Rafael Rosengarten - Part 2: Marine Biology to Biofuels - Building the Future of Synthetic Biology

Intro - 00:00:01: 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. In our last episode, we explored Rafael Rosengarten's early journey, from his upbringing in a South Carolina salt marsh, to his academic adventures at Dartmouth, and his foray into the culinary arts. If you missed it, be sure to go back and listen to part one. In part two, Rafael reflects on his graduate studies at Yale, where mentorship from Stephen Dellaporta and Leo Buss shaped his independent and creative approach. We'll also discuss how his diverse marine biology and genomics projects prepared him for synthetic biology. Lastly, we'll talk about his postdoctoral work at the Joint BioEnergy Institute, where collaboration and access to cutting-edge technology helped fuel his passion for innovation and entrepreneurship.

Rafael - 00:01:13: So my graduate advisor, his name was Stephen Dellaporta. And again, I met Dr. Dellaporta, I met Steve because he was the really close collaborator with this evolutionary biologist, the marine biologist I was working with. And Steve came from a classic genetics background. He had run Barbara McClintock's program at Cold Spring Harbor for years and years before coming to Yale. But he's also one of those old school scientists. He's been in the same corner office at Yale as a faculty since he was like 27 or something. Like, you know, he got his faculty job young, was really good at it, got tenure, stayed. He's just a great guy. I mean, he was, and Leo Buss, my other advisor, also in his own way, a fantastic mentor. They were very different people. Steve, being a plant geneticist, didn't really know the organisms I was working on. So Leo continued to advise me and mentor me on the organismal biology. But Steve came from the old school molecular biology crowd, right? We each had a copy of Maniatis on our bench and we were expected to read it. We were expected to learn how to do things the old-fashioned way. He used to, you know, in his sort of, I walked to school uphill both ways kind of fashion, would talk about purifying proteins, purifying restriction enzymes, and selling them to lab mates to get beer money and, you know, that sort of thing, right? So old school stuff. But he was great because in some ways his outsider approach to the systems I worked on meant he wasn't constrained by other things. He was like, well, what if you took these cool new molecular techniques or whatever and applied them here and figure out how to do that? And again, this was the era when genome sequencing, short read sequencing was becoming a thing. 454, I don't know how many people remember the 454 sequencing. That company was started just half an hour up the road from Yale. And so that was one of the two early short read sequencing companies. So, you know, we did a lot of homebrew, high throughput cloning, shotgun cloning, sequencing. And he's like, you need to learn how to handle the data. So I had to teach myself enough bioinformatics to at least do genome assembly and to do like, you know, recursive blast searches and stuff like that, nothing sophisticated, but enough to mine my own data. And he, Steve kind of, he knew the writing was on the wall. Like genomics was the next huge thing, right? Because he had helped usher in functional genomics with the lab work he had done and the discovery of transposable elements and things like that. And he's like, we're going to be completely inundated with these data. And people who know how to look at the data and query the data are going to have an edge up. And he was talking to a wannabe marine biologist, washed up has-been cook who was not, I am not tech savvy. Like, I didn't want to become a programmer. In fact, I probably couldn't have even if I tried. I wrote a lot of Perl scripts that were held together by chewing gum and paperclips and stuff. I used to regularly crash the high throughput computing cluster, get it in a do-loop because my code was so bad. Anyway, Steve was great. The lab was super supportive. About half of the lab at that time was working on these marine systems and half the lab on corn genetics. So we did have, you know, I wasn't alone. But my thesis was kind of a dog's breakfast. I started out. With a rotation project working on one group of organisms called glass sponges, hexactonellids. These are in the phyloperiphera, which at the time were thought maybe were the earliest branch of the animal evolutionary tree. So I did some mitochondrial genomics on that and learned about evolutionary typing of mitochondria. But that was never meant to be my project. It was working, so I kept doing it so I could get a paper. And then I switched to Trichoplax, which again was the organism I had worked on as a technician and was kind of the thing I really wanted to break ground in. We just could not get funded to work on that. So I tied up what I had been working on, published some studies actually on some comparative genomics and Trichoplax, looking at the origins of the tumor protein 53, the TP53 gene family. There's a lot of, in my opinion, very interesting evolutionary theory of these early clonal organisms and how they circumvent getting cancer because they have immortal cell lines. And so they have certain cell lines that remain pluripotent for their whole lives. And so if they get cancer, they're kind of effed. It was kind of a made-up project. It was using these bioinformatic techniques to kind of put these organisms in place, but we couldn't get funded. And so then I switched to the hydroid model, which had an outstanding grant, so at least I could fit it. And I did some cool work on that and ended up figuring out a mechanism for the generation of an obscene amount of immune diversity that looked a lot, felt a lot, smelled a lot, like the way human major histocompatibility complexes create diversity of immune molecules. But this was in a hydroid that was like 500 million years removed from us, but it used the same – I mean, it had all the same bioinformatic and structural signatures in the data and the protein. And it was just wild to me that these are not the same molecules, but there's structural constraints or functional constraints on the way that molecules could figure out how to become diverse. And I actually got really passionate about this idea of diversity generation at the molecular level and finished up the last few years of my PhD doing that. But my thesis was like three separate research topics, three separate phylum of organisms stapled together with a preface that said, is this enough? Did I do enough? Can I get out of here? But it was fantastic. And Steve and Leo both were really – They were the kind of mentors who they were stable in their careers. Right. So they were there for the success of their students and not the other way around. They were interested in us becoming independent and figuring out how to like, you know, it was up to us to figure out what to do. Right. They would certainly weigh in on it. Gosh, they had opinions, but they weren't going to tell you what to do. And, you know, that's that's the mark of a good graduate mentor is someone who's going to foster independence, but also, you know, go to the mat for their student success.

 Jon - 00:06:56:

Absolutely. And I think about like grad experiences like that, where your advisor kind of just like. Lets you kind of like feel around. And obviously, they're going to like kind of like-

Rafael - 00:07:07:

Right.

 Jon - 00:07:07:

If you need some help, they're going to like nudge you in the right direction. It's almost kind of like a, it's kind of like what company buildings like.

Rafael - 00:07:14:

It's what good board members do, right? Like they're not going to, they shouldn't ideally interfere with the operation of the company. You're the expert, right? That's the expectation. But they'll rein you in if necessary. And they'll, you know, even bail you out if necessary, right?

 Jon - 00:07:27:

Yeah, exactly. Exactly. And I think, you know, whenever I speak to grad students, They're like, I don't know how to run a business. I'm like, well, you have, you just got through grad school. So it's like not too dissimilar, like where you have to figure it out on your own. And it's like multifaceted in that way.

Rafael - 00:07:47:

Oh, we'll come to it. But I absolutely think the first couple of years of entrepreneurship are a lot like what I imagine the first couple of years of being a pre-tenure faculty are like.

 Jon - 00:07:56:

Yeah, I can see that too. I guess you mentioned something during the sequencing, being really close to you at Yale. Was Jonathan Rothberg doing all his sequencing stuff at that same time that you were there?

Rafael - 00:08:10:

Yeah, yeah, yeah. So that's when Rothberg, I don't know if he stayed affiliated with Yale, I presume he did, but he had gone up the road to Brantford or wherever and started 454.

 Jon - 00:08:18:

Cool.

Rafael - 00:08:19:

I was really good friends in grad school with a guy named Chris Mason, who's a faculty at Weill Cornell Med School. And Chris was one of these guys, still is, who, I don't know, maybe sleeps three or four hours a day because there's just so much going on. He wants to do so much and get, and he was really involved in like, what can we sequence? Let's just sequence it all.

 Jon - 00:08:36:

Yeah. Yeah. Yeah.

Rafael - 00:08:38:

And so I remember, I remember late nights with him and, and, and his, his colleagues from 454 would come down and we'd, we'd go out and, you know, close the bar and be having discussions about like, what's the next thing you could do with a short read sequencing? It was just, it was so much fun to watch and to be part of.

 Jon - 00:08:54:

What a kind of like cool time to be around that. I was kind of like watching from afar, but just seeing it kind of go was like. It felt like a kind of like a wild west. Obviously like next-gen sequencing and all that stuff is kind of like very, very developed now, but very cool that you had a front row seat to that. And so as you're wrapping up your time at Yale, did you know what was next after that for you?

Rafael - 00:09:17:

Absolutely not. I've never made these kind of big life choices based on sort of a deliberate plan. There were a handful of things going on. So one is, it was pretty obvious to me, like I wasn't gonna be a good academic faculty. Like I already, I had had three different projects in grad school and wasn't the expert at any of them. I did, however, have a postdoc idea in mind at University of Queensland in Brisbane, Australia, with a guy who studied similar kinds of problems. But again, this was just me saying, I'm going to get off the grid and go be a marine biologist and live at a marine lab and not take too much seriously. Typical for sort of my story, what got in the way of that is I got together with a girl and she had actual career prospects and they were going to at least be stateside for a while. And she worked in the energy sector. And at the time, so she was working kind of traditional energy. My brother had gotten really interested in climate science and that sort of thing. And I was just kind of immersed in these two worlds and having a lot of conversations. I was like, you know, what if I split the difference? There's this new emerging field around biofuels. And they need biologists who have my skill set, which is I could build gigantic cloning libraries. I was really good at cloning. And again, I was kind of a benchtop cook, right? Like I could just clone without a recipe. I committed Maniatis to memory. And I could probe the data and figure out what's going on in the data and automate things and stuff. And I kind of knew that I wanted to go back to the West Coast, right? I'd gone to the Northeast for college and I'd stayed. So, you know, I'd been at that point in the Northeast for almost 13 years. It worked out that my then girlfriend could get a job. Her job would rotate her out to the West Coast. So we could at least live near each other for a little bit. And so I just I interviewed a postdoc exclusively on the West Coast and managed to be the first postdoc hired in the synthetic biology group at the fairly newly opened Joint BioEnergy Institute in Emeryville. So Jay Kiesling, who's a fairly storied professor at Berkeley and at Lawrence Berkeley and National Academy of Engineering and so forth. He's a chemical engineer. He was the head of this thing. But it had. You know, Department of Energy funding and congressional mandate and was in this big, new, shiny glass building in Emeryville. And for those of you who don't know, I mean, Emeryville now, that's kind of is lots of that. But back then it was still pretty shady. It was like the second or third nice building that had opened. There were a couple of publicly traded companies. Amherst was one of them. It opened on the floor below us. A couple of restaurants, some condos that you really had to be speculative to consider buying. It wasn't what it is now, but you could sort of see it coming.

 Jon - 00:11:57:

Quick question. Was the Ikea there yet?

Rafael - 00:12:00:

I don't. I think so. Yes. The Trader Joe's was down the road and you could cross the train tracks and there was a place to get like boba tea.

 Jon - 00:12:07:

Yeah. Yeah. Yeah.

Rafael - 00:12:08:

Yeah. There wasn't a whole lot, but it was a new place and it was neat. I mean, again, I had no idea about biofuels or whatever, but I knew I could clone stuff. I knew I could analyze the data. I knew I wanted to be on the West Coast and I knew that I wasn't going to be a great academic. So I wanted to start working on things that had commercial import and it's hard to. Overstate what a big change that was in my mind state. All through grad school, I was the asshole who was like, no, no, no, we should do science for the purity of science. I didn't even work on translational systems. I didn't work in cancer. I didn't work on anything that was remotely relevant to human health. There was no reason to fund the research I was doing except that. Every time we fund basic science, we discover amazing things, right? You know, CRISPR came out of studying bacterial restriction enzymes, came out of studying bacterial immune system. CRISPR came out of bacterial immune system, GFP out of pretty jellyfish. Like all the cool tools we've got come from just studying basic science. And I knew that history and I believed in it. But if I want to have a job one day, I figured I better do something closer to the value chain. Right. And the JBEI, the Joint BioEnergy Institute, had a mandate. I don't know if I'm going to get this right, but it was supposed to like it was Congress graded it based on economic production. So it was supposed to spin out companies. It was supposed to generate intellectual property by way of patents. Publications were important, but they were like the third thing. Right. So it wasn't your typical academic lab. It also was just a blast. It was this whole institute. And there were like some VP level people like muckety mucks at Lawrence Berkeley. But it was run by a bunch of people in their 30s just out of their like my postdoc advisor had just finished his postdoc. Brilliant guy, but young. Right. I was his first trainee in that regard. You hand a bunch of 30 year olds the keys to the kingdom, a virtually unlimited research budget. Like no one there did Western blots. We had a whole room full of mass spec machines. You don't know if your proteins express mass spec. I mean, it was crazy, right? So in a lot of ways, the trainees weren't necessarily learning how to do the old school science that I had learned. But the flip side of that is we were all empowered to just go like we knew what the mission was. We were empowered to design experiments and just go big or go home and throw ourselves at them. And it was a blast. I made some amazing friends there. The quality of science was pretty high. A lot of companies grew up out of it. Some of which have gone on to some real success. And there was a hot minute where oil prices were so high that we thought biofuels might one day be economical.

 Jon - 00:14:38:

 That's a lot. Again, you're kind of at the ground floor of these kind of like emerging kind of waves. When you landed that that gig at JBEI, was it kind of like similar to your Tribeca experience? We're just like handing out resumes or like how did you land it?

Rafael - 00:14:54: No, very similar. In fact, I had had some interviews down at UCLA. Maybe at Stanford, at Berkeley College, University of Berkeley on the campus. I kind of fall in love with the idea of doing synthetic biology. And I don't really know why. I guess just because it was new, right?

Jon - 00:15:09: Yep.

Rafael - 00:15:10: And involved cloning, which I could claim to be good at. But most of the people I was talking to were chemists, like chemical engineers type. And I went to JBEI and I interviewed, I went for a postdoc interview. And I met the woman who was sponsoring the role. And she gave me the interview, but she was like, I have to be candid with you. I've already kind of found my candidate for this. I filled the role of someone who's got real experience with the organisms. He's worked in yeast. I'd never worked with yeast, right? But... My colleague... Is trying to fill a role. Would you like to talk to him? And so literally I went for a job interview, didn't get the job. She walked me next door and I left with a handshake offer. 

Jon - 00:15:50: That's so cool. Also, it's kind of a testament to like, you just never know. You just have to go get out 

Rafael - 00:15:56: there. You really have to shove your foot in the door. You really do.

 Jon - 00:15:59: There's like a meme for it, but just like, if you go through these kind of like, kind of normal processes and just like form fill on like an internet page, it's like you're, you like send over your CV, just goes right back into like the recycling. You kind of have to like go out there.

Rafael - 00:16:16: I had the experience years ago. This was 2016. Gosh, long time ago. I got to give the commencement address for my old, my high school alma mater. And I don't know why they picked me. I hadn't accomplished anything at this point, in my opinion, but this was actually on the, this was kind of on the eve of it was the, you know, the spring before Trump was elected the first time. And it was clear to me that there was a ton of noise on Facebook and social media. Just a ton of disinformation out in the world and in the ethos. And so the theme of my, my commencement address was this idea of trying to like know when to leave the digital world behind and really lean into the analog world. And the story I gave was actually how I got together with the woman who is now my wife and who was the girl for whom I moved to the West Coast for my postdoc and did not go to Brisbane. And the story was that, you know, we had known each other in college, but didn't date. We were connected on Facebook. We had a lot of friends in common. And the day before we got together for the first time, she just sent me a. HBD on my birthday, literally three letters, HBD, right? A happy birthday on Facebook and, you know, a million other people wishing me happy birthday. But we started chatting and she invited me to come up to Boston for drinks. And the difference was I went, right? And so the moral of the story is if you show up, good things happen, right? But you have to show up. And likewise, you know, you put your foot in the door for a job. You might not get that one, but you might get the next one or the one across the hall.

Jon - 00:17:38: I love that because I think especially with just like... Things feel more accessible because the internet kind of like, obviously there are connections being made on the internet that never would have been made, but exactly what you're saying, leaning into analog, the analog and just like. Getting out there there's no replacement for it but like when you when you have all these connections on the internet and just like you can kind of like put you in a like false sense of like complacency yeah I'm getting busy. Like I've fired off a hundred applications to just like click it down. But like, there's nothing that like exactly what you said, just like going, going to Boston for drinks or just going from like in New York, just dropping off resumes for at these restaurants or going out to, you know, the West Coast and like actually just knocking on doors really opens up opportunities outside and even just beyond jobs too. Like a story for me when I was, you know, this was a, you know, a long time ago, like very, very early days of, of Excedr before we had formal relationships with the capital markets. I went door to door to talk to banks. Like I was just like this, like bushy tailed, wide eyed, just like.

Rafael - 00:18:50: Oh yeah.

Jon - 00:18:51: And I look like I'm 16. So they're like, what's this kid just coming in and asking for money at these banks. I'm like, but, but I still talk to those bankers that the ones who are not retired now that I met when I was just hitting the road, I was just like, go, going through and I still keep up with them. And we worked together on deals like to this day. And I had no idea that that would come of it, but it was like, I'm a more introverted person that I might put out on the internet, but like, it really took like a lot for me to go do that, but I don't regret it. It was uncomfortable like doing it, but it was like so critical and pivotal and opened up so many doors.

Rafael - 00:19:30: No, I think the interpersonal relationships are key. And I'm probably getting ahead of the narrative for the podcast series here. But the biotech markets have been kind of depressed now for over three years, right? Since September 2021 is when the bubble officially burst. And a lot of companies that sell tools and services into the market are struggling from a revenue perspective. And some of that is that the capital from the capital markets haven't returned anywhere near the force that maybe we had hoped. But I think there's another reason. And I think it's a combination of this sort of like post-COVID era where so much has moved virtually that we don't have as many opportunities to get out and do this face-to-face stuff. And we're kind of out of habit. So like, think about it for a second. If you are marketing a product to a pharma company or to a biotech, what are your channels, right? And you've got LinkedIn, I guess. You've got podcasts. You've got conference stuff, magazine adverts, you know, online and emails. And it's all this outbound. But where do you go to actually get around a water cooler anymore? How do you go and meet people, right? Conference attendance is way down at so many different conferences, right? People are so used to just doing things virtually. You can't even call someone on the phone anymore because they're not going to be at their. They're going to be at home most of the time. And so I think that there's this realignment where a lot of us haven't figured out entirely. How to restore that balance to create the kind of handshake environment that I think is really important. For getting business done in a productive way. And I don't know what the solution is. Hopefully things will right side or normalize eventually. But I do think that we've become too complacent in our digital worlds and it's making it harder to do business and collaborate in a lot of ways.

Jon - 00:21:11: Absolutely. And I can't pretend to have the solution to it either. But at least like going down our offices in downtown San Francisco, it was for a moment, I was like, oh, God. San Francisco is cooked. There's like no like empty buildings. No one's going to show up. No one's going to actually do anything in person anymore. But at least now, like it feels like it's healing and people are starting to embrace like actually what you like exactly what you described. People going out for lunch, people doing like these types of things. And you're exactly right. I think. There's nothing that replaces it. And just so incredibly valuable to have to make those connections. And. I won't jump too far ahead. But that is exactly, I think, in this day and age, a necessity that we have kind of neglected for the past couple of years. But now, you know, to get back to your experience at JBEI. It sounds like you had a lot of autonomy to just like really. Big budget, basically do a bunch of cool work. Can you talk about the work that you were doing? And then, you know, maybe a little bit about your experience working with Jay and the team and all those all-stars over there.

Rafael - 00:22:22: Yeah. So again, I was in the synthetic biology group at JBEI. And initially it was very small. It was me and my official advisor, Nathan Hillson. And we had a lab tech working for both of us. And Jay Keasling was pretty involved also, like, you know, because it was a new group. I guess our mandate was to build tools. For the rest of the organization. So we were hyper collaborative, right? We would go to, you know, each working group. So I don't remember the org chart exactly, but there were a bunch of different groups. It was fuel synthesis. There was plant genomics or plant engineering. There was a chemistry group and like sort of an informatics group. And, you know, we each had our mandates. We each had working groups under there. So it was kind of this, it was more of, I would argue like a European research institute's hierarchy, right? But each of these working groups was working on stuff and we'd go to all their seminars and be like, hey, can we, you know, how can we help, right? And so a lot of what I was doing was building giant sort of expression libraries, right? So we were interested in if you mix and match all of these regulatory, genetic regulatory elements and parts in bacterial or yeast cells, can we make them produce more of what we want? Or in plant cells, can we make them behave more how we want? And some of that was through rational design of these parts and circuits, right? And some was through just kind of brute force. So just to take a step back for the listeners, if you're not familiar with the field, when synthetic biology was kind of coming of age, and this is, again, 2010, 2011, I guess a simplification of the idea was that we could take electrical engineering principles, where you have a catalog of parts with known specifications and a manual of how you can... Recombine those parts and then the circuits the systems you build will behave according to the rules of of the engineering guide right and it falls apart in a hurry when you stick it inside of a cell but that was the idea. So we were working on building these catalogs of parts, on constructing them, on tweaking them, on figuring out their principles and properties, on recombining them into circuits. So our projects were things like, could we come up with a chemistry and a methodology and a tool to build a combinatorial library of 30,000 plasmids that all had different variations of a circuit and then just run some lab evolution experiments to have them out-compete either on terms of production or growth or whatever. At the same time, my advisor, my mentor had developed a prototype of a software. At first it was called Johnny-5. And trademark infringement. We shortened it to J5. And it was kind of biocad software, so design software, where you would have access to a library of these parts and you would insert them in various orders. And it would figure out, here's all of the synthesis and cloning that you had to do. And even here's an order, like here's a list of all of the oligos you have to order from whoever we got our oligos from in order to do it. And so we iterated this design software, both in terms of the capabilities of its design, but also... So it's outputs and how those outputs could be tied to robots. And in an ideal world that we imagined, you would basically say, I want to build a library of plasmids that have these properties, press play, and it would go all the way through ordering the damn parts, putting them on robots, building all the things, screening it, and you could get these kind of closed-loop systems. I didn't stay long enough to get it truly closed-loop, but by the time I left, I was in the high-throughput robotics lab a lot. But we solved a lot of the high-throughput chemistry. Now, this was at the... Same time that folks on the East Coast had also nailed some of this work and were starting companies like Ginkgo Bioworks. And I actually remember when Ginkgo started, their original cloning chemistry was very well worked out. It worked really well, but it was a little less sophisticated than some of the stuff we were using. And, you know, it's kind of hubristic academics. We were like, ha, they're using this chemistry and it leaves a two-base scar, blah, blah, blah. What we're doing is way more elegant. And, you know, it was elegant, but it wasn't a billion dollar company. It was, you know, lab tech. It's worth noting this was about two years before CRISPR. Patents started coming about. So we weren't using CRISPR because we were using other things. And we hadn't figured out, well, our group hadn't figured out CRISPR. The world wasn't on to CRISPR yet. But yeah, it felt momentous. We were at the age where you could start building things at massive scale. And so I got my name on a paper and a patent for the J5 software. There's actually a company called TeselaGen that licensed that tech from Berkeley and still got running. And they do, again, biocad and biological systems design in the Bay Area. And the fun part, though, for me was that it was so collaborative. I got to support the research projects of dozens of other scientists across the organization. I made some very good friends through that process. Given that I was only at JBEI for 18 months, the friendships I built there have been really durable. And they're some of the people I value most in my life in general, irrespective of our professional trajectories.

 Jon - 00:27:33: Very cool. Sounds like a really rad lab experience. And as you look back on those 18 months, what would you say are some key takeaways for you personally and professionally from that experience? 

Rafael - 00:27:45: So what was interesting to me is in grad school, I described my graduate mentors as being very kind of nurturing, but in a hands-off way. It didn't always feel that way in grad school, though, because they were always present. It wasn't until I stepped into the postdoc lab that I really felt like I had this kind of autonomy to kind of figure out what it was I wanted to do and just go do it. So a key takeaway for me is I think that that is an essential phase of any scientist's career. And not everyone's ready for it at the same time. Some people need more hand-holding in grad school. Some people need less. But my guidance to young scientists, a big part of it is choose your lab environment based on. How much either freedom or nurturing you feel like you need. Like how much handholding do you need? If you need a lot, find someone who's going to give it to you. If you feel like you're ready to run, find some open air. The second thing is that culture matters a ton. Now, there were some aspects of working at JBEI. I'm not going to lie. It would have been like HR's nightmare. It was not a PC place. It was, again, a bunch of 30-year-olds with fuck all. Like we just, we did what we wanted. It was a lot of fun. But culturally, it was like the people were just so good, right? Like life is way too short to work with people you don't enjoy working with. And so that was a big lesson was just find a place where going to work is going to be fun, where you like the people.

 Jon - 00:29:09: Absolutely. I couldn't agree more. I think, especially when things get hard and inevitably they do whatever you're doing out there. Like you got to find a reason to get out of bed and like push through it. Cause if like exactly what you said, if you're like, if you're working with people that you don't enjoy working with, you're not going to, I mean, at least you're going to be far less motivated to push through whatever that proverbial wall is. And if you don't push through, you're not going to ultimately succeed. 

Rafael - 00:29:36: The last lesson, I don't want to forget this because I actually think this is probably the most important one to what we're talking about is. Certainly at Yale at the time was no real tradition of entrepreneurship. Interestingly, my graduate advisor had started a company previously. We actually had an empty champagne bottle from the NASDAQ opening of a previous company of his. Oh, wow. But that was super rare back then. Obviously, the Bay Area, there's a long, long tradition of entrepreneurship coming out of the academic labs. In fact, some of them exist for that and probably in the MIT ecosystem similarly. But I wasn't native to that. And so it was at JBEI where I saw with my own eyes that you could finish your PhD and go start a company. You could quit without your PhD and go start a company. You could leave a postdoc and go start a company. You could do something else. And I run into this a lot now. I live in Houston, and I spend a bunch of time at the Texas Medical Center, including a lot doing career guidance. Houston is also a city that historically does not have kind of this native entrepreneurial ecosystem. It's way better now than when I first moved here. There are a lot of people very dedicated to it, doing hard work to create it. But most trainees I meet, most graduate students or whatever, postdocs. Don't know what it takes to make that jump, don't know that it's possible to make that jump, or, and this is the worst, have been taught or had it ingrained in them that Leaving academia is somehow betraying your degree. It's a betrayal of your advisor. It's a spelling out or whatever. And the big lesson from JBEI is that you can do cool science, amazing science, impactful science, maybe even better science in a private setting, in a company setting, in an industry setting. You do not have to be on a tenure track in a professor's lab to do heavy hitting science. You can, but I suspend all value judgment around that. And I didn't know, I couldn't appreciate that until the experience at JBEI.

Jon - 00:31:35: That was amazing. Because, yeah, I mean, that was my experience. I probably told this story before, but when I was like. I was doing my market research for Excedr, as one should do market research before you start a company. The way you described it was, I couldn't have said it better. It kind of felt like at least... People are, oh, you're going to the dark side. Or it felt like a betrayal to go into industry. And there's nothing wrong with going on the academic track and vying for a tenured position. But that is, in essence, like trying to get into the NBA. And there's only so many spots in the NBA.

Rafael - 00:32:11: Or even worse, it felt to me like very much like a pyramid scheme, right? Because there are only so many professorships. And my professor, my boss had one. So either you have to wait for someone to retire or having forbid pass away. I really saw this after the Bay Area when I moved to Houston and I was at a large medical center. And there were just armies and armies of postdocs, mostly from overseas, who would then just become research scientists because there was nowhere for them to go to the top of the food chain.

Jon - 00:32:38: Yep, absolutely. And yeah, I was just like, what if I just don't get there? So I was like, okay, maybe I'll like try and like blaze this path myself. But I'm glad to hear that there's now. It is becoming more common and more the academic world is at least warming up a bit to the idea of like industry and translating work because definitely it wasn't always like that.

Outro - 00:33:06: Thanks for joining us on this episode of The Biotech Startups Podcast featuring Rafael Rosengarten. Be sure to tune in for part three as Rafael reflects on his time at Baylor College of Medicine, as well as the pivotal collaborations in synthetic biology and machine learning that led to the founding of Genialis. If you enjoyed this episode, subscribe, leave a review and share it with your friends. 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.