James Evans - PhenoVista Biosciences - Part 1

Intro - 00:00:00: Welcome to The Biotech Startups Podcast by Excedr. Join us as we speak with first-time founders, experienced scientists, serial entrepreneurs, and biotech investors about the challenges and triumphs of running a biotech startup. Gain actionable insight into navigating the life sciences industry in each episode as we explore the business of science from precedent to IPO with your host, Jon Chee. 

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Jon - 00:01:10: My third guest is James Evans, founder and CEO of PhenoVista Biosciences, a contract research organization that works with biopharma clients of all sizes, from startups to established global companies. PhenoVista develops and implements high-content imaging-based phenotypic cellular assays for lead optimization, mechanism of action studies, and target validation for preclinical models. Before starting PhenoVista, James spent a decade at MIT's Whitehead Institute for Biomedical Research as a postdoc, a research scientist, and finally, director of the Bioimaging Center. After MIT, James went on to serve as a director at numerous venture-backed biotechs before founding PhenoVista Biosciences to offer his expertise to clients around the world. Over the next three episodes, we cover a wide range of topics, from his late-blooming love of science, his time at Harvard and MIT, his move to San Diego, and his bootstrapped entrepreneurial journey with PhenoVista. Today we'll chat about the early years, how skateboarding and video games honed his problem-solving skills, the Belgian lab that sparked his drive for science, and his experience joining MIT's Whitehead Institute. Without further ado, let's dive into Episode 3 of the Biotech Startups Podcast.

Jon - 00:02:15: What was your childhood like, and how did you get into science and entrepreneurship?

James - 00:02:18: I guess I'm a late starter, is what I would call myself. My childhood, I spent a lot of time skateboarding and playing video games and stuff like that. I really was an underachiever, and you know, it was bright enough, I guess, but I was always told I could try harder. And I really didn't apply myself until the last year of my undergrad. Like I really, the light didn't really go off for me until I stayed a year abroad, working in a lab in Belgium. And, you know, my dad is an engineer, and my mom is a nurse, so that's backfitting the data. You're like, "Oh, okay." Well, I kind of do sort of, you know, life sciences and concepts, and that's kind of engineering. You can kind of see the two hemispheres there, but I was in no way a bookworm or else sort of like a science dad growing up, kind of a non-traditional approach.

Jon - 00:03:01: Yeah, and honestly, for me personally, I was also a skateboarder, and I also played a lot of video games as well. So sometimes I feel like I got a late start as well. I thought I was going to be a lawyer at one point in time, skating and playing video games. I don't have as much skateboarding, one thing I probably would feel very much injured nowadays. Yeah, but for video games, you know, my wife and I play video games on our free time. No, I certainly have a similar upbringing, but you know, I thought it was really interesting that you mentioned that your parents were both scientists, but you know, perhaps only when you look kind of retrospectively, it was what brought you to it. But when you were growing up, was Science always a presence in the household, or was it a thing where you like rebelled against it? My dad's an engineer, so I know I kind of did.

James - 00:03:49: Yeah, not at all like science. I don't remember it being present at all, like compared, you know, I have young kids now, and we have things that come in the mail every couple of weeks, little science kits and stuff. And, you know, my son and I do get stuff to build hydraulics and really cool stuff. But yeah, I didn't do any of that growing up. I suddenly don't remember really that much. I think a lot of my childhood was just spent being super energetic, like just running in circles. And my mom just laughs at me now when she sees my kids doing the same. It's just like, "Yeah, that's how you were, just full of energy." And going back to skateboarding and video games, I mean, one of the things that did resonate with me and listening to Jake and Steve and their podcasts was sort of, you know, problem-solving and resilience to adversity and things like that. And video games teach you how to solve problems. You know, it's all like puzzles, really. And then there's, in a way, skateboarding is like that too. You know, you have to learn a lot of technical aspects to control your body and also interact with the environment and stuff. When you break it down, there are a lot of transferable skills to entrepreneurship, I think, that maybe go overlooked.

Jon - 00:04:53: Absolutely. And it's really getting me fired up because I spent a lot of time growing up skateboarding, and that problem-solving like I still remember trying to figure out how to land my first kickflip. And you kind of have to break it down. Like, "Alright, pop the tail, but you need to sequentially do the flick" and everything like that. And like really chunking it out.

James - 00:05:12: Gotta get your back leg higher than you think. Yeah, yeah. That's the thing, people don't think about that. Yeah.

Jon - 00:05:18: Exactly. And I also, again, this is like personally, but I think there was a certain amount of perseverance that skateboarding, you're running through proverbial walls to try and do the trick, but you're just failing and failing. So I completely think the same thing about skateboarding.

James - 00:05:32: Yeah, and there's the kind of the going against the grain and the kind of rebellious aspect of skateboarding. And in the UK, you know, kind of very non-mainstream. You know, everybody's playing soccer in the UK, and skateboarding was kind of very counterculture. And I think it is in the US still. But yeah, I mean, you need that a little bit of, 'cause it's hard to start a company and, you know, decide you're going to do that. But yeah, so those things all sort of contribute, sort of aside from the science aspect of things, the personality aspect, I think is an interesting part of the puzzle.

Jon - 00:06:00: Absolutely. And so as you were growing up, you're going through middle school and high school. Was there any sort of inkling of science at that point in time? Or was it something that kind of spurred like when you got to your undergrad? 

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James - 00:06:12: Yeah, I was thinking back quite this, and you know, I had a really good high school biology teacher, Mrs. Akhtar from Birmingham in England. And she was really good. I remember, you know, learning about different aspects of biology and plant biology, just finding it attractable. Like, you could learn things, and it wasn't like you just had to sort of memorize it, but it was so varied that's carried forward to right now, like, you know, dealing with our clients and so on, learning about their biology and the diseases they're trying to treat. And you just are constantly surprised by like all the depth and breadth of biology and how it works. And, you know, for me, my A levels, which in the UK are the subjects that you specialize in prior to going to university. And, you know, I had a really eclectic mix of biology, English literature, and economics. English literature was good 'cause it allowed me to write. Like, I was pretty decent at writing, but I always looked at that and I was like, well, what job am I going to do with a degree in English? Yeah, yeah, yeah. You know, you'll be a teacher basically is the only kind of avenue. Economics, I just really struggled with whether my teacher wasn't the best or whenever I'd learn something in economics, the rules never seemed to apply or hold true. And I'd be like, this just seems like bullshit to me. I can't learn this stuff. And so I, that really didn't stick with me. So that, that left me with biology. And so I sort of forged ahead with that. And, you know, then I got into this undergraduate program, which was somewhat unique. It was a four-year degree. And the third year you spent working in the lab, so we had this Erasmus program. It was a European Union program that allowed you to travel to a lab in the European mainland. And so I went to a lab in Belgium, and that was transformational for me because I kind of really at that point started working alongside all those people, grad students and postdocs, and they were all, you know, multilingual, they speak French, Italian, English, and, you know, collaborating with labs in California. It really kind of lit a fire in me, just sort of seeing the application of the stuff we were learning back in college and stuff. And so when I came back from Liège, I really applied myself in the undergraduate studies. And so that was a real turning point for me. But my one defining memory of the lab in Belgium was resustending bacterial pellets. So there were these like big vats that were like, you know, five inches across big vats, and bacterial cultures, and you'd spin them down, and you'd have these big chewing gum-like pellets of bacteria in the bottom. And this is back from the day we were doing mouth pipetting, which shows how old I am. But we're like, have these like 25 mil mouth pipettes. And we're like pipetting it up and down to resuspend this like chewing gum clump, and I'm doing it and like, you know, after a while, eventually a clump would get stuck in the pipette and he'd be sucking on it, and then it would let go. I flew into my mouth, and I'm like, "Oh my God." And I'm like, "I'm like, Oh, I'm looking over at the grad student next to me and I was like, 'Oh, it went in my mouth,' expecting him to like, you know, bust into some kind of medical scenario. Like, 'Okay, we're going to, you know, something we're going to take care of this and like call the medic and all this kind of stuff.' And he just looked at me and he was like this really suave, you know, French-speaking guy. And he's like, 'Yeah. Tastes like corn, doesn't it?' And I'm like, 'What?’ And I Just get back to work. You know, it was just hilarious.

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Jon - 00:09:20: Oh my goodness. 

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James - 00:09:27: So Calgary's like, yeah, been there. Welcome to the lab.

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Jon - 00:09:28: That reminds me, I was actually chatting with a family friend. He was mentioning how when he was at a lab at Berkeley, back when mouth pipetting was like totally the kind of status quo, and they would just be like mouth pipetting like DMSO, and just casually, just like, yeah, this is not problematic at all.

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James - 00:09:46: Yeah, it's alright. A little thidium bromide, and yeah, that's fine.

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Jon - 00:09:49: Yeah, this is, this is totally okay. But yeah, this program sounds incredible.

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James - 00:09:55: Oh yeah, it was good. I mean, the university that I went to, College University, was really a little bit ahead of its time. There's a lot of hierarchy in the universe, I guess, like there is in the U.S., right? So this was that, like, you know, top-tier university compared with like, you know, Cambridge and Oxford, but it was a very functional university in that it had a lot of good relationships with industry. And it is most sort of famous for its relationships with the automotive industry. A lot of car designers that go on to work for like, you know, Range Rover, British marks and stuff, but had a really good applied biology program. And they were also so well-connected with these European initiatives to sponsor young people to get research exposure. I mean, it made a huge difference to me. There were, I think, about 50 of us that all went to different places around Europe, and two or three of us that went to Belgium, and Belgium was great. I've never been back. It's been 20 years plus now, but I keep thinking I got to go back, and the food, the waffles, and the chocolate and stuff were really great. I would say it was great, and the funny thing there is too, is like every Friday in the lab, they'll have beer and cheese tasting laid out in the conference room. And this is like my first exposure to working in a professional sort of lab. And so, you know, I'll get used to that. And then I remember going to like, I think it must've been a grad school lab. And I'd be like, and it'd be like Friday afternoon, and I'd be like "Where's your beer and cheese? That's a Belgium thing, not a lab thing." I was like, man, it's too bad 'cause that was a good perk. 

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Jon - 00:11:20: Absolutely, yeah. That's amazing. Like for us, it was just, yeah, we got some pizza from time to time.

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James - 00:11:23: I would kill for some beer. Yeah, these guys would have all the different flavored Belgian beers and stuff like cherry, and all the different, like, yeah, it was pretty amazing.

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Jon - 00:11:32: That's awesome. During your time in that program, was there any specific moment where youview the fuse was just like lit? Where you're like, "This is exactly what I want to be doing," or were there, perhaps, a mentor or someone who took you under their wing?

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James - 00:11:45: Yeah, not a huge mentorship. I mean, I did work with a couple of grad students. I mean, I was so green. I mean, they were friendly and supportive, but I think it wasn't until I got to grad school. So I came back and, you know, worked really hard in my last year of undergrad and turned around my grades and everything. And that got me to a point where I think about, you know, what should I do as far as next steps? And I wasn't really sure as to what job I wanted or, you know, a lot of people just get a degree and then don't continue in biology. They just use it as a sort of a generic degree. And I started thinking about, you know, grad school, having been working alongside people doing PhDs in Belgium and applied to some programs. And I got an interview at the medical research council after Edinburgh. And I really honestly didn't know what I was signing up for when I applied. I just sort of thought, well, you know, I mean, it is, it's much like starting a business, you know, knife in you, you might not do it. Other people have done it. So, you know, I should be able to do it. And I went up and had an interview, and the head of the lab, Alan, Professor Alan McNeely, who's a really accomplished scientist in endocrinology. Yeah, he was just really down to earth and, you know, had all these like massive tomes up on the wall, people's names and dates on them. And I remember looking over his shoulder and just seeing them and realizing they're putting sort of two and two together and going, "Oh, you have to write one of those." I'm like, "Oh, I was like, you know, okay, I guess, well, these people did it, I can do it," and Alan was really the first person who was, you know, quote-unquote accomplished, you know, and he's like a senior guy, and I remember him saying, "I'm not any smarter than you, of course he is, but he would say, like, you know, I'm not any smarter than you, I'm just older," and the things I'm telling you, I've learned through trial and error, and you just made more mistakes, and that really resonated. And that's where it stuck with me. I've said that to people working in my lab or people who have worked with us, just when you're like in your early twenties and you're working with somebody in their late thirties, they've got like nearly 20 years head start on you in terms of stuff they've messed up in the lab that they just pass along to you. And that really stuck with me as kind of a way to nurture that, 'cause I think it would be really intimidating. I think even more so these days, it's just people are so accomplished and it's so like in your face, you know, about how well everyone's doing, and it could turn off people.

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Jon - 00:13:52: That really resonates with me because I think sometimes, especially in the age of the internet, what's presented almost feels like, you know, people just stick the landing. Like they do the triple backflip, stick the landing.

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James - 00:14:03: First-time, no problem.

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Jon - 00:14:05: Yeah, no problem. They land the kickflip first try instead of having to, like, you know, hyperanalyze it. And I can think about so many times in my lab experience and even just with Excedr. It was just raw trial and error. It was almost like a forcing function of just trying to see what works, but it doesn't sound elegant, like really. But I guess there's an elegance to the simplicity of it, which I completely agree with. And as you were in Alan's lab, what was the focus of his lab? What carried through your grad program and up to when you started to think about making the move? You're in the United States now, like that you wanted to continue that in your journey.

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James - 00:14:41: Yeah. So I was kind of an outlier within Alan's lab. His lab was an endocrinology lab. They were looking at LH and FSH hormones' secretion as part of the estrous cycle. So he used a lot of in vivo models, sheep and rats and mice, things like that. And when I came into the lab, I worked alongside a sort of a senior scientist in his lab, Pam Brown, who was really instrumental in giving me the fundamentals in, this is in the late nineties, we're relatively cutting-edge techniques of molecular biology and plasmid cloning and GFP fusion protein construction, linker proteins, and all that kind of thing. So our job, Pam and I, was to sort of get some in vitro assays together to complement these in vivo approaches. And that's actually very similar to what we do at PhenoVista right now. You know, that's where I learned about, well, some GFP and imaging, but also critically learned about subpopulation effects. So like if you're transfecting one of these endocrinology, so endocrine cell types that are really hard to transfect, especially back in the day, using the tools we had then, you might get one or 2% transfection efficiency. And so if you're expressing a mutant in those cell types, but 98% of the cells are unperturbed, you're just doing, you know, you're not going to be able to measure anything. You're doing a radioimmunoassay or something. Like it just doesn't make a dent in it. So what happened was we ended up getting a unit there, a reproductive biology unit. They got a really nice ZEISS confocal. And we started doing imaging and looking at those individual cells or clusters of cells that are expressing the fusion protein. And that was just hugely transformational for me. I mean, I really got into, you know, the power of doing imaging and it was really cutting-edge stuff. So, yeah, I mean, that was a jumping-off point from there. I applied to some postdocs in the U.S. and for me, so yeah, I grew up in Saudi Arabia. Actually, my dad worked there and my two brothers were born there and I grew up in kind of an American culture, kind of an expat culture, expat American engineers. So for me, it wasn't as daunting to move to the States because I kind of felt like I had some sort of cultural understanding of the differences and the distance didn't seem like a big deal. I used to travel back and forth from England to Saudi Arabia as a small kid. So I applied to some postdoc programs in the U.S. and came over for that in '99 and I ended up in a lab that was affiliated with Harvard Medical School. I wish I was like super blown away by the opportunity. I was like, "Wow, made it. This is like crazy where I'm like going to Harvard." And it was a really eye-opening experience. But what I found out very quickly was that at the time, and this is in the late nineties, the medical school there hadn't really invested in imaging tools the way that other places had. And I was coming from, you know, the lab that I had where we had this LSM 510. Yeah, they had a Bio-Rad system, which at the time was not as good. And I found it really frustrating to the point where I looked around online to see who had an LSM 510 in Boston and found that the Whitehead Institute had just brought one. And so I kind of reached out to the head of the facility there, Paul Mazzabera, and said, "Hey, you know, is your LSM 510 available for outside users?" And he's like, "Yeah, it is. Get in contact with your core manager." And so a few minutes went by, and I was like, I just sent him another email and said, "Hey, by the way, I'm really not happy with my lab here. I was hoping I could come and chat to you about maybe switching labs." And it was just on a whim. I just kind of wrote it and then just hit send. And then he got back to me, and he agreed to meet with me. And, you know, fast forward, I ended up working with Paul for like 10 plus years. And later on, he confided in me that he took that meeting thinking I was somebody else, and he didn't really know who I was. And I ended up coming in and meeting with him, and I'm just, you know, telling him about my, like, you know, what I want to do and how passionate I was about imaging. And he just straight up took a chance on me. And, you know, like I said, I ended up working at the Whitehead and at MIT for over 10 years. That was a hugely, hugely, I mean, after Alan, Paul was the next huge mentor in my scientific career. He had a really amazing combination of talents in his lab. Like I think at one point, Paul and I were the only biologists in the lab. Like everybody else had a different background, whether it was computational or chemistry or biophysics and something like that. And so it was a real cross-disciplinary environment. And then a couple of things went on. We were doing like pretty high-end. At the time, you know, computational imaging using deconvolution and big datasets using like Silicon Graphics computers, like cool data. Yeah, it was cool, but really slow. But I had a friend, Sanjoy Ray. I still have a friend called Sanjoy Ray. He was in Peter Kim's lab next door at the Whitehead. And they were a really high-flying lab at the time. And it was a really crazy sort of environment to be in where, like, you know, budgets were just not a problem. We'd spend 10, 20,000 dollars on some dot block matrix. And then it would sit in the fridge for six months 'cause you can't get around to it. It was like, wow. Yeah. I remember asking, "Hey, can I order this?" And they just looked at me like, "Why are you wasting my time with that? It's like 10,000, just do it." And you're like, "Wow." It was different times. It could change while I was there, but when I first got there in the late nineties, it was really spendy. But one of the things that, so Sanjoy was involved. He had a structural biology background. He was managing the computational infrastructure for the Kim lab. And then, so Paul and I were using a lot of the resources that the Kim lab had as far as Silicon Graphics instruments and stuff from them. So when Sanjoy was looking over my shoulder one day and was seeing me struggle with these big image and data sets, he was like, "Man, you really need some more computational horsepower." And I was like, "Okay, you know, sure." And so then he went away and started working on getting us, like, a million-dollar mainframe computer-type, big 64-bit Silicon Graphics computers for crunching images. And it was huge. Like, it really kickstarted us into the computational aspects of imaging. And by the time Sanjoy and I sort of finished working at the Whitehead, we had the second biggest server room at MIT. We had, like, a 40 feet by 20 feet server room with like, you know, big computers from IBM and SGI and terabytes and terabytes of storage. And I mean, it doesn't sound big anymore, but, you know, but yeah, so it was that and around the turn of the century, so early 2000s, there was a big move in systems biology. And within Paul's lab, there was a lot of collaboration with industry and technology platform providers. You know, it wasn't like we tried to build everything in-house. So it was much more like collaborating with these other microscope vendors or software companies or computer storage folks and all that. And then with the computational systems biology initiative at MIT, there was a real push to take a systems approach to biology. And that was really eye-opening and sort of like using imaging to collect a lot of data about cells and models was, I mean, that's all we do now. For, you know, a few minutes, that's like, that was really good training and really good exposure to see if that scalable automated quantitative approach.

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Jon - 00:21:44: Awesome. Honestly, that sounds pretty badass. 

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James - 00:21:47: Oh, yeah.

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Jon - 00:21:48: From one meeting that was like by accident, unfolded into a just super badass experience. At least what I would imagine sounds amazing. And it was funny when you were mentioning the LSM, and I just had a similar experience, you know, having gone from like a lab that wasn't as well funded to a well-funded lab and just experiencing the dichotomy. And I honestly just remember getting really tired on Berkeley's campus. We were at the very, very bottom of the hill, and the core facilities were at the top of the hill. I would have to run samples up every day to get to the core facility. And I was just like, "Oh man, I am so tired. Can we get the flow cytometer into our lab? I like, I can't do this anymore." Yeah. You know, while at MIT, it sounds like you spent a fairly long time there. Yeah.

James - 00:22:33: Yeah, 10 years.

Jon - 00:22:35: 10 years. You know, I think it's not a common experience to have core facility experience. What was it like when you were using a lot of equipment? You know, I'm sure you were probably managing other labs who were like, "Hey, we need you to use the equipment." So, what was just like the experience operationally, obviously with handling all the data, handling all the equipment, whether it be MIT or Harvard or any of the labs and industry partners?

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James - 00:22:57: Yeah, it was a little bit of like branding, in terms of there was a core facility at the Whitehead that was a more traditional core facility. And then Paul set up this Whitehead/MIT Bioimaging Center. We definitely had access, and we opened it up to people, but it was more of a collaborative rather than a fee-for-service type approach. So there were aspects of my job supporting Paul as the head of this, which involved budgets, data backups, and performance of equipment, that kind of thing. It was a pretty cool environment because I got tasked with supporting a lot of grad students and postdocs from mostly at MIT, but sometimes from the larger community, who would come to me with a problem like, "Hey, I want to measure this translocation effect in a particular cell type over a period of hours. And I think I should use time-resolved in 3D." And I'm like, "Yeah, you could, but you know, when do you want to graduate? You could just do a lower resolution, more automated approach, get the numbers you need, and get out of here." And they'll be like, "Yeah, I'll do that one." So, you know, it's like taking a common-sense approach to like, "What's the question that you're asking, and what's the quickest way to get to that?" And that again is another thing that's translated to my day job now, or at least the folks that sort of interact more directly with their clients, advising them on not doing the most convoluted, fanciest approach, but what's going to get you the data in the most reliable, cost-effective, time intensive or time-expedient manner as possible.

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Jon - 00:24:31: That's incredible! I mean, that type of advice to a grad student or postdoc is invaluable. Not everyone gets that advice, and they do the fancy, you know, all the bells and whistles, but the time just expands and expands and expands. I have colleagues who went the fancy route and then exactly what you described happened to them, and they're like, "God, I wish I did it." The other way and could have shaved off some years off of this. I mean, that's incredible that you had the opportunity to do that. 

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James - 00:24:59: Yeah, we have really. So Colm Matts Nero went to grad school with Lance Taylor, who was the originator of high content screening. So back in 2000 or 2001, these high-content screening instruments were really only in a few big pharma companies. And they were built for looking at GPCR internalization, and that's all. They were really sort of fit for purpose, and that was great for other people, but they weren't user-friendly at all. And so coming from a completely academic background, you know,  any tool was available and you had complete freedom, that sort of constraint was incredibly frustrating. It was really hard to make that transition, but once we did and we figured out how to use that automated platform, it became really valuable. I was doing all these very sort of like Swiss watchmaker-type 3D time-lapse imaging experiments, which would take hours and hours to collect, and they were very low yield. You know, they wouldn't all work. And so knowing which conditions were going to yield the most useful information was really important. So you kind of use this automated high-content approach to map the sort of the topology of effects and say, "Okay, here at this particular dose and time for this particular drug, you get an unusual phenomenon, and all of those cells are displaying a weird phenotype." So let's do some higher-resolution imaging and then see what's going on there. So that's the way we used to combine those two approaches. And that was a relatively novel approach. 

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Outro - 00:26:26: That's all for today's episode of The Biotech Startups Podcast. We hope you enjoyed our insightful conversation with James Evans, covering his younger years, his initial foray into lab work, and his journey overseas to pursue his passion for imaging research. To learn more about James's journey, be sure to tune into next week's episode. If you enjoyed this episode, please subscribe, leave us a review, and share it with your friends. Thanks for listening. And we look forward to having you join us again for part two of James's journey for an in-depth discussion on his time at MIT's Whitehead Institute, his path to entrepreneurship, and how different company cultures affect your work-life balance.

‍Final Outro -00:27:08: The Biotech Startups Podcast is brought to you by Excedr. Don't want to miss an episode? Make sure to search for Biotech Startups Podcast in Apple Podcasts, Spotify and Google Podcasts or wherever you get your podcasts and click subscribe. To learn more about our leasing program, visit our website, www.excedr.com. We provide research labs with equipment leases on founder-friendly terms to support a path to exceptional outcomes. On behalf of the team here at Excedr, thanks for listening.