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Episode 31: Always bet on the surgeon—Discussing the value of outsiders and risk-takers in biotech with Dr. Sasha Krupnick

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June 22, 2023

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Episode 31: Always bet on the surgeon—Discussing the value of outsiders and risk-takers in biotech with Dr. Sasha Krupnick

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Drug development is a highly expensive, risky venture for investors and researchers alike. Dr. Sasha Krupnick, chief of thoracic surgery and director of the lung transplant program for the University of Maryland Medical System, joins Justin to discuss why biotech needs more outsider perspectives, government support, and risk-takers to get the next industry-shaking innovation off the ground. Dr. Krupnick explains what led him from surgery to oncological drug discovery, why Big Pharma isn’t healthcare’s big bad, and why you should always bet on the surgeon.

Justin and Dr. Krupnick have a lively conversation around some tricky questions: What’s wrong with the drug development process today? What’s the role of small biotech and venture capital organizations in an industry dominated by massive developers? And why are so many potential cures for life-limiting illnesses dying on the vine?

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Episode transcript

Definitively Speaking is a definitive healthcare podcast series recorded and produced in Framingham, Massachusetts. To learn more about healthcare commercial intelligence, please visit us at definitivehc.com. Hello and welcome to another episode of Definitively Speaking, the podcast where we have data driven conversations on the current state of healthcare. I'm Justin Steinman, chief marketing officer at Definitive Healthcare and your host for this podcast. Surgeons occupy a somewhat unique place in our healthcare system. They're the kind of doctor you hope you never have to see, but if you do have to see them, well you're sort of volunteering to let another human being open you up with a knife and mess around inside your body. There are all sorts of surgeons without question. One of the most complex and challenging types of surgery is transplant surgery, and now imagine for a second that the surgeon performing your lung transplant is also a successful businessman, someone who has started two healthcare businesses and sold one of them in his, I dunno, for lack of a better word, spare time. By now you're probably like, "Come on Justin, there's no way that someone can be a thoracic surgeon and a successful entrepreneur." Well, I'm here to tell you that such a person does exist and he's my guest today here on Definitively Speaking. Dr. Alexander Krupnick, who goes by Sasha, is the Peter Angelus distinguished professor of surgery at the University of Maryland where he is the director of the lung transplant program and the division chief of thoracic Surgery. Dr. Krupnick is a general thoracic surgeon who specializes in the treatment of lung cancer, esophageal cancer, lung transplantation, as well as benign thoracic disorders. He immigrated with his family to the United States in 1979 from the former USSR and he grew up in the Midwest, receiving his undergraduate and medical degrees from the University of Michigan, go Blue. In addition to his clinical work, Dr. Krupnick runs an NIH funded laboratory, which he started after finishing his training in 2007. His laboratory mirrors his clinical interests and focuses on the development of new and novel mechanisms of immunosuppression for the long allograft as well as cancer immunotherapy. He has specifically made the discovery that the immunologic control of lung cancer, depends on the inherent function of a cell population known as the natural killer cell, and we'll get into exactly what that is in a little bit. Dr. Krupnick's laboratory has developed a drug specially designed to improve the natural killer cell function, which is expected to begin human clinical trials and partnership with Beyla Health soon. Wow Sasha, welcome to Definitively Speaking and thanks for fitting me into your schedule, good Lord.

No, thank you Justin for the nice intro and I specifically appreciate the go Blue shout out it, I like it.

Excellent, all right, we got a lot to cover here. You have an impressive background, a lot to cover? Let's start with beginning, why did you choose to get into thoracic surgery?

You know, it's an interesting question. You know, actually when I started in medical school, I wanted to be a pediatric surgeon and operate on children and as I got through residency, you know, a lot of work were influenced by what we see, what we do, the people around us. I really enjoyed thoracic surgery. One of the funnest parts is it lets me deal with a lot of disease processes. So things are becoming more and more specialized. Justin, you know, people kind of get in where they do one or two operations, especially in high powered academic centers. Thoracic surgery is one of the few specialties where I can do cancer, I can do transplant, I can do benign disease, I can think a lot of different disease processes and specifically what you learn in one field you can bring for the other, because a lot of times the people kind of don't cross paths. You have just transplant surgeons, they don't really get involved in cancer. You have the cancer surgeons. Thoracic surgery is really one of the specialties that lets you think about and do a lot of different things, so I found it most exciting. It wasn't an epiphany, it was kind of a rational conclusion and I enjoyed doing it to this day.

Yeah well, you know, let's go back to University of Michigan here, 'cause I got a stat from them. We love data here on Definitively Speaking and according to the University of Michigan, about 2000 people receive a lung transplant each year in the United States. For comparison's sake there are almost 18,000 kidney transplants performed in the US annually, because of the fragility of the lung, the survival rate for a lung transplant to patient are not as good as other solid organ transplants. I'm sure you know this, but maybe our listeners don't, the five-year survival rate for someone with a lung transplant is about 50 to 60%. So, you know, why did you choose to get into a field with such a low rate of success?

Well, where's the excitement of getting into a field where it's 100% successful? That's the field you wanna get into, you wanna challenge, you wanna improve something, and you're right, you know, lung transplant is probably the newest, most recent organ transplant with, you know, true successes being done in the late 1980s, 1990s, and you're right, you know, the survival is much worse, but the approach that we took, again, it's an exciting field, it's a challenging field and quite frankly, despite the fact that we only do 2000, you know, there are a lot of people waiting on the list, there are a lot of people that could benefit from a lung transplant if you increase the accessibility, but I found the field a challenge, and one of the interesting things that kind of goes through kind of the theory of the way we approach things is people learned immunosuppression. Essentially if you get a lung transplant, heart transplant, kidney transplant, you're basically getting the same drugs, and that's almost irrational in a way, because they're not the same organ, they don't need and they're not gonna be successful using the same form of immunosuppression, and I want to change that immunosuppression to immunomodulation and when we got into the field of lung transplant, that's exactly what the lab set out to tackle, that the lung is different than the kidney, and we wanted to figure out the way that lung transplant avoids rejection, the way the cells involved in lung transplant rejection, and see if we can modify immunosuppression, make it lung transplant specific, and that's what we've worked on in the lab. We've developed some models, specifically the model of mouse lung transplant. Most models in immunology actually involve mice. The immune system of mice is very, very similar to humans and it allows for rapid data turnover and sort of increased number of attempts and goal, but to answer your question, you know, lung transplant is a challenge and you know, we all want a challenge in life, you know, to improve something.

So you mentioned your lab, did you actually bring a drug from your lab out to kind of address this immunosuppression for the lungs?

So that's the process we're working on right now. We actually have a couple of candidates, a couple of patents and things we're working on, we have yet to develop a drug that we start moving from mice to kind of preclinical work to clinical trials, but that's definitely on the agenda and it has yet to come, so hopefully stay tuned, hopefully we'll have something soon that we're working in that was developed in the lab.

Right but you have started the company, as I mentioned earlier, Courier Therapeutics. What was the idea behind the company? How did it get started? Did it come out of your clinical work? Tell me that story.

Well, it's actually an interesting story. So the company was started in 2015 and we exited the company about two years ago. It's actually a little bit of a personal story, kind of introspection. So I joined the faculty in 2007 and I was doing a lot of research. In order to advance in academic medicine, you need to do research, and a lot of times it's based on, you know, needing to advance from assistant professor to associate professor to get tenure, all those things that were required and that's what I was doing. I was what I call being on the academic merry-go-round where the purpose of the research was almost as much to advance my career, then to advance the benefit of mankind, and then my brother-in-law, I'm an only child and I was pretty close with him, was diagnosed with lung cancer even though he was basically my age, never smoke, was very healthy. It's a little bit of a guilty statement, even though I take care of lung cancer patients primarily, this really hit me hard. So around 2012, approximately five years after we started the lab, I basically changed the direction of the lab from one of discovery and one whose vehicle was to advance my academic career to one that's gonna discover novel drugs and get 'em to the clinic and that was Courier Therapeutics. We started in 2015 based on a drug and a principle that we'll developed in lab to treat lung cancer, and again, just like I talked about, lung transplantation needing specific immunosuppression, this is a drug that's geared for lung cancer and works in other cancers, rather than the current lung cancer drugs, which were developed for things like melanoma and retooled for lung cancer. So this is truly a rationally designed immuno stimulant that is based on some preclinical mouse data, where we figured out what aspects of the immune system control lung cancer and we developed a drug specifically to arm those aspects of the immune system to target lung cancer. Now it works in other cancers, which is great, but it's a lung cancer specific drug, and again, that's the approach we took and we came at it a little bit from the outside where I never really studied cancer or lung cancer before I was a transplant surgeon focusing in transplantation. So we were able to ask some pretty simple questions that nobody had ever asked, what part of the immune system controls lung cancer? Is it the same part of the immune system that controls melanoma or colon cancer? And those are some simple basic questions that people who, you know, work deep inside the field never bothered to ask, and it was actually pretty simple experimental approaches that led us down this path and, you know, we'll see if the drug is successful, clinical trials determine everything and that's what we're waiting for.

So you mentioned something interesting there, you said you kind of came in as an outsider and the people in the field never asked those question. Why do you think that is? Why is an outsider important? Why didn't they ask those questions?

No that's a great question. So again, being an outsider, I don't know that, you know, one of my beefs with the whole all fields essentially is you have all these fields which are dominated by what people say, call thought leaders. In other words, there's a leader and again, now that I'm in several fields, specifically cancer and transplant. I go to a transplant meeting and it's, you know, one or two guys dominating the conversation, influencing the way everybody thinks and you take in other fields and other two guys, and I think that type of approach limits novel approaches, limits people that disagree, limits people with different ideas, and I think that's a major problem. So I always try to be the outsider because again, that gives you novel approaches, you have no preconceived biases, you just come in with essentially free thought. Now being an outsider is hard because a lot of times, you know, things are a club or people that are known or known and getting grants when you're an outsider and you just start in a field is very, very hard, because there are certain people who kind of dominate the thought process, and those are the people that essentially lead funding through the study sections, but I think we have to take the view of the outsider and let other people in with even crazy ideas, because as you look at medicine or any field, it's always been somebody with that crazy idea who makes a giant leap forward and then all of a sudden everybody jumps on board. So I enjoy that process, I enjoy getting into different fields, you know, the recent field that we started is RAS biology, which is completely new to me, but that's the approach we decide to take and that makes it more fun, and it also, I think has an ability to add something to drug discovery and scientific discovery.

Got it, so you just mentioned RAS biology, I'll tell you, I don't know what that is, and is that related to your second company AskY Therapeutics?

Yeah, AskY.

AskY, okay, good, thank you.

Related to that company, and again, we took the same approach where we knew nothing about RAS biology. So RAS, it's one of the first mutant genes that was discovered in cancer, but yet that's still a problem that hasn't been solved, and RAS is a molecule that essentially acts as a switch point between signals from the outside of the cell to the inside of the cell. So if you think about it from a cancerous point of view, where they just wanna basically turn the cell on to go, go, go, it's a perfect protein to mutate, and that's actually one of the most common mutations in human cancer and again, a lot of very smart people working at it. We took an outsider's approach with no preconceived notions, and we made a very interesting discovery that we're slowly taking hopefully to therapeutic avenues within the next couple of years, but again, we continue this approach of, you know, with no preconceived notions coming into a field, learning enough about it to be able to design experiments, but not everything about it where our thoughts are clouded by one or two thought leaders who may be going down the right path, maybe going down the wrong path.

So it sounds to me like frankly you have some issues with how kind of labs are funded today, right? And the drug development process? So what's wrong with that today?

Well, gosh, I wouldn't use the word wrong. You know, the United States of America, National Institute of Health is the biggest funder of biomedical research in the world. Look, I see nothing is more important. You know, there's world peace, there's all that stuff, but basically health is everything. If you don't have health, you don't have happiness. So being an insider of the field, it almost makes me angry. I got very angry when my brother-in-law in his 50s, actually late 40s, got lung cancer. So why in 2023 when the war on cancer was declared by Nixon, what was that 50 years ago? Why are we losing the war? There's a lot of money spent, but this is one of the few fields where truly investment will yield results. There are very few fields you can throw money at, and get success, world peace no, you know, in fact, you know, building up the military probably could have a counterintuitive role, but the more money we spend, the more research we do, the higher the number of the attempts and goals, the higher the chances of us making the discovery and again, you know, the whole point is that there are a lot of discoveries made in lab. They have to be taken to clinical trials, because that's the only thing that's gonna tell us if anything works and the more times you shoot and go, the more you increase your chance of success. So I wouldn't say that it's wrong, it's just literally not enough money put into the academic labs. However, the whole system could be done a little better, and if you think I have solutions, I just have ideas. So for example, you know, just what I mentioned before, academic labs you have a researcher, you know, a PhD level researcher or an MD level researcher or somebody who does both like myself, who's doing research in lab, and the whole research is funded by grants from the NIH that, you know, last four or five years, and you basically have to renew the grants. If you make a discovery and you wanna make a drug, you have to get off that path and spend an insane amount of time getting somebody to invest in your drug, usually this is venture capitals, capitalists. There are some government programs that'll invest in it, but again, the money is not enough to take a drug to trial. So you have to basically get off this path, take a risk in your career, and try to move your drug down the path. So again, somebody like myself who makes a living operating on people, I can do that. I have limited risk if I don't get my grant renewed, well it's okay, I still have a job, but if you're somebody who makes essentially you're living doing research and you don't get your grant renewed, you could lose your job. So how many people want to get off that sort of wheel and say, "I'm gonna take a risk with my whole career on a drug where, you know, you know that 99% of the things that work in the lab are not gonna end up panning out, and you just have to test more and more and more." So that's the problem and I don't have a good solution. We just have to be less risk averse, put more money into the system and not penalize people that actually take their discovery and spent five, six years advancing the drug that in clinical trials may fail. You know, you could say the whole thing's a failure, but it's not, look you tried, this didn't work, let's move on to the next thing, but it's hard and it's, you know, hard, especially if your livelihood depends on the ability to get grants and maintain an academic lab.

Do you feel like we're missing opportunities for innovation?

Big time. You know, and big pharma and pharma in general is fairly risk averse and as you look at advances in biomedical treatment, it's not a slow and steady pace forward, it's a huge leap with everybody, you know, jumping on bandwagon, you know, checkpoint inhibitors, which, you know, have revolutionizing therapy for cancer. Original discovery, you know, in the 90s, Jim Ellison won the Nobel Prize for it, but all of a sudden there was a huge discovery, some success, and everybody jumped on the bandwagon. Everybody has their own checkpoint inhibitor. Every big pharma has spent a lot of money on a me too type of thing, rather than saying, "Okay, we got the checkpoint inhibitors, what else is out of there? What else can we combine it with?" So we are missing opportunities and again, it's hard for venture capitals, big pharma to spend a lot of money on something that has over a 90% failure rate, and it's a little bit easier to say, "Okay, this work, let's tweak it a little and have, you know, an off target or off product that's very similar, that's a little less risky." And it's a problem 'cause it hurts us, it hurts the whole biomedical research environment and it hurts that whole drug field, but I don't know how to fix that.

Yeah, I mean the average price of a clinical trial sits somewhere between 15 to $20 million and these big pharma people, they're accountable to their shareholders.


So, you know, and that's perfectly rational from the economic system that we have set up. So, you know, they are, as the CEO, he wants to keep his job, she wants to keep her job. So they are gonna, you know, minimize their risk or their reverse to risk, when perhaps true risk is actually necessary to drive real innovation.

Yeah, I mean, and I don't have a solution, maybe the COVID pandemic is a very good model. You know, the United States backed a lot of big pharma saying, "Okay, try this crazy mRNA vaccine and see what happens." And that basically ushered in a whole new field, but again, we had a worldwide pandemic, a crisis, but I would argue that, you know, a lot of the health issues we have now, you know, how many people die of cancer? It's a slow, steady attrition, the whole economy doesn't get shut down, but boy, it is very frustrating that in 2023 we're farther ahead, but we're not where we should be I think.

You know it was almost like the US government backstopped the risk and so-


Yeah and we just can't do that all the time.

You know, would Pfizer have done this if they took all the risk on their own? I do not know, I do not know.

Yeah it's an interesting question about the altruism of these big corporate entities, right? Or lack thereof.

Well, no, I wouldn't say that, you know, big pharma is the reason that, you know, my family has familial hypercholesterolemia, my dad had serious issues, but my cholesterol's fine all thanks to Crestor, Lipitor, all those things. So I'm actually a big proponent of big pharma, but again, there are things around the corner, exciting things and we just need to take the risk and fund them and know that there's, you know, potentially a high price to pay in failure, but it's something we learn, you know, something that had rational hope, we did clinical trial didn't work, okay, let's publish it, let's get the data out there and move on to the next thing. How to fund this, I don't know and honestly, you know, it's 15, $20 million for big pharma, it's not that much money. You know, if one out of 10, one out of 20 trials yield something promising could be worth it, could be worth it.

But isn't that also the role of the small biotech and venture capital and private equity to kind of start these smaller companies to get them growing?

Sure and there's plenty of very good venture capital firms just like that out there, but again, they're beholden to the same financial pressures. You know, how many tries and goal can they do that miss before they go belly up? So the answer is yes, being a little less risk averse, I think would benefit us as a society as a whole, trying out crazy ideas, driving 'em to trials and getting things done.

Yeah, you know, speaking of crazy ideas, you know, you and I were corresponding over email before we got on this podcast today as kind of prep and you sent me an article around how families and private donors are stepping in to fund drugs that big pharma won't develop. Is that model sustainable?

You know, I don't know, but I like that model, because everybody who's got a stake in the game has motivation. You know, that's why, you know, the drugs that we developed, they're my babies, I wanna see 'em through. So the answer is, yeah, you know, the article I sent you I think was kind of a negative connotation that families sponsored some drugs and then certain pharma companies buried it. So it was a little upsetting and probably upsetting to these families as well. That is definitely one model, you know, another model is just somehow decreasing the financial risk for venture firms, a small pharma that take a large number of attempts and goal knowing that they're doing the rational thing and just simply don't know what drug will fail or will succeed, 'cause I can tell you that's what I'd like to see. I'd like to see, you know, more and more effort.

Yeah, but it's gotta be hard from like the network and maybe this is a business opportunity, I don't know, but, you know, I went to MIT and there are people, you know, wandering around MIT like, Well-heeled a venture capitalists, they know Langer Lab, they know all the big inventors, and they can say, "Hey, talk about this drug." If you're a private individual and you're not a professional VC, how are you gonna find the right people to invest in and solve your problems?

No, that's a problem. Right, you know, Robert Langer, once he got a start, he's a superstar, you know, people listen to him, but you know, I can guarantee you one thing that the cure for many cancers has already been discovered. It's simply died in the vine, because either the person who discovered that couldn't make that next step, didn't want to take the risk, or somebody just wasn't willing to put their faith in. So Robert Langer is great, but I can guarantee you there's 1,000s of Robert Langers out there that haven't made it and have failed, and it's the missed opportunity. You know, you don't know what you miss and the general public doesn't know what they miss. I see both sides of the fence, and that's what gets me upset is I can guarantee you many cancers killing people today, the success has already been developed, but it never got taken and ripened off the vine, it rotted.

So how do we get it off the vine?

Oh these are difficult questions.

That's what we're here talk about.

All right, well look, you're asking me what would I do?

Yeah, what would you do?

If I had capital, I would start a small biotech company that takes good ideas and takes it to trial, knowing that for, you know, a biologic, a protein therapeutic is probably 20 million and for some of the small molecules, potentially even cheaper, and if you try 20, 30 of them is gonna have some success. That one is gonna have to pay for all the negative trials. Could the US government, which funds a lot of things, essentially make the financial risk a little less, more palatable to the investors? Could there be tax breaks? Could the companies that tried 30 things and had one success be allowed longer patents, be allowed, more leeway? Could they write off some of the negative trials showing we did everything right? It's just that, you know, now that we peek behind the curtain, this great idea that worked in mice, that worked here, worked there simply didn't work in man, the trials were well executed. Can the US government sponsored some of that? I would like to see that, because then it takes a lot of the pressure off, you know, here's 20 drugs we're trying, one will likely work. So that's one solution I can come up with off the back. It's very easy, again, if the pressures are financial... We saw this with the COVID pandemic, take those pressures off, decrease the risk and increase the reward. You know, some of the rhetoric I hear about big pharma being the enemy, that's ridiculous, that is ridiculous, it gets me angry, that's the only reason we're living longer that my cholesterol is good. Yeah, there's some bad actors in it, there's some bad actors anywhere. Big pharma is good, pharma and general is good. We are working to improve the most important thing in humanity, our health. It's just how do we do it quicker? How do we do it better? How do we do it smarter? And how do we increase the number of attempts and goal without increasing huge financial risk that makes it almost unsustainable?

Got it, so you told me earlier that surgeons have a unique perspective on drug development and that perspective is underappreciated. Tell me more.

Well, you know, so again, we talked a little bit about the discovery of insulin, which to me is one of the most pivotal discoveries, and this is in, you know, 2013, right before we started Courier and when I started thinking that I'm gonna retool the way I do things. I actually read a book about the discovery of insulin that got me thinking. So this is a classic story. This is a surgeon who knew nothing about insulin, but had an idea named Frederick Banting. This was in the 20s and it was in Toronto in Canada essentially, walks into the lab of a huge diabetic researcher, big name this and pitches him an idea, and the guy poo-poos it and he says, "I want you to spend the summer reading, thinking." And this surgeon... Surgeons generally have chutzpah, so I think that plays well. He says, "No, no, no." Frederick Banks says "I'm not gonna read about the failures of others. I've got my own ideas, I want to execute them." So McLeod, who was a big researcher is like, "Fine, look I'm leaving for vacation for a couple months, here's some dogs, here's a medical student, good luck. I can't believe you won't read anything." And, you know, he felt insulted. Well when the guy comes back from vacation, you know, insulin's discovered, Cox Botch fulfilled, you know, he is able to isolate insulin from the pancreas and keep other dogs alive, and you know, it leads to a Nobel Prize and probably the biggest drug discovery of last century for sure, and I decided I'm gonna shape my own approach to discovery based on Frederick Banting. Yeah, I've got some ideas, I've read a little bit, this is not completely out of left field, read a couple of articles, have some ideas, nobody believes in it, but you know what, I believe in myself and I'm gonna do it, and that's how we approach it, and it's very interesting, it's actually a wonderful book. The other aspect of that puzzle, getting back to the last question about big pharma, is so Toronto obviously saw the financial potential and basically formed a small biotech company around insulin and in those days, this was before transgenic technology couldn't just make insulin, you know, essentially in the lab as we do now, they actually had to isolate it from pancreases and it was cow pancreases and they couldn't get enough, and Eli Lilly heard about this and I think the CEO of Eli Lilly had somebody, you know, who passed away from diabetes in their family. So they called Banting in Toronto and they said, "What do you guys need?" And it was a crazy number, like we need 20 tons of bovine pancreases a week, insane. The CEO of Eli Lilly picks up the phone to the guy who was in charge of distributing and says, "I would like 20 tons of bovine pancreases delivered here." And the guy's like, "Yes Sir." So big pharma can do what nobody else can, and you know, together with a discovery of a surgeon, a chutzpah attitude and big pharma, you know, diabetics are living... In fact, I was at a wedding this weekend with a close friend I haven't seen for seven years who was diabetic and, you know, I explained to him like, "Look, you're living a normal life, but a 100 years ago you would not be." A little over a 100 years ago, so to me that is the prototypical system that due to luck, due to something fell together. You had a surgeon with an idea, you had a world leading expert in an establishment who didn't believe in the idea. The surgeon had the chutzpah, he tried a crazy idea and you know, there was a 99% chance it wasn't gonna work, but it was a 1% chance gonna work, and it really changed the field and again, how many ideas like that are out there, but how many people don't, you know, have the perseverance, and how many of these things rot in the vine? We have to prevent that as a society, and yeah, the solutions are hard. They require some coordination but basically a lower risk and the ability to take chances financially on crazy ideas and other aspects and then we have a chance to kind of improve humanity in a major way.

So it's almost like you're telling me and it's counterintuitive, are surgeons big risk takers in your opinion?

Yeah, that's all we do. Of course we're the biggest risk takers out there, you know, this crazy idea, but it's very exciting. You literally go in and cut things out, as I tell the residents, sometimes we cut things out, sometimes we take 'em out and put new ones in, but that's basically what we do. Yeah, surgeons are very big rust takers. We generally tend to believe in ourselves, you have to or else you really can't survive in this field. So I think for that reason, surgeons kind of become good researchers. The problem that we have when we talk about this in national society is, you know, fewer and fewer surgeons are doing biomedical research, 'cause it's very hard to get funding. It takes a lot of time, takes you away from the field that you make a living. Essentially a surgeon who spends a lot of time doing biomedical research really does cost university money. You know, the salaries are substantially higher than a peer researcher, yet you're spending a lot of time doing research, but you know where the needs are, this goes for any clinician scientist, you know what's needed in the clinic. You don't have to have anybody tell you, I can tell you what I want, I can tell you what's missing, I can wait for somebody else to do it or I can just go to the lab and do it myself, after a while you get frustrated and you say, "I'm just gonna do this myself."

Got it, so you told me a little bit, always bet on the surgeon, you told me a story about, you know, doing some investing, surgeons had the right chutzpah, they've got the right, you know, instincts. Why do you always wanna bet on the surgeon?

Well it's funny when you and I talked before this, I actually gave a talk like that to some residents. You know, I had to come up with a title of the talk, 'cause you have to put the first slide and I always said, always bet on the surgeon. I told them the insulin story, but another true story, this is very interesting. So I spent a little bit of time running the lung transplant program at the University of Virginia and my oldest kid was very interested in finances, started a finance club where we actually gave them money and they invested it and I guess because I was in the medical field, they put him in charge of biomedical discovery and I think this was probably 2017 if I'm doing my math correctly, and a big thing then was CAR T-cells and there was no FDA approved CAR T-cell therapy, obviously Carl June, you know, had a long-term cure, it was wonderful, Novartis picked up all that technology and my kid had to put a little bit of money in something in biotechnology and I thought CAR T-cells would be hot. So I took a list of all CAR T-cell companies and originally I was just gonna tell 'em to buy 'em some Novartis stock, because once those were FDA approved, I figured even though Novartis is a huge company, the stock would go up a little bit. And then I looked at list of all the companies doing CAR T-cells and it was like 30 of them, and I noticed one thing, one company called Kite Therapeutics had a surgeon as a CEO, small company, I think they had 50 people at the time, and without anything but that to go on... I didn't have time to do market research. I mean I was busy, I told my kid, "Go ahead buy Kite." Well a month later, Kite is of course the first one to get FDA approval. They beat Novartis, beat Carl June and a week later Kite is acquired by Gilead and their stock goes through the roof, and my kid made a lot of money for his finance club and you know, everybody thought he was a genius, and it was literally only one piece of data I had. There was a surgeon running the company. I said, "You know what? The chance of him succeeding is probably higher." And so it turns out, so always bet on the surgeon, that was the name of the talk and I kind of like that. I kind of like that, it's good for our field.

And you think he's had a higher chance of succeeding in that situation for the stuff that we were just talking about, right? The fact that he willing to take a chance, understood what the customer needs were 'cause he was the customer.

Correct and you're just motivated and you know, in anything, there's a lot of bureaucracy, you know, when there's a challenge people will step down from it and let you know the process, the naysayers win. Surgeons will not do that, we just don't step down, don't step down from a challenge. So no, you know, there's a challenge, somebody tells you no, that motivates you more to tell 'em "No, this is exactly what I'm gonna do." And you know, a lot of the breakthroughs like that, you require somebody who doesn't listen to the naysayers and is able to push back and you need a certain personality to do that. You know, Winston Churchill would've been a great surgeon 'cause I can tell you he didn't back down.

You know, it's interesting to hear you talk though, because in some regards, you said today outsiders drive paradigm shifts, right? And the healthcare system needs reform and it's gotta come from an outside perspective, and yet you could argue that the surgeon is frankly the ultimate insider. I mean, who's at the very heart of the hospital doing the most complicated cases? It's the surgeons. To some degree would you say surgeons are the ultimate insiders?

Not necessarily, not necessarily, some, you know, yeah, departments of surgery for most hospital, the biggest profit that generate the most revenue, but I can tell you we also cause the most headaches for the administrators. Any administrator listening to this will tell you that, but yes, so we are the insiders, but a lot of times we're the ones driving the change and pushing things forward. So yes and no, you know, if department of surgery were to disappear, I think the hospitals would do worse, not just financially but also from change and patient perspective. So yes insiders, but probably the ones on the inside doing the most pushing and causing the most headaches with the administrators, correct.

Got it, so you're the insider in the surgery, but you're the outside in the drug discovery process, but you're all over the healthcare system.

Correct, correct.

Got it, got it, got it, got it. Well, Sasha, I wanna say thank you for your time today, this conversation's been a blast. We've covered a heck of a lot of ground. So I have to ask you though, at the end of the day as a solution to fixing the healthcare system just to bet on the surgeon?

100%, I like that Justin, I like that.

100%, all right then, well then thanks for joining me today, this has been great and for all our listeners out there, thank you for joining us today on Definitively Speaking, a Definitive Healthcare podcast. Please join me next time for conversation with Joe Lim, the SVP of growth and engagement at Babylon Health. According to their website, Babylon Health has built the industry's leading AI-driven, digital first primary care service to manage population health at scale. Today Babylon's technology and clinical services support a global patient network across 15 countries, and it's digital health care platform is capable of operating in 16 languages. Joe and Al will be joined by Definitive Healthcare's chief product officer, Kate Shamsuddin Jensen for a wide ranging conversation on health equity and health disparities in the context of women's healthcare. I hope you'll join us. If you like what you've heard today, please remember to rate, review, and subscribe to the show on Apple Podcasts, Google Podcasts, Spotify, or wherever you get your podcast. To learn more about how healthcare commercial intelligence can support your business, please follow us on Twitter at Definitive HC or visit us at definitivehc.com. Until next time, take care, stay healthy and remember, always bet on the surgeon.