Intro - 00:00:08: Welcome to The Biotech Startups Podcast by Excedr. Join us as we speak with first-time founders, serial entrepreneurs, and experienced investors about the challenges and triumphs of running a biotech startup from pre-seed to IPO with your host, Jon Chee.
Jon Chee - 00:00:29: My guest today 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 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 this episode of The Biotech Startups Podcast. What was your childhood like and how did you get into science and entrepreneurship?
James Evans - 00:01:39: 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, I was bright enough I guess, but 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 spent 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 back-fitting the data. You're like, "Oh okay. Well I kind of do sort of, you know, life sciences and quantities. 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 science nerd growing up. Kind of a non-traditional approach. Yeah.
Jon Chee - 00:02:21: 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. And skating and playing video games, I don't have as much—well, skateboarding, one thing, I probably would get very much injured nowadays, 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, but yeah.
James Evans - 00:03:09: 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 with little science kits and stuff. And you know, my son and I do get stuff that build hydraulics and really cool stuff. But yeah, I didn't do any of that growing up. I don't remember really that much.
I think a lot of my childhood was just spent sort of being super energetic, like just running in circles. And my mom just laughs at me now when she sees my kids doing the same, and she's like, "Yeah, that's how you were, just like full of energy." And going back to like skateboarding and video games, I mean, one of the things that did resonate with me in listening to Jake and Steve in their podcast was sort of, you know, problem-solving and resilience to adversity and things like that.
Video games teach you how to solve problems, you know, like puzzles, really. And then 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 Chee - 00:04:12: 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.
James Evans - 00:04:22: Yeah.
Jon Chee - 00:04:23: 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 really like chunking it out.
James Evans - 00:04:33: Got to get your back leg higher than you think. Yeah, yeah, that's the... people don't think about that.
Jon Chee - 00:04:37: Yeah, exactly. And I also, again, there's like personally... but I think there was a certain amount of perseverance in 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 Evans - 00:04:51: Yeah. And there's that kind of going against the grain, and the kind of rebellious aspect of skateboarding. And in the UK, you know, it's very not mainstream. You know, everybody's playing soccer in the UK, and like skateboarding was kind of very sort of counterculture, and I think it is in the US still. But yeah, I mean that you need a little bit of that. Because 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 sort of personality aspect, I think, is an interesting part of the puzzle.
Jon Chee - 00:05:20: 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?
James Evans - 00:05:32: Yeah, I was thinking back on the process, and I had a really good high school biology teacher, Mrs. Akhtar from Birmingham in England, and she was really good. I remember learning about different aspects of biology and plant biology and just finding it tractable. 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. And English literature was good because it allowed me to write. Like, I was pretty decent at writing, but I always looked at that, I was like, "Well, what job am I going to do with a degree in English?"
Jon Chee - 00:06:27: Yeah, yeah, yeah.
James Evans - 00:06:28: You know, you'll be a teacher, basically is the only kind of avenue. And then economics, I just really struggled with whether my teacher wasn't the best, or whenever I would 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 that really didn't stick with me. So 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 these people, grad students and postdocs, and they were all, you know, multilingual, speaking French, Italian, English, and, you know, collaborating with labs in California. And it really kind of lit a fire in me, sort of seeing the application of the stuff we were learning back in college and stuff.
And so when I came back from Liege, 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 resuspending bacterial pellets. So there were these like big vats that were like, you know, 5 inches across, big vats of bacterial cultures. And you'd spin them down, you'd have this big chewing gum-like pellet of bacteria in the bottom. And this is back in the day, we're doing mouth pipetting, which shows how old I am. But we'd have these like 25 ml mouth pipettes, and we're 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 you'd be sucking on it, and then it would let go and it flew into my mouth, and I'm like, "Oh my God." And I'm like, "Oh!" I'm looking over at the grad student next to me, you know, and saying, "Oh, it went in my mouth!" and expecting him to like, you know, bust into some kind of medical scenario, like, "Okay, we're gonna, you know, we're gonna 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? Just get back to work." And it was just hilarious.
Jon Chee - 00:08:40: But oh my goodness, so casual, like, "Yeah, been there, been there."
James Evans - 00:08:46: Yeah, welcome to lab.
Jon Chee - 00:08:48: Yeah, 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 like casually just like, "Yeah, this is not problematic at all."
James Evans - 00:09:05: No, it's alright. A little ethidium bromide and all that. Yeah, that's fine.
Jon Chee - 00:09:09: Yeah, this is totally okay.
James Evans - 00:09:11: Yeah.
Jon Chee - 00:09:11: But yeah, this program sounds incredible.
James Evans - 00:09:14: Oh yeah, it was good. I mean, the university that I went to, Coventry University, was really a little bit ahead of its time. There's a lot of hierarchy in universities, I guess like there is in the US, right? So this was definitely, 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 mostly famous for its relationships with the automotive industry. There's a lot of like car designers that go on to work for like, you know, Range Rover and British Marques and stuff.
But it had a really good applied biology program. And they were also sort of well connected with these European initiatives to sponsor young people to get research exposure. And, 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'm going to go back. And the food, the waffles, and the chocolate and stuff were really great.
And the funny thing there, too, is like, every Friday in the lab, they would 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 get used to that. And then I remember going to like, I think it must have been grad school lab, and it'd be like Friday afternoon, and I'd be like, "Where's your beer and cheese?" And they're like, "Oh, that's a Belgium thing, not a lab thing." I was like, "Man, that's too bad, because that was a good perk." Absolutely.
Jon Chee - 00:10:39: Yeah. That's amazing. Like for us, it was just, yeah, we got some pizza from time to time. I would kill for some beer.
James Evans - 00:10:44: Yeah, these guys would have all the different flavored Belgian beers and stuff, like cherry and all the different... yeah, it was pretty amazing.
Jon Chee - 00:10:51: That's awesome. During your time in that program, was there any specific moment where you knew the fuse was just like lit? Where you're like, "This is exactly what I want to be doing?" Or was there perhaps a mentor or someone who took you under their wing?
James Evans - 00:11:05: 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 in my undergrad and turned around my grades and everything. And that got me to a point where I was thinking about, you know, what should I do as far as next steps?
And I wasn't really sure as to sort of 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 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 up in 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's much like starting a business. You know, if you knew, 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, Professor Alan McNeilly, 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, 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 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 just made more mistakes." And that really resonated, and that's really stuck with me. I've said that to people working in my lab or people I've worked with is just when you're like in your early 20s and you're working with somebody in their late 30s. They've got like nearly a 20-year 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, because it can 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.
Jon Chee - 00:13:11: I think 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.
James Evans - 00:13:23: First time. First time, no problem.
Jon Chee - 00:13:25: Yeah, no problem. They land the kickflip first try instead of having to like, you know, hyper-analyze 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, 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?
James Evans - 00:14:00: Yeah, so I was kind of an outlier within Alan's lab. His lab was an endocrinology lab. They're looking at LH and FSH hormone secretion as part of the estrous cycle. So they used a lot of in vivo models: sheep and rats and mice and things like that. And when I came into lab, I worked alongside a sort of senior scientist in his lab, Pam Brown, who was really instrumental in giving me the fundamentals in—this is in the late 90s—what were 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 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 some GFP and imaging, but also critically learned about subpopulation effects. So like if you're transfecting one of these endocrine cell types that are really hard to transfect, especially back in the day, using the tools we had then you might get 1 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 not going to be able to measure anything like a bulk measurement when you're doing a radioimmunoassay or something—it just doesn't make a dent in it. Yeah.
So what happened was we ended up getting a unit there, reproductive biology unit. They got a really nice Zeiss confocal, Zeiss LSM 510. 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 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 US. And for me... so, you know, I grew up in Saudi Arabia actually. My dad worked there and my two brothers were born there. And I grew up in a kind of American culture because it was an expat culture of 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 US and came over for that in '99.
And I ended up at a lab that was affiliated with Harvard Medical School. I wish I was like super blown away by that opportunity. I was like, "Wow, made it. This is like crazy. I'm 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 90s, the medical school there hadn't really invested in imaging tools the way that other places had. And I was coming from the lab that I had where we had this LSM 510, you know, they had a Bio-Rad system which at the time was like 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 bought one. And so I kind of reached out to the head of the facility there, it's Paul Matsudaira, and said, "Hey, you know, is your LSM 510 available for outside users?" And he's like, "Yeah, it is. Get in contact with the core manager," and so on. And 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 like coming in and meeting with him and just, you know, telling him about what I want to do and how passionate I was about imaging. And he just straight-up took a chance on me.
And yeah, like I said, I ended up working at the Whitehead and at MIT for over 10 years. And that was 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, really Paul and I were the only biologists in the lab. Everybody else had a different background, whether it was computational or chemistry or, you know, biophysics or something like that. And so it was a real cross-disciplinary environment.
And then a couple things went on. We were doing pretty high-end at the time computational imaging using deconvolution and big data sets using Silicon Graphics computers. Like data... Yeah, it was cool, but like really slow. Yeah, yeah, yeah. But I had a friend, 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. You'd spend 10, $20,000 on some dot blot matrix and then it would sit in the fridge for six months because you couldn't get around to it. It was like, "Wow." You know, I remember asking somebody, "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." You're like, "Oh my God." Yeah, yeah, yeah. It was different times, like it changed while I was there.
But when I first got there in the late 90s, it was really spendy. But one of the things that... so Sanjoy was involved, he has 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. And then Sanjoy was looking over my shoulder one day and was seeing me struggle with these big imaging 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, like 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 you know, 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-foot by 20-foot server room with like, you know, big computers from IBM and SGI and like terabytes and terabytes of storage. And I mean, it doesn't sound big anymore, but it was at the time. And so it was that.
And around the turn of the century, sort of early 2000s 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. 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 using imaging to collect a lot of data about cells and models was... I mean, that's all we do now for, you know, PhenoVista. So that was really good training and really good exposure to sort of that scalable, automated, quantitative approach.
Jon Chee - 00:21:04: Awesome. Honestly, that sounds pretty badass.
James Evans - 00:21:07: Oh yeah.
Jon Chee - 00:21:08: 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, you know, having going from like a lab that wasn't as well-funded to a well-funded lab and just experiencing like the dichotomy. And I honestly just like remember getting really tired on Berkeley's campus. We were at the very, very bottom of the hill. And the core facilities at the top of the hill. I would have to run samples up every day to get up to the core facility. And I was just like, "Oh man, I am so tired. Can we get the flow cytometer into our lab? Like, I can't do this anymore." You know, while at MIT, it sounds like you spent a fairly long time there.
James Evans - 00:21:53: Yeah, 10 years.
Jon Chee - 00:21:54: 10 years. You know, I think it's not a common experience to kind of have core facility experience. What was it like when, you know, you're using a lot of equipment? You know, I'm sure you're probably managing other labs who are like, "Hey, we need to use the equipment too." What was just like the experience operationally, obviously, with handling all the data, handling all the equipment and whether it be MIT or Harvard or any of the labs and industry partners?
James Evans - 00:22:17: 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. We opened it up to people. It was more of like a kind of a collaborative rather than a sort of fee-for-service type approach. So there were aspects of my job supporting Paul as the head of this, which involved budgets and, you know, data to backups and performance of the equipment, all 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, you know, from the larger community who come to me with a problem of like, "Hey, I want to measure this, you know, effect, this translocation effect in a particular cell type over a period of hours. And I think I should use, you know, time-resolved FRET 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 is, you know, sort of 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-expedient manner as possible.
Jon Chee - 00:23:50: That's incredible because I mean, that type of advice to a grad student or a postdoc is invaluable. And I feel like 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. And I have colleagues who went the fancy route and then exactly what you kind of described 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.
James Evans - 00:24:18: Yeah, we had really... So Paul Matsudaira went to grad school with Lance Taylor, who was the originator of high content screening. So back in like 2000, 2001, like these high content screening instruments were really only in a few big pharma companies and they were built for looking at like GPCR internalization and that's all. And they were really sort of fit-for-purpose and that was the only purpose. They weren't very flexible or user-friendly at all. And so coming from a completely academic, "any tool is available" and sort of complete freedom to that sort of constraint was incredibly frustrating and 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 like very sort of Swiss watchmaker-type 3D time-lapse imaging experiments which would take, you know, hours and hours to collect and they were very low yield, they wouldn't all work. And so knowing which conditions were going to yield the most useful information was really important. So we kind of used this automated high-content approach to map the topology of effects and say, "Okay, here at this particular dose and time for this particular drug, you get an unusual phenomenon or the 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.
Outro - 00:25:46: 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 in to our next 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. The Biotech Startups Podcast is produced by Excedr. Don't want to miss an episode? Search for The Biotech Startups Podcast wherever you get your podcasts and click subscribe. Excedr provides research labs with equipment leases on founder-friendly terms to support paths to exceptional outcomes. To learn more, visit our website www.excedr.com. On behalf of the team here at Excedr, thanks for listening. The Biotech Startups Podcast provides general insights into the life science sector through the experiences of its guests. The use of information on this podcast or materials linked from the podcast is at the user's own risk. The views expressed by the participants are their own and are not the views of Excedr or sponsors. No reference to any product, service, or company in the podcast is an endorsement by Excedr or its guests.
