Quitting Physics to Treat Biology Like an Engineering Problem | Richard Yu (Part 1/4)

Intro - 00:00:06: 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. Our guest today is Richard Yu, co-founder and CEO of Abalone Bio, a therapeutics company developing functionally active antibody drugs for challenging membrane protein targets like GPCRs. Before founding Abalone Bio, Richard served as scientific and operations director at QB3's life sciences incubator in San Francisco, co-founded Green Pacific Biologicals focused on algae biofuels, and was a research fellow at the Molecular Sciences Institute studying cellular information processing. At Abalone Bio, Richard leads development of the FAST platform (Functional Antibody Selection Technology), which uses engineered yeast cells to screen 100,000,000 antibodies simultaneously for functional activity rather than just binding affinity, integrating synthetic biology with machine learning to discover GPCR agonist antibodies. With a research collaboration with Pfizer, breakthrough CB2 agonist antibodies showing efficacy in models of liver fibrosis and diabetic neuropathy, and a background spanning structural biology at Yale, computational protein engineering, and serial entrepreneurship, Richard's journey demonstrates how interdisciplinary experience can unlock previously undruggable targets, making this a conversation you won't want to miss. Over the next four episodes, Richard shares how growing up in Ohio as the son of Chinese immigrants shaped his values. Discovering biophysics at Berkeley transformed biology from operational science to an engineering discipline and transitioning through Yale structural biology to systems biology and synthetic biology work. Today, we'll hear about Richard's early days in Ohio and New Jersey, how his parents' experience taught him to figure things out, and discovering biophysics at Berkeley through a friend who promised proteins that eat dirt so you'll never need a vacuum cleaner. We'll hear about Yale's structural biology program working on membrane fusion proteins and learning the cultural differences between East Coast academic rigor and West Coast entrepreneurial energy. Lastly, we'll hear about the transition from computational modeling to more applied work, the formative experiences that shaped his path from physics to biology to entrepreneurship. Without further ado, let's dive into part one of our conversation with Richard Yu.

Jon Chee - 00:03:24: Rich, so good to see you again. Thanks for coming on the podcast.

Richard Yu - 00:03:27: Thanks for having me, man. Good to see you.

Jon Chee - 00:03:29: Yeah. It's been a while, and I, you know, been really looking forward to this conversation. I just I mean, it's been months, and the time is here. And in traditional podcast fashion for us, we always like to go all the way back and really just, like, learn about your upbringing and how it influenced your business philosophy, leadership style, and really what got you into STEM. So take us all the way back. What was Baby Rich like?

Richard Yu - 00:03:52: So the Baby Rich story starts in Ohio. I was born in Ohio, and there's, like has this is such a great opportunity to, like, go back and think about common threads and the overall narrative arc. Right? I think there's, like, a core of an immigrant story underlying everything. Right? My parents immigrated here, and it's both immigration and also, like, what that implies, which is this sort of, like, intersection of two different worlds. Right? But I've only sort of, like, been in that middle too. Right? I mean, the STEM, you know, wet lab computational. Uh, I was, like, writing a list out. There's, like, 12 things of, like, you know, point counterpoint where I feel like I'm in at this intersection. But to answer your question yeah. So, uh, born in Ohio. I grew up in New Jersey afterwards in my formative years, and then I came out to California. We'll go through this later on. But I always joked that I have this, like, deep, dark, New York cynical core. Right? And then, like, it's, like, mellow, you know, dude on the outside, California.

Jon Chee - 00:04:47: You're on

Richard Yu - 00:04:48: the outside. But then I realized just, uh, this past year that it's, like, actually, deep down, I have, like, this nucleus of, like, Midwesterner. You know? Like, it was just a recent realization. You know? That's where I think, yeah, a lot of the sort of core values that I have today were sort of generated. It's like, you know, sort of like kindness and politeness and, you know, like, assuming the best of other people. You open doors to your neighbors, you know, like, growing up in the seventies in the Midwest, like, having those real early informative years. I think the program for some of those, you know, went to those seeds really early. Right? Absolutely. So, uh, my dad was an engineer, but even he had a lot of these sort of intersections in multiple worlds. Right? Because before that, he was a pilot in the Chinese air force. And then the late nineteen hundreds was sort of a difficult place to be, China. Right?

Jon Chee - 00:05:33: There's a

Richard Yu - 00:05:33: lot of Yep. Drama. So he went through the familiar path of going through Taiwan and then into the US eventually. He was also at the sort of, like, intersection of two worlds, like, sort of pre-America and post-America. So, yeah, engineer, dad. And then my mom, traveler. She was an airline attendant for a while, uh, but then became a, like, a computer programmer. Early days, like, with, like, Fortran, COBOL, and, uh, you know, Chase Manhattan. So, yeah, I've always had this, like, sort of STEM-y background. My dad was, like, a constant tinkerer fixing stuff around the house, and but definitely picked some of that stuff up. And, of course, you know, grew up with LEGOs and and all that. So yeah. Yeah. So so, definitely, I always sort of like a builder maker drive behind me. So after that, grew up, like I said, in New Jersey for most of my, so I would call it, middle school and high school years, which I think was probably on the border of, like, the there's, like, a whole section of town that had, like, all the wealthy bankers and stuff, and then there's, like, the working class out of town. It was, like, it was, like, literally in the middle of it. I'm not using this as, like, just like a a pure narrative conceit. Like, it's actually true. Like, there's all these intersection

Jon Chee - 00:06:36: Yeah. Yeah. Yeah. Yeah. Yeah. Yeah.

Richard Yu - 00:06:37: experiences I had growing up. It was, like, sort of weird to see that as I was going through the notes and and sort of thinking about my story for this call.

Jon Chee - 00:06:45: Did your parents move for work?

Richard Yu - 00:06:46: Yeah. Yeah. You know, back then, you would do that. Right? Nowadays, like

Jon Chee - 00:06:49: Yeah. Now you can work.

Richard Yu - 00:06:50: If I have to drive more than, like, 45, I'm just gonna find another job. But, yeah, my dad definitely took those jobs where he had to do, like, hour-plus commutes, but then moved the family for the job. Right? Yeah. So we moved the family to New Jersey, and from there, did my high school. And then I, one, had this formative summer where I went to Harvard summer school. I think it's my junior year. And, uh, it was, like, purely a social thing. Right? Like, you know, it wasn't, uh, I think I took a biology class, and I have no memories of that, but I have all the memories of what seeing, like, what the world was like outside of, like, a somewhat sheltered suburban life. And I was like, I wanna go there for for my undergrad. And I applied. I didn't I think I got waitlisted or or or something. But, uh, I remember my dad having to write an application for Berkeley, the UC Berkeley. And I didn't you think about California is very sort of, you know, northeastern provincial mentality. Right? And I got in, and I remember when I got the envelope, the acceptance letter, he's like, okay. You're okay now.

Jon Chee - 00:07:45: Yeah. Yeah. That is the classic immigrant parent just like, okay. I can sleep better now. Exactly. Like,

Richard Yu - 00:07:53: Yeah. Perfect. You know?

Jon Chee - 00:07:54: Like Yeah. Exactly. For them, they're like, my god. The weight of the world. Like and up to that point, were you, like, already on the STEM path? Yeah. Okay. So you you kind of knew early on, like, even in high school that STEM was gonna be kind of a focal point?

Richard Yu - 00:08:10: Definitely. Yeah. I was always, like, playing around with computers. And this is, like, again, this is sort of, like, the seventies and early eighties. So a lot of, like, the Apple II. Right? You know? A lot of, like, phreaking and using modems and stuff. Built-in boards, that sort of thing. Right? So more like hardware physics, electronics, and stuff.

Jon Chee - 00:08:26: Okay. So not so much biology yet. Not at that point.

Richard Yu - 00:08:29: Definitely not. I mean, I think even up to my first years in Berkeley, so I entered, I guess, in the very late eighties, early nineties was my undergrad time. '89 is when I got to Berkeley. Right in time for the earthquake.

Jon Chee - 00:08:41: Uh, the

Richard Yu - 00:08:42: eighty-nine earthquake. Yeah. I mean, there, I went in and started as a physics major just because of, like, I was good at math and just sort of came easy. Path of least resistance. And very quickly, I realized, like, I could do all this math, but I have, like, no idea what this is useful for. So a friend of mine in the biophysics department who had gotten me into motorcycling, and he's like Oh, nice. Super cool to, you know, like, head shaved and, like, ponytail and,

Jon Chee - 00:09:10: you know,

Richard Yu - 00:09:11: looked like, uh, he has like a prototype for a Trent Reznor, like, Nine Inch Nails, like

Jon Chee - 00:09:15: Yeah. Yeah. Yeah.

Richard Yu - 00:09:16: So I sort of barnacled on him and went into the biophysics. I didn't even know what biophysics was. I thought it was, like, exercise physiology or something. And he's like, no. No. No. It's like protein engineering and modeling. And the example I always bring up is he's like, dude, we're gonna engineer proteins to eat dirt. You'll never need a vacuum cleaner again. Right? Yeah. And that really did set the stage for this integration of physics and STEM in biology way before the sort of systems and synthetic biology era because, yeah, it was, like, just this idea that biology wasn't just this observational thing where you're, like, counting butterfly species in a field somewhere, but it's more of, like, an engineering discipline. Right? Like, making stuff. So, yeah, that really just changed my mind about the whole thing. So protein engineering and protein structure was sort of where my focus was as an undergrad. Experimentally first. So I worked with a guy named Bob Glaser in the biophysics department, and that, I think, was a a real formative experience in terms of, like, what a mentor could be because he's this very much just like a patrician old school physicist, not like the sort of cutthroat molecular biology department.

Jon Chee - 00:10:22: Yeah. The MCB department. Yeah.

Richard Yu - 00:10:24: Yeah. It was more just, like, biophysics. I think it was its own separate department back in the day, you know, up in Donner Hall or something. Uh, you could, like, smell the radiation, like, coming off the brick walls, like, since we're Yeah. Postwar.

Jon Chee - 00:10:35: Yeah. Yeah. Yeah. It's like a brutalist building too. Exactly. Yeah. Yeah.

Richard Yu - 00:10:39: Yeah. So I did that, the experimental side. I tried to do crystallization of some proteins. That's where I got a first taste of biology and what that means, um, in terms of, like, thinking about science. Right? Physics sort of teaches you to be this very bottom-up type thinker, first principles, and then building up more ever more complicated models. I'll never forget when I was did my first rotation with a guy named Chen Wu, who's over at Eureka Biosciences now. He's a grad student in Giovanna Ferro-Luzzi Ames' lab. And, uh, he's like, alright, Rich. Like, make this buffer. We need this, like, HEPES buffer at pH seven. Right? So I was like, cool. I got this. I'll, like, get a piece of paper out. I busted out the Henderson-Hasselbalch equation, and, you know, I'm, like, calculating stuff. And then he's just like, what are you doing? I'm just

Jon Chee - 00:11:22: like go to the he said, come on, man.

Richard Yu - 00:11:24: He's like, there's a pH meter right there. Just, like, add hydrochloric acid. So it's it's like, you know, just, like, make the thing. Like, what are you doing? I was like, I just didn't even think about that. You know what I mean? So it's like, this idea just, like, slight perturbation. I mean, that's my whole idea behind, like, a a negative and a positive control. It's like, you change one variable at a time, then you have these, like, signposts so that you sort of know that you're not straying too far. And you can make, like, strong conclusions based on, like, a a single lever being being pulled. Right? That was a a lot of, like, informative, you know, educational experiences there. Um, that's where I also got really interested in computer science. You know? Again, like I said, I was playing around with Apples and and, uh, programming and BASIC, you know, way back in the day, and Pascal and all that. And then right around then, it was, like, '91, '90, '91. There's this, like, real sort of, like, AI—or they didn't call it ML. They called it AI back then. There are some of the first forays of applying that into protein structure prediction. And at that time, it was mostly about secondary structure prediction. There are only about 400-ish protein structures in the PDB. And I always joke is, like—and 350 of them were lysozyme. You know? Like, it was

Jon Chee - 00:12:29: like Yeah. Yeah. Yeah. Yeah.

Richard Yu - 00:12:30: It wasn't much, like, yeah, generalizable data back then. There's just a lot more data on the sort of secondary sequence to helix data, you know, coil-type predictions. So, yeah, I worked with Teresa Head-Gordon, who's then at LBL, who's now at the chemistry department, and, yeah, just busted out, uh, you know, some multilayer neural networks to try to do that. And we we, like, you know, did a little some few tweaks. There's a publication floating around out there in PhysRev on that. But, yeah, it's it's pretty cool. Right? I was like, oh, this is, like, a totally different field. And, like, this is, again, this, like, intersectional thing. Right? The magic is always at the intersections.

Jon Chee - 00:13:04: Yeah. Yeah. And I guess, like, of that intersection, intersection, where did you spend most of your undergraduate, like, laptop?

Richard Yu - 00:13:09: Yeah. It was, I think, in the wet lab. Yeah. Because wet lab is just, yeah, just, like, very time-consuming. Yeah. Yeah. Materially and, like, you know, your soul. It takes a lot of your soul as well, which I would learn later on in graduate school.

Jon Chee - 00:13:23: Yeah. Especially as an undergrad, you're like Yes.

Richard Yu - 00:13:27: Yeah.

Jon Chee - 00:13:27: Yeah. Like, your postdocs and PhDs is like, yeah. I need you to just go do that work for me.

Richard Yu - 00:13:32: Yeah. Yeah. Exactly.

Jon Chee - 00:13:32: I'm gonna go—I'm gonna go on lunch. And so, like, as an undergrad, you're just like, alright. Like, I'll go make the media.

Richard Yu - 00:13:40: I had great mentors. Like, yeah, between, uh, Bob Glaser, my faculty connection, and and Shank, there's the graduate student at the time. Yeah. I mean, they they were fantastic as as an I I could not have hoped for better undergrad interactions with with folks. Yeah. And then this application of bringing one world into another, I was like, wow. This is amazing. Like, there's so much to be done here. Right? It's like a whole wide open field. So, uh, I was thinking about what to do for grad school at the time. You know, again, sort of Asian upbringing. Of course, you go to grad school. I didn't even think about other options. Right? Some—I was just in the car the other day, and people were like, if you could go back, like, this time or that time, what like, what are the key things you would do differently or or not even do differently, but if you could take a look at yourself in a parallel world, like, what would you be most curious about? And this is one of them. This is where I have this, you know, dual degree in biophysics and and computer science from Berkeley in 1993, like, right at the dawn of, like, you know, the .com boom. Right? And I decide to go into structural biology on the East Coast and leave the West Coast. Right? So it's, like, very good for me intellectually. No regrets. Like, I'm very happy with where I am in my life, and I know I couldn't be here if I didn't take the path I took. But That being said

Jon Chee - 00:14:46: Yeah.

Richard Yu - 00:14:48: There's some people—I remember this guy, one of my friends who I did a computer graphics final project with. So, yeah, I just joined this company called, like, Netscape. Like, I'm not really sure what you say it is. Right? And then another friend's like, yeah. There's this thing called Yahoo. Like, I don't know. And then, like, the next year, he's like, I just bought another house in the Oakland Hills.

Jon Chee - 00:15:06: I'm like, yeah.

Richard Yu - 00:15:07: I was, like, making, you know, $14,000 a year, like, you know, for an NIH grant.

Jon Chee - 00:15:11: God. Like, what am

Richard Yu - 00:15:12: I doing?

Jon Chee - 00:15:13: And that's actually an interesting, like, question. It's like—so I guess, like, when you landed in Berkeley from, you know, having spent, you know, your upbringing on the East Coast in New Jersey, what was it for you, like, personally? Like, just, like, being on the West Coast, particularly in Berkeley, which I think is, like, a unique cause and very different. What was your personal, just like, experience with that?

Richard Yu - 00:15:36: Yeah. You know? Yeah. This is, uh, sort of the late eighties, and I grew up in seventies. So another formative sort of seed that's planted is always that, like, outsider feeling. Right? There was, like, two Asian people in my school growing up. Right? The other person was, like, a girl. And, like, it was, like, we just, like, avoided each other as much as possible.

Jon Chee - 00:15:54: Yeah. Yeah. We did. Yeah. Yeah.

Richard Yu - 00:15:56: Yeah. And then—so getting to Berkeley and seeing, like, a vibrant Asian community was like it—it was really—it's very interesting. I've had to work through a lot of this with, like, coaches and and therapists. Right? But it's very illuminating thinking back about it, but it was a culture shock. Right? It felt weird to see so many Asian people around.

Jon Chee - 00:16:12: For sure.

Richard Yu - 00:16:13: Because, like, in my mind, I was sort of programmed to be, you know, Italian American or, you know, you're you're growing up in New Jersey. So, yeah, that, I think, really informed a lot of, uh, obviously, even all the way up to my, you know, current company experience—that's sort of, like, always sort of feeling a little bit like an outsider. Right? And that has its pluses and minuses. Right? But, yeah, to the answer to your question—that—that was one of the key elements. But also just Berkeley, California, that that time was just—it—it—it just really opened up my world so far beyond than any prior experience. Right? There's a glimmer of that, uh, when I spent that summer in Cambridge for, uh, Harvard summer school, but this is like, okay. Now I'm, like, living life. And I was 17. Right? I—I—I think I skipped first grade or something. I was a little bit younger. And it's so funny too, like, to compare this to, like, my boys' experience. I had a 25-year-old and a and a 21-year-old, almost 26-year-old. And, like, just how different our experiences are. Right? Like, so so many of my—our—my cohort, we weren't financially independent by 17 or 18, but we were out of the house and, like, you know, it was just a different thing than a lot of people who are still living with parents and stuff like that.

Jon Chee - 00:17:16: So—And and Berkeley too, I feel like, is just kind of, like, just throws you into the—in the deep end, both academically and—no coddling. No. There is no coddling. They're like, oh, you're fucking up? Yeah. Exactly. Don't care. Don't care. Hey, man. Yeah. It's on you. Like Natural selection. It's like a selective process.

Richard Yu - 00:17:35: This is another one of those elements. Right? It's so—I'm so glad you brought that up because I've talked about this with my boys who went to Berkeley High, which is a sort of like a microcosm.

Jon Chee - 00:17:42: Also went to Berkeley High. Okay. Yeah. Yeah.

Richard Yu - 00:17:44: So you

Jon Chee - 00:17:44: know what I'm talking about. I know exactly what you're talking about.

Richard Yu - 00:17:46: It's like, if you can thrive, you can, like, kick ass. Right? And, you know, I'll think of all the famous people that come out of there, musicians and actors, actors and scientists, otherwise. Right? But you can also, like, get eaten alive. Right? Yes. Yeah. You could be the fertilizer for someone else's greatness. Right?

Jon Chee - 00:18:02: That's exactly—and it doesn't stop just at Berkeley High either. It's consistent. Like, you go up the street, and then you're at UC Berkeley, and you're like, oh, they have the same mentality. Like, you're just like, figure it out,

Richard Yu - 00:18:14: which I actually really appreciated. It's like it teaches you something about life as long as it doesn't make you cynical and, you know, for, like, nihilistic or something.

Jon Chee - 00:18:23: I think it made my dad a little bit cynical.

Richard Yu - 00:18:25: Oh, did it?

Jon Chee - 00:18:26: Yeah. Yeah. My Berkeley upbringing and experience, I have a great appreciation for it. It's kind of a very much the life comes at you fast, and you just, like, have to, like, figure it out. No one's gonna, like, show you how to navigate this thing. I'll—like, my dad, when he was in grad school at Berkeley, he was just like, this is bullshit. Like, I didn't sign up for this. I, like, immigrated for this, and I'm just, like, getting kicked to the curb. Like, no one's helping. I just gotta shoulder this load, and I'm like, oh, I'm sorry, dad. But it cuts both ways. But I empathize. I definitely empathize.

Richard Yu - 00:18:59: Totally. I totally empathize too. And, again, there pluses and minuses. Right? And it's like—I think about this in the—for my parenting days, like, you know, how much do you guardrail and coddle, and how much do you, like, let them make mistakes? And, like, you know, it's like, we're all just, like, chattering monkeys trying to figure this shit out. You're right. Yeah. No—no one really knows what the hell they're doing. Right?

Jon Chee - 00:19:17: But—Yeah.

Richard Yu - 00:19:18: Yeah. Try to make it up as we go along. Again, that's sort of, like, uh, really much a a culture shock. And—and that really did plant seeds for—it's so hard to say whether it's causal or not or whether it's selected for me because I've thrived there. Right? It's like, always been very much an autodidact. Like, I just, like—I—I can't imagine what it's like if I could grown up in the era of YouTube and, like, you know, the modern Internet, oh, man. That would have been incredible. Right? Because, like, you know, downloading stuff from, like, bulletin boards at, like, 300 baud or 1,200 baud. You know? Like, that was—I—I was trying to figure out stuff back in the day. Yeah. It was, like, amazing. So, yeah, in any case, back then, um, yeah, the Berkeley experience was very much informative for the startup thing. Yeah. I think for all these threads that we've been pulling, intersectional science stuff, but also culturally and sort of, like, mindset. Right? Like, yeah, you just gotta, like, go out and get it, man.

Jon Chee - 00:20:06: No one's handing you

Richard Yu - 00:20:07: to school. Nobody. Nobody.

Jon Chee - 00:20:10: And as you were, like, thinking about your grad school, I haven't gone to school on the East Coast, and I'm gonna imagine when you chose to go back East, it was probably a vastly different experience than your Berkeley experience, I'm gonna assume.

Richard Yu - 00:20:22: Yeah. Yeah. I mean, uh, I went to grad school at Yale. Right? And, you know, I wish I could say my selection process was about the science and about the—but it was a fantastic structural biology department. And the person that I got hooked up with, Axel Brünger, who's now at Stanford, was, like, off the bat, really supportive. Like, I wanna take a half-year off to, like, uh, I had this opportunity to go travel to the Far East with my parents. You know? I was like, plea—I just, like, want to take a little bit of time off. And he supported it, which was awesome. It was sight unseen. Like, he didn't know who the hell I was. So I—I really appreciated that. And he was also starting up a lab at, again, the sort of intersection of experimental and computational biologists. Like, perfect. But, yeah, culturally, the sort of dichotomy between the sort of West Coast, like, Silicon Valley entrepreneurialism, like, I didn't—wasn't—at least as an undergrad, I didn't really experience that. Though even as I was leaving—this is, like, '93, '94, and this is when I was working for Teresa Head-Gordon in the sort of gap year between graduating from grad school. A guy who scoped me out, like, based on that graphics class that I had taken—we did this, like, juggling simulation on, uh, it's like Silicon Graphics, like, Iris machines or something. I—I can't remember details, but it was pretty dope. Alright? So

Jon Chee - 00:21:36: Hell yeah. Yeah. Hell yeah.

Richard Yu - 00:21:37: So it got, like, posted somewhere, and some guy, like, actually came to me. He's like, oh, we're making—we're, like, doing this game thing and, like, you know, you wanna join stuff and, like—yeah. So I guess there was a little bit of entrepreneurialism because he is like, I'm a graduate student here and, like, I made so much money, like, selling this, like—I think he did, like, a—it was like a 3D Tetris or something was his first game or something. Yeah. Wow. This is, like, jogging a whole bunch of memories. This is great. I'm sitting outside, uh, the fountain outside of Cafe Strada, and he's like, this disc has made me, like, $10,000 this month.

Jon Chee - 00:22:04: I was like, oh my god. You know? Like, that's incredible. That's so Bay Area, also just, like, very Berkeley.

Richard Yu - 00:22:11: Yeah. Yeah. It's so funny. Right? But, uh, you know, my family was, you know, was, like, devoted to the sciences and the education, so I have to go get my grad degree. I think let's just say that businesses and, you know, even working for biotech, uh, is more or less viewed as, like, being a sellout. Right? I—I think that was the—the culture. Right?

Jon Chee - 00:22:30: For sure.

Richard Yu - 00:22:31: Of course, therapy did very well, but, yeah, I think it—Yeah. So you had the same similar thing? Oh, for sure.

Jon Chee - 00:22:37: For sure. Like, you even contemplate going into industry, you are on the dark side. Like, you're on the dark side. And I was like, I'm just trying to help. I don't—I don't know. I'm just trying to help. Just—like, I feel terrible for trying

Richard Yu - 00:22:51: to help.

Jon Chee - 00:22:51: This sucks. Yeah. It's like

Richard Yu - 00:22:53: I actually just wanna, like, do something instead of, like, just published papers. But—Yeah. So I was there from '95 to 2000. So my class there was actually an article written about us in—I—it was either Nature or Science—of, like, the class of '95. What happened? You know what I mean? Because, like, yeah. So it's, like, you know, preeminent MB&B department. So, like, we were—I can't write this—interject here. It was, like, at the transition between the old, like, you know, you do that and you train, you get into an academic position. Like, that's the pyramid scheme. You're getting to the top of the pyramid. And, you know, our class, like, the majority did not go into academia, which was like a—there was like a first class where it—it, like, dramatically shifted. So they're like, you know, is this a—portending something for the future? What's it's like there's like an actual article written.

Jon Chee - 00:23:40: Yeah. Yeah. Yeah. Yeah.

Richard Yu - 00:23:41: On, like, our class, right, which is pretty amusing. Yeah. So definitely a different culture there. So much so that even my PI, who is much more California, and he didn't—make his way out to Stanford. Actually, when I graduated within the year, he also came out to Stanford as well. So—and a lot of the other drives were—you know, my girlfriend at the time had never been out of California. She was born and raised in—in, you know, California, so she's like, cool to check out the East Coast, and yeah, we had a great time. I actually really enjoyed it. You know, if I'd gone to, I don't know, Scripps or, you know, UCSD or something, I—I would have not gotten any work done now. Like, that was—Yeah.

Jon Chee - 00:24:17: It's just—yeah.

Richard Yu - 00:24:18: Like, way too nice.

Jon Chee - 00:24:19: It's too nice out here. Way too nice. Yeah.

Richard Yu - 00:24:21: You're just

Jon Chee - 00:24:21: like, you mean I gotta stay under the hood? Like Exactly. You go to the beach.

Richard Yu - 00:24:27: It was just nice enough so that, like, I got, like, really into motorcycling. I—I mentioned my—my friend who got me into biophysics as a motorcyclist. So—but out there, it's like—it was awesome. So, like, I would, like, work really hard. I was just—I was just relating the story to my—my wife earlier today about a mutual friend that we just had a—a call with. One of his stories is, like, when he first—he's a couple years behind me, and he's like, I remember one day coming into lab at midnight to start something, and all of you fuckers were there. Like, all of you.

Jon Chee - 00:24:54: Right? Yeah. Yeah. Yeah.

Richard Yu - 00:24:56: I mean, even Axel was there because he had just started the wet lab, so he was, like, interested in trying it out. So it was like, he was there pipetting stuff at, like, late hours. It's so funny. Yeah. It was, um, but it's, like, very—I mean, we did it because we wanted to. Right? And I don't think I felt forced to do that. Um, and then—and played hard on the weekends too. I'd go off on for cycle rides for surgery days and stuff and stuff. Yeah. So that cultural shift was just great to see the—the two different mindsets. And, you know, again, being at this intersection of sort of experimental structural biology and—and comp—I did a little bit of computational work. It was, again, formative in—in my—my later years, you know, just being able to think about data in a much more quantitative way. It's still so curious to me how—you know, my—well, my postdoctoral work was very much a fusion of the—the experimental and the computational work. But you—you think it'd be much more common these days, but it still seems pretty rare where people are very comfortable with both, right, to think about biology and biological data in—in a much more quantitative way. It's—it's still surprisingly rare, at least in my limited experience with—with people.

Jon Chee - 00:25:56: And at Yale, that lab, did you feel like it was—I mean, it sounds like Axel was—it was kind of like a—at start-up energy, but in an academic setting, it's kind of like punk rock. Was it just, like, startup chaos? Or, like, how did Axel structure his lab and, like, how you guys do your work? Was it just, like, be free?

Richard Yu - 00:26:14: Yeah. It was very much that. Yeah. Yeah. Which I think informs a lot of my management style and—and—and action style too. It's like, surround myself with, like, really capable, smart, awesome people, and this is, like, just try to, like, give them the resources to do awesome stuff. You know? What—yeah. It's like, pause and pause it. Sometimes you need to—well, we can go into the whole, uh, personal discovery stage, you know, that happened in my later years, but very much the startup energy. It was very much, um, yeah, sort of like an infectious tribe. Like, we—we definitely felt like we were part of something big. Yeah. So much so that—I mean, he's, like, this computer guy. Right? He'd written some of the most famous X-ray and NMR structure refinement software, X-PLOR and CNS. Yeah. I mean, he's just like, I'm gonna start generating data myself, which is—I mean, it's actually what we're doing in our company now. Right? So it's like—it's just very interesting seeing these echoes and ripples through my path. Yeah. So, uh, he was just, like, there—like, again, like I said, you know, using a pipette at midnight at night, uh, over along with the rest of us, and it was a very formative experience.

Jon Chee - 00:27:12: And when you had that experience, like, you said that whole class was, like, don't think we're going the academic route. Was there a moment where you're like, it's not for me, or did you even remotely consider it?

Richard Yu - 00:27:23: I think I felt the pressure to do it so much so that I, like, did a postdoc, but I—I think I was already resisting the tractor beam, you know, because I didn't do a traditional postdoc. So as I was looking for postdocs, I was looking at for much more applied stuff. Right? So I wasn't looking for, like, a super famous name necessarily. So, like, one of the things I was considering was working for—it was, like, called the Population Council or something like that. Basically, doing, like, protein cell engineering for, like, birth control, right, or, like, fertility issues. And there's some opportunity in New York. And, again, there was a lot of social elements. I was like, do I wanna, like, spend some more time in New York? The twenties were very good to me. Like, grad school, it was, like, awesome. Right? So, like,

Jon Chee - 00:28:02: pretty—pretty sweet. Right? So I'm like Yeah. Yeah.

Richard Yu - 00:28:04: I could see this. But, uh, towards the end of my graduate school life, my wife came out, and we—we got married, and I had my first child when I was, you know, wrapping up my grad school career. So I was like, oh, maybe New York. I don't know. Like, maybe a little too much. Right? So, fundamentally, I always, uh, you know, after my undergrad at Berkeley, I'm like, this is where I wanna raise my kids. Like, it's, like, it's so nice out here. So, yeah, we came back to Berkeley, and I saw an opportunity at Berkeley. Roger Brent had posted this paper or an essay on, like, systems biology. Like, what is that and what does it mean? Sydney Brenner, technically, had started this institute called the Molecular Sciences Institute down San Diego a couple years before, but—so this would be 2000. They're just moving up to Berkeley, right outside the Berkeley, uh, downtown station—downtown Berkeley BART Station. And it seemed, like, very off the path, you know, off the beaten path, I guess. He was, like, super charismatic, and he's like, come join me on the raft or something. He used, like, his raft imagery. It was—it was really cool. And that was my postdoctoral work. Right? So it wasn't definitely not, like, thinking, okay. This is my—you know, I'm gonna work for, you know, this famous guy or gal, and then, like, that's my stepping stone to a—a great academic job. It's more like, no. This is actually way more interesting. Right? This idea that, like, okay. We're right on the path to sequencing the human genome. How do we make sense of all this data? What is 30,000 interacting genes, like, mean? And how—how can it possibly give rise to complex human-ness? Right? Like, it's just sort of weird. Right? The whole concept is really right? So it's systems biology. And that's always sort of, uh, interested me too. Like, you know, like, how flocks of birds, right, they form these, like, cool patterns and stuff. Right? And, uh, I remember we did that as a exercise in—in that graphics class that I've, like, referenced, like, here four times now. But it—it—it's—it's all these simple rules. Like, okay. It's like this, you know, n follows, like, the previous bird. And if that bird is within this, you know, angle of you, you turn right or you turn left. And, like, you just—so simple rules repeated over and over again give these, like, beautiful patterns and stuff. And that—that's always sort of interested me. So, yeah, I, uh, joined this Molecular Sciences Institute, and the—the mission there was to, you know, understand how complex systems give rise to biology. And that's where there's another ragtag group of, like, truly intersectional, truly interdisciplinary, merry motley crew assembled. Right? There's, like, a dude who he made his own, like, compiler, uh,

Jon Chee - 00:30:24: sake. Yeah.

Richard Yu - 00:30:25: It is, like, crazy. Some of the early dudes or early—yes, people—in synthetic biology were there. Drew Endy, Rob Carlson, we were all there at the same time. Lots of people doing tool development, being verbalist, doing stuff on how do you PCR proteins, right, technologies, how to do that. So and they—they all came from all different areas of life—math, computer science, cell biology, genetics, engineering. Right? So that was really a formative experience for me in the—the Molecular Sciences Institute. I think it's a very unappreciated little gem in history. It should get a lot more recognition for its place in—in the history of the development of what I would consider sort of modern biology and modern science. It is quite a

Jon Chee - 00:31:09: special place. And when you were there, were there any particular colleagues or mentors that kind of, like, had an outsized impact on your experience there?

Richard Yu - 00:31:17: Yeah. I mean, the founder and the director, Sydney—I mean, god, the dude. So, like, I—I didn't work with him that closely unlike some of the other people who were directly recruited by him. I'd more or less bumped into him in, you know, cocktail parties and, like, when he won Nobel Prize, he, like, came by. But he's, like, one of the legends for a reason. Right? I mean, he's just someone who can, like, extemporaneously just, like, have, like, the most profound and amusing lectures of a—of a—he's, like, standing there, like, uh, with his cane. And, like, you know, he's just the energy that dude gives off is just—is unbelievable. He's one of the greats, you know, one of those old school, like, um, I mean, I put him in the class of, like, the gentleman scientist, you know, of a—of a bygone era. You know what I mean?

Jon Chee - 00:31:56: It's not like Yeah. Yeah. Yeah. He didn't

Richard Yu - 00:31:57: do it to, like, oh, I'm gonna do this so I can start a biotech company so I can, like, make a bunch of money. It's just like—it's a calling. And similar with—with Roger. Right? I mean, he was actually, again, very much at the early forefront of the sort of, like, more systems thinking, you know, one of the codevelopers of the two-hybrid system to map out protein and protein interactions at, like, uber-large scale. He was amazing too. He still is amazing. But in terms of the impact on me, really to think very clearly about science and scientific problems and to write—we had this, like, epic four-year paper that ended up getting into Nature, so perhaps worth it. But, I mean, I literally spent, like, significant numbers of minutes on literally every word in that paper. It was, like, it was absolute torture. Torture. But it was a—a fantastic experience. And now, I mean, that really helped me learn how to, like, write well, um, and express myself well. Perfume. Maybe not in an interview like this, but, you know, if I have time to, like, you know Yeah.

Jon Chee - 00:32:49: Yeah. Yeah.

Richard Yu - 00:32:50: Masticate on words. Uh, Yeah.

Jon Chee - 00:32:52: Yeah. Yeah. Different format. Different medium.

Richard Yu - 00:32:54: He taught me how to—how to do it really well. So really combining these interdisciplinary aspects in—into a single unified goal. I didn't really see much of that. Right? I mean, there are all these, you know, the nineties, there's all these, like, interdisciplinary departments or umbrellas being put over existing departments in—in various schools either at Yale or—or Berkeley or—or other friend schools. But it always seemed like a bit of, like, uh, yeah. We're gonna do this so we can get some money that funds you. Or, like—like, I'm just gonna keep doing my own thing in my lab. And, you know, they—like—it—it didn't seem like, uh, uh, super genuine or, uh, maybe I'm not being fair. But, yeah, in any case, this is like—like a unified, like, we're gonna do this. I'm like, that, again, was a very, very formative experience for my later scientific experiences.

Jon Chee - 00:33:39: And how did your experience change? Because I know you were there for a long time. Like, as you kind of became more senior at the institute, how did, like, your experience change?

Richard Yu - 00:33:48: Yeah. I mean, I started off as, yeah, again, like a postdoc, and they took pains to say, you're not a postdoc. You're a research fellow. So fine. Research fellow. Sort of like how my personal development now happened. A lot of the later stages of my personal development happened in the course of this company development. I think that—that work then did a lot of the—learning how to think, essentially, coming up with—with your own ideas, I think, was forging your ideas in a—in a more sort of coherent way. I mean, I was there for, yeah, eight years formally as, like, a full-time person and then was still on as the PI on the grants. So, yeah, I think it was learning how to, like, formulate and then communicate ideas. It takes time to do that in a lot of practice. Right? I think the most important thing that came out of MSI was meeting my co-founder for what would become Abalone Bio, Gustavo Pesce. Uh, so he was a geneticist and cell biologist. That was his, like, sort of bucket that he was put in. Right? But, you know, later on, I learned that we both apparently had done the same exact thing in our early years on our Apple IIs. We had programmed our own text-based Space Invaders game. I, like, I couldn't believe it. I was like, there's no way you did the exact same thing. And, like, we described it to a T as—as just, like, you'd shoot, like, exclamation marks, like, up

Jon Chee - 00:35:00: and down.

Richard Yu - 00:35:01: I don't know when that happens. I love when that happens.

Jon Chee - 00:35:03: It's so awesome. I was like, dude, no way.

Richard Yu - 00:35:06: Yeah. So hey, guys. Yeah. So I met Dan, and we became, like, pretty close. He taught me a lot about what kindness is, and that isn't being my natural default, which is, like, nonconfrontational and, like, trying to smooth things over. But it's, like, actually—and sometimes it can be, like, being really direct and, like, being really truthful and honest. Like, I—I remember at one, um, retreat we had, I gave this talk, and I was, like, super nervous. And I didn't—didn't really have much data to show, and everyone else held this data. Like, it was a terrible talk. Right? So afterwards, while I was standing outside, some people were like, you know, this is back in the day, and people smoke cigarettes. Right? Sounds like crazy, but, you know, people were like, oh, yeah, man. Good talk. You know? I was like, uh, thanks. You know? And, uh, because that was there, he's like, what are you talking about? Like, that was terrible. What happened, dude? Like, you have awesome stuff. Like, why'd you fuck it up? You know? Like Yeah. Like, we actually sat—he took the time to go. I was like, look, dude. You did this. You did this. You showed this. No one knew that before. Like, just—just say it. You know? I was like, oh, yeah. It was, like, too much in my head. Like, I just couldn't—couldn't figure it out. So it was awesome. You know? And I just so appreciated that. I try to, like, try not to be a dick about it, but I do try to, like, you know, keep that thread.

Jon Chee - 00:36:10: I love that, and I think my co-founder does that for me too. And sometimes that shit hurts.

Richard Yu - 00:36:16: Yeah. Dude. Painful mirror. Right?

Jon Chee - 00:36:19: But, yeah, it's a painful mirror, but, like, you know, at least they take the chance to do it.

Richard Yu - 00:36:24: Yeah. Oh, yeah. Yeah. Yeah.

Jon Chee - 00:36:25: And that—it shows that they care. Right? Absolutely.

Richard Yu - 00:36:28: Yeah. I mean, I think he didn't do it from a perspective of, like, I'm going to sacrifice. Probably, that's just, like, the way he is. Like, he couldn't help himself.

Jon Chee - 00:36:35: You know

Richard Yu - 00:36:36: what I mean?

Jon Chee - 00:36:37: Like, he just, like, blurt

Richard Yu - 00:36:38: it out. But—but, yeah, ultimately, it was, like, it was a huge gift to have that viewpoint and—and that sort of honesty.

Intro - 00:36:47: That's all for this episode of the Biotech Startups Podcast featuring Richard Yu. Join us next time for part two, where Richard recounts co-founding Green Pacific Biologicals in 2008 to engineer algae cells that secrete biofuel oils, why his first VC pitch was cringingly bad with just two slides of pure science, and landing QB3's incubator after learning that science alone is wholly inefficient for value creation. If you enjoy the show, please subscribe, leave a review, or share it with a friend. Thanks for listening, and see you next time. 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.