Transformation in Trials
A podcast about the transformations in clinical trial. As life science companies are pressured to deliver novel drugs faster, data, processes, applications, roles and change itself is changing. We speak to people in the industry that experience these transformations up close and make sense of how the pressure can become a catalyst for transformation.
Transformation in Trials
Bridging Academia and Biotech: Creating Innovators of Tomorrow with Jonathon Hill
Jonathan Hill takes us on a fascinating journey through the cutting-edge world of DNA sequencing and its revolutionary potential for early disease detection. As both an academic professor at Brigham Young University and co-founder of Wasatch BioLabs, Hill shares how third-generation sequencing technologies are transforming our ability to identify diseases years before symptoms appear.
The conversation centers on a groundbreaking approach using native methylation calling—a method that identifies specific chemical modifications to DNA—to detect neurodegeneration in conditions like Alzheimer's and Parkinson's. Hill explains how these diseases damage the brain for up to a decade before symptoms emerge, creating a critical window where treatment could be most effective. By detecting the unique methylation signatures of dying neurons from cell-free DNA in the bloodstream, Wasatch BioLabs' technology aims to revolutionize diagnosis and treatment monitoring.
What makes this platform particularly powerful is its versatility. The same technology that identifies dying neurons can be adapted to detect signatures from other dying cell types, potentially offering early diagnostics for autoimmune diseases, various cancers, and other conditions—all from a simple blood draw.
Beyond the science, Hill reveals his passion for nurturing the next generation of biotech entrepreneurs. He's created a unique ecosystem at BYU where students with innovative ideas receive the mentorship, lab facilities, and business connections needed to translate academic discoveries into real-world applications. Drawing parallels to the tech boom of Silicon Valley, Hill emphasizes that biotech is experiencing its moment of explosive innovation, though with unique regulatory and infrastructure challenges.
The episode concludes with a thoughtful discussion on regulatory hurdles in life sciences and how streamlining these processes—while maintaining safety standards—could accelerate innovation and save countless lives. For anyone fascinated by the intersection of cutting-edge science, entrepreneurship, and healthcare transformation, this conversation offers an inspiring glimpse into the future of medicine.
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Welcome to another episode of Transformation in Trials. I'm your host, ivana Rosendahl. In this podcast, we explore how clinical trials are currently transforming so we can identify trends that can be further accelerated. We want to ensure that no patient has to wait for treatment and we get drugs to them as quickly as possible. Welcome to another episode of Transformation in Trials. Today we're going to be diving into the topic of shaping the innovators of tomorrow and today. In the studio with me I have Jonathan Hill. Hello, jonathan.
Speaker 2:Hi, thanks for having me on today.
Speaker 1:Jonathan, I have been very much looking forward to speaking to you today. Based on the pre-call, we have some very interesting topics to cover, but before we get started, could you tell our listeners a little bit more about yourself?
Speaker 2:Yeah, my name is Jonathan Hill. I have two hats that I mainly wear. I'm an associate professor at Brigham Young University, but I'm also a co-founder and VP of science and technology at Wasatch Biolabs.
Speaker 1:Very cool at Wasatch Biolabs Very cool. So let's start by diving a little bit more into the science part before we get into some more industry stuff, Just setting the stage for our listeners. Could you tell us more about which trends we're currently seeing in DNA sequencing?
Speaker 2:Yeah, so Wasatch Biolabs, this company that I've co-founded with another professor here at byu and some other individuals is really focused on what is generally called third generation sequencing. So your kind of first generation is what might be considered classic sanger sequencing. It's very low throughput, you're getting a single sequence at a time. Second generation or next gen sequencing really boosted that throughput, but they were short reads Right now you can kind of get about 300 bases per read on those. And then the third generation technologies like Oxford Nanopore and PacBio can do a couple things that previous technologies could not do. First of all, they can do much longer reads.
Speaker 2:Oxford Nanopore specifically, is actually read length agnostic. It can do anything from a couple hundred bases up to they've gotten as far as a megabase of sequence in a single read, and so really long, really short, really great for assembling genomes, things like that. The other thing that these technologies can do is they can do native methylation calling. The other thing that these technologies can do is they can do native methylation calling and this is where we're looking at cytosine specifically to see if they've been chemically modified by the cells in usually a gene regulatory sense and use that to study aspects of biology or in diagnostics, and so we're really trying to leverage that native methylation call capability to advance research and also to create diagnostics in the clinic.
Speaker 1:Very interesting, and how long are these generations of DNA sequencing technology?
Speaker 2:Well, you know, it seems like about every 10 years or so we get a new technology, and so Sanger sequencing came out in the 90s, illumina sequencing, which was the major next-gen platform, was in the early 2000s, and then both PacBio and Nanopore technology came out within the last 10 years. So that's where we're at right now.
Speaker 1:Very interesting, so a new wave may be on the horizon in a couple of years.
Speaker 2:Yeah, we'll see, although you know, one of the trends I think right now is actually utilizing nanopore technology and others for amino acid sequencing. So protein sequencing might actually be the next wave that comes out, and that'll be really interesting to see how that plays out.
Speaker 1:Yeah, absolutely. And how does Wasatch BioApps platform fit into this evolution in the field?
Speaker 2:Sure, yeah, our focus really comes down to now that we can do this native methylation calling. Can we use this as a novel biomarker in the clinic to look at the progression of disease, or to look at cell origin of dying cells, or to look at a number of different biological processes through this novel lens? We've known that this chemical modification to DNA happens regularly. It's part of aging, it's part of cell differentiation, it's part of disease states, it's a part of immune responses. There's even imprinted genes that have different methylation patterns on the copy you got from your father versus the copy you got from your mother.
Speaker 2:Right, we've known this is everywhere, but to be able to access it and really look at it in the detail that we can now just has not been available, and so we're looking to leverage this to really try to push diagnostics forward, and I can give you a couple of examples of applications we're working on. Yeah, so one big application that we're looking at is neurodegeneration. You know you think about Alzheimer's, parkinson's, als, a number of debilitating diseases that are quite common out there, and yet neurodegeneration, the neuronal cell death that underlies these diseases, happens for years, perhaps even a decade, before you ever see symptoms Right, and so that makes diagnostics really really difficult to do.
Speaker 2:But as these cells die they release their DNA into the bloodstream and eventually your body has systems for cleaning that out.
Speaker 2:But for a while you have that DNA floating around and using methylation signatures on the DNA that are specific to populations of neurons.
Speaker 2:We are working out models right now to measure and to classify what types of neurons that cell-free DNA that we can access in the blood came from, and by doing that we can quantify neurodegeneration and so that gives us a pre-symptomatic screening tool to diagnose these diseases which allows much earlier treatment of this right and this is big, because right now there's several drugs coming out to treat Alzheimer's disease specifically, and the problem has been is that they'll do these trials but then they'll find in the clinic we're diagnosing people too late for these drugs to be effective.
Speaker 2:So we need to get that early diagnostic in there so we can get the treatments at a time point when they're really going to be effective, because they're going to slow decay, they're not going to bring back function. So we want to catch that as early as possible. We want to catch that as early as possible and we're hopeful within the next few months we'll have our data ready to go and be able to start our kind of clinical validation tests to test this in real-world scenarios, and we're really excited about that.
Speaker 1:Yeah, and also so soon. And addressing some of these neurodegenerative diseases. I recently read a book where they claim that this is like one of the four horsemen of health in our society. So that is a big game changer to be able to find the murder.
Speaker 2:It is especially as our population ages and we have more and more people coming into this phase of life, where this becomes an important thing, not only for them, but for their families and their caretakers, and so we want to be able to help these people out the best that we can.
Speaker 1:I'm curious. So the solution, the diagnostic solution that you're working on, it's a platform. What are the benefits of it being a platform?
Speaker 2:It is a platform, and so what we found is that neuro test that I just talked about was our first kind of foray. Right Got us started. But as we developed the technologies and the models and bioinformatic analysis pipelines etc that we needed to do for this, we realized that any kind of degenerative disease, whatever cell type might be dying, could be recognized using this exact same technology. You just have to change out what cell type you're trying to identify within the mix of cell-free DNA. So you think about autoimmune diseases like lupus or rheumatoid arthritis or celiac disease. They're all causing cell death and so they're going to spill cell-free DNA into the blood and we can identify those tissues as well.
Speaker 2:We've had people approach us with different kinds of cancer applications. Cancers are not healthy tissues. There's a lot of cell death going on within that tumor and a lot of that cell death is necrotic and so it's spilling DNA into the blood and we can identify unique cancer signatures as well. And our hope is one day that we can look at not just you know is it cancerous or not, but specifically what type of cancer you have, without ever having to identify a tumor by just a simple five milliliter draw right, your kind of standard blood draw.
Speaker 1:That would be amazing.
Speaker 2:And so, yeah, building this platform, though, gives us huge advantages, specifically in a regulatory kind of sense.
Speaker 2:Right, every technology that's going to be used in the clinic has to go through extensive testing for safety and efficacy and those kinds of things. Right, these are just blood draws, so the safety is there. We're really focused on the efficacy how accurate are our calls and by putting everything on a common platform and just making slight changes to the predictive models for each, we really help streamline that regulatory process, right, because now a lot of that paperwork can be reused. The regulatory reviewers have seen this before and they're just seeing a new application, and, in fact, many of our tests to show accuracy of the platform itself carry over from test to test, and so that's our real model. Can we create this platform that then can be applied to many different models, mainly in partnership with other people that have disease-specific knowledge in those areas, and then streamline the regulatory process areas and then streamline the regulatory process, have a clinical grade laboratory centralized where we can run these, all of these kinds of things that just make it easier to get this out there and get people using it?
Speaker 1:Very interesting. Have you had any curiosity from companies trying to treat some of these diseases, interested in getting better diagnostics?
Speaker 2:We have. I can't talk about specifics right now, but, yes, another application of this is, instead of trying to do that initial diagnostic, we want to make sure that the drugs that people are taking especially because they can be quite expensive are actually being effective. And if you think about neurodegeneration, for example, someone might get diagnosed. They decide to go on a drug that's going to slow that neurodegeneration. But of course they want to know is it working right? And you know there's no real kind of signs or symptoms that you can look at for that. And so we create a biomarker where we can look and say, hey, your cell-free DNA content is changing, less of it is neuronal, which tells you that neurodegeneration is being inhibited and the drug is being effective. And so we have multiple drug companies that have reached out to us along those lines, looking for a kind of diagnostics that will look at the effectiveness of their drugs.
Speaker 1:It makes sense. If you offer treatment, it's valuable to figure out how do we follow and see if the treatment is actually helping, even on this level.
Speaker 2:Yeah, and our initial ones will be in clinical trials. As you're doing the clinical trial, you have to establish that, but our hope is that will then translate to the clinic as well. Establish that, but our hope is that will then translate to the clinic as well, right? Um, they'll kind of both be validated at the same time and become a pair that gets, uh, gets monitored all the way through treatment, and it will be a real benefit that way very cool.
Speaker 1:well, jonathan, that is just one of the hats that you wear then the other hats is still in academia, as far as I understand, so tell us more about how you're kind of still positioned in both worlds here.
Speaker 2:Yeah, so I do try to bridge both and it's a lot of work. I'll tell you that. If anyone's considering, hey, that'd be fun to do, just know it's a lot of hours to try to do both, but I think it's a really valuable investment that we're trying to make At Wasatch Biolabs. We realized early on, as a company that came out of the university itself, that there are a lot of bright, innovative young minds in these universities, right, and they have this kind of fire and passion and ability to just try something and go for it kind of thing and an ability to just try something and go for it kind of thing. And yet universities aren't really set up to do that. We think of universities as innovative places, but it's usually kind of a basic research type of innovation where we're writing grants, the government is funding us, we conduct research in the lab and then we try to publish those results for everybody out there, right. And in my experience, what I found is a lot of times I would be writing in these grants or especially in publications saying, hey, look at this cool, finding this could benefit people in X, y or Z ways, right, but then it goes on to a library shelf and doesn't really get anywhere, got to do that. We got to become that transition to be able to help move our technologies out into the clinic ourselves if we want to see that impact occur. Right yeah.
Speaker 2:Now what we found is, especially when you build something like a platform, you start getting students that say, hey, you know, I have an aunt that has lupus, for example. I want to see if this platform will work within that disease model and they're going to dive in and they're going to really care about this and they're going to give it all the effort that they can to make this work. And so we've created kind of a bioinnovations program is what we call it, and it's growing and expanding right now where they take classes structured around innovation and entrepreneurship kind of things in the life sciences and they get opportunities in the lab to conduct that research, to chase their dream right. And we've had multiple students already go through this program, found their own small biotech startups and become CEOs of those startups and, through funding and through the university and connections we can make with investment, really get them launched and out there. And this is a goal that we have going forward. I think you know, philosophically we're at a turning point within biotechnology. Just a little bit of my background.
Speaker 2:I grew up in the silicon valley in the 80s and 90s okay, and I see biotech early days, yeah, and I see the same energy we saw in in tech and computers in the 80s and 90s. I see that in biotechnology today, where you've had some core key technologies come through that are allowing us to just innovate like crazy. Right, we had to wait for those core technologies. They're there now and we just need to get people excited and involved and going and just like tech. A lot of those people, if you think about the founders of these companies, they were students at a university that spun this out, oftentimes dropping out themselves in that case. Um, to go into these and create, you know, facebook and whatever else they made, right, that was the model.
Speaker 2:In biotech, there's an extra challenge, because you can't start a biotech company in your garage. That would be illegal. They, they would shut you down, right, you've got special lab spaces you need. You've got regulatory approvals. There's a whole layer that they didn't have when they were building internet companies, right? And so that's what we're trying to provide. We provide that structure, that mentorship with faculty members, we provide lab space that has the certifications the university has IRB and IACUC and all those kinds of things that we need, and so we're trying to, you know, fix that problem or bridge that gap, so that these students do have a chance to take it and run with it, like the tech founders did 20 years ago.
Speaker 1:In your experience? What is the thing that these bright minds who are interested in science and who see some sort of application for their idea, what is it that they need to be trained in or learn to be able to actually take it from the idea stage into the market, or at least the long road to the market?
Speaker 2:Yes, and it is a long road. I think the first thing they need is they do need faculty membership. On mentorship, I should say on the actual technology itself, these are complex, deep technologies. With you know, any living system is insanely complex, and so they do need more mentorship than you might need, say, with an Internet company that you're starting up, right. And so we try to pair those students with faculty that have the skill sets that they need, and that varies.
Speaker 2:But the other side is most of us faculty are not trained on how to take a product to market. We're not trained on how to raise venture capital funds. We're not trained on the legalities of forming a company. We're not even trained really on protections through patents and other IP, right. And so that's where we find the students can struggle. They'll be excited, they'll have an idea.
Speaker 2:They've been working in a lab with a faculty member and they both really want to see this go out there, but they just don't know how to do that Right. And my co-founder at Wasatch and me we've actually both founded other companies beforehand, and so we've been through this a few times and we've now built up that skill set of how do I make sure things are patented correctly? How do I form a company? Where do I go to start trying to find funding, right All of these kinds of things. And we've also built partnerships with the Entrepreneurship Center here at BYU, the Tech Transfer Office, right these other groups that also have these skill sets, and connect those students so they can get the training and understanding that they need.
Speaker 1:Well, that sounds awesome. It sounds like you've really built a unique ecosystem where you've connected the dots from the science part to the business part, but also providing facilities that are needed to be able to conduct research and build your products.
Speaker 2:Right. I mean, that's what we're trying to build, right. Like I said, it's growing and expanding and we're filling in things and we're learning lessons as we go on gaps we still need to fill, et cetera. But that's really the mentality. Our mentality here at BYU is always how can we make sure our research is impacting the world in a positive way? And we found that there were these gaps and we thought you know what we can address these gaps? And that's what we've been trying to do.
Speaker 2:Are there any things that you've had to forego. Straddling both worlds, doing both entrepreneurship and academia. Sleep and hobbies have gone to the side. Uh, I I forego is interesting. I mean, luckily I'm in a good department where my department chair and, uh, even the college administration have been flexible with some of the kind of expectations that they have, Right. Uh, for example, here they're counting patents that come out of my lab as academic production.
Speaker 2:Right, it's not just because my publication rate has gone down slightly, but my patent rate has gone up. My teaching has gone down a little bit, but I mentor more students. Right, They've been flexible with some of those things to really help us. Now it does change some things. Right, I have stepped back from some of those true academic circles and networking kind of thing because I'm now focused on this other area. But I think it's a sacrifice that's well worth it to give these students a kind of mentored opportunity that they would not have at most places.
Speaker 1:Oh, absolutely. For some of the students that you mentor, who may be in doubt of whether to pursue, whether to put their heart into the company that they have a chance of building or keep pursuing their academic career, what is your advice usually?
Speaker 2:It's hard and I refuse to make that decision for them. Sometimes they come in and they kind of want me to tell them what to do right, as a young adult, but I refuse to. And I think the biggest thing is we found you do need that student who's willing to put everything on hold and go for it for a few years. It may not pan out in the end, et cetera, and they can always go back and go to graduate school at that point, but they need to be committed to do that. If someone's truly torn, they're like I really like this, but I just really feel like I want to go to medical school or to graduate school. Often what we do is we partner them with another student who is willing to stick around and then they get the experience, but everybody knows that they're going to hand it off eventually. They're kind of sidekick in that case. Yeah, so we find room for them the best that we can, um, but we're just up front with them on the commitment that it's going to take and the fact that as adults now they have to make those decisions and and then go with it right and live with your vision oh, that, that makes, that makes sense I will say more commonly, we get students who come in planning to go to medical school and then decide not to yeah
Speaker 2:so we see a lot of that going on. Um, and a lot of it, I think, comes down to their motivation was hey, I'm good at biology and I want to help people, so I'll be a doctor kind of mentality. And then they see how much of an impact they can have in the biotech space. Uh, helping a lot of people, right? Not just the people walking into the clinic, but across the entire world. And so they say, hey, you know what? This actually fulfills my career goals better than my previous career path, and that's always a positive when they can see that.
Speaker 1:That's an important point, like there is a point in time where one must decide well, do you want to make that one, one at a time personal difference, or do you actually want to invent new treatments, because those are two very different paths.
Speaker 2:They are very different paths but you're right, they're both impactful, they're both needed and I'm glad students are going down both paths Right.
Speaker 1:Yeah.
Speaker 2:And we're just helping them make that clear decision for themselves.
Speaker 1:Yeah, Well, jonathan, how did you end up on your path and how did you end up being in a position where you didn't have to choose? But you can do both.
Speaker 2:Yeah, that's a rare position. I mean, we'll see if I have to choose someday if I can keep it up. You know, I was in the same shoes as a lot of my students. I started out as a pre-med student actually here at BYU, and my reasoning was that I was good at science and biology in high school and I told my teachers that I wanted to to benefit people's lives and help people out in my career. And they said well, you're good at STEM and you want to help people, you should be a doctor. That's that's how they push everybody. So I was pre-med going through and for me it really changed when I started TAing a class. I got a position.
Speaker 2:One of my friends recruited me to be a TA for genetics class and I started doing research in a lab and I just started looking at it and thought this is a really great life, right, you get to wear kind of two hats even that way doing research and teaching, yes, which in itself gives you two ways to help out people. I have good positive experiences with students in the lab and with the research itself and the discoveries we're making. I also have great experiences with students in the classroom and seeing the light bulb go on Right, and those are both very fulfilling things to see. And so I switched my junior year in college and said you know what? I'm not going to go to med school, I want to be a professor instead. So then I went into graduate school and I started seeing that kind of grant publication cycle that we talked about earlier and started thinking you know, I went into this because I really wanted to benefit people's lives and I hope that in some way my research is and I really respect, of course, everybody that's doing that basic research. That's also something that we very much need.
Speaker 2:But for me I guess I don't know, maybe I'm a little short sighted or something I struggled a little bit with that big picture idea. I wanted to see direct impacts of what I was doing, right, I wanted to see it make it to the end of the row, and so I started also finding that I was very interested in developing technologies themselves. It's just kind of a passion of mine. The rest of my family is all engineers and programmers, so maybe that's a little influence where I was going to design things. And so I started getting into it, and my first experience was actually with a student in my lab that came up with a cool new way of enzymatically creating CRISPR guide libraries for gene editing.
Speaker 2:And you know he said, hey, I want to take this out. And we just kind of started figuring out what would it take to actually get this technology out there where people could use it. And it was a technology where it was pretty basic but it had a lot of like custom components and things, and so it would be beneficial if we kidified it and got it out there. And so that just got me going down that road. And so when another student came with this other professor and said, hey, I think I've got a diagnostic for neurodegeneration early on, but we need some skills that you have I've been doing sequencing and data analysis for a long time I said, sure, count me in, I want to go on this adventure with you. And just kind of ended up going that way. And so I think the draw was always there, the motivation was always there, and then the opportunities came up and I took them.
Speaker 1:Yeah, I think the taking of the opportunities is also important here, that you said yes once they presented themselves.
Speaker 2:Right Yep.
Speaker 1:What about this ecosystem that you have built at BYU? It sounds like you intentionally been trying to build it out over some time, adding more and more different offerings, more layers. If a different place in the world wants to do something similar, where would you recommend them to start?
Speaker 2:The place unfortunately you would have to start is talking to the tech transfer office at the university. I've been at several universities over my career. I've interacted with the tech transfer office at every single one and they have different attitudes et cetera. And we've been fortunate here at BYU that the tech transfer office has been really willing to work with smart small startups. They do that by having you know favorable royalty schedules or taking equity in the company instead of charging upfront fees, all those kinds of things.
Speaker 2:And you really have to get the university on board saying you know there's going to be some give here, there's going to be benefits in the future, but right now you're going to have to be patient, kind of thing. And then the next step is just to find those students who have this passion. Yeah, get them going on it. Usually the faculty will buy in, usually the faculty. The only thing stopping them is they don't really know how to do it and they've got a lot of other things to do. Right, but if you can get those students to buy in, then you're running.
Speaker 1:Yeah, that's great advice for those of you out there who are curious in making the same transformation happen.
Speaker 2:then there you go yeah, we have had other universities reach out to us saying how can we do this too, and we actually had some angel investors with our company early on and they've been willing to sit down with these people and say, hey, here's what it took to be able to get this going. Uh, kind of thing and it's I hopefully it's been very beneficial. We'll start to see this grow at many different institutions yeah, and it's.
Speaker 1:It's also a meta way of making lives easier. If we can create the proper circumstances for more innovation to happen, that makes more innovation that can help more people. Yeah.
Speaker 2:And I'm a big fan of dispersed innovation, right. We don't know where the next big thing is going to come from. It's not necessarily from the classic places, right. It might be someone working outside of their field, kind of on the edge, at a smaller university, et cetera. So we need to get as many people and opportunity as possible to have that innovation come out and not centralize everything and fit everything into one single box kind of thing.
Speaker 1:Absolutely agree. Well, Jonathan, as we start rounding off, I always ask my guests the same question in the end, and that is if there was one thing you could change about the life sciences industry, what would you choose to change?
Speaker 2:Oh, that's a great question. Where my mind immediately goes is regulation, and it's a hard one for me because I see the need for it right. We want to make sure that things coming out when they affect healthcare and people's lives so intimately that things are safe and well vetted. But so often the process is overly bureaucratic and stifles innovation, and so if we could figure out a way to overcome those hurdles and streamline the process, I think we could get a lot of things out to people a lot faster and save lives literally with it Right. So it's not a get rid of regulation but a make the process better kind of situation.
Speaker 1:That's a great wish, and I completely agree. It's not the amount of regulation, it is more. How do we navigate it seamlessly where there's often a lot of doubt? That's a great wish. Mm-hmm, that's a great wish. Well, jonathan, if other universities out there want to talk to you or any listeners are curious about the technology that you're developing, where can they reach out to?
Speaker 2:The best place to reach me is to go to wasatchbiolabscom. You can set up a call, you can send an email through there. We're a pretty small company so it's very easy to just through that channel, say, hey, I talked to Dr Hill or I heard of Dr Hill on a podcast. I want to talk to him, um, and they'll get hooked up with me.
Speaker 1:That. That sounds awesome. Well, otherwise, thank you so much for joining me for this conversation. I have learned a lot.
Speaker 2:Thank you, it's been fun, loved it you're listening to transformation in trials.
Speaker 1:If you have a suggestion for a guest for our show, reach out to sam parnell or ivana rosendale. On linkedin. You can find more episodes on apple podcasts, spotify, google podcasts or in any other player. Remember to subscribe and get the episodes hot off the editor.
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