← Solutions with Henry Blodget
Solutions with Henry Blodget
An Extraordinary Gene Editing Treatment Could Mark a Turning Point in Medicine
00:47:13
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Maybe someone recommended this podcast and here you are. But home projects are a little different. If the podcast isn't your thing, you might lose a few minutes from your day. But if you hire your cousin's neighbor to mount your tv, you might end up with a lopsided screen and wall damage. I know a guy isn't a good strategy for your home. That's why thumbtack works so well. It matches you with top rated local pros. Local with photos, reviews and credentials all in one convenient place for your next home project. Try thumbtack. Hire the Right pro Today, Optimists in the longevity community see a future in which nanobot doctors swim through our bloodstreams and cure every disease. We're a long way from curing every disease, but a new technology sounds a lot like those nanobot doctors, and it's already being used to treat rare and likely fatal genetic mutations, as Dr. Jeff Collar of Johns Hopkins described in a recent New York Times editorial. A team of doctors and scientists recently used gene editing and MRNA technology to treat a patient who would otherwise likely have died. So how does this treatment work and what has to happen for it to go mainstream? I hope you enjoy a fascinating conversation with Dr. Koller. Jeff, so great to have you. Thank you very much. I think I and thousands of other people found your op ed in the New York Times incredibly fascinating. I personally have been hearing about CRISPR and other technologies for years, have not really had the chance to dive in and understand them. We're going to do that today, which is very exciting. But first, why don't you start by just sharing the anecdote that you share at the beginning of your op ed?
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Yeah, sure. So first of all, thank you for having me here today, Henry. It's a pleasure to be able to share these stories with your listeners. So the story really begins in August of 2024 when KJ Muldoon was born in Pennsylvania and he was diagnosed very early on with an ultra rare genetic disorder. Disorder that only affects like 1 in 1.3 million children. And that was a deficiency in an enzyme called CPS1. And essentially what happens when a child has this particular mutation, they can't process proteins in their body appropriately. And this is a disease that primarily affects the liver. And so what happens is that since they can't process proteins, they build up toxic amounts of substances within their bloodstream that essentially will kill them. And the only real answer for most of these children is, is a liver transplant. And of course, a liver transplant can't take place. I mean, there's multiple barriers to a liver transplant. One, you have to be healthy enough. It can't occur on a child before six months of age. And the other side of it is, of course, the liver transplant is really, it's working off of someone else's tragedy, right? So it's not a preferable option for anybody in a situation like this. And so the researchers at the Children Hospital of Philadelphia, they really moved heaven and earth to find an option for this child in order to save his life. And so they quickly worked together with a bunch of companies and they made a personalized gene therapy which was based on several unique technologies, some of which I'm sure your listeners have heard of. It was a technology where they married CRISPR based editing technology with MRNA technology, the same exact MRNA technology that was used in the COVID 19 vaccines. And essentially what this technology allowed them to do was to put this therapy into baby KJ and correct the mutation within his liver. So there was a single letter within the genetic code that was in error, and they corrected it. And this led to a restoration of his liver function. And today he's little over a year old now and is walking and thriving and is doing quite well. We can't say that it's a cure for him, but it is a step in the right direction. He hasn't had to have a liver transplant. He'll be monitored, obviously for his entire life. But it's really inspired the entire community to think very differently about treatment options for these conditions that we call ultra rare genetic disorders. And what's really interesting about people when they hear the word ultra rare genetic disorder, what they probably don't realize is that yes, they're rare as an individual disorder, but they're not rare in aggregate. 1 in 13Americans, 1 in 13Americans suffer from a rare genetic disorder. So that's an incredible number. And in aggregate makes one of the biggest unmet medical needs in America and in the world.
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And it's just such an incredibly inspiring story. In a few minutes, I want to Talk a lot about actually what happens in the technique because it's fascinating and really unfathomable to somebody like me who grew up in an era where surgery was always knives or lasers or what have you. But just for now. So give us a, give again a picture of how many people that affects in the United States and why our current system is not addressing these diseases.
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Yeah, so again, the, the, if you look at statistics that come from organizations like nord, which is the National Organization of Rare Disease, they estimate that it's about, there's about 7,000 known rare genetic disorders. And as a whole class, that affects about 25 million Americans. And so that's about 1 in 13Americans. So half of all of these rare genetic disorders are affecting children. And about 30% of children who are affected by a rare genetic disorder will not live to see their fifth birthday, which is sort of a staggering statistic. And as an entire class of diseases, this is about a $400 billion burden to our healthcare system. But the reason why we don't have solutions for this, and in fact, only about 5% of all of these disorders have an FDA approved drug, despite the fact that it's 25 million Americans. So why is that the case? Well, what it comes down to is really a question of economics. And the Baby KJ story is really highlighting, and it's something I made clear in the piece, is that the science now exists to start tackling a number of these rare genetic disorders. We can't go after all of them, but we now have technologies that really can push us into places that we just weren't able to touch before. But the economics of the issue is really where we're failing. And if we think about this, over the last 50, 60 years of modern medicine, we've created institutions like the FDA and our incredible biopharma and biotech industry that what they do is they make breakthrough drugs for your listeners. The easiest thing to think about right now, which everybody's excited about, are GLP1 inhibitors. Here's a drug that can be tested rigorously in biopharma, in a clinical trial, go through the rigorous approval process of the FDA and then manufactured at scale to be injected into millions and millions of Americans. And so the return on the investment is significant there. And so the development of those drugs might, you know, I don't know what is for GLP1s, but it may be in the tens to hundreds of millions of dollars to make those drugs. But then you imortarize that cost over the entire patient population. So individual patients don't see that cost to them. But when you have ultra rare genetic disorders where you only may have one patient, maybe 10, maybe 30 in the world, if it costs $100 million to make a drug, that cost now gets passed on to the patient. So this is where the system really breaks down. The system has been created to make blockbuster drugs that affect, that can be used in millions of patients, not in tens of patients. And that's the problem that we need to solve. Because the science there, this is just a regulatory and commercial problem at this point.
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And it brings up just a torturous ethical issue, which is previously, in cases of a lot of these or in other accidents or diseases, you're in a position where there's just nothing anybody can do. And that's terrible, but there's nothing anybody can do here. What you're describing is we now actually do have technology and science that can cure or at least make people much better than they are, and yet we can't afford to do it or we don't have the infrastructure to do it.
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It.
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So solving this problem is critical and in, in so many different ways. And, and it also seems, as I do more research into it, it's not just the rare genetic disorders, but somewhat less rare like sickle cell anemia and others, that this technology could be used for to make a huge difference.
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Absolutely, yeah. I mean, as you say, it's really now a moral imperative. Twenty years ago there were. We may not have the ability to, or we didn't have the ability to go after some of these disorders. But now that we do, and the only thing standing in our way is really bureaucracy and an economic model, then that's solvable, that's something we can do. Science is much more difficult, but policy and commercial success is something that we can tackle. We have very smart people that can address these things. So it does become a moral imperative.
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B
And let's go into the actual therapy though. What happened? And again, I think most of us have at least heard about crispr. We know it has something to do with gene editing. Speaking for myself, gene editing sounds extremely futuristic. I'm not sure how it works. If you could tell us what you had to do or what, what doctors had to do to create, to treat KJ and others, that would be terrific.
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It's really a culmination of a bunch of incredible technologies. And so the first story really starts back about maybe 15 years ago when researchers that were working in bacteria had discovered that there was a system that existed within these bacteria that allowed them to cut DNA at very specific locations, and that's important. So DNA is a double helix. So there's two parts to it. So it kind of, you know, it's like your two fingers sort of wrapped around each other, and. And you need to be able to cut a piece of DNA in order to get a particular. In order to have a editing possibility, or at the very least, what you need to be able to do is direct an activity, direct a surgical. Let's call it like a scalpel. You have to be able to direct it to a very specific location within the DNA. So your DNA is enormous, right? It's absolutely enormous. There's billions and billions of what are called base pairs or letters within that sequence. And to find the right letter, we need a way to direct the scalpel to the right area. And that's where CRISPR came in. So this discovery that came out of the world of bacteria was that bacteria, again, had this system that allowed proteins, allowed these scalpels to be directed to very specific locations within the DNA. All right? So that's the first piece of it. And then other researchers built upon that and added components to those of scalpels, those scissors that would then, when you directed this CRISPR protein to the right location in the DNA, these additional factors would then correct a mutation. And so you're localizing this machine to the right region in the DNA, and then you're bringing with it another factor that can then change the mutation into the correct letter of the genetic code. And you do that using these little tiny pieces of RNA that can tell the cell exactly where to make that editing happen. So that's really what CRISPR is in a nutshell. But the brilliant. So then the third piece of this, the really brilliant aspect that the CHOP researchers did is that they married those two technologies with the MRNA technology that was developed for the COVID 19 vaccines. And the reason why this is so brilliant is because everything I just told you about making a machine go into DNA and make changes, if it's always there. If you leave that scalpel within the patient, that's not a good thing, Right? You can't, for the lifetime of a patient, have a machinery that's constantly trying to correct their DNA because there's always the possibility that it's going to make a mistake and cut somewhere else. And that can happen. Even if that's at a very, very, very low rate over the lifetime of a patient, it will do it, and that can have a bad consequence. But the beauty of taking all of this and putting it into The MRNA technology, MRNA is uniquely suited as a platform to deliver this stuff, because mRNA. So let's explain what MRNA is first. Thank you. DNA is like your cookbook that tells you how to be you. All right? So it tells you to make all kinds of different recipes. And each page in that cookbook is a recipe. And that recipe has to be taken to a specific place within a cell, which is basically the kitchen. All right? And that recipe is the mRNA. So you go out of the cookbook and you take that recipe and you go to the kitchen and the chef reads it. And this is the key part. As soon as the chef reads that recipe, he tears it up and throws it away so that it doesn't keep making it. And that's what MRNA is. MRNA is a set of instructions, a natural set of instructions read by the body to tell the body to make something, but then as soon as it makes it, it destroys that mRNA. And so it's by taking these scissors, these CRISPR scissors, putting that into a transient delivery system, an mRNA, you're delivering this editing capability only for a little bit of time, just a few hours in fact. And so this allows you to go in just like a surgeon would, make a cut, and then remove the instruments, and the only thing left is the correction. And that's what's so beautiful about the three pieces of technology that went into this baby KJ story. It's very complicated, but hopefully that made a bit more sense.
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B
Yes, it's extraordinary. Let me ask a few questions that I hope will help really sort of create images of what's actually happening. So first, when you say the DNA, the DNA in what, what are the cells that you're targeting?
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Yeah. So again, every cell in your body has DNA. And in this particular case, we're talking about the DNA within baby KJ's liver. And so the liver is the place where we detoxify our body. And in his case, he had this enzyme that was mutated that was not functional. He was not able to deto chemicals in his body, so he built them up as toxins that were potentially going to kill him. And so that was the DNA. The DNA in his liver is where the scissors were directed, the CRISPR was directed.
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B
And as I understand how it works, you actually extract cells from his liver. So you have them in the laboratory, and then that's when you apply the crispr?
- [17:21]
A
Well, no, not in this case. And that's what made this so incredible, because we have had other examples where CRISPR's been used in what we Call ex vivo. So cells have been removed from the body and then treated. But in baby KJ, nothing was removed. The CRISPR was injected as an MRNA, just like the vaccine, the COVID 19 vaccine. It was injected as an MRNA encapsulated by a fat bubble that just went to his liver. And so since it went to his liver, it did the correction in his body. So it was very minimally invasive. It was a syringe.
- [17:58]
B
So that's. This is what, as I was doing a little bit of research to get ready to talk to you, it sounds like the doing it outside the body is now relatively well understood. We're still talking about hundreds or thousands of patients, not millions. It's incredibly expensive and difficult. And in vivo, actually in the body, as you've just described with KJ is the technique that is much more promising. Where it's injection, it happens. There is no removing cells from the body and changing them and putting them back.
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Yeah, and that's the place where people are excited because again, that could help reduce cost because it requires a lot less in terms of the procedure where you have to take cells out of a body, culture them, keep everything super sterile, do the editing, then place it back. And that has been done successfully with certain blood disorders where you actually can get access to those cells, but in other areas like the liver or the heart or the brain. And just to be clear, we actually don't have the technology right now to reach some of those other tissues, but we do have the technology to reach the liver, which is will help hundreds of thousands of patients around the world that have some of these ultra rare genetic disorders. And again, it's much more simplistic. And so that reduces the cost and the barrier to making this work.
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B
You're referring to CRISPR as a scalpel, which certainly helps me understand it relative to traditional surgery. But it's not a scalpel, is it? So, so what exactly is going on? And when you're talking about a strand of DNA that as you say, is humongous, how is it finding the right place? How is it actually slicing the DNA and then how is the change being made?
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Yeah, I mean, the way it's really working is that the there's with base editors, which is a crispr, plus another protein that actually changes the DNA. There's a small piece of rna and RNA is analogous to DNA and what that RNA is like an exact image of the DNA, but this is really tiny now. So if you have your DNA, you know, if you stretched it out, could go from here to the moon. Okay? And this small piece of RNA would only be about literally a millimeter in that space. And so what that little piece of RNA does is it basically has the exact sequence, the exact letters of the region of the DNA that we're trying to target. And you can think of it kind of like a magnet in some ways, with those exact letters. It finds the place in the DNA where the mutation it is where the mutation is, and it sticks to it. And the CRISPR actually helps that happen. That protein that we refer to as a CRISPR protein is helping that little piece of RNA find the right place in the DNA. And then what scientists have done, and this is mainly work from a guy at the Broad named David Liu. He's taken CRISPR and then put other proteins on that. These are proteins that can change those letters. They can change. So there's four letters in the genetic code, and they're A, G, C, and T. And when one of those letters is changed, that's a mutation. And so what these proteins that David's lab has engineered can do is then change the letter back to the normal letter. And that's what's happening. So we're using the small bit of RNA to target the editing enzyme to the right region within the cell, within the DNA. And then the second activity that's associated with the CRISPR molecule is making the change to the right letter.
- [21:56]
B
So it's all biological. You're effectively taking biological material and saying, go fix this biological problem, just to finish discussion about exactly what is happening. The other thing you talk about in your article is the importance of the delivery system. You just mentioned it in passing. Oh, we stick it into a fat bubble, and it goes into the liver and finds the right places. And that we don't have the technology to deliver this little biological doctor to or scalpel or whatever we want to call it, to the brain and other places. So talk about that. The fat bubble. What does that mean? It goes into a syringe. You just inject it into the body. It finds its way to the right place. How does that work?
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Yeah, these are things called lipid nanoparticles or LNPs, and they are little bubbles of lipids, which is like a fat. And they have been used to deliver various small molecules and nucleic acids in the human body. If you received the COVID vaccine, there was a lipid nanoparticle that was that encapsulated, that wrapped around the MRNA that was used in that vaccine. It's important because the cell, every cell in Your body has a fat layer on it. And to get through that layer of fat, these lipids, you kind of need another lipid. And. Cause there's this old saying, like, dissolves, like, all right. So when you put a lipid on top of a lipid, they're going to fuse together. And that's exactly what happened. They fuse. And so that's really what it is. It's a way to get. To make a delivery vehicle so that it can fuse into a cell and deposit material within that cell. So the lipid nanoparticles, or these little fat bubbles are routinely used, but they also have very low what we call specificity, meaning that we don't have the ability to deliver one of these fat bubbles specifically to your pancreas or to your heart or to your kidneys. We could inject it directly into that organ if we wanted to. But of course, getting access to that is difficult. But if you inject almost anything in your body, it doesn't matter what it is, it'll always go to the liver, because the liver is the place that your body detoxifies. So everything goes there. And so that's why we can so easily deliver things to the liver, because we're just working off of what mother nature does. But the truth is, this sort of technology is fairly new now. It's new in the sense, like, it's been around for a couple decades, but in terms of what has been going into the human body, it's still relatively new. There's decades of research on it, but we're just now seeing the utility of it. And when we scientists like myself and others, when they start to see that these things are going to be promising and be therapeutic options, well, then we begin to dream and we begin to experiment and we begin to develop new ways to. To augment and to change them. And that's exactly what's occurring now in the scientific community. You have whole groups of researchers that are literally trying to develop new types of these lipid nanoparticles that can target to the brain, that could target to the heart, that could target to different tissues. And we will get there in time with the appropriate resources and regulatory structure and scientific support that we need and this technology deserves. But we're not there today in 2026.
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B
And in the case of KJ, is it just him? So is it custom to the individual, or are there others with that specific genetic disorder that it could be used on?
- [25:40]
A
Well, this is where it gets really interesting. When you think about this new technology of mRNA, crispr based editing, because it has three components. It has an MRNA that encodes the scissors, you know, the scalpel, if you will. It has the little fat bubble that gets it into the cell and then it has a small RNA that guides the scissors to the right place in KJ's DNA. And the only thing that would be different between KJ and another patient is that little guide, that little tiny guide. Everything else would be the same. And so one way you could think about reducing the cost of these drugs is to manufacture the MRNA base editor and the fat bubble, the lnp, manufacture that and produce it at scale once, so that you have an FDA approved scissor, right, or scalpel. And then for every new patient that comes along with one of these metabolic disorders, you have that little tiny guide. That's the bespoke part you need to make. And if we could work out a economic model where we could scale the scissors to where we could treat thousands and thousands of patients, but then have the medical centers be able to produce the little bespoke part, then we can make this economically feasible. Because the only thing that has to change is that little tiny part. And that's a lot more, that's a lot less expensive than manufacturing the entire platform every single time that a patient comes along.
- [27:28]
B
So that's a great step into the last section of what I want to talk to you about, which is really what has to happen to make this available to a lot more people. But before we do that, let me make two observations. One, lots of people will occasionally say, hey, you follow the news, like, is there any good news in the world? Like, is anything positive happening? And what I always come back to is just the incredible advances in medicine over the last century, but even over the last decade, and boy, is this one of them. I mean, it's almost unfathomable just to think about exactly what's happening and the technology and the research that has to go into that and the extraordinary things that can do. And then the second comment is, anybody who follows the Silicon Valley longevity, we're going to figure out how to stop aging and live forever. Community will know that one of the things that everybody's very excited about is the day when there are going to be, quote, nanobot doctors that swim through our bloodstreams and fix everything. And at least from my perspective, what you have just described is exactly that. So it is already here. And just judging from the KJ story, there is a heck of a lot of, or there should be a lot of excitement around that. I was thinking it was just something that people in Silicon Valley say, but it actually already seems to be happening.
- [28:46]
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Yeah. I mean, the truth is that we're developing technology that really can correct mutations, and we know a lot about the human being and what goes wrong, and we just haven't had the access to be able to correct these mistakes. And this is just the tip of the iceberg. I mean, these are early days. I wouldn't want your viewers or your listeners to think that tomorrow we're going to solve all rare genetic diseases or any other conditions like aging or heart disease, whatever. But, you know, this is a moment. This is a moment in human history that people will reflect upon in a hundred years and say, do you remember when, you know, people were dying of, you know, cystic fibrosis or other rare genetic diseases? And now they're not because we have these tools. So it is a very positive story in a troubling time. Absolutely. When you need to build up your team to handle the growing chaos at work, use Indeed Sponsored Jobs. It gives your job post the boost it needs to be seen and helps reach people with the right skills, certifications and more. Spend less time searching and more time actually interviewing candidates who check all your boxes. Listeners of this show will get a $75 sponsored job credit@ Indeed.com podcast. That's Indeed.com podcast. Terms and conditions apply. Need a hiring hero? This is a job for Indeed. Sponsored Jobs Eczema is unpredictable, but you can flare less with epglis, a once monthly treatment for moderate to severe eczema. After an initial four month or longer dosing phase, about four in 10 people taking Eblis achieved itch relief and clear or almost clear skin at 16 weeks. And most of those people maintain skin that's still more clear and one year with monthly dosing.
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- [31:43]
B
all right, so let's talk more about what has to happen. We've talked a lot about cost, and I think there's another component to that which is you described of the three technologies here, we can make two of them on the shelf and one is custom, and that really reduces the cost. My understanding is that this in the body treatment is already radically less expensive than the way it's been done outside the body, where you have to extract cells and work on them in the lab and then put them back, in part because there's chemotherapy involved and so forth. What else is creating the immense cost here and what might we be able to do about it over the next five to ten years?
- [32:21]
A
Yeah, I mean, the first barrier has been the regulatory barrier, which is the way the FDA works. And this is but there is, there's positive news in this way. So the FDA is the gold standard of the way we do medical intervention around the world. And that's just the truth. We, we've established this agency for the the people of America in order to ensure that when we make a drug product that it's safe and that it does what it's supposed to do. And that requires rigorous clinical trials. And a clinical trial is basically in three phases. And it's a way to gradually test whether a drug is going to be safe and whether it's going to have efficacy, meaning that it actually does what it's claims to do. And clinical trials are better when you have large populations. And the larger that population, the better the data are because there's such a diversity within the human population. You have men and women, you have different ethnic groups, you have different weights, different ages, everything. So the way people respond to drugs are dependent upon those various factors. Now, if you think about a drug like a GLP1 inhibitor, you've got millions of Patients you could test it on. But now think about an ultra rare genetic disorder where you might only have 30 patients worldwide. And how are you going to design a clinical trial for patients when there's not enough patients to have? The clinical trial becomes the treatment, essentially. And so that has been a barrier to cost. But the FDA is moving in the right direction. There. There have been a guidance framework called the plausible mechanism framework that came out Undercarry's direction, and that is under review and comment section right now until April 27, I believe. And the hope there is to change the way the FDA regulates these drugs for ultra rare genetic disorders such that you reduce the need for rigorous clinical trials. And that's a positive move in the right direction. But even with that, we still have the other barrier, which is what I alluded to earlier, which is the manufacturing piece. And the manufacturing piece is the thing that is really standing in our way. Because if you have to make a drug at such a high standard that to ensure its safety and its efficacy, it drives up that cost. And of course you have to amortize that cost, overpopulations, like I've said, but that's difficult to do with rare genetic disorders. Instead, you put that entire cost on 20 patients. And the solution here is to find a way to change the economics of this. And I'm not saying that I have the solution. This is a difficult. This is a difficult enterprise to undertake. And it's going to require that we totally rethink the way in which we do drug discovery and drug commercialization in the United States for these particular approaches. But one possibility is to move it away from a commercialization platform where. And you can think about with this, with the CRISPR base editing that we've been talking about, where you have a component that has been rigorously tested that can be used on a lot of patients, but then you have an individualized component that will be bespoke for each individual. And if you can take that tier one approach, that first component, test that like crazy, make sure that that's perfect. But then the bespoke component, you can't have the same sort of rigorous manufacturing and quality control systems for that. Instead, what you have to do is you have to regulate the platform. Meaning you're going to say that I'm going to regulate, let's say, the machine that makes it, so that the machine that makes it is held to a standard, but it can make thousands of these in unique ways. And then it's like calling up the pharmacist and saying Hey, I need this drug today or I need that drug tomorrow. But it's all going through the same. Let's say it's a machine. And if you could do that and regulate it as a platform and not burden the manufacturing cost on the individual bespoke component, you have the potential to significantly change the economics such that it's much more affordable. And if you also can then at the same time change the way you build this, meaning that it goes to a procedure rather than a product, then insurance companies are more likely to be able to reimburse because now it's a surgical procedure rather than a pharmaceutical drug.
- [37:01]
B
And for everybody who immediate, the immediate reaction is, oh, well, insurance companies are never going to approve this anyway. One of the arguments there is that some of these diseases cost so much to treat over a lifetime that in fact, if there is even an expensive treatment that changes the course of the disease, it actually saves a huge amount of money over time. So there is hope there. So what has to happen for what you described to happen where effectively as, again, to use a really simple analogy, you're almost saying like, yes, we need to approve the kitchen and we will know that a lot of different foods are going to be made in the kitchen, and they don't each have to be made to a particular standard and approved ahead of time.
- [37:42]
A
I mean, what has to happen is you have to have conversations like we're having today and like what everybody is having in this next, you know, this last year, since baby KJ in the next few months as well, is you need to get all the stakeholders at the table to talk. This isn't an FDA problem, It's not a biopharma problem. It's not an academic problem, it's an economic problem. It's all of the above. So everyone needs to get together to really talk about the issues and try to work them out, including the insurance companies. You need to get them involved. And so that there's a framework that everybody agrees upon. Right now, we tend to, with any of these sorts of medical interventions, we treat them and deal with them sort of siloed. The scientists work out all the science, the biopharma works out kind of manufacturing and commercialization, the regulators work out the regulation and policy, and the insurance companies do what they do. And everybody needs to come to the table in order to figure out what would be an appropriate economic model for this to work and to work with a common vision. Because it goes back to something you had said earlier today where this isn't a question of, you Know, can we do it? We can do it. So it becomes a moral imperative. In the past, I think it was convenient for people to say, well, you know, that would be great if we could harmonize across all of these agencies and bring therapies to ultra rare genetic disorders. But you know, they're all one off products. You know, there's a product that deals with cystic fibrosis, there's a product that deals with sickle cell anemia. But there's nothing that we can do to try to uniform the way we treat all of these diseases. But that's changed now with what happened with baby kj is we now have a moral imperative to solve this. And I think that's what's bringing people to the table and why this conversation has ignited in the last year.
- [39:28]
B
And there's a lot of talk for very good reasons in this country about just inequities in healthcare and how you are in much better shape in terms of being able to get what's out there and available. If you have a lot of money, if you're a billionaire today, can you fund your own treatment on this? Or is it something that's even so far beyond that that you do need a special case like who paid for baby kj?
- [39:53]
A
I mean, a lot of this comes out of philanthropy. That's just the fact that there's, yeah, a billionaire could do it if they wanted to, you know, and that a lot of what we operate on with these ultra rare genetic disorders are really the generosity of high net worth individuals. And the rare disease community is very thankful to those individuals, but it's not sustainable. And you see this a lot where there will be an individual of high net value that may have a family member that's afflicted by some disorder and then they'll donate a large amount of money to in fact, you know, go after that disorder. But it's a one off academic exercise and it's sensational when it happens, but it's not viable. And we can see that's exactly what's happening here with baby kj, where to replicate what they did. It already has this huge $7 million burden on it. It's just not going to happen again. The companies that are involved, they need to be able to recoup their costs. The medical centers that are involved also they have to recoup costs. You can't just do all of this for charity. When it comes right down to it, you have to have an economic model that will work.
- [41:03]
B
And coming back to what you said earlier, about government funding and the importance of that. So where are we in that? We're all hearing all the time that more and more funding is being cut, national institutes of health funding and others. And there is certainly a view that a lot of the money was wasted and we should spend it more in a more disciplined fashion. What's happening to the money for this kind of treatment going forward, and how much of this can be solved by government funding?
- [41:33]
A
Well, I mean, what's been happening to the funding structure in the United States is really appalling because we have been. We have invested into the health of Americans through science and discovery over the last 60 years through the national institutes of health and the national science foundation, Department of defense, et cetera. And you could say that that's wasted, but there's all kinds of statistics out there that show that for every dollar of spending in research and discovery, it pays back threefold, and probably even more, when you really think about it. And all of these. You know, a good example of this is. And I'll keep using this because I think Americans are fascinated by GLP1 inhibitors right now. The discovery of GLP1 inhibitors that came out of research that was done on Gila monsters, literally Gila monsters. This is this, you know, ugly little lizard that exists in the American southwest, right? And nobody would think, oh, I want to go study a Gila monster. Is that going to ever do anything for human health? Well, here you go. Right? So doing research, the investigators that were doing some of that science on Gila monsters discovered these chemicals that they could then develop and become these GLP1 inhibitors that are going to save countless numbers of lives by reducing the burden of obesity in the American population. So here's a direct benefit, economic benefit. The discoveries that came out of crispr based editing, those were based on studies of bacteria. And most of that research really started in folks in Europe working in the yogurt industry, where researchers were trying to figure out why sometimes their yogurt cultures were dying. And they looked into this more and more, and they found they discovered this CRISPR system that was previously unknown about and never would have been discovered if you weren't doing some of this basic science. And so dismantling the infrastructure around the national institute of health, which is what we're seeing in the last two years, is going to have devastating consequences to our ability to continue to develop these therapeutic options. And it really. I've been doing science for well over 30 years, and this is the first time that I feel like we can make a huge difference in these rare disease populations because we've taken all of this technology and put it together and now have the ability to correct mutations and treat these conditions that were previously untreatable. And we have to keep investing. And I'll just use one last analogy which I think people may resonate with is in 1940, if you were a parent, one of the diseases that you were really scared of was childhood leukemia. And childhood leukemia in 1940 had a 95% death rate. Absolutely. If your child was diagnosed with childhood leukemia, they'll be dead in a matter of months. And in 1950, we took that rate. So we thought, scientists in the medical community thought this was unacceptable. And by 1950, we continued to invest into research into childhood leukemia. We changed that number from 95 to 90%. In 1960, we changed it to 85, 1970 to 80, so on and so on. Incremental advances in science and research changed the outcomes for children with childhood leukemia. So that by 2026, if you're diagnosed with childhood leukemia, you have a 95% chance of survival. We've taken 95% chance of death to 95% chance of survival over a generation with incremental investment into research and development. And so thank God that our grandparents did that so that our children don't have to worry about these devastating disorders. And that's the moment we're in now. Are we going to invest into the future for our children so that they, that 1 in 13Americans don't have to be burdened by these disorders that they're living with today?
- [45:28]
B
And just to underscore that point, so in the leukemia example, that's government funding is doing a lot of that.
- [45:35]
A
All of it. I mean, for the most part, all of it. If you, if you look at, in the technologies that we've been talking about today, the mRNA, the crispr, the base editor, that's all government funding. And the government invests in its people and takes care of its people, and that's a good government. And no other group is going to do that. Biopharma doesn't have that kind of money to do that. And you know, and goes back to the underscores, the point that we were talking about where you have to experiment to see whether things are going to work. These base edit CRISPR MRNA based editors. This is really an amalgamation of several technologies that have been thrown together and to do something incredible. But that comes out of laboratories, in academic centers where people have dreamed about doing things. There's a lot of failures that happen in academic labs Trust you me, I know that. But every once in a while when you have a bright idea and it works, then you can really change the world. But that's something that has to occur through research.
- [46:35]
B
We're not government budget analysts, but can you give us a sense of what
- [46:38]
A
the budgets look like?
- [46:40]
B
Like what is the NIH budget compared to, say, defense or some of the other big, the actual big things?
- [46:48]
A
It's a fraction. I mean, we, you know, every time we get involved in one of these skirmishes around the world and we talk about a missile launch and scientists think how many grants just went into the air and blew up. I mean, the average NIH grant is, you know, maybe a million dollars per year versus what's the cost of a, you know, a missile per missile. Right. I mean, that, I think that's a good way to put it into perspective is that researchers that develop some of those life saving therapeutics combine their combined grants are probably less than the cost of, you know, one Tomahawk missile.
- [47:28]
B
Jeff, this is incredibly, inspire, inspiring. I'm so grateful to you for writing the article, doing the work, and also taking the time to explain it to us. And a lot of us will be watching and quite incredibly closely as this continues to develop going forward. So thank you.
- [47:43]
A
No, thank you. And I appreciate your time.