Episode 90. Masonic Cancer Center (ft. Dr. David Largaespada)

What is the nature of treating cancer? The field is moving tremendously fast: medicine is changing, and new forms of therapy are becoming the norm. 

“There’ll be ways for us to detect cancer years earlier than we do now, and that's going to allow us to treat many more patients successfully.”

Dr. David Largaespada (Deputy Director of the Masonic Cancer Center) joins us this week to share insight on the latest research and collaboration going on. From mouse genetics and gene modification to cell biology, it’s time to put on your lab coat and power up the centrifuge.  

“The relationship with Masonic Charities has been critical for our Cancer Center. We wouldn’t be where we are today without the backing of Minnesota Masonic Charities.” 

Transcript

0:00

What motivated you to pursue cancer research? Well, it's a great question. Uh, when I was an undergraduate at the University of Minnesota, I took. A 1000 level course on the biology of cancer. And it was that course. And, uh, understanding that it was a huge mystery that led me to cancer research. I'd always been interested in biomedical research and science. My dad's a physician. Um, but when I was an undergraduate, I thought. Okay, I'm interested in biology. What are the big mysteries out there? And two of them that I've really worked on, what's the human genome like? That was a huge mystery back then. And what is the nature of cancer? And so those are the two things that I feel like I've pursued during my career. Um, it was really just the mystery of it. It wasn't because of, uh. You know specific family members or friends who had suffered from CA Cancer. Although that certainly happened, it was the mystery of trying to understand what was really happening with this disease. we are honored to welcome Dr. David Larga PhD to our studio today. David is a professor in the departments of pediatrics and genetics, cell biology and development, and the Associate Director for basic research in the Masonic Cancer Center at University of Minnesota. You are an authority on mouse genetics, gene modification, and cancer genes. Can you tell us a bit more about the gene modification? The mouse genetics? Fascinating. So I've been working with mice as a model for understanding human cancer since I was in graduate school. And, mouse research has made a tremendous, you know, impact on our understanding of biology in general, including cancer. And the reason we use laboratory mice is that they're easy to house. you can reproduce. Mice very quickly. So from a single pair of mice, in theory, a year later, you could have 15,000 descendants. So the gestation period for malice is only 19 days. Uh, and once, once they're born a. Four weeks later, they're ready to breed. Wow. So that's how that can happen. So they're easy to house. We can make a lot of them. Also, you can create inbred strains of mice that are genetically identical. So this removes that variable of differing genetic background in the experiments we've done. So it's like we have cohorts of identical twins that are as big as we want, that we can use for our research. The last thing I would say about it, that got me interested. About using mice in my research and that have has helped the field so much is that we can take mice and we can add genes to them or we can modify the genes they already have. And this has allowed us to really understand, uh, a lot about the human genome and the development of human diseases because the core gene set. That, uh, mice have, we have too. It's common in all mammals. Hmm. Uh, and in fact, much bigger domain of life. So for every gene that we have, mouse has their own version of it, pretty much. There's some exceptions to that, but that's why we use mice. And, um, it's been a big part of the research that we've done in my lab is to develop new ways to study cancer, uh, in mice. And I would say a big. Thing to emphasize here is that all cancer is caused by alterations to genes. And so a, a huge part of cancer research has been identifying the genes that when altered could cause cancer. And we did a lot of that work actually in mice first and have, you know, later asked is that, is that same gene involved in human cancer? You received a BS in Genetics and cell biology from the U of M Twin Cities, 1987. and a PhD in molecular biology with Dr. Rex Risser at the University of Wisconsin Madison in 1992. Also, a fellowship at the National Cancer Institute working with world renowned geneticists, Dr. Nancy Jenkins and Dr. Neil Copeland, where the Leukemia and Lymphoma Society of America awarded a post-doctoral fellowship. You joined the faculty at the University of Minnesota in late 1996. Currently holding the Hedberg Family Children's Cancer Research Fund Share in Brain Tumor Research, you are awarded the American Cancer Society Research Professor Award in 2013. That is the highest award given by the A CS Dr. Larga Botta. I must admit that's in these moments of recording our podcast, that I solidify being the dumbest person in the room. Not at all. Not at all. just means I've been in the field a long time. Well, we're happy to have you at our Masonic Cancer Center here in Minnesota. Can you tell us a bit more about a specific research project that you've led or, or something you're currently working on? So earlier we talked about how important mice are for biomedical research and for cancer research generally, and probably what our lab is best known for. Is developing a technology that allowed us to find what genes and genetic pathways can contribute to different forms of cancer. And we used that to study brain tumor development, development of nerve tumors, liver tumors, and many other forms of cancer. And it gave us sort of a genetic fingerprint of how these tumors develop. And that's been very useful because some of that information actually ended up motivating clinical trials that were tried later. We've taken that same technology that we developed for that purpose, which was called Sleeping Beauty Transpose on Mutagenesis. And we've generalized it now so that we can use it to understand other biological phenomenon. And particular, what I'm really excited about right now is we're using it to try to figure out how to better modify. Human T-cells so that they can be used as medicine to treat cancer. So you might have heard of a technology that's FDA approved now to treat some forms of cancer called chimeric antigen receptor or CAR T-cell technology. Yeah. Yeah. Where a patient's white blood cells are taken out of the body. Genetically modified so that they can recognize a tumor is foreign and put back in the body. And there's been some tremendous advances with that therapy, especially for treating leukemia, lymphoma, and multiple myeloma. But it's been unsuccessful by and large to treat solid tumors like brain tumors, which is something we work on. What we're U doing now is using this sleeping beauty transpose on eugenics method to find genetic edits that we can make to these T cells so that they can home to a solid tumor, infiltrate it, survive in the harsh environment of the tumor, and actually do their job and start killing the tumor. We started to find genes that we can alter that will have this effect. So far we've tested in mice, but. The work that we're doing is exciting to me because it's a new way for us to use this technology that we developed a long time ago and first published in 2005, but use it in a new way. You have an interest in biotech. Can you expand a bit more on that? Sure. So when I was a postdoctoral fellow at the National Cancer Institute, my uh, mentors, Neil Copeland and Nancy Jenkins participated in forming a biotechnology company called Millennium Pharmaceuticals. It's very successful and I saw that they were able to balance a career in biotechnology and industry and AC academic pursuits. And so I wanted to do the same thing when I started my lab at the University of Minnesota. And so I've started four co-founded, four different biotechnology companies, and the way I see it is that. I've always been interested in technology development. In my lab, we sort of balance hypothesis driven research with research designed to develop a new technology. The the new technologies that we work on are useful for answering research questions, and an example is one I brought up earlier, the sleeping beauty transpo on system. It was very useful as a research tool, but it also has real world applications as a tool that can be used for gene therapy. So I got interested in this idea that what we do at the university we can use to make research more powerful, but we can also use it for real world, world applications like human gene therapy or to improve cancer therapy. And I thought also that it would be great if we were able to help start a biotech industry. In the state of Minnesota. And so this is the reason I got interested in doing this. And um, it's been fun to do and it's sort of a different way for a faculty member to influence the outside world. So we train people, which is great, and I love the trainees, what we work with. We publish papers that tell the outside world about what we found, but we can also help start new companies, create jobs for people and also. Figure out a way for what we're doing at the university to influence the outside world faster by participating in these spin out companies. As you're describing this, I'm thinking that between the Masonic Cancer Center at the university here. Mayo and Rochester and elsewhere. How, how much is Minnesota leading the way right now in some of these research breakthroughs, these initiatives with technology? I, I feel like we're further ahead of the pack than maybe the general public might appreciate. Um, so one area in which we certainly are, and, and most people know this, is that Minnesota's a hotbed of research and industries in the medical device field. So that's been our traditional strength. I think we could do the same thing in cell and gene therapies or human disease, which if you think about are just molecular devices, uh, for treating disease. and so I think that, cooperation between the university and Mayo Clinic with their incredible clinical. Um, resources is one way to do that. And the state of Minnesota has realized this. So the Department of Employment and eec e Economic Development Funds, grants that, uh, where there has to be a, a pair, someone at the University of Minnesota side and someone on the Mayo Clinic side that work together to develop some new, biomedical technology. And, you know, some of that research has certainly. Brought the two institutions closer together and also fostered some of the development of new companies. So I really think, you know, we have, um, this incredible healthcare infrastructure. We have this medical device industry, uh, and know-how about how to create companies like the, like these, I think it, we could move it into the field of cell and gene therapy as well, How challenging would it be to bring all of those parties to the same table and to get this really moving with a purpose? I think one big challenge is just how is it funded? So the venture capitalists, and when they think about the state of Minnesota, they think about medical devices and not biotechnology companies. And so it's been difficult to bring investment here. And yet, you know, if you think about the advantages we have. Compared to places that are hotbed for this, like the Bay Area in California or Boston. the cost of doing business here, the Twin Cities is lower. We have well educated public, we have, you know, lots of trainees interested in cell and gene therapies and biotechnology, so it should be appealing to venture capital. Uh, and yet we just have to get the word out there more. And this is something we've experienced with the companies that. I was involved in co-founding here in the Twin Cities. Most of the money that we've been able to get for these companies has actually come from strategic partners or other companies rather than venture capital. Can you tell us a bit more about those companies you founded and what some of the progress that has been made, breakthroughs, some exciting things, kind of that, that look inside the lab, so to speak? Sure. They've been involved in, uh, the. Human gene therapy or, uh, cell therapies or cancer fields. Uh, one of them, um, called Beam agen. We sold the biotech bio knee, which is, uh, the largest, biotech company in the Twin Cities. and it was focused on a new delivery method that allows you to genetically modify human white blood cells, um, and that fit their portfolio of what they wanted to do. Another of the companies was initially called Discovery Genomics, was then acquired by a company in Seattle called I Usoft. They're a clinical stage company that's taking B cells, a special type of white blood cells from circulation of patients who have certain genetic diseases adding in genes that they're missing, are dysfunctional in those patients and putting the cells back. And they've actually, uh, started to treat patients. Who have a type of disease called a storage disease, where if you replace an enzyme in the B cells, you can, um, have a beneficial effect. So that's super exciting. And the most recent company's called Luminary Therapeutics. We are a clinical stage biotechnology company with uh, three open clinical trials to treat cancer and autoimmunity using gene modified human T-cells. As you're describing this in just a handful of these ventures, so many potential breakthroughs happening. Is it possible or how do you stay current with advancements or developments in research because you're doing that on your radar, and then there's a company in Boston, then there's Seattle, San Francisco, McGill, and Montreal. Are all of these parties sharing notes along the way, or is, are you, you're not in a silo doing this right? It, it's hard to fathom things moving so fast in this breakthroughs, How does everybody stay on the same page? That's a great question. You know, I think. These days, it's easier and easier for us to keep abreast of what else is happening in the world just because we're all connected, you know, on the web. And we can even use AI to help analyze the literature for us so that we know, okay, what's happening? Um, you're right, the field's moving tremendously fast. Medicine is changing. New forms of therapy are becoming the norm. and there's a tremendous amount of. Competition and collaboration going on. It's a real mix of things. We collaborate widely with people around the country. Um, at the same time we're aware of other people who are doing similar things. I think there has to be a healthy mix of those two things happening, and that's how progress is gonna get made. There has to be the right incentives in place, uh, for, so that there is an investment in these new technologies. Unfortunately, a lot of'em are really expensive at first for patients, and so that's a whole other, challenge for the field is how do these breakthroughs make economic sense so that the public and patients can afford them. So that investors can see a return on their investment. So it's a challenge. The business model is also a challenge. So we are in the midst of a 70 year relationship with the Masonic Cancer Center and the Masonic Children's Hospital. All of our endeavors at the university between Masonic Charities and the Grand Lodge of Minnesota. How much has that helped you and your team in tackling some of these. Potentially new breakthroughs in research as you work so diligently on all of these fronts. The relationship with Minnesota Masonic Charities has been critical for our cancer center. It's our, uh, part of our identity too now, really. and I would say we wouldn't be where we are today without that backing of Minnesota Masonic Charities for sure. we are a top echelon. Comprehensive cancer center. in the country, what we're doing, it's challenging and expensive. And when you think about it, the research that we do is risky. It's inherently risky. And so the public, in the form of taxes, we pay to the government, state, and federal helps. Support that early risky research and so do partners like Minnesota Masonic Charities. It's an incredible gift to make to support that early high risk research. the pharmaceutical industry doesn't get involved. T typically, until an idea has been vetted by prior research, a lot of times not even tell it's been used clinically. Perhaps phase one or phase two trials. Okay. Wow. So you think about what Minnesota Masonic Charities is doing is putting in that earliest money that helps support the real breakthroughs that happen. And you know, if we look back at the history, the, you know, most of the new therapies that we have today. They started in a lab somewhere that was funded by philanthropy, um, and or, you know, grants from the government. the way I think about it is that that's money well spent because, otherwise we won't really have a pipeline of anything new. All that you describe is exciting. I can't imagine how you turn it off at the end of the day'cause they're just to be immersed in this. But that support is really a, a source of pride for Masons of Minnesota and, and outside of our state even, who have contributed to some capacity towards, through Masonic charities to all of those endeavors, to to have a front row seat towards cancer research, leveraging of technology. And knowing that those gifts, whether it's a charitable remainder trust or a a, a relatively small donation, all of that, I believe your colleague, we, we quote Dr. Douglas Yale a lot when he said more or less, that nobody knows who's$5 or$500 will be the difference maker to push something into the next echelon of a breakthrough. Yeah, that's absolutely right. So the Masons should feel proud. Of what they've accomplished by partnering with us and, uh, we're proud of this relationship and working together. You think about it, the support has helped University of Minnesota Masonic Cancer Center improve, develop, and improve bone marrow transplantation to treat patients with leukemia and lymphoma and multiple myeloma. You know, this money has helped us better understand. Tobacco carcinogenesis and how, uh, tobacco products cause cancer in ways to help people, uh, quit if they want to quit. Mm-hmm. has influenced public policy around tobacco, tanning breads and other thing, other exposures that cause cancer. So it's not been just about treat new treatments. It's also helped us work with legislators to develop better policy. That will protect, uh, more people from ever getting cancer. The money has helped us do research to try to take care of patients who've recovered from cancer treatment, live a better and healthier life after cancer. I mentioned before two of my siblings have cancer. They're successfully treated at Fairview University hospitals and clinics and both doing well, and. healthier, uh, because of research that's, uh, been done to figure out how do survivors do better, after they've recovered from their cancer treatment. You mentioned those two siblings. How many you have a significantly. Pretty big family, right? Yeah. Of of siblings. Yeah. I'm one of eight kids and I have two stepsisters also, so I'm number six out of eight. Wow. Not a particularly special position, but um, yeah. Where did you grow up? So I was born in Indianapolis, lived there till I was 12, and then we moved to Minnesota Twin Cities area. And I've lived, uh, here in Minnesota ever since, apart from the five years where I was getting my PhD at University of Wisconsin, Madison, and then five years. As a postdoctoral fellow at the National Cancer Institute in Maryland. So my wife and I left Minnesota, for those 10 years. Came back to Minnesota with, and then we left with no kids and came back with three sons. Oh, wow. And we had in the interim, uh, and it's been great that we, we got to come back to our hometown, uh, where our kids had cousins, aunts, uncles, and grandparents in town. How old are your kids now? So, um, our oldest Sam is 33 and we have 30-year-old twins. Anton and Nathan. let's go back 30 years when that update, by the way, there's two. Yes. How does that feel as a new, new parent? Yes. With one already? Yes. Yeah. As I was a postdoctoral fellow then. Oh, no. And, uh. yeah, it was a shock. As soon as I saw the ultrasound though, I, I could see there was two, two in there. I didn't say anything right away, but I was like, oh boy, that looks like two. We didn't think that it was gonna happen. My wife was measuring big. Mm-hmm. And we thought, well that happened with the first pregnancy, so it's no big deal. But yeah, instead it was twins. It was quite the ordeal, uh, to do when I was a postdoc and we were trying to publish these papers. We had the 3-year-old, then my wife was on preterm labor. So the only way we made it through that time was my mother-in-law moved in with us for the three months. Before the twins were born and she stayed for the three months after they were born. So she a real angel, an incredible person who helped us out a lot. Huge. Yeah. As you look back on that, what was more difficult? The postdoctoral work or the family front? Yeah, probably the family. And then after my mother-in-law left I, every few weeks I was going to the airport to pick up a new person who was gonna stay with us and help, help out with the twins. So we got a lot of support. That's huge. Um, yeah. I have to say it was all sisters, not brothers, but typical brothers. Typical brothers, exactly. Brother will call and say, let us know how it's going or Right. The let me know if you need anything. Yeah. But, right. Yeah. We don't, we know how that goes. Yeah. A few moments ago you mentioned challenges in certain aspects of what you do and what your, your team is working on. What scientific challenges do you think cancer researchers will face in the years ahead? Yeah, so that's a great question. I think a huge challenge is detecting cancer early, deciding who's at high risk for cancer, figuring out how to detect it early, when we can treat it more successfully. I think that's a really exciting cutting edge area of research. We now know that. When someone develops cancer, those tumor cells are, and DNA from those tumor cells is shed into the blood and circulates. And so it's possible that there'll be ways for us to detect cancer years earlier than we do now, and that's gonna allow us to treat many more patients successfully. it's likely that there are ways to take people's. Uh, DNA, sequence it and decide what cancer risk they might have. Not just that, but also ask what are the exposures that they've had during their lifetime? That together with those, their genetics might influence their risks. So we can sort of stratify people better, see who needs. Early screening and more intensive screening so that we can catch more cancers early, those technologies will come together, um, to make this a reality. I believe. So that's a huge frontier. I think that, um, is exciting. The other is that we'll start to replace the toxic therapies that we use today. With immunotherapies and targeted therapies that are a lot safer, that's exciting. So for years, you know, what we've had is the traditional trio radiation, cytotoxic chemotherapy, and surgery, and that's it. Uh, now we have lots of new ways of treating people using drugs that are much more specific and where we know the mechanism of action. Using the immune system in a lot of different ways, and those therapies generally, not always, but generally there are fewer side effects and I think that we'll get to employ them in more and more situations and employ them earlier and earlier in the course of disease, right when someone's diagnosed. A lot of the new therapies that are being developed now, you know, they're approved, but after someone's failed, um, or that therapy has failed them, I should say. Therapy has failed them. That we have, you know, the first, first line or second line. What we're seeing is a lot of these new therapies are being moved up earlier and earlier. so I imagine, you know, that you could imagine a future where we don't use radiation. Yeah. Wow. Where you, you can avoid certain surgeries, um, because the therapies we have are so good and so complete. I, you know, I imagine that that will happen too. So a recent trip to the doctor for the annual physical. We talked about health and family. I lost a brother last year to a multiple myeloma, the little handout, the pamphlet, they, they give that more or less said that. Significant portion of cancers are preventable through lifestyle choices. Pretty obvious stuff. Healthy weight and avoiding smoking. Early detection is so key. How important is it for men, well, for people in general, but specifically men, to be taking their health seriously by age 40, if not sooner. Yeah, so it, it's a great question. You know, if you. Look at the statistics. Unfortunately, men are less likely to use their healthcare dollars, right? Than women are. And we should, I believe strongly. If you paying for that, you know you're paying for that, right? You should use those healthcare dollars. Uh, and we know prevention is, uh, an early detection is, um, is much better than having to treat full-blown disease. So, um. I think it's critical. Just as an example, we know that at age 45, everybody should get screened for colorectal cancer one way or another. And if we did that, we'd eliminate half of the deaths happen in this country for colorectal cancer. Half, yes. Now the age at which screening was recommended, used to be 50, now it's 45. And for people with a family history of colorectal cancer, it's even younger. Uh, so that's just one example of something men should do. It's not necessarily real pleasant, but of course I've been through it. I'm actually due for another one right now. is, needs to be, um, more widely utilized, especially by men. And, you know, some research that's happening at our cancer center is actually on how do we make these screening technologies that we already have that are proven to work, how do we make them, uh, more available to people who are under-resourced? What It's been a regular discussion within our organization for men to take that vested interest in their health. We can't keep doing certain things, activities, indulging in or ingesting certain things after a certain age. Yeah. We're not in college anymore. We're not, and yet it's that, well, I'll get to that someday and, and I'm amazed how many men are unaware. Going in for a physical, for the prostate exam is a lab test. Now it, it's so easy now. That's right. Yeah. So prostate's another important one. Yeah. Uh, because it starts to become quite common as men get older. Um, you know, I had my own scare with it. Did you really? Yeah. My PSA was high. I was experienced in some symptoms. My dad had, prostate cancer, but was successfully treated. He's still alive at 93. Wow. Um, I had symptoms, uh, it turned out to be what they call benign prosthetic hyperplasia. I. Which was eventually treated surgically, quite successfully. I'm very happy with it. Um, but there was a concern because my PSA was high for someone my age, but it turns out that can also be from this benign hyperplasia of the prostate, not prostate cancer. So I was lucky in my case that it wasn't prostate cancer. Well, and as you said, the colonoscopy prep. Well, it's no fun. Right? But you can be sort of comical in hindsight after the fact and it's what, every five years? It depends. So it depends. Um, at age 50, if when they do it, if they find a polyp, they'll remove it and suggest another that, that you do it again in five years. If they, if they see nothing, they say, come back in 10 years. Okay, now that's what the situation was for me when I was screened at age 50. These recommendations do change. So you should check to see what they're recommending. Now, I mentioned earlier, for example, they now screen recommend screening everybody at 45 instead of 50. That's right. Yeah. So men that are listening, use your benefits. Use your coverage, right. Schedule that annual physical, absolutely easy. Yeah. Not only that, you know, look how incredible. The advances have been in reducing death from cardiovascular disease, and that's all because of testing to see, oh, there's high blood pressure, stop right there, there's high cholesterol, and we can do something to prevent the disease that would, that would develop. So there's a lot that we can learn in cancer from what the cardiologists have have learned how to prevent disease. I certainly didn't mean to turn this into a sermon to our listeners, but I know way too many men who are waiting for someday to take action on this, and someday should be now it should be. You have quite a resume. Obviously, you've gone to school for things that most of us can't even fathom. In your opinion though, what's a lot harder than it looks in the job that I have? Anything? Uh, well, what's harder in, in my job than uh, people might understand is. How we have to hustle for the funds to keep our research going. it's, you know, a third of our time at least is, it really is spent just writing grants and hustling for money. So, um, that part is gotten more intense. It didn't used to be that way. So, it's a little more challenging now. So it's something that's a major part of the job is, is just hustling for, um, how do I support this important research that, that we're doing. you know, the th I almost wanna turn the question around too, because, um, there are things that people may not know about the job that are more rewarding. More fantastic than they know. And one of them is just the joy of working with trainees who are undergraduates or who are graduate students earning their PhD or postdoctoral fellows in my lab. Working with them, seeing them develop and go on to independent successful careers is one of the most satisfying things about what I do. we're doing this for basic research hoping to, um, make breakthroughs. and I would love to make more than we've made, but one of the things that I can feel great about is that at least I trained others in how to the scientific methods and how to go out and become independent scientists of their own so that we keep this enterprise alive. This whole thing we call science, which is what gives us progress, which can grow our economy and make our our lives better. That part is, gives me a great deal of satisfaction. Um, and, and is is a wonderful part of the job that people may not know, may not know about. As you described that the thought of the mentor mentee relationship, that has to be Absolutely. It is how gratifying. It's super gratifying to see, um, these people and they're so talent. There's so many talented, uh, young people out there, who are excited and earnest about doing this. And it's just really gratifying to see what do people occasionally wrongly assume about you? Oh wow. That's a great question. Um, maybe that I don't have outside hobbies or anything. No, because. They think, well, you must be really busy with these companies and, and your work at the university. So do you have time to do anything else? And do you have any fun outside of the work? Do you have any fun? So they don't know that Yes, I still go to First Avenue and see, uh, shows. And I like to ski, uh, and bike ride. And I still hang out with my old high school buddies. Do you? So, yeah. What do you see at First App? What kind of music are you into? Well. Um, a lot of different kinds, but I guess my favorite music is the music that came out in the sort of the grunge era of the eighties in the Twin Cities. So Replacements. Suburbs. Suburbs, yeah. Oo. I like that. Music. And music from that era. Saw the Pixies recently, I missed that show. It was really great. Love Wilco. a lot of bands from back then. What's a genre of music that you have never been able to get into? Bluegrass. Sorry for all the Bluegrass fans out there. I just can't get into it. There's a lot of talent to it, but yeah, a little bit of a monotony factor. Yeah. After, after a bit, what's your unpopular food opinion? Wow. These are tough. These are tough questions. to tell you the truth, uh, I like everything and my family is known for that, being big eaters. Okay. I, uh, yeah, I can't think of anything, offhand, although a liker dislike. I do, I do, I do encounter people every now and then who say they can't stand olives, and I just can't understand that at all. how can you not like olives? What do you think that is? Is it texture? Is it sodium too salty? Or that maybe, I don't know. I don't know what it is. The slight bitter taste. Well, there was a certain time in my life when Olive was really enjoyed because there was a martini involved. Yeah. Yeah. I like that too. You had a big family, lot of siblings had to be competition for the tv. What show did you love as a kid? Hogan's Heroes. I think we all liked it though. I still hear the theme song. Oh yeah, for sure. Favorite character. Hogan, of course. Yeah. It's a great cast. Although I, I like Lebo also. Yeah. Frenchman. It was always strange to see very stylish Richard. Yeah. He was Richard Dawson to later be on Family Feud. Yeah. And he was kind of a lethario on that show. Yes. Yeah. And he was such a proper. Good actor, I guess. Yeah. I have to say we also liked Brady Bunch a lot too. Yeah. That eight kids and we had eight kids. Mm-hmm. So, you know, we could relate Similar dynamic of Yes. Yeah. even the young people today, we talked to some younger folks that, yeah. They've never seen the Breakfast Club movie. It's only 40 years old now. Right. They've not seen some of the classics that you and I and yet the Brady Bunch. Totally. They know it. They know that. The whole thing. I, I didn't, I'm surprised by that. Yeah. But yeah, same. I thought maybe that would've been opposite, but Yeah. But who knows? Some things are timeless. And I remember realizing that some of the plots in the Brady Bunch were identical to the Dick Van Dyke show. So were they? Yes. So they stole stuff, you know. Is that Sherwood Schwartz? I don't know. Maybe. I don't know. But you know, I remember seeing it thinking, Hey, this is just like that episode of, of uh, band show, which. Proves that I watched too much TV as a kid. That's all we had. Yeah, no internet. Do you ever think of that in looking back on college days of not having the iPhone, not having the texting and the constant connection? Does that just make you, and I sound old that we appreciate that? Or is it just a Yeah, it's possible. We are old. Um, but yeah, we sometimes, my wife and I sometimes wonder how, how did we get anywhere, uh, back then. Do you remember? Vacations and I guess we used maps. Yeah, printed maps. Uh, but yeah, that's a thing of the past. And you had to arrange to meet someone at a certain place at a certain time and you couldn't just text them. I was just thinking we planned more. We did. And family vacations. As a kid, your neighbors didn't have any idea where you possibly were, couldn't contact you. That's right. That was truly off the grid. That's right. Unfathomable to the young person or even young parent of today. Yes. The eight kids that you shared a car with as a child, there were no DVDs, there was no entertainment. I know. And we took Pontiac station wagon from Indianapolis to Western Minnesota every summer. Wow. For a family reunion. So 10 people in one Pontiac Station wagon. How many stops it was and we stopped in Rochester. That was, it stayed with, uh, cousins dad said, this is the LA we're not stopping till Rochester. That's right. So do your business. Yeah, right. Exactly. It was always touchy getting through Chicago. Yeah. Well, Dr. Larga Badda, it has been a pleasure to chat with you today about your research, about all the great things happening at the Masonic Cancer Center at the U of M I'm, and to hear a little more about you on a personal side with family and hobbies and music, I hope to see you at First Avenue sometime Yes. On cross paths. That that would be awesome. Well, good talking to you Reed. And thanks to, uh, Minnesota Masonic Charities for all the support for what we do at the university in the Masonic Cancer Center.