Advances in Canine Hemangiosarcoma and Longevity Research with Dr. Jaime Modiano

Karin (00:00.314) Welcome so much to the podcast. I'm really thrilled that you are here, Dr. Modiano. It's really a pleasure to have you. Jaime Modiano (00:10.744) Thank you, thank you for the invitation. It's a pleasure to be here. Karin (00:14.938) So would you mind starting us off by telling the listeners about your background and your education and in particular about your lab's research on canine and human forms of cancer? Jaime Modiano (00:29.592) Sure. So I am originally from Mexico, born and raised in Mexico City, left home and went to college in Texas. I guess we all make one mistake in our lives, but I did go back. No, just kidding, for all of those people in Texas, love you, absolutely. After college, I went to the University of Pennsylvania. Karin (00:46.264) You Jaime Modiano (00:57.966) in Philadelphia where I went through the combined degree program at Penn. So it's a program where you spend seven years and you get the veterinary degree, which at Penn we call VMD and a PhD in immunology working with Peter Knoll. And I chose Peter Knoll's lab because he is essentially the father of modern cancer genetics. I was very interested in how chromosomes get messed up during cancer. And he was the first person to report a non-random translocation. So two pieces of chromosomes getting jumbled apart and then put back together in a cancer consistently and being really sort of diagnostic and prognostic for that cancer, which is the Philadelphia chromosome, chronic myelogenous leukemia. And I remember he was really my role model. He is just an amazing guy. at that point, he told me that cancer genetics was a dead end and I should become an immunologist because that's what was big at the time in the early 80s. And I followed his advice and I became an immunologist and then eventually circled back to do both immunology and cancer genetics, which is really exciting. I did have... Sorry, go ahead. Karin (02:12.644) So you, were you... sorry, were you studying human cancer, human leukemia at that point? Jaime Modiano (02:22.398) Yeah, so no, actually, you just can't imagine what a great person he was. But one of the things he taught me was that in order to understand abnormal pathology, you need to understand normal physiology. So he convinced me that I shouldn't fall asleep in my physiology courses in vet school and I should pay attention. So in our discussions back then, we were talking about how cells divide and particularly we're using T cells as a model. T cells are the white blood cells in the body that mediate immunity against infections, viruses and stuff. So these are the ones that don't make antibodies, the cell mediated arm. And so he always taught me that to understand abnormal, you should understand normal. And we knew that when you tickled the cells on the outside, there was a big black box of things that happened. and then the cells would divide. And so he encouraged me to find something in the big black box. And so my PhD was looking at the mechanisms that make T cells divide. And so that's what I did for my PhD. And I specifically looked at sort of early and midterm signals that were delivered through calcium and a series of proteins that are part of the protein kinase C family. And then when I finished with a PhD in vet school, trying to decide what to do, I thought that after spending all the time learning clinical medicine, I should still do something with my clinical skills. I did a post, I mean, I did a residency at Colorado State in clinical pathology, or as we used to call it back then, bioanalytical pathology. It was the clean side of pathology where you get fluids and you put them through fancy machines that go ding, as opposed to having to be in the in the dead room as we call it. And then after I finished my residency, I realized that I really missed research. So I did a postdoc at National Jewish with Erwin Gelfand and Erwin, another fantastic mentor. He was the first person to successfully transplant kids with cancer. So do bone marrow transplants in kids with cancer and autoimmune disease. I should not neglect to mention my residency mentor, Dr. Mary Ann Throlfe from Jaime Modiano (04:47.896) whom I learned everything I know about pathology. And then I went back to Texas and set up my lab in Texas, really studying cell division in normal lymphocytes. So at the time, we had transitioned from trying to understand the gas pedal in the T cells to trying to understand the brake pedal. So it turns out that lymphocytes run around the blood and they are not dividing in the blood. people thought that they were not dividing because they weren't seeing anything that made them happy and dividing. But during that time, we actually found out that the reason they don't divide when they're running around in the blood is because they actually have to put a parking brake. So this is a very active process of them staying quiet. And when those processes go wrong, you can get autoimmunity. And so we were focused on that. And my wife, who has taught me everything I know about being a normal person, was doing a residency at the time. And it's a very long story, but I'll keep it short. She decided that as part of her residency projects, she was going to focus on looking at genetics of melanoma. And when I asked her whose lab she was going to work on, she said that she was going to work in my lab. And I promptly reminded her that we did not do dog cancer genetics. And her answer was like, well, you do now. And so. Karin (06:12.42) Thank Jaime Modiano (06:14.4) So really she is responsible for bringing me back to the dog world. When I was in Peters, I was a graduate student. had actually done, Dr. Noll was very, very supportive of the vet school in general. And I was his first vet student, but he loved the idea of comparative medicine. And so he had jokingly told me that since he discovered the Philadelphia Chromosome in humans, I should have discovered in dogs. And I kind of thought he was nuts at the time, but. I'll come back to the fact that he was very prescient, but he had been great about letting us essentially bring dog blood samples into the lab and play with dog T cells and try to figure out how similar or different they were. So even back in the eighties, we were doing this comparative work and it sort of picked up steam in the nineties. And we got some funding through Canine Health Foundation and we've got funding from Morris and and a number of other foundations. And ultimately, the federal agencies, NIH and DOD, has supported our work. But it really grew from being just a of a side project in my lab to now really encompassing, I would say, 100 % of what we do is focused on canine cancer, both for dogs and really to understand the context of cancer in a larger scale and how it impacts humans. So from Texas, we moved to Colorado. I spent a decade at the medical school in the department of immunology where I was affectionately known as the guy that does crazy dog research. People thought it was really cool that there was this guy at the med school doing dog research. And then I had the opportunity to come to Minnesota for this endowed chair to really sort of build or rebuild the program in comparative medicine with oncology as a cornerstone. It was a great opportunity and a great vision with a lot of support. And it's been a really fun ride for 17 years where I think our contribution is that we have learned that 99 % of everything we thought we knew was wrong. So we are spending a lot of time rewriting textbooks of things that we thought were right, but are not necessarily correct. And I think a lot of that comes from looking at biology from Jaime Modiano (08:43.598) a comparative lens, really thinking about evolution. So Doshansky famously wrote in 1973 that nothing in biology makes sense except in the light of evolution. And we tend to agree with that. So that there's a lot of things that, you you discover something and you assume that that applies to the whole world. And then you realize that it doesn't. you know, undoing what we thought we knew is pretty hard work. So I think we've we've really started to convince people about the impact. So humans and dogs have really overcome longevity barriers that were sort of part of our adaptive evolution as a species, right? So for tens of millions of years, dogs and humans adapted to live in particular environments. And that adaptation came with essentially a defined lifespan, right? There's a reason why a mouse lives three months and a fly lives 17 years on the ground and then two hours in our environment and why whales can live 200 years. And so once we actually started thinking about and understanding the evolutionary context, we realized that humans and dogs have been really good at expanding their lifespan by more than two times, mean, for dogs, maybe four times what they would live in a state of nature. So we call the evolutionary adapted lifespan. so cancer risk is pretty static. It's very, very close to zero or maybe 5 % of a population during that lifespan. And it's only when you cross that boundary that you start seeing this rapid increase. in cancer susceptibility. And we've actually been able to show correlation even in the cancers where there's strong environmental influence like tobacco associated cancers in humans, where people start smoking in their teen years and they make it to their 40s with almost no cancer, The lung, leukemia, bladder, all the things that are associated with smoking don't happen in that time span. people had... Jaime Modiano (11:07.528) mostly attributed that to latency. You need all this time for cells to form, but when we do it in a mouse, it happens in a span of 14 months. In humans, it happens in a span of 40 years. That idea of, the cells are dividing at the same rate, there's got to be something else. When you actually think about how we've adapted to our lifespan, it makes sense that we have these mechanisms that are that are strongly protective for a certain period of time and those mechanisms start breaking down. So we are really spending a lot of time trying to understand what are those mechanisms. So we could eliminate cancer if we all died at 45, right? The cancer would not be an issue. Obviously, we don't all want to die at 45. We like living past our expiration date. So as we think about what is that black box, James de Gregory calls it Karin (11:54.298) Right, right, right. Jaime Modiano (12:06.486) loss of youthful fitness. So it's associated with essentially aging, but it's not just aging, it's aging beyond where we are sort of programmed to be in the best health. And so if we can figure out what are the things we lose and how we can recover them. And if we understand that a dog is not a small person and a mouse is not a small dog, so what we find in one species might apply to another, but might not. we can make a bigger dent. And so I think the Shine On program, which I think may be what triggered the interest in this, started out as an interesting confluence of projects where we had maybe a test that could detect cancer early and maybe a drug that could work to treat cancer. And it very rapidly evolved to a project where we can understand how that cancer permissive environment forms. And when I say cancer permissive environment, I'm not talking about the cells becoming malignant and growing, but it's actually, if you saw a field of dreams, there was a saying that said, if you build it, they will come, right? And so as we age, the body is unfortunately building that field of dreams that cancer cells can come and play in. And the cancer cells will almost inevitably eventually appear. And so, Karin (13:31.258) So if we start, you know, many people are interested in extreme longevity, not something I'm interested in personally, but if we start regularly living over a hundred or 110, this will be amplified. Jaime Modiano (13:32.355) Go ahead. Jaime Modiano (13:50.542) If we are correct, you know, it's a very, very hard thing to test experimentally. But if we are correct and the answer to your question is a little bit complicated. So I'm going to say that the inference would be that if you get to live to 120, the rate of cancer will increase. But there's this really interesting phenomenon. It turns out that Karin (13:56.898) Right. Jaime Modiano (14:20.458) In humans, extreme longevity is associated with mechanisms of cancer and neurocognitive protection that we don't really understand. So when you see these centigenarians in Italy and Spain and other countries, they actually seem to function quite well. So they didn't make it to 105 with an intact brain and without cancer. really by chance. There seems to be something peculiar about those individuals or families that is better adapted to the current environment that we live in and to really have that longevity. You know, it's not a single trait. It's not something that we could easily pass on. In mice, if you take young mice and you collect blood and you use their serum and you inject the serum of young mice into old mice, you essentially reinvigorate the old minds. They don't become young in years, but they become young in their activity and their metabolism and their tissues. And nobody really knows what is the magic in that serum, right? There's a lot of stuff in that serum that is associated with that observation. So there's this other really interesting observation that in humans, Karin (15:38.778) Mm-hmm. Jaime Modiano (15:47.214) If you reach the age of about 93, and it's not a hard-hung hospital, right? That's sort of a fuzzy 93. But if you reach the age of 93 without cancer, up until 93, your relative risk of cancer increases with every day that you're alive. And if you make it to 93 without cancer, your relative risk of cancer actually starts decreasing after you reach that age. So... In humans, if we actually get to this extreme longevity of 120, it may be that for those people that reach the 100-year mark, their cancer risk might actually be no different than an 80-year-old and maybe lower than a 90-year-old. So I think that what that is and how it works, we don't really know. But I think that the other analogy is that if we took elephants that essentially have evolved to live 60 to 80 years, and we were able to maintain them in an environment where we could actually increase their lifespan to 160, they would get the same rate of cancer as dogs and humans get in the modern environment. So my dad was always fascinated when I told him elephants in captivity, whether they're working a tree farm in Thailand or they're in a sanctuary or they're in a zoo usually die at 60 or 80 because they can't eat. They wear down their teeth and we don't have good elephant dentistry to give them implants. So they don't die of the things we die of. They die because at that point the stuff is working but they can't eat. And again, that's an oversimplification. And if there's any elephant biologists out there listening to us, Karin (17:32.313) Right. Karin (17:38.372) We apologize in advance. Jaime Modiano (17:39.702) Yeah, we apologize for oversimplifying the biology of elephants. But it's really just an illustration that things work for a determined period of time. So I think that the thing with dogs is there was some work that David Waters at Purdue did maybe a couple of decades ago. And his inference was that in your average large dog, and at that point he'd been working a lot with rottweilers. Karin (17:48.964) Right? Jaime Modiano (18:10.014) But I think this would apply to many large breeds. That if they made it up to sort of 12, 13, he saw the same thing, that the dogs that sort of passed that boundary. And again, it's not a threshold effect, right? There's a lot of fuzziness because we don't really understand what it is that makes it so. But the dogs that passed that boundary had less probability of dying of cancer than dogs that were sort of in the nine to 10 range. So it seems like there's also some longevity component operating in dogs and that in some individuals reaching that age almost becomes protective or they're just not as prone to develop cancer. So in our work, we're trying to understand what Karin (18:44.602) That is very. Karin (18:50.874) Mm-hmm. Jaime Modiano (19:04.212) What is that environment? What creates that field of dreams for cancer to be able to grow? Because we know we're generating cancer cells all the time, every day. And so when we're young, we have certain mechanisms that make the cancers. It really disfavors the growth of those cancers. We have robust immunity that can kill the cells. We don't have environments where they can grow. We have sort of anti-aging mechanisms that are working optimally and we know what some of those are for some species. We don't really understand them extremely well for humans and dogs. So we've got a little bit of a room entering understanding, but we've got sort of this concept. And at some point, you know, those stop working really well and then you build the field. So why is it that you build the field at, you know, five years old for some breeds of dogs or some individual dogs and you build the field at nine years for? other dogs and is there really a heritable component to this? it simply size and metabolism? Is it pure random? know, like it's your exposures. We don't know. So we're trying to define what the field is so that we can look for it. The Shine On project was really good at identifying what that field is. So now we have a pretty good sense of what the field is. the really surprising aspect. So everybody says, how come you're not out there? How come you're not out there? How come you're not out there? Well, I can say that we are not out there for a couple of reasons. One is we want to be sure that whatever we report, if we're going to be out doing clinical testing, is absolutely accurate and trustworthy. And there's still some gray areas that we don't entirely understand and where we think that there's potential for harm if people get a result that they don't understand or particularly show a result that's not actionable. And that's the other thing is if we tell people your dog is at elevated risk of developing cancer, right? So we know that our tests can divide dogs that are at much greater risk to develop cancer over the course of six months, a year, three, four years. And Jaime Modiano (21:25.93) And that's a relative risk. It doesn't necessarily mean absolutely. So if your dog is at higher risk of developing cancer, but it might not, what do you do about it? Right? And other than worry. So worrying is not a good thing. It changes the relationship of the dog with its human family, because human families are really bad at handling emotion. The dogs don't care. The people do. So we are working on the interception side, which is Okay, so let's say that you are high risk and you have a 30 % probability of developing cancer in the next 14 months and a 50 % probability of developing cancer in the next two years. Well, that still leaves you at a 50 % probability of not, right? So one possible action would be to do nothing and see what happens. That, you know, it costs you nothing and you've still got a 50 % chance. But if you feel like you want to be sure, then Can we develop an interception to do that? And so we are testing EBAT as an interception. The data look awesome. We have very few dogs enrolled. We've got 10 dogs enrolled. The data look really, really good in terms of seemingly reducing the probability of cancer in those dogs. EBAT is not available yet commercially and when FDA approves it, it's not going to be approved as an interception or a preventative, it's going to be approved as a treatment. So if anybody wanted to use it, it would be off label, which carries all sorts of other things. So we're really trying to understand, you know, we understand the environment and what EVAT does, we're asking, there, and, you know, EVAT is probably going to be expensive. It's going to be limited availability because of the manufacturing distribution issues. So we're trying to essentially figure out like, what other interventions can we do that are easier? Is there a way to refine the test so that it's easy and inexpensive and accessible? We don't want our test to be a thousand dollar test. And then the interception, we don't want the interception to be a $10,000 interception. So, ideally we'd like to make this accessible to all dog owners. So I think what ShineOn has done is it's given us the Karin (23:33.539) Right. Jaime Modiano (23:48.014) proof of concept that it can be done. We can develop tests that are not just telling us that cancer is present. That's great, but it doesn't really help you all that much because cancer is there, right? Our testing is actually going to basically say you have an elevated risk of cancer. So if you jump off the cliff, you might not die, but there's a pretty good chance that you will, right? Karin (24:01.754) Mm-hmm. Jaime Modiano (24:16.428) So the question is, how do we keep you from jumping off the cliff? Well, we put a barrier. And so that's essentially what we're trying to do is improve longevity. at the same time, paying, we are diving in fully into the concept of understanding aging. And again, that sounds really naive, not coming from the aging field. All of my colleagues in aging are going to be like, yeah, cause you're so smart, you're going to understand aging after we've been studying it for. 50 years and we have no clue, right? So that's not what I'm saying. We really are trying to incorporate metrics so that if we are successful in increasing longevity without cancer, are we creating damage? Are those individuals developing other chronic conditions, including chronic diseases of of cognition or other issues of brain. Because we don't want our dogs to live 15 years or our human relatives to live 120 years where half of their life is not present. We don't want dogs that are 14, but they're head pressing in the corner and eliminating inappropriately because they're not aware of their surroundings. So we're paying a lot of attention in into extending, into creating the highest possible quality of life for as long as we can, rather than having a target that says, you know, we all want our dogs to live to 17 without cancer. And I think at the time as we're doing that, we're battling a lot of other things that are out there. You know, the number of people that empty the shelves at GNC and give their dogs all sorts of supplements that are Unproven untested, but heavily advertised and you know, there's whatever influencers on social media talking about the wonders. I mean, it's a, it's a multi-billion dollar industry where people might feel good because they think they're doing something, but they really aren't right. So when people ask me, say, you know, go to your local pet store and buy a really fun toy or go to the park and get a stick and throw it for your dog for an hour. And your dog is going to be so much happier. Karin (26:19.63) Mm-hmm. Karin (26:38.979) dog. Jaime Modiano (26:43.106) than eating all this other stuff and it's gonna cost you a lot less, right? The steak at the park the last time I checked was free. And the benefit of the dog having that interaction and the benefit of the human having that interaction, right? Playing with your dog reduces your blood pressure, it makes you more active, it relaxes your brain. There are so many benefits. So, you know, we are sort of a little bit on a bandwagon of trying to remind people that... Karin (27:01.38) Make sure you're Yep. Jaime Modiano (27:10.016) If you wanna feel good about yourself and what you can do for your dog, do the simple things because we have pretty good evidence that those are helpful. Karin (27:17.956) I think we see a very similar trend in human nutrition, right? We see people wanting a quick fix rather than eating well and exercising and doing those very simple things, taking supplements, all of those negligible issues. Jaime Modiano (27:38.358) Yeah, absolutely. think it is true that there probably are some things that we need. There's a reason why bread and cereal are fortified because we do need vitamins and minerals in our diet. So those things are necessary. I have read so many papers about multivitamin supplements with the vast majority of them saying the floucens and vitamins taste good, but they don't do anything. you right or the one a days or whatever. But there might be some benefit in some supplements, but there's so much stuff out there that is because they're not regulated. It means they don't really have to go through the process of showing claims, right? And the marketing is incredible because they know what words they can use, but advertising sells and it's really, really powerful. I think that, you know, as we try to stay with good science and we try to really help the community understand these concepts that are, you know, they're not very easy. And I find that a lot of times you try to, you know, sometimes you bring up the word evolution and some people will just shut you off. They either have a personal belief that counters it or they heard something negative about it. or they never were exposed to it in school and either their core beliefs are different or they think it's really difficult. so trying to really sort of explain to people, it's really not that, it's not that hard, right? I mean, it's a concept that we understand really, really well and it's happening every minute of every day. I mean, it's happening in our intestine, right? You don't have to go very far to understand the evolution. Karin (29:36.324) Right. Jaime Modiano (29:37.998) But it is challenging. And so these forums, I mean, I realize that we're not talking specifics or we're talking very, very high level concepts, but it is helpful, I think, hopefully for people to hear that, hey, wait a minute, what do you mean that evolution is important in cancer? And maybe a few months from now, they'll be able to just look it up in Wikipedia, as opposed to having to go to the hardcore scientific journals and Karin (29:47.726) Right, right, Yeah, that's. Karin (30:08.312) Right? Jaime Modiano (30:08.396) you know, go through data. Karin (30:11.418) So would you mind talking a little bit, so in my day job, I work in proposal development at a university and I have been reading a lot of proposals that talk about machine learning and genomic discovery. How big of a thing is this, how much impact is machine learning having on your understanding and not you specifically, but. you know, scientists in general. Does it have a lot of importance right now for you? Jaime Modiano (30:44.974) It is totally game changing. I think that there's a lot of fear about the things that could happen with AI. And I think those fears are not unfounded because every new technology can be used for harm, but it really has been a game changer. I'll just give you an example with ShineOn, but this is something we're applying really across our discovery platforms. When we run a sample for ShineOn, we get a blood sample and we isolate, we get rid of the red blood cells in that blood sample and the platelets and we keep the white blood cells. And then we add some stuff that paints the white blood cells or the nucleated cells in the blood in different colors. And we run that through a machine called a flow cytometer. Karin (31:42.906) Mm-hmm. Jaime Modiano (31:43.822) and then we do analysis. And so normally we run a million cells through and we end up getting rid of 99.9 % of the cells. And we run our analysis on that 0.1 % that remains. But across the scope, across the boundary or the field of the sample, every cell that we collect Karin (31:51.95) Mm-hmm. Jaime Modiano (32:13.238) we actually collect between 30 and 50 individual parameters. So before we can do anything, for every sample, we've got somewhere between 30 and 50 million data points. That's a really, really big spreadsheet. mean, if people have ever looked at a spreadsheet, it's hard enough to look at a six by six, right? But imagine looking at a spreadsheet that has one million rows and 50 columns. That's big. so trying to parse that out manually would be almost impossible. So what we've done is we've used machine learning. And what the machine learning does is it basically, you allow it to learn from patterns. That's what machine learning means is that you basically say these Karin (32:45.338) Brett. Jaime Modiano (33:11.566) these are blue and these are red. These are men and these are women. These are normal and these are abnormal, right? So you create your groups and you can create as many groups as you want. The more data that you feed into the system, the more it can incorporate outliers into its predictions. And so when you feed new data into the system, into a trained algorithm, what the algorithm will do is it'll look at all the parameters that you're looking at and it'll say, it looks most like this one and the probability is X. So if we have four groups and basically the machine learning algorithm tells us each group has the 25 % probability of being right, then we know that it doesn't look like any of them, right? It's not particularly useful. But when the algorithm says it's got 70 % probability of being group B and 10 % probability of being group A and the other probabilities divided between C and D, we can then assign a value and we can assign a level of confidence. So obviously if it tells you it's 99 % likely that it's B, you're pretty confident. If it's only 26 % likely that it's B, then you're less confident. So you have to sort of understand what machine learning does. The other thing is that since the invention of neural networks, People have created many different types of algorithms that use different mathematical approaches in terms of how they group the data, how they parse the data. this is, know, developing that is far above my pay grade. I just know that there are different families and I sort of understand the basics of how the families work. But what we decided to do was we said, if we assume that each machine learning algorithm is an individual. And we take individuals out to the lake and we ask them to tell us what color the trees are. If 12 individuals tell us the trees are green, we can be pretty confident that when our prediction says the trees are green, we're going to be right. But if we go out to the same lake and we ask 12 individuals to tell us what color the trees are and Jaime Modiano (35:34.414) the three short guys tell us they're green and the three tall guys tell us they're red and the three medium guys tell us that they're blue, then we know that there's some bias, right? That the answer we're getting is very dependent on the algorithm and not so much on the data. So what we've done is we have basically done our training sets using a family of 12 different algorithms. And if we don't get at least 10 or 12 giving us the same answer, we don't believe it. we think it's essentially what people call a hallucination or wrong inference. And so this gives us lot of confidence that when 10 algorithms from different families are using different methods and coming up with the same answer, we're like, yeah, this is good. So this is the control set that we developed. Instead of relying on only one that we like because it gives us the answer that we think we want, we are asking multiple algorithms to tell us the answer that they trained on. And if they don't agree, then we know there's a problem. And so that has been really, really helpful to build our confidence. And it is different. We're working with a number of other groups and companies that have their preferred algorithm. This is the one that they've used and they've adapted. And we do worry that if you're sort of over-reliant on a single algorithm, you are more likely to maybe get answers that have bias that you are not aware of. So this really has given us tremendous amount of confidence. And I'm really excited about what these new large language models are going to actually allow us to do going maybe a little bit further. think right now, many of us are still skeptical of deep learning. There might be, you know, there's a lot of things that happen in deep learning that nobody understands. Even the most learned people just don't understand what computer deep learning is because there are so many calculations and events happening in such a short period of time, our brain just doesn't get them. So I think deep learning right now is still more prone to giving you bad information or giving you information that has strong biases. So we are not going into deep learning, but we are trying to take advantage of, you know, Jaime Modiano (37:55.592) modern machine learning and maybe incorporating some of the large language models into what we're doing. And it is incredibly exciting. we are, you know, we're very fortunate that one of the people on our team decided to essentially go and become an expert in AI. And I think if we had not had him as part of the group, so this is Dr. Ali Khamanova. If Dr. Khamanova had not had this training, we would have never had the opportunity to apply this to the data and all of our projects would essentially be dead. So the bioinformatics skills, the genomic skills to handle big data are really, really important. We have people on our team that are really, really good at that. And that was essential. But I think getting to the next step of being able to understand and use AI was really critical. I am a proponent. think that AI is not going to... It is going to take jobs away. It is going to make life different, but it's not going to be bad because the jobs that are disappearing are jobs that are more efficiently done by instruments, robots, computers. And it'll free up people to do different things that are where you still require human judgment. And I think that there's always pain because many people will have to be retrained and the job market will change. you know, I was talking to someone about, you know, investments in this field or that field and the negative impact on an industry. And I think that There's always winners and losers and we can't, you I think that if we are too choosy about winners and losers, we maybe lose sight of what's going on in the future. So again, not being disrespectful of those people who could be impacted negatively by all of these advances in technology. I think it's really no different than, you know, when we put horses out of work because we had horseless carriages, right? And when we... Karin (40:18.105) Right. Jaime Modiano (40:21.038) I don't remember the last time that I ran into someone who was a telephone sanitizer. I think that it is a problem, right? Not having public phone booths means that Superman doesn't have a place to change clothes. so maybe that's a reason why I haven't seen Superman flying over Minneapolis for a while, but... Karin (40:38.702) You Karin (40:47.034) Yeah. Jaime Modiano (40:48.374) You know, in a serious note, think that there is a lot of fear and anxiety, I think for us, sort of in being able to deliver information that improves human and animal health, that improves productivity and creates new opportunities. think AI as a field is going to be transformational. I think there is going to be pain associated with that. If we don't think about that, we're not thinking about the whole thing, right? So I can't really sit here and say, well, I'm a veterinary pathologist or I'm a researcher or I'm an immunologist. And I just do this in my little silo and I don't really care how it impacts the rest of the world. I think if we do that, we're doing a disservice to the community that is supporting us. After all, we're operating on your tax dollars and we're operating on donations and we're operating on sponsored research from companies. We sort of have this diverse portfolio and we have to pay attention to what benefits, what actually is important for the greater good. I always say if we're just doing research for ourselves and we don't really care about anybody else, we should be paying for ourselves. So we do think a lot. mean, our lab meetings and even our teaching meanders into all sorts of areas where People say, wait a minute, you're teaching me cancer pathology, but you're talking about veterinary economics. What gives, right? Well, understanding cancer pathology is really important, but you can know everything about cancer pathology. And if you're not helping your patients or their families understand what cancer is and why it happens and how you can treat it, then we no longer have King and Pope. patrons that pay us just to do fun things. it's, I think we have to be part of the world as we work on this stuff. Karin (42:54.446) Yeah, I love that sentiment. We are definitely beholden to people who are sponsoring things like that. So as we bring it to a close, would you like to talk about your own pets? I am guessing that you have some dogs at home. Jaime Modiano (43:03.438) Thank you. Jaime Modiano (43:11.616) I do. So full transparency is we love cats, but my wife is deadly allergic. So a decade or so after we got married, our kitties, the kitties that came with me passed, we did not repopulate our kitty side of the family. But people always ask me like, why are you so dog-centric? Why don't you hate? Why do you hate cats? And I do not hate cats. I love cats. just, my wife was tired of having red puffy eyes all the time. So, and I... Karin (43:41.25) at that because I also, thought I was a cat person, but I just suffered with allergies for most of my life and finally got a dog and you know, my life changed. Jaime Modiano (43:50.35) You know what? Jaime Modiano (43:55.23) I have horrible, horrible hay fevers. so I really, I can really relate to her because, you know, spring and fall, I suffer through the runny nose and the puffy eyes and stuff. So anyway, we love cats. We just don't have any cats in our household. Right now, we have two German Shepherd girls. Their names are Alcie, Alcie for Alsatian, and Mora. Karin (44:06.297) Right. Jaime Modiano (44:23.808) She actually was named, well, it's a long story, but her full name is Zarza Mora, which means blackberry in Spanish. And she's got a cute blackberry color. so we say, Alce is confident in her own inner champion. And so she doesn't have to prove anything to anyone. Her job is to be pretty and play. Karin (44:50.33) Mm-hmm. Jaime Modiano (44:50.42) And Maura is young and very active. And so she's starting in agility. And she just did her first trial, her first competitive trial. And of course, she double queued and came in first place on both standards and open and jumpers. So my wife, Michelle, is the one that does all the agility. I just cheer them on and think it's fun to watch and play. it's Karin (45:16.376) Right. Fantastic. Jaime Modiano (45:19.298) Yeah, so it's very exciting. Alce is five and a half and Moira is three. And they're great. Yeah, they're both young and they're very much fun. They're just such good girls. I say that after COVID, they get separation anxiety when I come to work, but I get more separation anxiety after being used to being with them all the time. So they're great dogs. Yeah, yeah, it is. Karin (45:27.332) So both young. Karin (45:43.736) It's hard, Jaime Modiano (45:47.546) They are absolutely integral parts members of our family and it's unconditional love, right? They don't ask for anything in return except maybe a cookie here and there. Yeah. Karin (45:56.686) No. Yep. Yep. And a few pets and hugs and all of that. Dogs are wonderful. Jaime Modiano (46:05.558) They are. They really are. And I think I know that you guys have worked with Dr. Steve Friedenberg a lot. you know, as you know, he's absolutely brilliant. I he's just one of a kind. But, you know, I think I've spent a lot of time working with the Portuguese Water Dog community. I have not had as much time to work or reason maybe to work with the Poodle community. It hasn't been a... Karin (46:12.602) Yeah, well. Karin (46:19.268) Peace out. Karin (46:26.382) Mm-hmm. Jaime Modiano (46:34.454) a long-standing relationship, but I hope maybe this is the start of a beautiful relationship and if there are things that we can do to help the community, questions that we can answer, we would absolutely love to have the opportunity to chat with members of your group and see if there are places where we can go together. Karin (46:46.148) Thank you. Karin (46:56.558) That is very generous of you. know that hemangiosarcoma is, many people have had experiences with it. My very dear friend and mentor has lost a dog from hemangiosarcoma. I lost my Jane at age 10. So many people that I know quite well have had this experience and, you know, I think you're shocked until it happens once and then you're like, yeah, that hemangiocarcoma is just the worst. So it is really nice to have an opportunity to raise awareness about this cancer so that people just have familiarity with it so that when something seems off with their dog, they can get to their vet sooner. And I will definitely post those other links that probably have... less of a philosophical bend to them than what we talked about today so that people can access that information. Jaime Modiano (48:00.77) Yeah, I I think if you want to give me one minute to sort of summarize what we've learned is that everything we know about Hemanja sarcoma was wrong. We have erased the slate and started with a clean slate and we don't totally understand the disease, but there do seem to be some breed predilections, but it is not a peculiar disease that happens in one breed. Every dog can get it at any age. We see it more commonly in older dogs. If you go to the vet because your dog is off and they find the mass in the spleen, don't give up. The majority of spleen masses, so more than half, are not hemangiosarcoma. They can still bleed. We still recommend taking out the spleen. It is the best way to ensure that your dog will be able to live longer. And then treatment generally is really very dependent on what the family's goals are. So for people that are very, very attached to their dog and they want to do everything, what we're starting to understand is that the tolerance for the fact that these tumors bleed and the tolerance that a bleed could be terminal makes it really big difference in how long the dog lives. Because when people are advised that, you know, this is a death sentence and why would you do anything? Or if they see their dog, you know, being off because they had a bleed and they're just lethargic and they don't want to eat. And they don't really realize that four hours later, the dog is going to be happy running around eating. It's very, very difficult. And so So I think in some cases, dogs are euthanized because it's the right thing for the family because it's too difficult. They just can't tolerate the process. Other times, dogs are euthanized prematurely because the family would very well be able to deal with that, but they get the wrong advice from friends or even from professionals. And so I think that probably the main cause of death for dogs with hemangiosarcoma is premature euthanasia. Karin (50:01.434) Mm-hmm. Jaime Modiano (50:24.14) I think that the reason that the statistics are so skewed with a disease being so bad is in part because the disease can be very bad. In part because there is so much fear attached to it that people just give up. So there are opportunities to treat. There are clinical trials going on. Some will not work. Some will work. Some will be a little bit good. Some hopefully will be very good. There is no evidence that that any supplement whatsoever works. And so when people tell me, you know, my friend had a dog or a vet tells me I had a case that lived for two years. My question is, you know, how many friends do you have that had dogs with hemangiosarcoma that took this stuff and were still dead two weeks later, right? Or for vets like, okay, so you got one success story. How many did you get that failed? And if you look at the statistics of doing nothing, there's no difference. So I think, going back to what I said earlier, when people go to the internet and they buy stuff for $2,000 a pop, just imagine how many really cool dog toys you could get with that money. just imagine all the fun that you could have if instead of spending $2,000 for your dog supplements, you just took a day off of work and you took your dog to the park. So I think it is a very, very scary disease. We're learning a lot from it. There are... Karin (51:28.73) We're going to. Jaime Modiano (51:44.738) there are at least three, maybe five and maybe more subtypes of manja sarcoma, each of which will be different. Maybe each of which will require a different treatment. And we are just, we're barely out of preschool. We're barely out of pre-K getting into the kindergarten of understanding the disease. I think people just, what I would advise people to do is to be less prescriptive and more open-minded in thinking, this could be a chronic condition. And if my dog gets a man just sarcoma, what are my goals? Do I want him to live a great life for two days? Do I not want him to suffer at all? Do I not want to suffer myself in seeing my dog? Do I want to enjoy him or her for as long as possible and realize that she might die in my arms or she might die in her sleep and I may not be able to say goodbye? Those are really, really hard questions. Karin (52:42.819) Yes. Jaime Modiano (52:43.374) But I encourage people to really be thoughtful. you know, I mean, it applies to, hematocircum is probably the extreme example where we have to really think about those conversations. any cancer and any chronic disease is the same thing. You we don't see the same fear attached to chronic kidney disease, right? People go and they say, well, you know, I'm going to try this diet and maybe it'll work. And there's really good reasons to try that diet for kidney disease because we have science that basically says it works. We don't have science to say the diet or you know, supplements work in cancer, we have data to say that other things work. And so in deciding whether to do anything, I think you should focus on doing nothing as an option. Pelliating is an option. But but really, I really would love to be able to have a megaphone that tells people don't spend your money on wisely. Don't go after false hope. You know, there's reality and there's no alternative reality. So let's just stick to reality and and do the things that work. if it seems too good to be true, it probably is. And when they say it's perfectly safe, so it can't hurt, in order to manage cancer, you have to kill cells. So if it's perfectly safe, it's not going to help the cancer. If you say, it stimulates the immune system, well, we know that stimulating the immune system can be deadly. So there's always risk. So I think it's a matter of really trying to help people become a little bit more informed. and do it in a way that is empathic and compassionate. we need to put ourselves in their place, come to where they are, rather than being patronizing and telling them, well, you just don't understand. Well, of course, they don't understand. They're stressed out. They're freaked out. And they probably didn't go to vet school, right? So I think that we need to be better communicators. We need to be empathic. And at the same time, we also need to maybe push back a little bit when people say, well, you know, my friend did this and it was great. It's like, well, you know, if you want to spend the money, but here's all the other alternatives. Right. So that's that's my side books. Karin (54:50.958) Yeah, I love that you offer alternatives. Yeah. I really love that you offer alternatives and you also remind us that we should go outside and play with our dogs in the park with sticks, whatever, and enjoy their lives while we can. Jaime Modiano (55:10.602) Every day is precious. Every day that I don't get a walk with my dogs is a missed opportunity. maybe I'm being prescriptive myself and sort of projecting what I love. But I think that having a dog as part of your family is a privilege. And I don't want to take it for granted. Karin (55:17.498) Thank you. Karin (55:29.902) Yeah, I love that. I am so grateful that you had time to talk to us today and I really appreciate the conversation and your expertise and all that you do for dogs. Jaime Modiano (55:44.52) I appreciate the opportunity. It's been fun chatting with you and thank you for giving me a little soapbox to go out and pass on our message. Our vision is to create a world where we no longer fear cancer because we understand that as long as we are alive and we're made up of cells, cancer is going to be with us. But if we can remove the fear, It makes our job in trying to actually help people live with the disease, help dogs live with the disease, potentially cure the disease, and most importantly, maybe at some point, prevent the disease and reduce its impact a lot easier. let's go out there and continue to learn and please join us on our vision to create a world where we no longer fear cancer. Karin (56:41.786) Thank you so much. Jaime Modiano (56:43.882) It's been a pleasure. Thank you.