The Intersection of Energy and Modern Medicine

Mary Carpenter This is Fissionary, a show exploring how nuclear powers your world. I'm Mary Carpenter.  

Jordan Houghton And I'm Jordan Houghton. Let's jump in. Hey, Fissionaries! Welcome to today's episode. And hi, Mary.  

Mary Carpenter Hey, Jordan. How's it going?  

Jordan Houghton It's going really well. I'm very excited for today's episode because we are talking to two researchers from the University of Missouri, which is where I did grad school. So, you're going to hear from them, but I'm also going to say, "M-I-Z" to kick off this episode.  

Mary Carpenter Well, I have to throw in a "Go Dawgs" now just because we talked a lot about Mizzou, so I just need a little call for the dawgs here at the beginning!  

Jordan Houghton You know— 

Mary Carpenter They were amazing.  

Jordan Houghton I think that this is this is actually the perfect time. We haven't talked about it yet this season—nuclear is everywhere at college game day.  

Mary Carpenter Oh my god, I love it, it's so fun to see all the signs. And I love how into it the students are getting. I need to see more, though. I don't think I saw one this weekend.  

Jordan Houghton I was going to—I was trying to remember. I missed most of this weekend, so I didn't see, but we were—it was almost every week in a row to start out, and then we talk about this later in the episode, but the Missouri football coach actually gave a shout out to the research reactor when he did his game day interview. And it's just like really wild crossover that I—it's like, is this real life? That there are—it's like, football and nuclear.  

Mary Carpenter And I love it. I think it's been like an organized movement with a bunch of students, and it's brilliant. I mean, what it—they get so many viewers on college game day every week. I mean it's such a great place to do it. So, I'm super impressed and hope that they keep moving. And if there's any students listening, if you guys need help and like—we can advertise on Fissionary, like whatever school they're coming to, so just let us know. We're happy to help the cause.  

Jordan Houghton Yeah, you know what we need? We need Fissionary signs at GameDay. 

Mary Carpenter Yes. 

Jordan Houghton That's what I want to see next. So, college student listeners throw up a Fissionary sign for one of the future games.  

Mary Carpenter Yes. That would be amazing. That would make my whole day. That make my whole season! Especially after the Bulldogs lost horribly this weekend. At least I could count on the nuclear energy students!  

Jordan Houghton I hope we see it— I hope we see it next season to be like—I hope it just keeps getting stronger every year.  

Mary Carpenter I know, they need to keep this up.  

Jordan Houghton So couple weeks ago, we had an episode talking about the Rhisotope project and how isotopes are being used to help with rhino conservation. This episode is great because it's going to give the basics of isotopes, and I think that's really important. We talked about nuclear medicine last season. We brought up isotopes this season. This is like a sort of 101 on isotopes.  

Mary Carpenter Yeah. Last season we talked about how it's saving human lives, this season we talked about saving rhino lives—yes, we just really dive in. We wanted listeners to be able to understand a little bit more how it works, where they come from. And the folks at MURR just did an incredible job explaining it in a way that's very easy to understand. And you can learn more about how it's fighting cancer in both humans and pets and all the other exciting work they're doing. So, let's dive in.  

Jordan Houghton Today, we're joined by two leaders from the University of Missouri Research Reactor, Mike Hoehn and John Brockman, who are at the forefront of nuclear research and education. Mike is the program director for NextGen MURR and is leading the charge to build a groundbreaking 20 MWt reactor designed to expand isotope production for innovative cancer treatments. Joining him is John Brockman, associate director of research and education at MURR, whose expertise and radio analytical techniques has made significant contributions to fields ranging from nuclear forensics to engineering. Gentlemen, it's an honor to have you both here. Welcome. I would love for you each to start out by telling us a little bit about your background and what led to your current roles at MURR. And Mike, we can start with you.  

Mike Hoehn Good morning. I'll give a M-I-Z shout out here to start. Yeah, my background started out—Missouri born and raised, and went to school here at the University of Missouri, Bachelors in Mechanical Engineering, and in 2006, I started my career at the Callaway Energy Center for Westinghouse four-loop pressurized water reactor. And really took my role in the nuclear energy field very seriously and took a lot of pride in knowing that I was providing safe, reliable, efficient electricity to our customers, into the world every day. Fulfilled various roles in that area from engineering, nuclear oversight and during design projects. In 2022, when I saw the university had started a pursuit of a new reactor, there was an announcement made for the University of Missouri to look at a new state of the art, larger reactor to build upon that experience and the success of Mizzou, University of Missouri Research Reactor became interested. It's hard not to become interested in something that important going on at your alma mater. And then I had the opportunity to interview and engage in this opportunity. And so, the NextGen MURR is an initiative to build, like you said, a new, larger state of the art research reactor to advance the lifesaving, life improving mission on the radio pharmaceutical side, as well as initiative to perform new state of the art nuclear science and technology research, and it is happening right in my backyard in the community that live where I raised my family. You know, I have three girls and I know what that could mean for their future and the generations to come.  

John Brockman So my name is John Brockman. And as stated earlier, I’m the associate director for research and education at the MU Research Reactor. I grew up in Southwest Missouri, where I went to Glendale High School in Springfield, and decided to study chemistry at Truman State University. And like most chemistry majors during school, I did not run across a radiochemistry class. We'll have the opportunity to take one. But towards the end of my senior year, I read Richard Rhodes’ Making of the Atomic Bomb, and that was quite a book, and it really made me passionate about trying to find a way to plug into radiochemistry, you know, at the graduate level. And so, it turns out that the University of Missouri had one of the largest radio chemistry programs in the country, anchored by the MU Research Reactor, and I picked a radio analytical chemist to mentor with and was off and running. So, I actually started as a postdoc at the reactor working for a nuclear engineer after I got a radiochemistry degree. From 2006 to 2008, I had the opportunity to learn MCNP, which is a code that you normally only see nuclear engineers run, and use that to design and build a new neutron beamline for boron neutron capture therapy. And then I was able to talk myself into a job here as an assistant research professor, and since then I sort of moved up the up the ranks here at the reactor. And so, in my current job, I have a split appointment between the Department of Chemistry, where I teach classes, and radiochemistry, and I take graduate students. And then my appointment at the research reactor, I oversee the umbrella research programs that we have here, and those actually are very multidisciplinary. So, it was mentioned that I'm a radio analytical chemist, but we also have a large radiopharmaceutical science program here that covers chemistry, biochemistry, all the way up to clinical science. And we've also had an archeology program here, which uses the reactor to do neutron activation analysis of ancient artifacts, and they use that to do provenance studies. It's really, really fascinating work. We've also done plant biology. We've done neutron transmutation doping, so some work in electrical engineering and I'll get a scientist interested in additive manufacturing, so making new parts for the next generation of small modular reactors, and then we will test them to see how they behave in radiation fields. We have groups working in materials science and nuclear forensics, the list goes on and on. So, it's really exciting place to be.  

Mary Carpenter This is very cool. Thank you both for joining us. We clearly have a lot to talk about. So, I want to start with how did the vision for NextGen MURR come about and what are the goals that you're trying to achieve with this project?  

Mike Hoehn Just to kind of put in perspective, you know, the University of Missouri Research Reactor (MURR) is the sole producer of four radioisotopes in the United States. And to think about state-of-the-art, 1966 reactor technology, is the sole producer of, you know, radioisotopes that are, you know, treating and diagnosing cancer every single day, kind of gives you some pause when you think about the fragility of the supply chain, especially domestically in the United States, as well as, you know, what it takes to keep a 1966 reactor at peak reliability. Now, MURR is an amazing facility, operates six and a half days a week, so we're able to operate 52 weeks a year and produce those short-lived radioisotopes that are used to treat and diagnose cancer. That makes us very unique, largest reactor—university operating reactor—in the United States. But when you kind of think about the fragility of that supply chain and the security of supply, you know, and then the expansion of radioisotopes, you know, and the ability to treat cancer and the clinical trials that are on the horizon. We think we're at the precipice of something very important. So, we saw the need to expand. Because MURR essentially nearing capacity in our ability to treat and diagnose cancer patients. Essentially, we have a flux strap that's, you know, 36 inches but the peak flex position is no longer than your forearm. Keep that in perspective. So, state-of-the-art 1966 technology, the length of your forearm is our peak flux positions where we're creating those radiopharmaceuticals, and we needed to expand that. So, when you think about that, you know, we have the ability to more than triple our radioisotope production capability, impact more lives. And there's also an opportunity to bring not just the radiopharmaceutical and the cancer fighting ability, but as John highlighted, we're doing some pretty amazing things on the research side. So, NextGen MURR, we also envision state-of-the-art neutron scattering potential. We want to pursue a guide hall, which will allow us to have 15 to 20 state-of-the-art instruments where we can do awesome, amazing neutron scattering instrument technology and really take, as John highlighted, you know, we want to support energy storage, we want to support new advanced materials research. We want to do new research not just on the radiopharmaceutical side, but also on—and the nuclear science and technology fields. So, the ability to impact our local, our state, our nation's economy, bring not just, you know, security of supply from radiopharmaceutical standpoint, but also expand the neutron scattering portfolio and work with the national labs, work with National Science Foundation and the National Institute of Science and Technology to pursue that that advanced portfolio. It's amazing opportunity.  

Jordan Houghton This is the first time we've had the chance on Fissionary to talk to a university-centric program and the timing is really great because a few weeks ago at the start of college football season, there was a nuclear engineering student in Texas who got his “I Love Nuclear” sign broadcast on College GameDay, and we've seen several more of those in the weeks since. And I'm wondering if there's been any sort of excitement around nuclear on the Mizzou campus as part of the football season. Are you seeing anything there, or what's the feelings with the students in general around the programs?  

Mike Hoehn I think it's not just the students. It's faculty, it's staff, it's the—you know, the state's excited. And for example, you know, our head football coach, Eliah Drinkwitz, was on College GameDay with Spot the robot, walking around on the football field. But you know he gave a shout out to the University of Missouri Research Reactor and the largest university operator research reactor in United States. So, when your head football coach of an SEC football program is giving a shout out to the research reactor, that's pretty special. And it's pretty awesome to have that energy, that excitement. You know, people were swinging by my tailgate this past Saturday when Mizzou is playing, and gave them a few stickers. And what's awesome about it is we get to tell the story, the amazing story of MURR, which I don't think has been told enough over the last 58 years. And then we also get to share this vision of what NextGen MURR can become operating in parallel with MURR.  

Mary Carpenter I saw that GameDay. I was so excited! That was awesome.  

Jordan Houghton It was almost surreal hearing a football coach talking about nuclear. It was like, is this this is really happening? How awesome is that?  

Mary Carpenter Yeah, and Spot was just walking around, that was really cool. So how is—I guess, how does having MURR on campus help get students involved and young people interested in nuclear?  

John Brockman So, we have a variety of outreach programs to get students involved, and that includes regular tours that we host for undergraduate students and the honors college and then many of the other classes that are on campus. We also teach classes using the MURR, so we have a laboratory, you can take an undergraduate course in radiation detection and measurement. It's either offered through the engineering school or through the chemistry department, depending on where you are and where you need the credit. And in that class, students are able to handle radioactive materials and including doing wet chemistry labs with radioactive tracers, which is pretty unique within the university system. There's not too many other places that you can go and handle a laboratory where you have access to chlorine 38 or more of these other short-lived radio tracers to do a chemistry experiment. We also host events like Boy Scout merit badge academies, and there's community outreach events to local high schools where we'll bring in high school teachers and tour them around the MURR, and give them access to kits where they can go back and do a radiation detection and measurement laboratory for their own high schools.  

Mike Hoehn I would just like to add, you know, what's pretty awesome about MURR and the vision of NextGen MURR is we have the opportunity to connect with every single school on campus. So, you know, obviously we've been working closely with the College of Engineering, and we met with the new dean of the  College of Engineering, and we've been talking about what we can do to partner with them as they pursue their Center for Energy Innovation at the University of Missouri, a new facility looking at, you know, energy, including the nuclear energy pursuits. We've been working with the College of Agriculture, Food and Natural Resources and how we can partner with them. Obviously, we have a strong presence there in the state of Missouri, so it's important we look at what we can do to help there. And then, you know, one of the things are just interesting, we have a pretty cool augmented reality and virtual reality lab, and we call it the iLab, the Department of Arts and Sciences. And we're looking at how we can partner with them for augmented reality and, you know, potential digital twin technology for NextGen MURR and how we can integrate that with MURR. But we also have, obviously, an awesome med school, and we even have an excellent precision health facility, where we are looking to have that whole bench, the bedside technology where we can do everything from producing the neutrons or radioisotopes and even doing the electrons here all within the campus. So, we're going to connect with everybody and we're looking forward to, you know, making sure that everybody has a part of MURR and NextGen MURR into the future.  

Jordan Houghton It's really cool to hear all the different age groups that you're working with. Boy Scouts, high schoolers and even undergrads. I feel like there is a perception, maybe, that to get into research like this, you have to be at a graduate level. So, it's really cool to hear that there's opportunities even for undergrads who might still even be figuring out what they want to do to get some hands-on research experience.  

John Brockman Yeah, you know, and to follow up on that, many of our laboratories will hire undergraduate students. Of course, we like to hire them as freshmen or sophomores because it takes a little bit of time to get somebody trained up as a radiation worker to work in one of these laboratories, and then, of course, we like to keep them full-time. And they do things that range from independent research, so they'll work with their advisor on a research problem, but we also have many other types of jobs where you can come to the reactor and you can work with an HP tech and learn how to do health physics. Or you can do a tour with operations over the summer and you can crawl all over the reactor and see where every pipe goes and where every lead brick is stored. And we also have opportunities to work in the analytical laboratories, like my laboratory or the archeometry laboratory, where you get trained to run a pneumatic tube system to irradiate samples much like you would do at a bank. So, you know, you send your check into the bank and they take your money or they give you something back, here we're doing the same thing. We have a new pneumatic tube system for the sample and it takes about three or four seconds to get to the core of the reactor, where it's irradiated for a few seconds, up to minutes, and then it comes back to the laboratory and the students are trained to do that process. And the gamma ray spectroscopy associated with a neutron activation analysis mission. So, you know, lots of different people from different backgrounds get to go through these laboratories.  

Mary Carpenter That's really cool. I want to back it up a little bit and kind of start with the basics, if you guys could just share what we're talking about. What exactly is an isotope, and why is it such a critical part of medical treatment?  

John Brockman Sure. Well, let's start by thinking about the periodic table. So, we all sort of remember the periodic table and we remember that each one of those boxes that you see on the periodic table, that's a different element. And the different elements are distinguished by the number of protons that they have in the nucleus. Each one of those elements, distinguished by the number of protons, can have different number of neutrons. And so, an isotope is an element with the same number of protons, but could have a varying number of neutrons. And one way to think about this, and I like to do this some time for the alumni, I'll show up and I'll have apples. And I have a red apple and a green apple. The apple is the element. And each of those apples taste the same, right? So, it has the same chemistry. But there's a difference in that the red apple has a certain number of neutrons in the nucleus, and the green apple has a different number of neutrons in the nucleus. So, they're both apples, but they're just a little bit different because they have different numbers of neutrons in the nucleus, so those are like isotopes. If I take one of those apples and I put it into the reactor, it gains neutrons, becomes unstable, and spontaneously decays into an orange, right? And that's what's going on when we do transmutation in a reactor, right? So, we're taking apples, we're making oranges. The orange is the radioisotope that I'm interested in making. And so, the radionuclide that I made in the reactor, the radioisotope, it's unstable, so it has excess energy in the nucleus, unstable number of neutrons and protons, and it wants to give up some of that energy. And because we've added in neutron, mostly those elements want to beta decay, which turns a neutron into a proton, right? And so, that's what we're leveraging to make our radioisotopes. Now, some of those radioisotopes are valuable for nuclear medicine and they have to fit a very specific criteria to be useful for nuclear medicine. So, you need something with the right half-lives. So, in theranostic nuclear medicine, the idea is that you create this molecule, and the molecule has some feature on it that targets a tumor cell. So, that could be on the molecule, it could be a peptide, it could be antibody, it could be a small molecule, right? There's some chemistry or biochemistry going on there. It's like a key that fits into a lock on a cancer cell and sticks there, ok? And then we have on the other side of that key, there's a molecule we call a linker, and it's just like a chain. You can think about it as a chain. And its job is to hold the radioisotope on the other side of that biological molecule, that key that goes into the cancer cell. And so, that radioisotope can either be tuned to do diagnosis, so in that case, we want an isotope that decays by positron emission, right? And so, you can use a PET camera in order to measure where the molecule went in the body, and—or, you could use it to deliver a killing dose of radiation, and in that case, you either want a beta particle that has a beta emitter that has high energy betas, or you want an alpha emitter, or you want something a little bit more esoteric, like an OJ emitter. And so, for a beta emitting isotope that you're going to use for therapy, you want something with like a couple of day up to maybe seven day half-life, and it needs to have a beta that's relatively high energy, so something in the—at least 100 KB up to maybe a 1 MB beta particle, which is a high-energy electron coming out of the nucleus, and then those beta particles, as they move through tissue, they give up their energy through interaction, mostly with water. And so, there's lots of water in your body, right? It's in your cells, it's all over. And so, as it's interacting with water, it's creating radicals and peroxides and all different kinds of reactive oxygen species and those reactive oxygen species then flood the cell, interact with the DNA, and ultimately cause cell death. So, that's what's going on in the diagnostic part. And so what makes theranostics really, really valuable is that it's precision based therapy, and that the physician knows that if they send in the molecule that's labeled with the diagnostic isotope and it lights up where the cancer cells are in the body, then they know that it's going to work when they deliver the therapeutic isotope because the therapeutic isotopes are going to go the exact same place as where the diagnostic isotope went and it's going to deliver cell-killing radiation. And that's what these new radioligand therapy drugs are based on. And what MURR does—Mike mentioned that MURR has this flux trap—that flux trap, what he's talking about is, the University of Missouri Research Reactor is unique amongst research reactors in its design. So, a lot of designs for these reactors are TRIGA designs, which is the old General Atomics design, and it's a grid style reactor where you have fuel that's arranged in a grid and you have openings between those fuel elements. The MURR reactor actually looks like one loop of the advanced test reactor. So, it's an annular core, the fuel is like a hollowed-out donut that's stretched out on one axis. And there's a space in the middle of that donut around the fuel and we call that the flux trap, and that's where the neutron intensity is the brightest. Neutron flux is the brightest there. And so, that feature makes—and the 10-megawatt power—makes the University of Missouri Research Reactor unique in its capability of doing this on a routine basis. And so, what we do is we make these four medical radio isotopes. They are iodine-131 for thyroid cancer, Y-90 for a treatment called TheraSphere, which is for liver cancer, iridium-192 seeds, which are for brachytherapy, and they're used in many diseases, prostate cancer being one of them, and then lutetium-177, which is made by radiation of ytterbium-176. And the really the high intensity out of the neutron flux and MURR's operation cycle make it possible, and only possible, at a research reactor, this research reactor, to be able to make those isotopes. And so, you know, we were involved early in the development of lutetium-177, actually 15 years ago, with AAA, which was bought by Novartis and provided that radioisotope for clinical trials, and have since gone on to now support those two drugs that are being made through routine production of an active pharmaceutical ingredient. And so, that also makes them more unique in that there is no other research reactor actually bringing active pharmaceutical ingredients.  

Jordan Houghton John, this is a great science lesson, very helpful for listeners. We talked to, last season actually, Dr. Paulien Moyaert, who is a nuclear medicine physician in Europe, and she was able to talk a lot about how the isotopes are used. It's really exciting to have the background now on how they're produced and where they come from before they actually get to the treatment setting. And can you tell us a little bit about how challenging is it to produce these isotopes? What's the—is it—is the process easy? Is it hard? Does it take a long time? What does that look like?  

John Brockman Yeah. So, you know, on the surface, the process looks easy, right? You take a sample and you stick it into the core of an operating nuclear reactor and wait and pull it back out again. And it doesn't seem like it should be that hard. But of course, in fact, it is very challenging. And the reason it's challenging is because we're doing this in volume and we're doing it under FDA guidelines and we're doing it under NRC guidelines. And we ship them with guidelines from the Department of Transportation, and oftentimes they go overseas, and so you have Homeland Security involved, and then you have to—have the regulatory agencies on the other side in the other country involved. And so, it's not as simple as you might think. It requires a lot of moving parts. And actually some of our core strengths are things that you may not really think about when you think about a research reactor. The reactors operate six and a half days a week, the operations crew is here seven days a week, 24 hours a day, and so, you know, there there's always somebody on shift. Our health physics team has to be able to take care of these high activities that we're making, right? And all there has to be proceduralized and they have to—once they're come out of the reactor, they have to go into hot cells. So, in this reactor we have something like 25 hot cells, soon to be expanded up into the 30s, for isotope production. And these hot cells are giant lead boxes with up to eight-inch-thick walls, and an eight-inch-thick wall lead hot cell weighs as much as Boeing 737 airplane, but it's in a space about the size of your bedroom. And then shipping is also very challenging. So, there's lots of rules around shipping radioactive material, as you can imagine. And you can't just ship it in any box that you buy from FedEx. So, we have extensive experience shipping radioactive packages. Last year, we shipped 7500 radioactive packages around the world. That requires quite a team. We do that by private courier. Sometimes they fly out of airports like Chicago or Saint Louis. We do that with FedEx. And there's all kinds of other options as well. And, you know, one challenging antidote is that an airplane pilot, so you may need to fly this isotope to Europe for a treatment or a or a research project that we're going to do over there. Every airplane pilot has control over their airplane, and they may decide today, I don't want to ship a radioactive package on my airplane. And so, we have specialists and logistics who are on the phone constantly working on all of these samples, making sure that, you know, this Pilot Smith won't take the radioactive sample, maybe we’ll get it onto Pilot Jones' airplane in a couple of hours. You know, there's lots of logistics work going on. And then the actual process of making the active pharmaceutical ingredient requires a large team. It's production radio chemists, but it's also a robust quality assurance and quality control team working together under FDA guidelines which are audited to produce a ray of pharmaceutical that's safe for humans to consume as part of a drug therapy. So, the total number of people that we have to do all of these things here is approaching 300 FTE, so it's quite a busy place. And I don't want to minimize the student impact. There are students that plug into all of these different areas under internship programs, we have our own training programs to train people how to do this because of course, you can't just go find somebody with a college degree and array of pharmaceutical development chemistry or array of pharmaceutical production chemistry, right?  

Mary Carpenter So is this why you are the only ones creating some of these isotopes? It's just the complexities from sounds like regulations to delivery?  

John Brockman So yeah, there's some of that. It's a unique facility, so, Mike has mentioned this 10-megawatt power that makes us unique. Our operating schedule makes us unique. We're the only reactor in the world, test reactor, research reactor, power reactor, that operates six and a half days a week, 52 weeks a year. We turn it off every seven years for two to three weeks to replace the drilling reflector in the test reactor. And you need that cadence in order to produce rated pharmaceuticals because these have a shelf life such that you have to use the isotope the week that you made it or it's not good, you can't store it. So, if we don't run this week, cancer patients are treated by the end of the week, they're not treated next week. So that's the challenge.  

Jordan Houghton I have a logistical question. Because you're mentioning having to use the isotopes within a week of producing them. So, you're producing them constantly to keep them going. What if there's, like, a snowstorm, and like what—you're just, what do you do?  

John Brockman Yeah. So, we are part of a group of reactors that include several in Europe, and there's some reactor support going on. So, if the reactor in Europe closes, like BR2, unexpectedly or they can't make a shipment, another reactor will try and pick up some of that slack. Yeah. And then there's all kinds of things that happen. So, there's snowstorms, there's volcanoes in Iceland that make flying airplanes over the Atlantic impossible, there's unstable political conditions, there are lots of different problems can arise where you can get your material. And it is true, I mean, that if these research reactors and these type of production reactors don't operate, then the people don't get treated. And a big example of that over the last couple of weeks has been a reactor in Europe that is shut down unexpectedly, and it's going to result in a Molybdenum-99 shortage. Molybdenum-99 is the parent for Technetium-99m. Technetium-99m is used as a imaging agent something like 30 to 40,000 times a day in the United States. And it has a 66-hour half-life, the parent does, and so if it if the reactor is not running, there's no Molybdenum-99 and Technetium-99m available for nuclear medical scans for patients across the United States. There is no domestic supply of Molybdenum-99, Technetium-99m right now. Everything has to come from Europe or Africa.  

Mike Hoehn Yeah. So just to kind of build on that, you know what—a couple weeks ago we were at the European Association of Nuclear Medicine. You know, a reactor in Missouri attending a conference in Hamburg, Germany. Why would we be there? Well, we got the opportunity to talk to those other reactors. And what's so important is we all recognize the impact to the patient in the end. You know, we're all producing, like—we like to use the analogy, we're producing ice cubes. And those ice cubes, you know, have to you know, they melt, you know, just like the radioisotope decays, and it has to be the right size when it goes into the patient to deliver the right dose. And so, it's an it's a time element that we all have to work together. That supply chain is fragile and it is weak and it's even more fragile domestically, knowing that, you know, we're the sole producer of those four radioisotopes that John highlighted. It's critical that we look to the future and expand that capability, and that's why we've been looking at NextGen MURR. And then instead of, you know, trying to retrofit, you know, a 1966 reactor to do the amazing things that it's doing, as John highlighted, we get to start from scratch. You know, we we'd start with the green field.  

Jordan Houghton What's the timeline for NextGen MURR?  

Mike Hoehn So right now the, the timeline is approximate eight to ten years to become operational, but there's a number of huge milestones that we have to go through. So right now, we're working with working through a negotiation process with a partner that would include an experienced reactor designer, architect, engineering firm with extensive large project experience, as well as a regulatory licensing specialist and we hope in the near-term be able to finalize that negotiation, announce to the world who that partner is going to be, that we will pursue an initial phase or will, you know, kind of finalize that scope and finalize the vision for the NextGen MURR ecosystem. And, you know, we envision, you know, approximately two years to be able to build out our conceptual design, build out our preliminary safety analysis report and the construction firm in application and then submit to the regulator. So, we're in our infancy and that initiative, but two or so years submit to the regulator, then we'll be subject to the quality of our submittal, and the regulatory review, which we're excited. And then, you know, at the end of that, you know, four so a year time frame, from conceptual design and scoping and the regulatory and licensing process, then we envision breaking ground, and then it takes 10 years for part of this critical domestic supply chain and in the overall world supply chain for radioisotope production, as well as expanding that nuclear science and technology or folio that we're excited to bring to the world.  

Mary Carpenter Well, clearly you're doing important work, and so this expansion is exciting. John, I want to go back to something you mentioned about how these treatments are kind of end-of-treatment protocols, and you're looking at moving it maybe ahead of things like chemo, which we know are difficult treatments to go through. How does this differ from something like chemo on the body?  

John Brockman Theranostic treatments are, for the most part, much less—I don't know if the right word is toxic—challenging for people that—they tend to have low side effects compared to chemotherapy agents. They're well-tolerated, is language that you often see used. And moving them up in the treatment cycle is important because we ultimately hope it will give a better outcome for the patient. So, by the time that you get towards the, you know, you've failed multiple cycles of chemotherapy and you're progressed under this radiotherapy, the cancer that you have, it's likely metastatic and likely heterogeneous, and that—it's many different kinds of tumor cells, not just one. And so, moving it forward, moving these radiotherapy treatments forward in the treatment could have better efficacy because the targeting that you've designed is for one particular type of tumor marker. And so, if your tumor is heterogeneous and has multiple different kinds of cells, you may not be able to target all of the cells from that particular type of cancer.  

Jordan Houghton It's so cool to hear. I mean, obviously the medical applications for humans and our favorite pets is amazing, but I love that it's going to open doors for other types of research as well, so I'm just speaking this aloud. Go to the University of Missouri to study because—well, first of all, it's an amazing campus, I can say that firsthand, but so many opportunities regardless of your interests.  

Mike Hoehn That's right. And take intro to radiochemistry!  But I—you know, I just—it's amazing now. But we really see this as a premier destination even moving forward as we pursue NextGen MURR and that's what's so exciting for the city of Columbia, Missouri, the state of Missouri, and then overall, the nation. What we're building here is going to—we're going to we plan on being, you know, the center for radioisotope production that we're—science and technology research in the in the Western Hemisphere. You know, we think we can, you know, build upon all that awesome workforce experience that that specialized research that's been done for decades at MURR, and then take all those lessons learned and apply them to NextGen MURR.  

Mary Carpenter So, we talked a lot about medical. I know somebody mentioned earlier carbon dating artifacts. I mean, there's seems like so many things you guys are working on. What are some new applications you guys are thinking of with NextGen MURR?  

John Brockman So I—I think the synergy around the ray of pharmaceutical space is our number one priority here. And so that looks like a reactor that's integrated into a research ecosystem that's capable of taking the isotopes that we make there and going all the way through discovery phase and the clinical science phase. And I think that's probably multiple buildings, you know, that would be synthetic laboratory space up to clinical trial space. And we're very excited to work on the next generation of theranostic isotopes and treatments. And then I think the opportunity for neutron scattering is—is very broad. So in this country, there are really two places you can go to do significant neutron scattering. One is at NIST, which is the National Institute of Science and Technology Center in Bethesda, Maryland, and there they have a guide hall next to their reactor that has something like 30 instruments. It's a user facility, so people from all over the world come to use it. And similarly, there's a facility in Oak Ridge National Laboratory, one at the High Flux Isotope Reactor, and another at this Spallation Neutron Source. And a unique feature of this is—a university proposed system is that is actually at a university. So, these other neutron scattering facilities, they don't have a workforce education mission. Their mission is to operate these beams and make as many measurements as possible, but not necessarily to train students. And so, we'll have a very unique role to play in neutron scattering in the future and that will be the place to be able to train the next generation of scientists that will go on to these other facilities. In addition to that, we anticipate that this program will be large enough to be a national user facility, so people from all over the country will come to Columbia, Missouri, to be able to make measurements on these beams and do everything from soft matter chemistry and physics to magnetic materials to imaging airplane wings to looking at new kinds of welds, to looking at fuel cells, lithium ion batteries. I mean, there's sort of an endless number of opportunities for science and these neutron scattering guide halls.  

Mike Hoehn Just to add that we don't necessarily know what is going to be needed or what the demand is going to be or what the research capabilities are going to be, you know, 40, 60 years from now. I think about 58 years ago, we brought a reactor online that today is, you know, impacting millions of lives in cancer, you know, treatment and diagnosis. We didn't—I don't know that they envision that, you know, 58, 60 plus years ago. And so our my role, you know, and our role from the NextGen MURR team is to design a reactor that can support the current tactical, you know, radioisotope, radiopharmaceutical, you know, vision and mission that we have at the University of Missouri, build upon the existing neutron scattering capabilities that that we're doing today, but also have the ability to break out the crystal ball and, you know, envision what it can be. So, we need to have it a reactor design that has modular, adaptable, flexible capabilities. And that's an awesome engineering design challenge that we're taking on. And hopefully, you know, who knows, you know, 50, 60 years from now somebody listens to this podcast and says, hey, they hit it right on the head.  

Jordan Houghton Okay, last question. Last TV show that you binge watched.  

John Brockman I think the Outer Banks thing on Netflix.  

Mary Carpenter Oh. I was literally watching that last night.  

Mike Hoehn I did watch Indiana Jones and the Last Crusade with my daughters over the weekend. It wasn't a TV show, though, it was a blast to the past.  

Jordan Houghton That's always a good one, right?  

Mary Carpenter That counts.  

Jordan Houghton You guys were great. I was sitting here. I mean, I could have gone on with, like, another hour's worth of questions. 

Mary Carpenter I know! 

Jordan Houghton Digging into all of these different research applications. It's just fascinating.  

Mary Carpenter I know. You guys did a great job explaining things so people are actually understand it, so thank you very much.  

John Brockman Yeah. No, thank you.  

Mary Carpenter I loved that episode. Mike and John are just so incredibly smart and they're truly doing so much to change the industry, the nuclear energy industry, but also the health care industry. I mean, the work they do of saving people's lives. So, that was a really great conversation.  

Jordan Houghton I am really mind blown about how extensive the logistics are. Once these isotopes are produced, making sure, I mean, it's basically a round-the-clock operation to make sure these isotopes get to where they need to be for patients who need treatment. And that honestly—it kind of gave me chills to know that this effort is going specifically to get these to the people who need the lifesaving treatment.  

Mary Carpenter Yeah. And it's—I hadn't personally didn't even know that it had such a short shelf life of only a week. So, I mean, that just adds so much more intensity to the supply chain. And I hope that they can, you know, with NextGen MURR and all the work they're doing, continue to figure that out. But also, I'm so excited about what he was telling us about the chemo treatments and how this could possibly be an alternative that is less harmful to the body and is an easier treatment for folks going through cancer treatments. I mean, what an incredible thing that they're doing.  

Jordan Houghton And it's only going to get more exciting with NextGen MURR over the next decade coming online, just really exciting. Very cool to have such a cutting-edge facility here in the States, and really look forward to hearing more about what they're doing in the years to come.  
 

Mary Carpenter Yeah, and if—listeners, if you have more questions, check it out. They're doing great work. Do a little bit more research on your own. Tell your friends. I mean, it's really, really incredible work that they're doing. So, thank you to everyone at MURR for doing what you're doing. It's really amazing.  
 

Jordan Houghton Yeah. And we'll link to MURR in the show notes. So, if you do want to click through, you can get directly linked up to read about more of the research that they're doing. And if you enjoyed the show, we'd love to hear from you. Support the podcast by subscribing on Apple, Spotify, or wherever you listen. And please leave us a comment and let us know your thoughts on the episode. We'll see you next time.