C (2:29)

Well, it's horrible, Kathy, and it's completely needless. So the math there is. There's Tens of thousands of these diseases. Overwhelmingly, they're genetic. Overwhelmingly, they start in early childhood. But there are adults listening to this podcast who have one of these diseases, and they've never been diagnosed. And so the diagnostic odyssey is because in general, the medical profession is really bad at detecting these diseases. And so patients go their lives misdiagnosed as having a common condition, when actually they have a rare genetic disease that's masquerading as a common condition. And for a very few, 5%, maybe they actually will get a precise diagnosis. And it's life changing. Suddenly they have a label, they understand what's wrong with them, they understand why they've not been responding to therapies. And it's just the gate opening to a whole new way of getting what we call precision medicine.

A (3:39)

How's the landscape changed then, say, in the past 10 years or so for diagnosing rare conditions? I'm assuming it's changed dramatically, Dr. Thompson?

D (3:48)

Absolutely. So I started here at Mayo just a little over five years ago, and that's when I met Stephen Kingsmoor. And, you know, here in the nicu, we would go through stepwise genetic testing for patients. And so they would get one test, we wouldn't get an answer, they would get another test, we wouldn't get an answer. Sometimes they would go home without ever getting an answer and then go on to have that long diagnostic odyssey. Whereas now, and really five years ago, we started this. In our nicu, we send what we call rapid whole genome sequencing, one comprehensive rapid test that can look at all of the genes that we know currently to cause disease and hopefully find an answer for families.

A (4:25)

Is that rapidly becoming standard of care in most NICUs?

D (4:29)

I would say not in most NICUs, but in a lot of NICUs in our NICU here at Mayo, it absolutely has become standard of care. Five years ago, we started a pilot in collaboration with Rady Children's Institute for Genomic Medicine. And since then, it was very clear that this is helpful for our patients and has become very much the standard of care. And so now when Baby comes to our level four nicu, we ask the question, could this patient potentially have genetic disease? Which is very much a paradigm shift from how we did it before. And, you know, we have a set of broad criteria, and if a patient meets that criteria, they're offered rapid genome sequencing.

C (5:03)

Mayo Clinics out in front right now, that's fortunate if you're in the network of Mayo Clinic, but for the rest of the world, it's not good news. There are a few dozen leading Centers around the world where what Whitney said is true. If you're a baby and there's any suspicion that you have a genetic disorder, you'll get a rapid genome, you'll get an instant answer. But that's not the standard of care. And most people are still trapped in that diagnostic odyssey. It's our mission, the three of us, to change that. We believe that now's the time to turn the corner and make this the standard of care. There's no reason not to, other than just a momentum shift.

A (5:49)

Sean George, why is this so important to you and your firm?

B (5:53)

Well, it's important to me personally. I've pursued genomics my entire career, from the very beginning when the Human Genome Project was announced. It just captured my imagination at the time that indeed we would be able to understand the genetic blueprint for life for every individual and improve healthcare outcomes and costs as a result. I'll say it's been a frustrating career. Things that, you know, I've been active on the technology tools, diagnostic services side. I've been, I've been actively trying for no lack of effort or funding, pushing forward to a day when the frustration expressed by Dr. Kingsmore, there's no reason at all why any of these kids would be bouncing around the medical system for decades trying to figure out what's wrong. And what I'm really excited about what inflection is doing is you can see these cutting edge dozen or so hospitals where children that have a genetic disease are getting diagnosed and then bleeding edge institutes like Mayo Clinics that are now pushing forward genetic therapies, NFLM therapies, bespoke medicines. That day is here. But the vast majority of children born are still born in an environment where that information, well, easier to get than it used to be, isn't acquired. That information then isn't put in play either in labor and delivery or in the NICU or the, in the pediatric wellness checks. That information is not being used by the average everyday practitioners. Inflection medicine is solving that problem by building a platform that acquires all that information rapidly, inexpensively, integrates it with the medical record and the, you know, the record of treatment in the hospital and then delivers to the clinicians and the care teams that maybe they don't have a team of experts and geneticists next door working on all of this, maybe however they want to provide the leading edge care given a genetic diagnosis, that's the platform we're building, that's what we're pursuing here in inflection medicine to kind of push this along so then we can get to the real game of what are the variety of new technologies we can put in play for these kids to improve these kids lives.

A (7:49)

Maybe this is a simplistic question, So I apologize, Dr. Kingsmore, for it. But I'm wondering, as we talk about sequencing to find the cause of some rare diseases, what have we learned about genetic disorders through sequencing? Are they much simpler than previously thought? More complex? How has it changed?

C (8:07)

Oh, the world has changed dramatically. I mean, it used to be a book we couldn't read. It was written in a code we couldn't understand. And now we do understand it. We can read it. It's a novel. We can read it in every person. We can point exactly to why they are sick and what we need to do to fix that. It's a revolution. What we've discovered is that the diseases are much, much more diverse than we thought. Take something like autism or infant death, sudden infant death. These are two projects I'm working on right now. The common perception is that sudden infant death or autism is a disease. It's a thing. They're not. They are an agglomeration of hundreds of genetic diseases that have a common set of symptoms or outcomes. And if you don't know which of those you have, you're giving a kind of generic treatment. It's kind of like you're going to McDonald's and they only have one thing on the menu and hey, I'm vegetarian. Sorry, you're getting a burger, right? We need to change this.

B (9:17)

Echoing those comments, I think kind of, you know, one thing as the codex has been unraveled over the past many years, the, the, the answer is more complex than ever. And I would however say that there's a lot more of it than there used to be. People used to assume the, you know, the genetic load, the, you know, the disease burden due to genetics was, was, was quite low, percentage of incidents in the population. It's becoming increasingly understood that genetics drives an awful lot of etiology, certainly anything going wrong with children and then even later in adult life. So you know, it's, it's certainly gotten more complex, there's a lot more information, but it's also gotten a lot more impactful in terms of its, its ability to kind of really, really impact healthcare. Phil Riley, I remember a conversation with him just even a few years ago, he was an early pediatric geneticist. And you know, I asked him like, what, what would he think? You know, kind of in, in back when he kind of first started practicing, you know, late 70s and early 80s, you know, with the tools that available. His comment was so quick, right off his tongue. You know, it would seem like magic. And I think that's the thing that, like some people forget is technological advances in the last two decades of genomics. If you go back 20 years, it would seem like magic how quickly and effectively and inexpensively we can get three gigabases of information, all of which is starting to be decoded again. I think what drives certainly the three of us and our colleagues in various aspects of the space is that so let's take advantage of this magic and try to do some good with it, not just continue to study it.

A (10:45)

I wonder too, Dr. Thompson, how has artificial intelligence, as you layer that over what is already existing when it comes to genomic testing, how is that changing the game?

D (10:55)

As both Shawn and Steven said, we learn more about the genome as we are able to read the code. There's still so much we don't know, not only in the diagnosis, so identifying a specific genetic variant and how that corresponds to the patient's phenotype, but then what do we do with that information? And so one of the very exciting things we're doing here at Mayo is using AI after we get that initial diagnostic genome result. And so we get that answer on the genome, and then we use an AI program called NIH Translator, and that helps us find potential drug repurposing hits. So drugs that are already available already have safety data for other conditions that we can then potentially tap into to target a patient's specific genetic condition. And that's something we're working on here in our initiative called babyforce.

A (11:41)

Tell people about this, because I'm thinking about a story that I know you had deep ties with Baby Jori is her name, and that was quite a story, how you helped her out.

D (11:51)

So I met Jori in the first couple weeks of my NICU fellowship here at Mayo a few years ago. And like many patients who come into our level four nicu, you know, she was born with multiple congenital anomalies and had some various challenges, which we had no unifying reason for. She was a great candidate for our genome sequencing program. And so we sent that rapid genome sequencing. Within her first week of life, we had a diagnosis. She had a condition or has a condition called desantoshenawi syndrome, missing part of her chromosome 10 and a gene called WAC or WAC. And like many of the patients who are getting these ultra rare diagnoses in our nicu, I went to the family and said, yes, it's Wonderful. We have an answer. We know what's going on, but unfortunately, we have nothing to treat this condition with. And that's the case for so many rare genetic conditions. And so, inspired by Jori and other patients in our nicu, we launched an initiative called babyforce. And FORCE stands for Functional Omics Resource. Jorie became our second patient as part of that program. And what we do is, as I mentioned, we use that AI tool, NIH translator. We input Jori's specific genetic variant. So in her case, she's haploinsufficient or missing one copy of the gene wac. We found some potential drugs that are already available on the market that might be able to upregulate that gene from there. As part of our Baby Force pipeline, we got a skin biopsy from Jorie and actually tested these drugs in her own cells in the lab and proved that one of these specific drugs could actually upregulate her WAC gene to wild type or normal levels. And from there we were actually able to then bring that treatment back to Jorie. And we've seen just incredible effects from that, really.

A (13:30)

How's she doing?

D (13:31)

You know, just within the first month of starting that treatment, she started walking, she started talking, and these were things that, you know, she'd really struggled with up until that point. And she's been making developmental gains, you know, far beyond what we would have expected from her initial trajectory. So it's been just incredible to see.

A (13:48)

That's quite a story. Dr. Kingsmoor, do you have a success story, something similar to that, using genomic testing and then AI?

C (13:55)

We've also been using a lot of AI. The genome is a book 400ft tall. Right. So for a human to read it, it's going to take them a year. Obviously, with AI, we can read that within a minute and achieve a diagnosis. And then, as Whitney said, the quest is on for a therapy, hopefully for a cure. And for most patients, that's not the case. Today, there are relatively few cures. We are entering a new era of genome medicines, but it's still early. There's still only 20 or 30 approved genome medicines. And so what people like Whitney and others are doing is what's called N of 1, which is where you focus heavily on a single baby and you develop a treatment specifically for them. This can be done in a year. This is amazing. The FDA can give approval within three months. And so you can go from concept or diagnosis to actually first dose administration in one year. So our equivalent of baby Jory is a Little boy called Connor, he's now a teenager. He went through the diagnostic odyssey and when he came to us, he already was a teenager. He was wheelchair bound. He had autism and his underpinning condition was a genetic epilepsy. But it presented in him at that age primarily as devastating autism. We were able to build through a partnership. This always requires partnerships across institutions and across organizations. But in partnership with several other organizations, we were able to build a specific piece of RNA highly related to DNA that sits down on the bad copy of his gene and switches it off selectively. So the normal copy, the gene's called SCN2A. The normal copy gets to express itself and the bad copy doesn't? Well, the first time we gave it to him, he stopped seizing, started to peel away his anti seizure medicines. And then just like what Whitney described, he started to rewrite the textbooks. When you have developmental loss, that's supposed to be irreversible. Well, these little kids, they're defying that. He also started to walk. And the medicine that he gets, he needs to get injected into his spinal cord every three months. And so it wears off. At the end of his dose, he again becomes wheelchair bound. But during the time when that medicine is active and we're still titrating the dosing, we're seeing these gains. He's seizure free. An awful lot of his behavioral symptoms associated with autism are no longer troublesome. And when you talk to him, we didn't realize he could communicate. Right. He was nonverbal. When I say we, I mean his physicians, not me directly, discovered he could communicate through a touchpad. And he said, my brain used to be on fire and now my brain feels comfortable. Can you believe it? We didn't even know he could communicate. Wow.

A (17:10)

Oh my goodness, what a story. When you mentioned his treatment, is this a type of gene editing technique? In a sense, yeah.

C (17:18)

There's now maybe 10 different. We call them platforms. They're different ways to bring the therapeutic side of DNA into the equation. It's something that Mayo is a leader in. It's something that we're trying to keep up with them on. And here in San Diego, we're very fortunate. We've got lots of biotechnology companies and some of them are masterful in what we call RNA therapies. They're not gene editing, but they are corrective. As I said, it's switching off the diseased copy of his gene and allowing the other copy still to function freely.

A (17:52)

This sounds incredible, but it also sounds incredibly expensive. Is that one of the big challenges

B (17:58)

Perhaps the other thing that you can do is avoid an immense amount of cost in the procedures and the testing and the diagnostic throughout. A diagnostic odyssey certainly in the acute setting, the work that was led by Dr. Kingsmoor and then spread into a variety of different groups, independent, peer reviewed, have demonstrated, you know, anywhere from 10 to $100,000 per bed savings by using genomic information instead of all of the other stuff that was being done to try to figure out what was going on. And then when you talk about some, it's not a large, but it's a non insignificant percentage of the pediatric population that for years bounces around from specialist to specialist to specialist. The cost avoidance by simply reading the book and understanding what to do is immense. Now with that said, you're, you're right, these bespoke NM1 therapies, they are expensive. However, if you really look, you know, close at the, you know, the inputs with scale and automation, a little investment, you know, we kind of, you can kind of see this in the world of genomics. As the technologies have advanced over the last call, 20, 25 years, you can easily see the cost of treating one of these individual kids coming down two orders, three orders of magnitude. That's going to be within reach for anybody that needs it. There's a sidebar here which is depends on what healthcare system you're in. Fun note clinical genomic sequencing. There is more of it being done outside of the US Than in the US right now. There's a lot of reasons for that. None of them are particularly good. But if you think about where the cost could go and the incentive structure's aligned correctly, this is going to be available to anybody, anybody who needs it. Not immediately. This is going to take a good many years to develop. But it's not as if these miracle stories, these amazing stories, are out of reach. With some investment, some, you know, diligent work, some, you know, some good old fashioned ingenuity, these will be in reach for the individuals that have it.

D (19:55)

Busy healthcare professionals.

C (19:56)

This one's for you. Find Mayo Clinic talks on your favorite podcasting app or visit Cell Podcasts to learn more. Every week we share succinct, relevant and practical medical insights tailored for healthcare clinicians that you can immediately apply to your practice. Each episode covers common health issues seen in a primary care practice shared by Mayo Clinic experts.

D (20:28)

Foreign.

B (20:33)

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A (21:13)

These technologies, Dr. Kingsmore, and maybe Dr. Thompson, you can jump in here too. These technologies, I'm wondering, could they be adapted perhaps and used over and over again to fix mutations in other places in a person's DNA?

C (21:24)

I think a lot of us are focused very, very hard on exactly that idea. How can we have a success with a baby Jory or a baby Connor and then scale that? So we say we can offer this for a disease community. I mean, right now it's going to be the centers of excellence who are in the therapeutic piece. I totally agree with Sean. Every NICU needs to have genome sequencing and be using it every single day. But for this specialized therapy development and then getting that to disease communities, that will happen organization by organization. But yes, we're thinking very hard about how do you go From n of 1 to n of many? Because think about it, so much of the risk in terms of development of a new therapeutic, you've solved for all of that, right? So you've taken 99% of the risk of out of the equation. It's now a matter of how do I make this applicable to the majority of patients. But a lot of that has to do with the fact that most of those kids are still on their diagnostic odyssey. And so even though we might have a brand new medicine that could be effective, in their case, we can't find them and they can't find us.

D (22:38)

I absolutely echo a lot of what Sean and Steven just said, that this technology should be in every NICU everywhere. I've seen firsthand just how powerful this technology can be. You mentioned the cost of all of this, and. Absolutely. But I've seen just how much cost savings there are when we implement this technology early within the first week of life for a baby in our nicu. And not only the cost savings, but the savings of so many different painful procedures and that long diagnostic odyssey that we've been talking about. And then from there, we can't even think about a therapy until we have the diagnosis. And so, absolutely, the diagnostics need to be everywhere. Now we have that technology, and a lot of the work that Shawn and Inflection Medicine are doing is to make it accessible everywhere.

A (23:23)

What's the experience, Dr. Kingsmoor, of Project Baby Bear, the state of California, that makes the rapid whole genome sequencing available. It's funded by the state of California.

C (23:33)

Right.

A (23:33)

Can other states look at that as a potential model?

C (23:36)

Yeah. So the story with Project Baby Bear was that for a while, the technological problem had been solved and a genome was very doable, and it wasn't too costly, and nowhere had really adopted it. There was no policy in any state in the U.S. that said, yeah, this should be used in these kids. And so the state of California coughed up $2 million to do an implementation project. So not research implementation, was this technology ready to be deployed and specifically in Medicaid babies. And so in five states in California, reflective of the entire state. And some of those places are very agricultural and some are very urban. We tested 184 babies as part of Project Baby Bear. We returned results in three days. We solved 40% of the cases, and we saved $2 million in hospitalization costs. So we took that back to the legislature and they issued a policy which said that for such babies, rapid diagnostic genome sequencing is now Medicaid policy for California. Well, then we had Project Baby Deer in Michigan, and from that we've had Project Baby everything. Everybody was thinking about what's their state animal and named a project after it. Now we have 20 states with Medicaid policies. So we're starting to see this trend where we're going from this being something that was used as a last resort in only a few babies in a few leading NICUs, to now starting to become something with universal coverage.

A (25:17)

Sean, I'm kind of curious then. How do you think this could be better democratized, you know, and maybe get this technology into the hands of so many other people across the world?

B (25:30)

What has to happen first is the. Is the work that Dr. Kingsmoor just mentioned. So those kind of studies are absolutely necessary. Everyone agrees. You've got to show in the real world, with real cases, that deploying the technology works and is cost effective. That groundswell has begun and it's happening state by state, 22 states or so I will point out. However, if you're a citizen of California, while your state paid for the study and deemed it not only actionable, cost effective, there actually isn't payment for that in the state of California. 20 or so states do pay for it, and undoubtedly that will pick up. I mentioned outside the U.S. again, any ministries of health around the globe. NHS in England, they're well ahead of this idea. They're beginning to put newborn screening, newborn sequencing policy in place. They're working on implementation. This is coming to a country near you and that will democratize the information and get it in the hands of people who need it. There's a bit of an issue and a massive complexity and then making sure the right information is delivered to the right people and made actionable. That's the problem in Fluxion Medicine, the company I run, we're trying to solve and it's largely an information play. With the genomic technologies advancing and especially AI, it's just the perfect problem for artificial intelligence to solve. And putting all those tools together, we feel will then democratize it even more.

A (26:47)

Dr. Thompson, do you want to make a comment about this?

D (26:50)

Yeah, I mean, getting our rapid genome sequencing program launched here at Mayo. I mentioned I reached out to Dr. Kingsmoor five years ago now and we started a pilot program together here that was very successful. We were able to scale up across Mayo and we've been so fortunate that, you know, I'm at an institution that is able to do that and to scale up this kind of technology and offer it to all of our patients. But I know that's not the case. Everywhere I've seen this technology is very important for our patients. It's really a tool now that I can't imagine not having as a frontline clinician in the nicu. And so I want that for clinicians and patients everywhere.

B (27:24)

You know, I'll add, Kathy, I think this is kind of the thinking, you know, we're a conceptual goal at Inflection Medicine is, you know, there will be a day. And I think certainly everybody in this podcast and certainly all of the colleagues that we have worked with and trained with, we all know this. At some point it's going to happen. But there will be a day where we will look back and think to ourselves, how did we possibly practice medicine without understanding, you know, the blueprint was right there in front of us and we weren't using it. That day will come. I think our collective goal is to make that sooner than later.

A (27:54)

Do you agree, Dr. Kingsmore?

C (27:55)

Oh, totally, totally. I mean, I've been on this quest personally since 2005 and we looked at the first medical genome in 2008. It was a middle aged Korean guy and he had a pretty boring genome. And frankly, back in 2008, when we looked at a genome, we weren't really sure what we were doing or what to do do with it. We found out that he had a gene for hard earwax. That was the sum finding, you know, but you know, he was a middle aged adult and he was healthy. And so maybe it wasn't so surprising that we didn't have any great insight. But it wasn't until 2012 that we did our first rapid genome and that was four babies. And three of them got a diagnosis. And we all looked at one another and said, what just happened? And then we found people like Whitney and said, hey, what do you think you could do with this?

A (28:50)

And wow, Baby Forest is a very interesting program that you've got there, Dr. Thompson. So what's the hope? What's the goal? The next stages?

D (29:00)

Two different things. You know, we talked a little bit about Jory's story specifically and how that's really an end of one success. And we want to take that From N of 1 to N of however many patients there are with desantoshenawi syndrome, we know of at least 100. And so we're working towards how do we scale up from this N of one therapy to a clinical trial for patients with this condition. And so we're in the process of figuring that out right now, and we really want to set the precedent with that so that with our next baby for success, we can quickly scale up From N of 1 to touch all of the patients with the condition. And so that's one thing we're working on. Alongside that, we are working on how can we scale this? We want this to be available to all of our patients here at Mayo and then all patients broadly who have a genetic diagnosis. And so thinking through each step of that process right now, there is a lot of human power that goes into that and there are a lot of bottlenecks. And so we're thinking about how we can bring AI into various components of that. We're working directly with the NIH translator team on how we can make some of those steps a little bit faster so that we're not having to bring the human power to do all of those steps. And then at the time in the lab, my lab partners are working to automate various steps of that as well. So we're really thinking about scaling. And one of the things I'm most excited for is, you know, if there's a way to potentially partner with the work that Inflection is doing. So we can really couple the diagnostics that will hopefully be brought to patients everywhere with the individualized therapeutics. So we can really make the greatest impact.

B (30:29)

Hi, I'm Dr. Bill Maurice from Mayo Clinic Laboratories. Curious to learn more about healthcare innovation. Dr.

D (30:34)

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B (30:43)

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A (30:51)

What one development do you three, whether scientific or regulatory or cultural, do you think makes you most optimistic, say, for the next, I don't know, five or 10 years?

D (31:04)

You know, I think it's really the work putting everything together. So we all need to work together on this. And I don't think there's any one thing, honestly. I think it's to really go from pre test to post test and make this a package that any nicu, or really any inpatient medical practice or eventually outpatient can implement without needing, you know, a whole workforce to do it. I think that's what's going to take this technology to the next level and make it available to patients everywhere. And then to go from certainly AI is going to be a big part of this. What we're already doing with babyforce and the hope is that we can not only bring these diagnostics, but hopefully therapeutics as well to patients everywhere.

C (31:44)

Yeah, I would just say the same as Whitney. We have been on an icebreaker ship, right, trying to forge a way through heavy pack ice at like 0.1 miles per hour. But what we're leaving behind us is open ocean that thousands of vessels can transport through. And that's what we're waiting for. That's what we're trying to do, is to open up sea lanes so that all babies can benefit from this. And it won't end with babies either. You still have your genome for the rest of your life and there's fresh insights to be had at every stage in life. And so it just so happens that babies come first in this race. That's the most important time to get it is the moment the baby's head crowns. There are other places where we're going to see similar transformative advances in outcomes. It's going to be so exciting.

B (32:43)

I talk to young people all the time with an interest in genomics and an interest in medicine and improving the human condition. I find it optimistic. Let's keep that optimism going would be my message. You know, you mentioned the regulatory. I think that it is slightly trending positive. The various regulatory agencies involved, the leaders of them are starting to understand, and I think legislators are as well, that overregulating the flow of information, healthcare, you know, probably isn't a great idea. And you loosen that up just a Little bit. Don't, don't regulate information like a medical device or a drug that you're putting in people. And that's helping. And I do see that trend. You know, I think that realization is happening now that these data sets are getting so large and updated so quickly. I think that's also a reason to be optimistic. And then on the cultural and societal right now, my view of this, the biggest ethics violation that we are collectively all performing right now is not using this information when it's available. These kids lives could be dramatically improved and we're not using it to the full extent. I think the reason for optimism is you can see that this is changing rapidly now. People are starting to get it.

A (33:49)

Sean opened the door and I think it's an interesting point, Dr. Kingsmorth that he's talking about. There is a definite line to dance, is there not? When it comes to the ethics of some of the testing and therapeutics?

C (33:59)

Yes. We have to be very, very aware that as in all of healthcare delivery, we have to be very respectful of the rights of human beings to realize we're dealing with a human being who's a sovereign individual and who has the rights to make their own decision, the rights to make decision for their children and also the right to privacy and confidentiality. And we need to also protect their rights against those who might try to impinge upon them, whether they're insurance companies or any kind of predatory behavior. And we have to be guardians of that. That's nothing new for medicine. You know, medicine has always been tied to human rights and protection of human rights and protection of disadvantaged people, whether they're sick or they're elderly or they're newborns. And that's not gone away any. It's become more complicated because we live in a digital, immersive universe that is something we could not even have dreamt about. And so some of the ethical concerns are different than what they traditionally were. But it's the same stuff about select groups of people being disadvantaged who really oughtn't to be. They ought to have the same rights and the same access and the same future and hope and expectation. And it really behoves us to do that. And yet the world has also changed in that medicine used to be really paternalistic. You know, trust your doctor. He, she knows best. And we're now in a different era where we realize that the patient doctor relationship is two individuals having a conversation rather than, you know, what it used to be. And that's a different dynamic as well. So it's Complex. And it's definitely a big part of the agenda for anything that's new or pioneering in health care.

A (35:56)

I have a final question for all three of you. I like to know what makes people tick, right? You've all been in this, this field for such a long time. What spurs you on, what ignites you to keep going to see where this all ends up, you know, to see your, your goals realized for this, this technology.

D (36:19)

For me, it's that there is just so much hope at this point for what we can do with this technology. And so I've, I've been in this field now for five years and looking back where we were five years ago to now, it's incredible the progress we've made. And I can't even begin to imagine where we're going to be five years from now, 10 years from now, 50 years from now. And I'm, I'm just excited to see where it's going to go throughout the course of my career. And stories like Baby Jory and I can tell you many other stories similar. That's definitely what, what keeps me going and makes me very excited to, to push on in this field.

B (36:51)

The impact that you can have for these people's lives. I mean mine, having it be real personal. You know, I now have a. Almost 16 and 18 year old. There are some diseases that run in our family, your extended family, in the older generations. You know, it's heartbreaking to think of, you know, my kids facing those and they're genetic, you know, so think of the impact of those on my kids when their time comes and the tools and technologies, you're starting to see the toolkit develop that actually that doesn't necessarily need to be the case. That's incredibly motivating. These parents don't have to spend years bouncing around trying to get answers. All the while they're trying to figure out what to do with their life. It doesn't have to be that way. It's my personal, personal burning goal to end that era.

C (37:33)

Thank you.

A (37:34)

I appreciate hearing that, Dr. Kingsmore.

C (37:36)

Well, my motivation has changed with time. A couple of years ago I had a grand niece born called Heidi. She was born in Northern Ireland and she was admitted to the nicu and she had respiratory problems and she was a little bit dysmorphic and she was discharged home. And my sister, who had been a NICU nurse for much of her life, recognized there was more going on. She went into the diagnostic odyssey mode. This was in Northern Ireland. They had never done a rapid genome ever. So after A period of time, her mom and dad got used to the fact that maybe a genome might be beneficial. And then we went through this nutty thing where we had to get a geneticist in Ireland to agree to send a blood sample to San Diego, which they did. And two days later we had a diagnosis. And unfortunately, it's a disease called Milan Syndrome. It's a difficult disease, and there's no effective therapy for it today. And the closest condition to Milan syndrome, it's a growth disorder, is Smith Kingsmore syndrome, which was named after me and my collaborator, Laurie Smith. And what are the chances my grand niece has a one in a million disorder? This is phenomenally rare. That's related to the disorder that's named after me. And so, you know, we now have a new mission, and it was both to get Northern Ireland to do their second rapid diagnostic genome and then their 2000th. But also it's to say, how do we really do this thing that Mayo's pioneering to get therapies for kids for whom we don't have them today? We've got time. These diseases, some of them are fairly slowly evolving. And so we've got a couple of years. How do we turn our genomic knowledge into practical solutions? They might not be cures, but how do we give them the best life they can?

A (39:28)

Dr. Whitney Thompson from Mayo Clinic, Dr. Stephen Kingsmore from the Rady Children's Institute for Genomic Medicine, and Sean George from Inflection Medicine, our true pleasure. Thank you so much.

C (39:40)

Thank you.

D (39:41)

Thank you so much, Kathy.

B (39:42)

Thank you, Kathy, very much. Appreciate it.

A (39:44)

Tomorrow's Cure is a production of Mayo Clinic with production help from the podglomerate. Be sure to follow Tomorrow's Cure wherever you get your podcasts. I'm Kathy Werzer. Thank you so much for listening. Hi, it's Kathy. If Tomorrow's Cure has opened your mind to the innovations and technology shaping the future of medicine, we'd love your help in spreading the word. Please take a moment to rate and review Tomorrow's Cure with. Whether you're listening on Apple Podcasts, Spotify, or your favorite app, your feedback helps others find these discussions and discover how breakthroughs in healthcare are becoming reality. Tell us which episodes or ideas resonated most with you? What surprised you, or what you're hoping to hear more of. Thanks for listening and for being a part of Tomorrow's Cure.