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Stephen Kingsmore’s quest to test every baby with genome sequencing

Episode Highlights

  • Genome sequencing is the process of determining the complete DNA sequence of an organism’s genome, which includes all the genetic information encoded in its DNA.
  • The goal of genome sequencing is to gain a comprehensive understanding of an organism’s genetic makeup, including its genes and other regulatory elements. This information can provide insights into various aspects, such as the organism’s biology, evolution, and potential health risks.
  • Different genome sequencing methods exist, including whole genome sequencing, targeted sequencing, and transcriptome sequencing. Each method has its strengths and weaknesses and is used for different purposes.
  • In the clinical setting, genome sequencing has significant implications, particularly in urgent situations where a rapid diagnosis is crucial. For example, in cases where a newborn baby experiences seizures that are unresponsive to standard treatments, obtaining the genetic information within 24 hours can lead to optimal outcomes. Without a timely diagnosis, the baby may experience long-term deficits or receive suboptimal interventions.
  • Genome sequencing is also vital in understanding and addressing genetic disorders. While some well-known genetic disorders like cystic fibrosis and spina bifida affect a relatively larger number of individuals, there are over 7,000 genetic disorders, many of which are rare and affect only a small number of people. However, when considered collectively, these disorders impact a significant portion of the population, especially in pediatrics. Genetic diseases are a leading cause of infant death and the primary reason for admission to children’s hospitals.
  • Efforts have been made to make rapid whole genome sequencing more accessible and mainstream in healthcare. Projects like Project Baby Bear in California and establishing a national network of hospitals have contributed to the adoption of rapid whole genome sequencing. The outcomes of such projects have demonstrated the diagnostic value of genome sequencing, with high diagnosis rates and significant impacts on treatment decisions and patient outcomes. Additionally, the economic benefits have been recognized, as rapid genome sequencing can lead to cost savings by reducing hospital stays and enabling targeted treatments.
  • Advancements in genome sequencing have also led to initiatives like BeginNGS, which aims to expand the scope of newborn screening by conducting rapid whole genome sequencing on all newborns at participating hospitals. This approach goes beyond traditional newborn screening panels and allows for identifying genetic disorders before symptoms appear, potentially enabling early interventions and preventing severe health complications.

Full Transcript

Stephen Kingsmore  on The Harry Glorikian Show

For February 14, 2023 

Full transcript

Harry Glorikian: Dr. Kingsmore, welcome to the show. 

Stephen Kingsmore: Thank you very much, Harry. Great to be here. 

Harry Glorikian: So, you know, it’s interesting because I’ve been I’ve been reading about you and the center for quite a while. And the reason I wanted to have you on the show is there’s probably no one in the medical world who’s more closely identified with the concept of rapid whole genome sequencing, especially in newborn infants, than you. I mean, you’ve published some big papers in the last few years in places like Nature and The New England Journal of Medicine explaining how you and your team are using whole genome sequencing to diagnose critically ill newborns in less than 24 hours. And you’ve written that in the future, which I’m hoping is sooner rather than later, it will be possible for clinicians to order a whole genome sequencing on morning rounds and receive a molecular diagnosis by that same evening. I’m not sure how many people understand how close that future really is or how much work it took to get to this point. But our show has a pretty broad audience, so I want to maybe step back and start covering some of the real basic science here and then we can work our way back to the healthcare implications. So if we can start with a few definitions, I mean, if you were going to explain to someone, a lay person, you know, what is whole genome sequencing, how is it different from some of the other sequencing techniques we’ve talked about? And, you know, why would we want to do a whole genome sequence? 

Stephen Kingsmore: It’s a great question. So let me start off with it. These days, post COVID, we all know about DNA, RNA and variants. We’re not talking about a virus. We’re talking about us human beings So packed into every cell in our bodies are two copies of the human genome, and it has all of the instructions for being a human being and all of the traits and attributes that you associate with me being me and you being you. Blue eyes, brown hair, height, weight, intelligence, not perfectly, but a good representation of all of that stuff is in there. And those instructions, if they were typed on regular pages like like this one, it would be a book 400 feet tall. So when we say decode the whole human genome, we’re talking about 6 billion letters of information, a book 400 feet tall that we are looking through and we are looking for all of those variants, all of the differences from what we call reference, because in that information, if you have a disease, we can find out what’s triggering it. 

Stephen Kingsmore's quest to test every baby with genome sequencing

Harry Glorikian: When you say rapid whole genome sequencing, Right. Rapid compared to what? I mean, how long would it have taken to sequence a whole genome, say, 10 years ago or five years ago? And, you know, truth be told, I was I was at ABI when we did the first genome. So I have a relative idea of how long it took us to do the first one. But, you know, if you could give people orders of magnitude of time that it took us and where are we now? 

Stephen Kingsmore: You know, so this is like any other world speed record where the time has been coming down over the last decade. If you had asked me that 11 years ago, the answer would have been months, six months. If you’d asked me that ten years ago, when we set our first record, it was 48 hours. Today it’s as little as 7 hours. We can decode all of that information. And we’re talking about receiving a blood sample, getting it ready to go on an instrument. So extracting the DNA, putting it on the instrument, getting the code, and then looking through all of that sequence information all the way to pinpointing a diagnosis, a disease or an illness that explains what’s going on in the child. All of that is now possible in about 7 hours. 

Harry Glorikian: Compared to when we did it, if we had said that to someone back then, they would have looked at us like we were completely lost, you know, had completely gone out of our minds. But, you know, I guess this is a a good moment to acknowledge, there is one company that’s probably done more than many others, to make large scale genome sequencing faster and more to more affordable. And that’s Illumina. Right. I know the chief medical officer there, Phil Febbo, I recently had him on a talk where we were talking about their Nova Seq. And you’re at Rady Children’s Hospital in San Diego and you’re the head of the Institute of Genomic Medicine. And I imagine it’s not a complete coincidence that Rady has an institute, given that Illumina is not far down the road. I’m assuming you guys do interact quite a bit. I don’t know if you can talk about the role Illumina has played in helping you achieve some of these speed goals. 

Stephen Kingsmore: Yeah. Yeah. We have been collaborating with Illumina since 2005, believe it or not, before they acquired sequencing technology. It was an English company called Celexa. 

Harry Glorikian: Yep. 

Stephen Kingsmore: So our first sequencer had Celexa stamped on it, and then it became Illumina overnight. So it’s been a 17 year relationship. And yes, we have walked hand in hand together across a ton of different milestones that now allow us to save the lives of critically ill children all over North America. And that continues to be a strong relationship. They’re headquartered 11 miles away from our hospital. And so we have certainly weekly contact with them, and contact at multiple levels. And it’s been hugely synergistic. We are, you know, at the bedside with children. They have technology. When you put those two together, you come up with solutions that really fit real-world needs. 

What is genome sequencing?

Genome sequencing is the process of determining the complete DNA sequence of an organism’s genome. The genome is the entire set of genetic information contained in an organism’s DNA, including its genes and other elements that regulate the expression of those genes. Genome sequencing involves breaking down the DNA into smaller pieces, reading those pieces, and then using computer algorithms to reassemble the sequence.

The goal of genome sequencing is to gain a comprehensive understanding of the genetic information contained within an organism’s DNA, which can provide insights into its biology, evolution, and potential health risks. This information can also be used to develop new medical treatments and to improve agriculture.

There are several different methods for genome sequencing, including whole genome sequencing, targeted sequencing, and transcriptome sequencing. Each method has its own strengths and weaknesses and is suited for different purposes.

Harry Glorikian: So stepping back still for the for the basic science question. Once it looked like it was possible to sequence a person’s whole genome in under 24 hours, let’s say, what were the most important possibilities you saw opening up for how to use gene sequencing in the clinic? 

Stephen Kingsmore: So in that timeframe, we’re dealing with the most urgent situations. Let’s say a baby is born and starts to seize, and that baby’s seizures, those epileptic fits, are not responsive to first-line drugs. That is a medical emergency. If we can find out the cause of that child’s seizure disorder within 24 hours, we will have an optimal outcome. They will not have damaged their brain substantially enough to have long term deficits. If they continue to seize for weeks, then, despite the fact that we found the cause of their condition, they are likely to have lifelong deficits. And that’s true of most organ systems, whether it’s your heart, your kidneys, your liver, your lungs, your brain. The clock is ticking and certain conditions, certain of the 7,300 genetic diseases, that clock needs an answer within hours. And no answer within hours means a doctor will do their best, blinded to knowing what is causing the illness. And the interventions they will give most likely are not optimal and sometimes are contraindicated. One example is the one I just gave you, a baby seizing. One of the leading causes of seizures in a newborn is something called hypoxic ischemic encephalopathy. HIE. The treatment for HIE is cool the baby’s temperature down. Artificially cool the baby, put the baby into almost a medical coma, and this preserves brain function, believe it or not. Now, if they have one of the genetic conditions, say a metabolic cause, that will most likely kill the baby. So you see the yin and yang, Right intent. I’m going to do the best for this baby. Wrong diagnosis. Because I didn’t have a genome information. Bad outcome. 

Harry Glorikian: Yeah. I mean, it’s, you know, if we talk about rare genetic disorders there’s a a handful of well know, well known genetic disorders, like I think most people have heard of cystic fibrosis or spina bifida. That I think affects I think it’s one in 3,000 newborns. But that’s the tip of the iceberg, as you said. I mean, in a sense. Right. There’s you said, I think, over 7,000 genetic disorders. 

Stephen Kingsmore: Correct. 

Harry Glorikian: Some of which are so rare, they might only affect one person in a million or even one person in a billion. Can you help people understand, you know, the scope of these problems and why this might be an appropriate way to…I like to tell people it’s almost like having a Google map, which maybe oversimplifies it, but just to get people to visualize it in their own mind. 

Stephen Kingsmore: Sure. You may be tuning into the podcast and you go, Hang on. This guy is dealing with diseases that affect one in a million people. Why am I wasting my time listening to this? Well, the thing is, there’s 7000 of them. When you add them all together, what you find is that they affect a couple of percent of the population. So they’re no longer rare. They’re common. And then furthermore, when you get to pediatrics, health care provision for children, they’re the number one cause of death in infants. They’re the number one cause of admission to a children’s hospital. If you get into the neonatal intensive care unit, at least 15% of the babies in that unit on any given day have a genetic disease. So, yes, our  rversion from our adult eyes is these are rare conditions and it’s mainly babies. But we are entering a new era when we realize that we have been in our minds only looking at the piece of the iceberg that we could see above the water and below the water was 99% of the problem. We never had a tool to find these conditions, and so we didn’t know that this is what was wrong with these babies. They are much, much more common than we had suspected. 

Harry Glorikian: Yeah. So, I mean, just coming back around to the work you guys do every day at Rady, right? Can you describe the work you’ve been doing over the past, say, eight or nine years to try to help rapid whole genome sequencing go mainstream. I mean, for example, there’s a demonstration project in California called Project Baby Bear, and you’ve also been building a national network of hospitals that send you samples as part of their own rapid whole genome sequencing programs. Can you talk about that a little bit? 

Stephen Kingsmore: Sure, sure. So we first got into this a decade ago. First couple of babies, one of them immediate impact. And we had that epiphany moment that people talk about where we realized… I’m a surfer and I just realized this is the best surf break in the world. I’m going to hang out here. And we decoded more genomes and more genomes. And what we found is that one in three babies we sequenced, we diagnosed, and that 18% of those babies — so, one in five — we changed the outcome. So fully 80% of those we diagnosed we changed the treatment. And one in five, we change the outcome. Now, that may not seem earth shattering to you, but that puts this into the realm of the top five ever, you know, medical interventions. That’s like penicillin for infectious disease. Right. That’s the sort of impact we’re talking about. It’s not a little thing. It’s transformative. And so realizing that what we needed to do was to industrialize this, we needed to get the message out. 

Stephen Kingsmore: So first of all, we had to tell physicians about this. Doctors don’t learn about this in medical school. They don’t learn about it in residency yet. And so we had a provider, a health care provider cohort who had no idea what we were talking about, no idea what to do with a genome if you decoded it. And then we had a public who also were uncertain about genomes and DNA. And is that even safe? You know, are you going to clone me? All kinds of questions. And then on top of that, we had no systematized evidence base. What was our playbook? Right. We were inventing a new sport and we had no playbook. So all of those things had to happen in the last decade. And now, as you say, the situation is that this is becoming standard of care, that in California and Oregon and Michigan and Minnesota and Louisiana and Maryland, Medicaid now covers this. Medicaid says this is a covered benefit if you’re a Medicaid beneficiary. So does Anthem Blue Cross Blue Shield nationally, so does United Healthcare Group. So we are moving from that initial phase to early adopters. We’re still not at the major part of the mainstream, but we’re getting there fairly rapidly, to where over the next couple of years we can realistically expect that no matter which intensive care unit your baby winds up in, they will be ordering a genome should your baby need it. And the impact is going to be immense. The economic impact.  

Stephen Kingsmore: You mentioned Baby Bear. So this was what we call an implementation study. The California politicians said this is cool stuff. We’re going to seed fund a test a bunch of babies at five sites and run the numbers. Right. We want to know how many diagnoses, we want to know how much it costs us. So we did it and we had a 40% rate of diagnosis, a bit better than our batting average. And we found that it saved $12,000 per baby tested — saved, not cost, saved $12,000 per baby tested. So when we brought that back to the legislature, they went, Hang on, hang on, hang on. This is an additional benefit for children. It’s effective. And it saves us money? This doesn’t happen. Right? So we are seeing rapid uptake even from hawks. Budgetary hawks are recognizing this is not going to break the bank. This is a benefit that will actually decrease our costs. And the reason is really simple. Many babies and many children will stay in a hospital bed until the doctor knows what’s causing the illness. A genome gives that answer in as little as a day, which can save days or even weeks off the length of a hospital stay. That’s why it saves money. 

Harry Glorikian: Right. I mean, you know, talk about that, I remember we’d call it the diagnostic odyssey, and it still exists. 

Stephen Kingsmore: Yes. 

Harry Glorikian: But, you know, it’s horrible for the parents and the child. Right. But now let’s talk about something called BeginNGS. And I think you pronounce it “beginnings.” Right, which is a research program you announced at the Institute in June of 2022, where you’re screening newborns for about 400 genetic disorders. But if I understand it correctly, what’s new and different about BeginNGS is it goes well beyond just infants who are already showing symptoms of a genetic disorder. It expands the rapid whole genome sequencing to all newborns at participating hospitals. So, first off, you know how are BeginNGS screening is different than I guess you would talk about the traditional newborn screening panels. 

Stephen Kingsmore: Well, let me tell you a story. Stories are always best. So a different baby comes into our intensive care unit and is paralyzed downrr  one side. We decode the baby’s genome, and the baby indeed has one of those illnesses you mentioned, the one in a million. It’s a very rare form of hemophilia. Now there’s an effective treatment. The baby needs that clotting factor to be replaced. This is pretty easy to do. It requires an infusion periodically of that factor, and that will have to continue for the rest of the baby’s life. Wonderful. Rapid diagnosis, immediate treatment. Oh, hold on. The baby’s paralyzed dowrn one side of his body. What we realized was a diagnosis in a critically ill baby was not always ideal. That what we needed to do was to get ahead of the illness. What if we could identify the illness before the baby had a stroke, before the baby had any symptoms? Could we maybe avoid them coming to hospital at all? And so we got our thinking hats on. And we realized that since the late 1960s, this actually had been done in the US for only a few conditions. About 34. The baby gets a heel prick test at birth. It goes on a filter card. It’s sent to a state lab and the baby is checked for, as I said, 30 or so genetic conditions. Some states it’s more, some it’s not so many. And it actually happens to 140 million babies all round planet Earth. What if we could use genomes and do that for hundreds or maybe even a thousand disorders? Every disorder that was like the one I described. I have an effective treatment. I want to get it to the baby before they get sick, because otherwise I’m closing ther r door of the barn after the horse has bolted. Right. So that’s the concept. 

Harry Glorikian: How does this work logistically? I mean, you’re working with multiple institutions in multiple places. I mean, how are you making it work? What stage is the project at now? Do you know how many hospitals may be involved? I mean, a little bit more information for all the listeners would be great, because I’m sure that there’s a lot of people that are, you know, in the “I may be having a child” stage soon. 

Stephen Kingsmore: So the project’s called BeginNGS for Begin Newborn Genome Sequencing. And it’s beginning, right? So it’s an apt title. We have been decoding babies genomes rapidly in intensive care units since 2010, 2011. We’re now at a point where that’s being implemented all over the country. BeginNGS started last year. So we have a prototype. We tested 454,000 healthy adults in England, and we tested two and a half thousand babies who’d already received a rapid genome because they were critically ill. And we proved out that this concept worked. It’s about 80% sensitive and it’s about 99.7% specific. That’s good enough to advance it. So what we’re doing now is raising funds, raising awareness, forming a coalition. T rhis BeginNGS consortium. It’s now about 30 organizations and preparing for the very first clinical trial ever to do this. And that will start, I hope, next month. 

[musical interlude] 

Harry Glorikian: Let’s pause the conversation for a minute to talk about one small but important thing you can do, to help keep the podcast going. And that’s leave a rating and a review for the show on Apple Podcasts. 

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It’ll only take a minute, but you’ll be doing a lot to help other listeners discover the show. 

And one more thing. If you like the interviews we do here on the show I know you’ll like my new book, The Future You: How Artificial Intelligence Can Help You Get Healthier, Stress Less, and Live Longer.  

It’s a friendly and accessible tour of all the ways today’s information technologies are helping us diagnose diseases faster, treat them more precisely, and create personalized diet and exercise programs to prevent them in the first place. 

The book is now available in print and ebook formats. Just go to Amazon or Barnes & Noble and search for The Future You by Harry Glorikian. 

And now, back to the show. 

[musical interlude] 

Harry Glorikian: So you talked about the cost-benefit a little bit. And it was interesting because I was thinking of like, well, he’s not a health economist, but I’m sure that these numbers, you know, are are up there because you’re talking to politicians and insurance companies. So you got to know some of them. But. What would it cost to screen the whole population of newborns in the United States for say 400 different disorders. 

Stephen Kingsmore: Yeah, it’s a great question. And there’s a little bit of looking into the future. All right, let’s understand that. And so this is not a hard baked number. But in California, the current testing, which, as I said in California, I believe it’s like 80 conditions total is $210. That’s the fee that every insurance plan has to pay for every baby. That’s 450,000 babies in California alone a year, $210. So that’s what we’re aiming for. How do we get this to $210? Now we can’t get it there immediately. But you had Illumina on the show recently. I’m sure they were talking about their $100 genome and it’s not quite there yet. And it’s certainly not a clinical grade genome. But that’s what we’re aiming for. We’re skating towards a puck and that puck is the $50 genome that really is something that’s clinical grade because that would allow us to have this amazing 15 times increase in the scope for about the same price. 

Harry Glorikian: And you just take that multiplication. If you said we’re going to save $12,000 per child. By the number of children that are diagnosed with some issue across that number. And I think it pays for itself if even above $210, if somebody were to sit down and do the math today. 

Stephen Kingsmore: Yes, that’s what it will cost. I hope. But let me just say, that’s out there, right? Today it’s expensive. Our diagnostic genomes are $8,000. So we have a ways to go. And that’s why it’s a different, it’s a very different product or service. We have to make it completely automated. We have to really be thinking about scale. So first of all, we’re going from thousands of babies with the diagnostic product for neonatal intensive care units to millions of babies for beginnings. So scalability, automation, and then cost reduction are the critical elements. 

Harry Glorikian: Yeah, but I mean, based on everything I’ve, you know, all the companies I interact with and things that I see, I just, you know, I see it as, the path is going in that direction. It’s never a straight line, but we’re all moving in that direction, especially if people want to do the level of screening that we keep imagining as we’re going forward with other diagnostic testing approaches that I talked to with Grail or with Illumina themselves.  

Harry Glorikian: Let’s talk about the relationship between, say, a diagnosis and treatment in this world of genetic disorders. So once you get a molecular diagnosis of a rare disorder, you often have to have either a technology to be able to treat it or you have to have a therapeutic product to be able to treat it. You know, how is that changing with what you guys are bringing to the forefront? In other words, you know, you talk about I believe there’s a tool you’ve been developing at the institute called Genome to Treatment or GTRx. Do you feel that as we’re getting more information, there are either a device or a therapeutic that is going to meet the challenge of solving that problem that you’re identifying? 

Stephen Kingsmore: Yes. So this is the other driver, the hugely exciting prospect. So there’s this huge misconception amongst doctors, genetic counselors, parents, the public, that a genetic diagnosis is a fixed thing, that this is not treatable. And so really all we’re doing is labeling disease. And that’s just plain wrong. As I said, we find 85% of the time we make a diagnosis, it’s changing the management of the baby. That does not mean there’s a cure, but it means that there’s changes in how the baby’s managed. Sometimes there are cures. Sometimes there are effective treatments that are not cures. There’s at least 500 conditions like that. Genome to Treatment is, it’s a website and it lists for a doctor, you just diagnosed this condition. You’ve never seen it before. You’ll never see it again. It’s very rare. Here’s what a world expert would do to treat that baby. It’s at your fingertips. We’ve got the names of the drugs, the names of the interventions, who they’re indicated for, who they’re contraindicated for. Who should you not give this to? What’s the first line treatment? What’s a second line treatment? How quickly should you start it? All of that information at a single source. And what we’re trying to do thenr  is upskill frontline doctors. If frontline doctors are going to be ordering genomes, frontline doctors need to know how to manage the conditions we diagnose. And they’re, many of them are, they’ll never see it more than once in a lifetime. So we’ve got to give that to them. If we don’t, we’ll make a diagnosis, but the child won’t receive the full benefits of of the changes of management that are available for that baby that would improve their outcome. 

Harry Glorikian: Yeah, it’s one of those it’s you know, whenever I talk to guests about these things, I’m like, why aren’t these things just standard? I mean, if you’re driving someplace and you’ve never gone there before, wouldn’t it be great to have a at least a guidepost or Google map to help you at least get to the right place? And it’s sort of you know, it boggles my mind that I really do wish this stuff would move a lot faster compared to as fast as it does move within the system we’re in. But you’re talking about “n of 1” disorders and different approaches that you need to take to get there. Do you believe that what you’re working on, and the direction that you’re going in, will unlock, say, faster therapeutic approaches to these n of 1 treatments, and I call it n of 1, although you said, you know, if we’re looking at, you know, a large number of babies, it’s more than an n of 1 because we’re only seeing them, you know, geographically as an n of 1 as opposed to an aggregate n of 1. 

Stephen Kingsmore: Yes. So something that your listeners may not be aware of is there’s a quiet revolution happening in drug development and it’s been slowly gathering momentum over the last decade. And the epiphany that the drug companies had was we should be making drugs for these rare diseases. Traditionally, if you go back even ten years ago, that was contrarian thinking. It was, no, we want a blockbuster drug, we want a new Viagra, a new cholesterol pill, because we want to sell a million pills a year. Right? Now drug companies are realizing I can be profitable and sustainable targeting rare disease. And there’s two reasons for that. Number one, the Orphan Drug Act that Congress passed gave special protections for these diseases in terms of the drugs. So the drug companies have a longer life of exclusivity. And second of all, the FDA realized we need a different rule set for judging these rare disease candidates, which has made it a lot easier. People may have heard that it takes ten years or 12 years to develop a drug, and it costs $1 billion or $2 billion. Well, no, the rule book has changed for these conditions, so you can do it in a couple of years and you can do it for a fraction of the cost and you have more protection. 

Stephen Kingsmore: And all of that means that even though you’re selling only maybe a thousand pills a year, you still have a very valuable product. That’s an immense change. Now the issue for those companies is they need genome sequences, because they need the babies to be identified to be plugged into the drug.  

Harry Glorikian: Right. 

Stephen Kingsmore: And so there’s a bottleneck for them. They can build a treatment now using genetic therapies for many, many conditions. But how are they going to find the patients? So we now have this really interesting situation where the pharmaceutical industry needs us and we need the pharmaceutical industry because many of the conditions don’t have effective therapies. And what’s hugely exciting is there are now almost 4,000 new drugs in development for rare genetic diseases. Can you imagine what that’s going to look like in five years? You know? And five years beyond that, we are going to see that we have ubiquitous genomes, timely answers, and effective therapies. 

Harry Glorikian: And it’s got to be, I mean, if you’re a physician and you’re not using this, how will you ever put the two pieces together to make that connection? I mean, you’ve got to employ technology to sort of practice medicine as vwe’re going forward into this future that you’re talking about. 

Stephen Kingsmore: You know, it’s a conversion experience. I think every physician I’ve ever talked to about this is, there’s the before and the after. There’s the before they ever got an answer on a child where there was an acute intervention. And then there’s the after. And before, there was some kind of healthy skepticism. And after they’re believers and they go, that was one of the more meaningful moments of my professional career. I like to do that again frequently. 

Harry Glorikian: You almost want to get them in one room so that we move this faster. But so, you know, asking you just how did you get interested in genomic medicine, you know, the possibilities of rapid whole genome sequencing. I mean, do you feel like your career was very clearly mapped out in advance, or was it a combination of, you know, maybe some luck and technology advancements. 

Stephen Kingsmore: Boy, that’s a deep question. Harry. Are you sure you want to go there? So I’m a person of faith, right? I’m a Christian, and I pray all the time. And I pray about research all the time. And I ask God, you know, you created all this, help me be smart. And he he talks to me and he tells me stuff. Stuff that goes, You kidding me? Are you serious? That’s my secret weapon. I don’t think I’m that smart. I don’t think I’m that lucky. God whispers to me, I keep asking him, you know, and he keeps giving me these nudges. And so as long as I keeps goin’, I want to keep going. The moment he shuts up everybody is going to realize how stupid I really am. 

Harry Glorikian: I seriously doubt that. But no, I understand what you’re talking about. I mean, every day I’m trying to keep up with what’s going on and realizing what direction we’re going in the and the opportunities that are there, which keep pulling me in the direction. And it’s funny because sometimes I wonder why would anybody want to work in any other field? I mean, thank God they do, because we need all those all those people to do what they do. But I think we worked in, we work in some of the most exciting and impactful space you could possibly ask. So I want to ask you to sort of make a prediction like, in what year, or maybe years, do you think it’ll become standard of care in the average hospital, in the average US state, not meaning California, for all newborns to receive, say a broad genome sequencing panel. And on top of that, what policy decisions or  r government investments or research advantage advancements could help make this happen sooner rather than later. 

Stephen Kingsmore: Well, I think the two are tied together, Harry. If indeed we have substantial support, this will happen a lot faster. So Genome England have government support, about $200 million, $300 million. And they will have such a program, I would say, in five years. Something similar is happening in China. In the US, we’re lagging, honestly. I’m knocking on all the doors and tapping on all the windows to seek funding support. And that really is the bottleneck. We have a technological solution. We now need to prove it out in clinical trials and then we need to implement it. Now for the NICU, for the neonatal intensive care unit, it  took us a decade to get to where we are today. I pray it’s not a decade before we realize this in the United States for all newborns. It would be possible to do it in five years. But you’re right, there needs to be the political will to catch us up. To socialize systems where sometimes these decisions can be made much more quickly. 

Harry Glorikian: Yeah. You’d almost want every every parent that has gone through this to make a trip to D.C. and visit every door and knock on every door and every window, and that might actually move it a little bit faster when they realize how many constituents there are that vote. So, look, it’s been absolutely fantastic having you guys on the show. I’m reading about what you guys are doing all the time and these records that you guys are setting, you know, just it’s fantastic. I hope it continues, it advances. And to be quite honest, it’s  an example for other whole genome sequencing approaches in many other disease states, because showing the technology works gives everybody the opportunity to start testing it out in other areas. 

Stephen Kingsmore: Totally. 

Harry Glorikian: So, thank you for being here. 

Stephen Kingsmore: It’s great to have been here. It’s been fun. You told me it was going to be fun. You’re right. It was fun. Thanks a lot. 

Harry Glorikian: Thank you. 

Harry Glorikian: That’s it for this week’s episode.  

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FAQs about genome sequencing and genetic disorders

What are genetic disorders?

Genetic disorders are conditions that are caused by alterations or mutations in an individual’s DNA. These mutations can be passed down from parent to child or can occur spontaneously. There are many different types of genetic disorders, and they can be caused by a variety of different mechanisms, including changes to single genes (single gene disorders), changes to the structure or number of chromosomes (chromosomal disorders), or a combination of both.

Some examples of single gene disorders include cystic fibrosis, sickle cell anemia, and Huntington’s disease. Chromosomal disorders include Down syndrome and Turner syndrome. Multifactorial genetic disorders, such as heart disease, diabetes, and certain types of cancer, are caused by the interaction of multiple genes and environmental factors.

The symptoms and severity of genetic disorders can vary widely, depending on the specific mutation and the genes involved. Some genetic disorders are present at birth and can be diagnosed through newborn screening, while others may not be diagnosed until later in life. In some cases, genetic disorders are treatable or manageable, while in others, they can lead to serious health problems or even death.

What is an example of genome sequencing?

An example of genome sequencing is the Human Genome Project, which was an international scientific research project with the goal of determining the complete DNA sequence of the human genome. The project was initiated in 1990 and was completed in 2003. The human genome is the complete set of genetic instructions for the development and functioning of a human being, and the project provided a wealth of information about the structure, function, and evolution of the human genome.

The information generated by the Human Genome Project has been used to develop new medical treatments, to improve our understanding of genetic diseases, and to advance scientific knowledge in many other areas. For example, researchers have used the information to identify specific genetic mutations that cause certain diseases, and to develop new drugs that target those mutations.

Since the completion of the Human Genome Project, advances in technology have made it possible to sequence the genomes of many other species, including other mammals, plants, and microorganisms. This has led to new insights into the biology and evolution of those species and has provided a valuable resource for various fields of scientific research.

Who is Dr. Stephen Kingsmore?

Dr. Stephen Kingsmore, is one of the people leading this whole revolution of genetic disorder testing and genome sequencing. Dr. Kingsmore grew up and earned his medical degrees in Northern Ireland, trained in internal medicine and rheumatology at Duke, and served as the Executive Director of Panomics at Children’s Mercy Hospital in Kansas City. And he’s now the president and CEO of the Institute for Genomic Medicine at Rady Children’s Hospital in San Diego. 

What are the benefits of testing every baby for genetic disorders?

There are several benefits to testing every baby for genetic disorders:

  1. Early detection: Genetic testing can identify potential health problems early on, allowing for early treatment or management. This can improve a child’s chances of a healthy future and can prevent complications from developing later in life.
  2. Family planning: Genetic testing can provide important information for parents and other family members who may be carriers of genetic disorders. This information can be used for family planning purposes and to make informed decisions about having children.
  3. Improved diagnosis: Testing every baby for genetic disorders can lead to earlier and more accurate diagnoses, reducing the risk of misdiagnosis and allowing for more targeted treatment.
  4. Better understanding of disorders: By testing every baby for genetic disorders, healthcare providers can gather more data and increase their understanding of these conditions, which can lead to better treatment options and improved outcomes for affected individuals.
  5. Advancements in medicine: Large-scale genetic testing can contribute to medical research and the development of new treatments for genetic disorders.

It’s important to note that genetic testing is just one piece of information used in a comprehensive evaluation of a baby’s health. The results of the test should be considered along with other clinical and family information to make informed decisions about a baby’s care and management.

Is DNA and genome sequencing the same?

No, DNA sequencing and genome sequencing are not the same thing.

DNA sequencing refers to the process of determining the specific order of the four chemical building blocks (A, C, G, and T) that make up the DNA molecule. This information can be used to identify changes or mutations in a person’s DNA that may be associated with disease or other health conditions.

Genome sequencing, on the other hand, refers to the process of determining the complete sequence of all of a person’s DNA, including both coding and non-coding regions. The human genome is estimated to contain around 20,000-25,000 protein-coding genes and a vast amount of non-coding DNA that helps regulate gene expression and other cellular processes.

So, while DNA sequencing focuses on a specific part of the DNA molecule, genome sequencing provides a comprehensive view of an individual’s entire genetic blueprint. The increased understanding of the human genome provided by genome sequencing has led to many important breakthroughs in medical research and the development of new diagnostic and therapeutic tools.