TGen Talks: Episode 45, Dr. Michael Berens
Karie Dozer [00:00:03] I'm Karie Dozer, and this is TGen Talks. While the science of genomics is often complex. TGen’s mission is simple. As a nonprofit medical research institute, TGen researches genetic components of diseases like cancer, neurological disorders and infectious disease so that treatment options become more personal and more effective. But how does TGen actually conduct that research? I sat down with one of TGen's founders and deputy directors, Dr. Michael Berens who was been with TGen since its beginning nearly 20 years ago as a director of the Cancer and Cell Biology Division. He is acutely aware of the need to find answers and personalized treatments for very aggressive types of cancer like glioblastoma. And he says it can be both heartbreaking and inspiring to conduct this research every single day. Dr. Beren's shared with me a little bit about the process of trying to find cures for cancer one step at a time.
Dr. Michael Berens [00:01:03] Yeah, it's an interesting process. Normally, as we grow the faculty and the faculty mature with their professional footprint and their spheres of influence, the projects emerge organically from that. And when I say organically primarily that I think a common thread is that the technology, the science and the practice of translational research meaning can discoveries we make in the lab touch how a physician thinks about caring for a patient coming into their clinic tomorrow or this afternoon, so that that's the practice of kind of the culture of teach and say, How do we put this to work? How do we take? What do I know into what I do that that really to me summarizes the magic, if you will, and I'll use that term intentionally. That's kind of the magic of TGen. Academics write papers, they do research, they write grants, they get financial support through various mechanisms and they publish that a teacher and we're really discontent with that. Being the end of our work, we want to connect what we do in the lab with the heart and mind of the caregiver to say. If you could know this about your patient, would you think differently about how you can care for them? So it's a curious thing where a basic science institute with the goal of changing the practice of medicine with a couple of key collaborative relationships where we actually get to touch the patient with our work. So when these projects grow organically in the course of ongoing work, people hear about what we're doing and they think, Gosh, I wonder if that would apply to this unmet medical need. And then we sit down and say, OK, here's the kinds of things we can do. These are the questions we ask. Tell us more about the unmet need and what would start to fill that unmet need. It's a big challenge to find the doctor who's dissatisfied with status quo. They're businessmen, right? They're running their practice. They're in an academic environment, they're running a program. So when you say I need to interrupt your workflow, so we think differently, that's usually a loss leader for sure. And so the practice of research in the United States around diseases has tend to cluster around academic centers just because the care of patients is in practice, not in research. And so they look for these centers to be the tip of the spear, to be the piercing point forward to say we've got to think differently about this. And frankly, the tool of genomics that launched TGen. And now it's extended to not just sequencing the DNA, but looking at RNA that comes from that and the protein products and the modifications of those protein products. All those now fit into this bigger umbrella of molecular profiling. And we're really good at it.
Karie Dozer [00:04:01] Do all great medical studies here at TGen or elsewhere. Do they all begin with one simple question?
Dr. Michael Berens [00:04:09] I'd like to think we're smart enough to say yes, but I don't know that that's really true. I think if you and you don't have a corner, a scientist to have them admit this, but my experiments fail more often they succeed, and that actually is not an apology or a regret. It says that when a scientist has an idea about, I think this is why this cell, this tissue, this organism behaves the way it does or suffers the way it does. I think it's because of this. And then we design an experiment to test how close to accurate or how close to reality was that guess we call it a hypothesis, and it's based on things that we know, but we make an educated guess. I think this must be what's going on. And so we do the experiment and the data comes back and says, Well, you weren't quite right. You weren't totally wrong, either. So it's iterative. It's getting it less wrong over time.
Karie Dozer [00:05:07] That in itself is an answer.
Dr. Michael Berens [00:05:09] Sometimes it completely is an answer, and people talk about Benjamin Franklin inventing the light bulb and all the mistakes that I've learned, the thousands of ways that a light bulb doesn't work to a certain extent. That kind of is the scientific method where I think it's this let me try not quite or no, and then OK, must be something else. And so there's a lot of iterative effort. And until you actually get an answer, yes or no, you stay wondering. So the exciting thing about science is we can find out and get it less wrong over time. And hopefully that leads to a breakthrough that says, Do you know there's subtypes of these diseases? It's not just breast cancer, there are all kinds of subtypes. And by the way, each one probably requires a different kind of treatment intervention. Thank goodness, right? So now we can be more precise or practice precision medicine. So as we but let's call it a divide and conquer, or we could say that Alzheimer's disease is it one disease?
Karie Dozer [00:06:10] Is any one disease, one disease anymore?
Dr. Michael Berens [00:06:13] It's not, and it shouldn't surprise us. The humble pie is, Oh gosh, we were wrong. Well, that's OK. You don't have a healthy serving and then figure out how to do better. And that's the exciting component to this is that we really focus on human disease as we bring the samples and the collaborative relationships with physicians that are caring for patients. We say we're going to approach a better understanding with utility coming out of the back end that knowing that there's these subtypes don't treat this subset with this kind of therapy. We know they don't respond well
Karie Dozer [00:06:46] to the non-medical person, most of whom are the people listening to this podcast. It seems that researchers like you. Yourself are eminently patient, you're always willing to wait, however long it takes to get those answers. It seems like most studies take an excessively long time. Do you have any idea when you set out to answer a specific question or set of questions, how long you'll be studying that question and how long it might take you to get an answer, even if the answer is we were wrong.
Dr. Michael Berens [00:07:16] The length of time that it takes, we can't really predict. What I can say is I'm going to do this experiment and then the results of that are going to lead to this experiment and then that will lead to this experiment. And each one informs the next series of experiments. But if the first step is a false start, then I'm kind of back at square one to try to move forward. So the timing of it is complex to try to figure out. But I still learn from each step, and it does move through a progression to say I want to narrow down the disease and to a certain genetic basis that drives this misbehavior. That's a bad outcome for a patient. We think we have small molecules or immune therapies, or maybe a way of rewriting the genome in the affected cells to remedy that. That's where we want to go. So how can I be sure that I'm editing something that's really the trouble spot? So I have to prove that that's driving the disease process. So getting there, it really is a progression in the timing of it is complicated. This morning, I was writing notes to families who've lost kids to a brain tumor close to the anniversary of their child passing. And it's, you know, we don't think of science being that emotional, but it really is. When you do translational research and you realize I wish we could have gone faster. And more significantly, it's a highlight and a lowlight for us as scientists. We think, you know, I'm so crushed that we couldn't move fast enough to make a difference. And yet, I'm so inspired and encouraged by the quality of people that say, You know, we want to travel with you and be an advocate and say, Let's, let's try to move this forward. So it's definitely destination focused and not so much calendar focus. We want to go as fast as we can without being irresponsible, like, Oh, I want to edit genes that I know participate in a malignant process. So I'm going to edit all of them. And then someone would say, Well, could he have done it on four instead of eight? So leaps typically don't take you where you want to go. It's methodical and. It's fraught with the bit of trial and error.
Karie Dozer [00:09:34] Do you ever feel satisfied? You've answered a set of questions and a study is completed. You close the book, published a paper and completely move on. Or does the nature of what you're doing here mean that one question and set of answers simply turns to the next set of questions that need answers?
Dr. Michael Berens [00:09:53] Yeah, that it sounds very self-serving. So every successful outcome of a research project leads to what could be three or four new projects, right? So you feel like, well, come on, you know, at some point, can you close the book and you could have fewer doing accounting and say, Look, Gate 2021 is over. You know, that's very definable, but biology wiggles. And so we do learn some things that are true in some respects and we push on them and we say it has an application there. And what about the ones we couldn't help? What's the right? So we do move forward so we can say this is a fantastic therapy. And yet there are those where we haven't been able to help yet. That becomes the next project. So when we talk about how do we decide what to do, we gravitate towards the unmet needs where there's human suffering and loss of human fulfillment. And we want to say, can we take what we do and what we think, how we think as scientists? And can we work with specimens or surrogate specimens, skin biopsies or things like that where we can develop models of disease? And can we set out to see in this instance, it looks like this is what's going on, what might be a remedy and a way to ameliorate some of that loss of fulfillment and human flourishing alleviate suffering. That's really where we want to go.
Karie Dozer [00:11:16] TGen can't do everything on its own. You'd like to answer every possible question, but there's not enough time and there aren't enough people. How does TGen decide to collaborate with another institute and a hospital? Any sort of research entity? How do you decide to collaborate and how do those collaborations, how do they start? How do they … how do they continue?
Dr. Michael Berens [00:11:35] I think the best way to put an image on that is to watch first and second graders on the playground and see which ones like to do hopscotch, which ones go to the teeter totter if they still have them? I don't know. I think they do that. Which ones go to the swing sets and write or play Foursquare, you know? And so you kind of have this self-association that happens. It's people doing what people do. And that is they, we, I recognize affinity. And when kind of the draw or the magnet is unmet medical need, then then things catalyze where the physician says, You know, I really want to better understand this so I can give better care. I need tools. And then a tool provider and craftsman at TGen is going to say, Hey, we have tools and we know how to think about how to use that information to tease out an understanding. And then then we can work with the physician who says, you know, I got samples, I have these patients or I'm running a clinical trial and we'll have specimens of the tumors pretreatment. Can you find a way to have known before we gave the drug, which we're going to be the responders and which ones weren't? Because I want to repeat the trial at a higher level and I want to not treat patients with this drug who aren't going to respond, wouldn't that be awesome, right? And so we feel like TGen is pushing the design of clinical trials, using our technology and scientific background to come up with molecular signatures to say patients just not likely to respond to that drug. Is there something? Oh yeah. Because of the molecular makeup of their disease, they're far more likely to respond to an immune therapy or a metabolic intervention, some kind of combination of growth suppressor that then triggers an immune reaction. Right. So we're going to tease these diseases into subgroups to the benefit of the patients, which is the kind of medicine every doctor wants to practice and every insurance company would love to say, Could you take care of this sooner? Yes, soon and be more precise and you know where people can get back on with life. So I think we're all pointed the same direction. I don't think there's competing agendas per se. It's just let's figure, figure it out. And so this profiling of disease with the intent to say, informing management of the disease or care for the patient, that that's actually so exciting and the tools available today continue to improve. So we're really excited about that.
Karie Dozer [00:14:15] You've been here at TGen since the beginning. You've seen it grow from renting office space or borrowing office space 20 years ago to where you are today. What are you most proud of as you look back?
Dr. Michael Berens [00:14:26] Wow, that it's here. I'm really proud that TGen is here in Arizona. I got to be somewhat of a cheerleader. Before we raised the funds to persuade Jeff Trent and the team that he wanted to assemble to say, you know, Arizona would be a good place to do this, and I say that as a Arizonan that I've been here since 1953. I moved here when I was really short.
Karie Dozer [00:14:55] Me too.
Dr. Michael Berens [00:14:57] But, you know, telling, telling my state that, you know, this is good for me as an individual. I think it's good for my, my parents, my siblings. I hope it's going to be good for my kids and my grandkids, which now has been the case. It's good for entrepreneurship. So the explosion of the bio sector written large write. More than a third of the scientists a TGen are computational computer scientists. They're coders, they're not biologists, right? And that's because we need help analyzing the genome. So. So what this does it, it expands and it grows. And we spin out spin out companies that are now part of the. Environment, heritage and creating jobs. And so, wow, you know, the scientists is gratified by the work and then moving forward for the state and the community, people say, how should we do these public private partnerships and should the it's good for everybody and local progress, we hope touches local patients for my collaborators here and Phoenix should be the first ones to say, I know we should do something different. Yeah, when we see these things in this disease. And so we're real excited about that.
Karie Dozer [00:16:08] For the casual TGen Talks podcast listener, what would be your final words for them? What should they know about TGen and why it's so important here in Phoenix,
Dr. Michael Berens [00:16:19] Putting the best science and technology in play to address human diseases is a merciful and exciting pursuit for a community. You can be proud of it. We can say where we're engaged. This is part of our ecosystem of who we are. We want to make a difference in fostering human flourishing. That's a that's a point of pride, if you will. It happens at all the academic and research enterprises in the state. The translational focus of TGen puts an element of urgency and. Proximal or close by fulfillment to that undertaking. And that's why I'm so proud and excited that I get to be here doing what I'm doing.
Karie Dozer [00:17:06] It's obvious it motivates you every day. Here's to more answers to more of those questions. Thanks for your time today.
Dr. Michael Berens [00:17:12] Thank you.
Karie Dozer [00:17:13] For more on TGen's research, go to TGen Dot Org Slash News. TGen, the Translational Genomics Research Institute is an Arizona based nonprofit medical research institute dedicated to conducting groundbreaking research with life changing results. TGen is an affiliate of City of Hope. You can find more of these podcasts at TGen Dot Org Slash TGen Talks or on Apple Podcasts. For TGen Talks, I'm Keri Dozer.