cook Children's system need? What do the Cook Children's patients need? And we are one of the largest community providers in the country. We're probably one of the largest community providers of pediatrics in the world and, current state, we're doing very little in research.
00:52:21
Dr. William Stigall: The scale of our system is amazing, and it's obvious that, wow, if we just did a little in the community health research world, we could do a lot of impact. So you can sort of see that there's opportunity everywhere. And one of my real problem sets, one of my real jobs, is okay, how to prioritize all these things and what order do we do them in? And so community health, for sure, is on the radar. For sure, we will be impactful, and we're working on establishing okay. What exactly does that mean? There's clinical trials that we can be doing out in the community. There are registries and population metrics we could do in the community. There's academic science work in community health that we could be doing, and that's all in the horizon of work in progress. The problem I have is that there's this wealth of opportunity, and we're taking advantage of all of the challenges that we can at the time, and then we're working on building out a map for okay, how do we start prioritizing and sequencing building up of all these research centers? Community health is absolutely on the radar.
00:53:22
Host: Looking ahead, taking all of this into account, what does the future of pediatric research look like, not only at Cook Children's, but globally?
00:53:32
Dr. William Stigall: The shortest answer for that is precision. That we're now in this world where we're going to be able to leverage so much technology, and not just treat you generally as a child with seizures or as a child with pneumonia, but we're gonna get very specific about , you're a child with pneumonia with this enzyme in your liver that makes you metabolize a drug faster or slower, and so we give you more or less of that drug. We do that a little already. We look at your weight in … in the medicine world, we say, you know, kids aren't just little adults. That's an axiom. In pediatrics, we actually recognize that an 80 pound 8-year-old is not the same thing as 150 pound 45-year-old, right? So in pediatrics, we weight-base things all the time. We also do things around body surface area for certain drugs, but those are really rough metrics for how to dose something, right? So what's available now? We're doing it. We have pharmacogenomics, where for certain subsets of patients that we're concerned about, we're running their genomes, looking at what variants they have in their enzymes that metabolize drug, and then we'll tell you that you're going to be an under responder and over responder. You should avoid this drug. You should use this drug. So we're doing that already in selected cases, hundreds of kids.
The future is going to be all the kids. We are absolutely going to be leveraging this kind of precision in every child. What I tell people is that precision medicine will just be called medicine in 10 years. So, that's the kind of short version. It's precision. But that also means not just precision drug, but it's precision interventions, precision guidance, precision treatments, that we are going to be better able to predict how this is going to affect you, both the disease you have and the treatment we give you, we are going to be able to tailor things to you. We are now in a world where, literally, we can build a drug for your disease. So we're actually a part of one of these called an N-of-1 trial, where a child with genetic disorder has had a drug crafted for them, to treat them. And that's an amazing place to be.
00:55:40
Dr. William Stigall: We're gonna scale all of that, figure out ways of building platforms to do this to where not everyone needs their own drug built for them, but it could be better designed, better dosed, better treated. That's on the sort of medicine and the research component that will be bringing that, all that to the bedside, right? On the research side, I think what we're interested in is how to build these things out strategically, how to build out these things in a platform so that we can offer the same kind of precision, depth, breadth in neurology, endocrinology, oncology, hematology, gas, neurology.
Current state, we're built where we've got tremendous depth in some areas, and then next to that, not near as much depth. And one of the things we'll be doing with research is sort of leveling that if we can offer this kind of care in epilepsy and movement, then we need to be able to do it in behavior, and really get at understanding how the intricacies of these behavioral problems have phenotypes and genotypes, match those things, predict those things, treat those things. The recipe, I think, now, is clear, and now we're going to be applying that formula over and over. It's just a matter of time and resources and drive. The good thing is that Cook Children's is on mission, and we live in this world where all of these things would have been prohibitively expensive, taking prohibitively long amounts of time, and now we live in a world where it's just all scaled to where we can do this. The Human Genome Project is an example of that.
The Human Genome Project finalized, President Clinton said we did it, and I think that was 98 it kind of had a tail on it, because we didn't really quite do it. We did, like 95% of it. It's taken us, actually 20 years to finish up the final 5% but in general, we finished the human genome project around the year 2000 and we did it, and it cost us a billion dollars through that first genome, and it took 20 years. And then now you can do a human genome sequence ... there's the fastest of them are in hours, six hours, and the cost, the cheapest of them, is on the order of $1,500. Those log order differences are an amazing place to be. And the same thing with computers, and the same thing with AI, versus doing it by hand on a calculator. All of that is coming upon us. And the good news is, Cook Children's is really, really well positioned for all those things.
00:58:06
Host: Before we close is there anything we haven't touched on that you'd like to add?
00:58:13
Dr. William Stigall: Gratitude. This is all exciting, and it's a really special place. So I'm personally thankful that this is the best job I've ever had. I'm a card-carrying nerd, and this is the first job that has occupied everything of all my interests. So I'm personally grateful for this, but even more than personally, I think we all ought to reflect on how special this time and place is, and how special Cook Children's is that we're blessed with this opportunity. The world we're in and the impact we make is just, as a father, it hits home that we're in this really blessed, gifted, privileged place.
00:58:59
Host: That's fantastic. Dr Stigall, thank you so much for being here and taking the time to share the great research happening here in pediatrics and especially here at Cook Children's.
00:59:08
Dr. William Stigall: Thank you for having me. This was fantastic.
00:59:11
Host: And for our listeners, find more information on research and the Endowed Chair program at Cook Children’s dot org. You can also access clinical pathways on the health professionals section of the website. And while you're there, sign up for our Doc Talk newsletter. Want to hear more Doc Talk? Get our latest episodes delivered directly to your inbox when you subscribe to our Cook Children's Doc Talk podcast from your favorite podcast provider. And thank you for listening.
