Curiosity, Resilience & Lab Innovation: The Making of a Biotech Leader | Eswar Iyer (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 Eswar Iyer, CEO and Co-founder at Aikium, a biotech company pioneering AI-driven synthetic biology to unlock the undruggable proteome. Under his leadership, Aikium has developed Yotta ML Squared, the first AI-powered platform capable of screening a trillion proteins. Combining generative AI with large protein display technology, Yotta ML Squared enables yotta-scale machine learning to tackle diseases once considered out of reach. This work builds on Eswar's deep background in AI, multiomics, and protein engineering. He holds over 100 patents and helped launch spatial biology platforms like Xenium and Visium HD during his time at 10x Genomics. At Harvard and the Wyss Institute, he led foundational work in transcriptomics, CRISPR screening, and tissue engineering. With deep expertise in synthetic biology and AI-driven discovery, Eswar brings a rare perspective on turning cutting-edge science into real-world medicines, making this a conversation you won't want to miss. Over the next four episodes, Eswar Iyer shares how his journey took him from a curious kid in India to a biotech founder, shaped by a lifelong love of building, a passion for translational science, and a desire to make research more impactful. He reflects on the defining moments along the way, from designing custom tools in grad school to helping launch cutting-edge products at 10x Genomics, and how those experiences led him to start his own company. Eswar also talks about the realities of early-stage biotech, how Aikium came together in a down market, how the team stays focused in a noisy space, and why clarity of mission matters most when you're building with limited resources and a long-term ambition. Today, we're diving into Eswar's childhood in India, his early fascination with chemistry and biology, and how a natural curiosity for the world around him sparked a lifelong passion for science and problem-solving. He shares stories of rescuing birds, building telescopes, and blowing up hydrogen experiments in the backyard, and how nearly failing ninth grade became a turning point that reshaped his approach to learning. We also explore his early research experiences, the mentors who opened new doors, and the moment a developmental biology class completely changed the course of his career. Without further ado, let's dive into this episode of the Biotech Startups Podcast.

Jon Chee - 00:03:30: Hey, Eswar. It's good to see you again. Thanks for coming on the podcast.

Eswar Iyer - 00:03:33: Thank you so much, Jon. It's good to see you as well, and great to be on the podcast.

Jon Chee - 00:03:37: Yeah. No, I appreciate you taking the time. As we were thinking about where to start the conversation, we always like to start in the earliest days because our thesis and belief is that one's upbringing has a great influence on one's trajectory and what folks are doing today and how you are leading your business or your career. And so if we turn back the hands of time all the way back, tell us about your upbringing. What was it like? What was your adolescence like? Were there any pivotal moments that really got you into science, got you interested in business, and how did this shape your business philosophy and leadership style? Take us all the way back.

Eswar Iyer - 00:04:19: Yeah. Thanks for that question. I grew up in India in various places, so I traveled a lot. My father was in a government position, which took him to various places. We were a pretty middle-class family, as in we have values, respect money, respect hard work, things like that. Mostly, my childhood was spent as a tinkerer. I liked taking things apart and understanding how things worked. I was not as interested in reading or, at least, traditional school academics. I guess it was not engaging enough, so I always liked taking things apart and understanding them.

Eswar Iyer - 00:04:58: I used to build telescopes. We had a solar panel, so I used to try making hydrogen from water—and that created a huge explosion once. I liked animals a lot, so there were a lot of animals where I was growing up, like migratory birds. And sometimes it would be very hot, so you'd find them needing a small rescue. More than anything, I was just curious, and I was trying to bring them home and take care of them for a few days. They would get better and then they would fly away. So I had squirrels, parrots, a cat, a dog, and a woodpecker once. It was very interesting from that perspective. So I had a very colorful, interesting childhood—just tinkering, breaking things, and all.

Eswar Iyer - 00:05:41: But the pivotal point that you asked about was when I was in ninth grade. I enjoyed these outside activities so much more that I didn't pay attention. I was so busy trying to invent things that I didn't pay enough attention to my schoolwork, and I almost dropped out. I failed the grade. So that was not very nice for my parents to find out.

Jon Chee - 00:05:58: Yeah, I'm sure.

Eswar Iyer - 00:06:00: My sister was very good in academics. And, typically, academia is valued very highly in our family. So it was a very hard time, but something flipped once that happened. I was always so afraid of failing and disappointing that once it happened, I felt pretty relieved that it just happened, and the stress came down. And I was very fortunate. Of course, my parents were so supportive that I felt like, okay, I had another shot at this. Thinking about how naive and optimistic I was that life will just work itself out—I think the probability was low, but in some ways, it has worked to my advantage.

Eswar Iyer - 00:06:45: So that was hard. I think something flipped inside me, and then I started figuring out how to learn. So, yeah, I failed ninth grade, but then I got back. I slowly became good at academics. I got into a good undergraduate school in India called BITS Pilani. It's considered one of the premier places in India. And there, too, I would always do a project. There was a festival of science projects, which was across the country, and I would always take some hard problem and work on it. I was fascinated with that. I worked on bio-batteries. I worked on devices that you strap on, and then you walk, and it converted your walking motion into electricity. And I worked on an airplane that flies by flapping its wings; it was an ornithopter. Now, I guess, you can get toys, but at the time, it was not common. I was fascinated as to how birds fly, and there's a whole mechanics to it. Like, bees are not supposed to fly. So I spent a lot of time studying all of these things.

Eswar Iyer - 00:07:42: So, yeah, it was just trying to keep up with academics, but at the same time, spending a lot of my time and resources on this. In some ways, this kept me away from trouble just because I was so into all of these things that I didn't have enough time to get into trouble. So I just made good friends, and I would spend most of my time building devices, telescopes, researching things, or interning in science. So that's sort of my upbringing.

Jon Chee - 00:07:59: Very cool. I was going to say, how did your parents react when you had all of the animals coming home?

Eswar Iyer - 00:08:05: They didn't like me bringing all of those animals in. Especially, in my culture, some animals are not considered good luck to bring inside the home. Like a crow. I even had a crow once. So I had to find arrangements that only I could manage. They were very supportive, though. I had to take care of it in my backyard and sort of create a little space for it, but they were generally very supportive.

Jon Chee - 00:08:27: That's really cool. I love that. It sounds like your parents were just really embracing this curiosity, and I think that's a wonderful thing to do for someone that's growing up. And also, something you said that stood out to me was you kind of had this optimism or naivete that everything is going to work out. And I think sometimes in entrepreneurship, you kind of have to have that because if you don't and you are constantly carrying the baggage of what can go wrong—starting a company is a crazy thing. There's an infinite amount of ways the thing can't work. It's a crazy thing. You kind of have to have this blind optimism and naivete. And so I think hearing that predisposition tends to show up a little bit early.

Jon Chee - 00:09:21: But I love that you had that moment where it's like, "I need to really just shape up here," because I had the same experience. Mine was right when I got into university, and I was like, "Oh, this is what smart is. These are smart people." I felt like I was drowning. So I was like, "I'm either going to sink or swim here. I need to make a decision." But I can empathize with that. You found out earlier, but as you were starting to embrace that curiosity, and also, it sounds like you had a bunch of extracurriculars that were embracing that curiosity in conjunction with your actual university studies, did you have a lab experience when you were in undergrad, or was that something you got into later on?

Eswar Iyer - 00:10:05: I did have some lab experience when I was growing up. It was hard to come by, but I was able to convince some of my professors to give me some time to work in their lab. I was willing to do anything that was needed. One of the professors said, "Okay, we have a fleet of about 100 mice. Some studies on six mice look promising. Now we want to do this on about 100 mice or so." And again, being naive and just really hungry to do that, I couldn't see anything else. I knew I had to get experience, so I agreed.

Eswar Iyer - 00:10:46: It was harder than I anticipated for two reasons. One is I like animals, so in the process, I had to euthanize some animals, and that was very hard. It was very hard for me to reconcile those two aspects of things. I'm doing this for science. Was what I was doing really that important? Was I asking the right questions? So I had to do a lot of self-introspection. And it was also just physically and mentally very hard to do. I had to sacrifice a lot of time away from my friends who were perhaps partying or doing other things. And sometimes you're coming out, and you have the smell of the animal facility, which is sort of ammonia-like. And you don't realize that because you've been there for six hours or whatever working on this.

Eswar Iyer - 00:11:38: Then, as part of my undergraduate, BITS Pilani is a very, very good school. They arranged a six-month internship in industry. So I worked at the Industrial Toxicological Research Institute, ITRC, for about five or six months, which was very nice. I also worked in a manufacturing facility for dental and oral hygiene. There was a two-month internship where I learned about QC and how things happen. So, yeah, I think I had some experience. Perhaps I've seen some people getting a lot more extensive experience nowadays with the latest technologies, but I did my best to do what I could.

Jon Chee - 00:11:58: Yeah. And I look at folks who are in grad school now, and all the stuff that you had to do manually... I feel like I was living in the Stone Age. I was like, "Oh my god. What? You guys don't do gels manually anymore? Everything is automated? Everything is a liquid handler now?" I would just pipette it, and now everything is just automated. I was just like, "You guys live in the future." I'm so jealous. But I totally think those early lab experiences are absolutely hard. When you come out of the lab, it feels like a bubble, and you come outside and all your friends are just like, "Where were you?" I was like, "I've just been running samples and managing cell lines for ages right now. I don't know where I am."

Jon Chee - 00:12:44: But from this formative experience, and it sounds like your university kind of lined up some industry experience too as you were approaching graduation, were there any specific mentors, professors, or colleagues that really influenced you during undergraduate or maybe took you under their wing?

Eswar Iyer - 00:13:05: That's a great question. There were certainly some professors that influenced me a lot more than others. Generally, when you're trying to figure yourself out in undergraduate, sometimes the subjects are interesting, and sometimes it's also the person who's teaching it. They can bring that whole subject to life. There are many people who made a difference to me. I would say my first and foremost mentor would be my father who, again, saw my potential and saw that, okay, I'm not doing well in academics, but there's something here. And he was an academic himself, and he sort of mentored me in a manner that really helped me see value in some ways.

Eswar Iyer - 00:13:46: But besides that, in undergraduate, there's a person called Ashish Das. He was teaching developmental biology. I was not interested in biology at all. In fact, I wanted to build these mechanical things with gears, motors, new-age batteries, and all of those things. But then I took this class on developmental biology, and everything changed. It was so fascinating that a single cell can grow into this organism, and it felt like a different kind of—almost an alien—engineering technology that was light-years ahead of where we are. Here we are trying to make these things with crude gears and things, and here are things that just self-assemble, self-organize, and grow, almost like soft robotics. I'm even using these terms because of the evolution that I've had. I didn't even have these words, but it just seemed so mystical and so complex and so elegant and beautiful and so engineering-oriented that I just got completely drawn into it so much that it guided me into doing my PhD in developmental biology later on.

Jon Chee - 00:14:42: Cool. That's awesome. I had the exact same moment, where I had a formative high school AP biology teacher. And sometimes it is just the mentor or the teacher that can make it come to life, it seems. Was it a similar thing for you where this teacher just showed you how cool it could be and created that initial spark?

Eswar Iyer - 00:15:06: I would say so. I think when you make somebody wonder about what's beyond the books, it really sparks something. It sets you ablaze. Many professors would come and they would start drawing things on the blackboard, and then they would start talking. And some of them are very popular. I just couldn't figure out why. But some people just have a way of creating curiosity or fostering that curiosity by saying, "Here are all the things we know, but there's so much more that we really don't know." And kind of laying that out rather than just saying, "Hey, we know all of this, and there's A, B, C, D." That, to me, just felt like, "Hey, this is interesting, fascinating. I just want to learn more."

Jon Chee - 00:15:46: Yeah, absolutely. And I think I felt the exact same way with the former, which you described of just, "Here's what we know, memorize it." I was just like, "Uh, this is a drag." But exactly that latter what you described of, "Here's what we know, and here's what we don't know," or "There's a ton that we don't know," and creating that sense of wonder... That style can also be transferred over to when you are outside of the academic setting. To get your team or your company to have that sense of wonder, of discovering adventure, is a powerful thing because you also have to keep your team fired up and curious and inspired. But if it's just this rote to-do list, you'll never get anyone fired up. So I love that style of teaching and, honestly, kind of leadership.

Jon Chee - 00:16:39: So as you were approaching graduation, did you know that you were eventually going to do graduate studies? Where was your head at? Were you contemplating going into industry? Take us through your mindset then.

Eswar Iyer - 00:16:50: Again, this naive optimism and deep interest and passion and curiosity predisposed me to certain kinds of things. I wanted to be an innovator. In other words, I guess I can articulate it better now, but I couldn't then. But I wanted to create useful things that would be helpful to people, that would be helpful to society in some way. And that's really where I wanted to be, and I knew that scientists are the people who can be curious and still invent or innovate new things. And I was told you have to do a PhD. So with that very limited information, I figured that I had to do a PhD.

Eswar Iyer - 00:17:41: So I didn't apply for any jobs. A lot of people were applying to and interviewing with many companies. I might have sat in just one interview, which I probably did really poorly in. So I kind of just assumed that I was going to go do this PhD. And it was hard, as in there was not a lot of information available. It was clear I wanted to go somewhere where I could do more inventive things. I knew I was not good at many things, but I knew there was one place where I had a shot at being good because I really just enjoyed myself doing those things. I couldn't even say that I was good at it, but I just knew that I could think longer and harder than many of my peers could. And I could just sit there and be lost in solving the problem. So I knew that was likely my place. And someone told me, "If you don't want to work all your life, find something that you are passionate about." So all of these things, in my state of mind, seemed like they were converging on one place. The question was, who was going to give me an admit? Figure that out, and then we can think about the next steps.

Jon Chee - 00:18:33: Yeah. Yeah. You said it pretty succinctly. You understood what you were not good at, but you understood your strength of being able to just think longer and harder about a given problem set. But that seems to really align with a PhD. Even though that was your only thought, all these other options just don't seem like a fit. "I'm just going to go for this." And people always talk about creating optionality, like having a backup to your backup to your backup. But sometimes if you just hunker down and focus on a specific path, you lean into your strength. And sometimes it can work magic, and it seems like you found that affinity. Now talk a little bit about actually getting into a PhD program. How did that opportunity come about? What were you looking at? What was your approach to that?

Eswar Iyer - 00:19:25: You know, again, there was the internet, but it was not as clear. And I did not have as much information as perhaps I would have liked to make good decisions, but I did apply to a bunch of schools. Some of these I realized, geographically, would not be the best place. And I got into George Mason University. That was really good, and there was another advantage there. My sister was also doing her PhD there. So my parents preferred it. "You know, you'll have somebody in a new country. You'll at least have somebody you know." So that was also appealing. So all of those factors converged on going to George Mason, which is a great school. I mean, it was still new for biology, better known for law, but I was very fortunate and grateful for the opportunity that they provided, and I learned a lot in that space. So that's how that opportunity came about.

Jon Chee - 00:20:19: Is your sister in a similar field of study or a completely different one?

Eswar Iyer - 00:20:24: In a similar field. We did our undergrad at the same school, and she was a few years ahead of me. And so she was in biology, and she was working on HIV with a professor at George Mason University. So that was very helpful. When I went there, I asked her, "Hey, who should I work with?" And she said, "Hey, these are the people that are good, and you should try to find a way to work with one of them." So that was very helpful.

Jon Chee - 00:20:50: That's like the stars aligning. You kind of have the playbook or a rubric ahead of time. That's pretty cool. And so moving from India to Virginia, how was that experience for you personally and maybe professionally? It's a brave new world. Can you talk about what your experience coming to Virginia was like?

Eswar Iyer - 00:21:10: Yeah. I was aware of some of the cultural elements in the US, and I was very excited to come. But when you experience it, it's different. It can be hard. Culturally, it can be pretty hard for someone who transitions from a different country. Speaking English was not as bad for me, and again, I've been very fortunate throughout my life. I had my sister, so I had someone I knew closely who I could lean on. So I was a little less stressed than if I had had no one. So that buffered things a little bit.

Eswar Iyer - 00:21:49: So it was new. It was exciting just trying to figure out the cultural differences, the communication styles. For example, the culture I come from, it's not considered very good to speak about yourself or sort of promote yourself in any way, whereas it could be seen as not very good if you're not able to talk about your accomplishments or achievements in some way. There are subtle things that I had to learn about. These are, I guess, common when you make the transition.

Eswar Iyer - 00:22:18: But overall, it was really positive. What was nice was everyone was very welcoming and understanding of the cultural differences, and George Mason is a culturally diverse school. It has such high diversity that I didn't feel that out of place, to be honest. So it was very welcoming. And now, after almost two decades, Virginia feels like home in a way because I spent all this time there. So, interestingly different, but I was fortunate to have some buffer, and everyone was quite welcoming. So that made it very nice.

Jon Chee - 00:22:40: That's amazing. Yeah. My parents, they moved from Asia for grad school. They first ended up in Texas. And it was definitely a cultural shift, but my parents always talked about how Texas still feels like home in a way. And then, ultimately, I ended up in the Bay Area from my parents moving for grad school, and I haven't really left since. I've just been in the Bay Area. But, yeah, it's kind of this thing where, exactly what you said, especially in these kinds of university settings, they tend to be pretty welcoming and diverse and embracing of cultural differences, which is really cool.

Jon Chee - 00:23:18: So now you're at George Mason. You're starting to embark on this PhD journey. Talk a little bit about the lab that you were in. How did you land in that specific lab? Whose lab was it? And tell us about your research.

Eswar Iyer - 00:23:32: Once I was there, I was trying to figure out my PhD lab, and my sister told me, "Hey, these are a few places that you should look at." And I was thinking of joining the lab that my sister was at because that seemed like a good lab, and she was excited. She talked so much about it. But when I approached that lab, it seemed like, "Okay, why don't you do some more rotations and then consider this?"

Eswar Iyer - 00:23:56: And I rotated in a lab by a person who had invented this technique called laser capture microdissection, Professor Lance Liotta and Professor Emmanuel Petricoin. They were experts in proteomics. They had deep expertise. The lab was really well run. And I was very, very fortunate. They took me in. My mental state was that I was willing to do anything. Like, I was willing to clean the floors, wipe the tables, as long as I got to learn. So I had no qualms, no assumptions. I just was so excited that this was like my dream come true. I was like, "Okay, I get to do science in a serious setting now where these experts are doing things." So I was very excited.

Eswar Iyer - 00:24:43: Virginia Espina, or Ginny, took an interest in me. She showed me the different tools and techniques, and the lab heads, Dr. Petricoin and Dr. Liotta, were also very friendly. So I had a very productive six months there. They, in fact, showed me some of their new tools, trusted me enough to actually work on them, and I kind of learned a lot. I also did other things, everything from cutting tissues to doing some basic maintenance, doing ELISAs. All of these, almost a decade and a half later, became very useful for a different thing. But, you know, just cutting my teeth on all these techniques in a professional environment... It's funny. The first time I was entering the lab, everything was so clean. I asked them, "Should I take my shoes off and come in?" I almost thought it was a deep-clean room. They were so surprised by this. But they said they thought that I must be very careful, but I was very naive.

Jon Chee - 00:25:32: I love that. "How is it so clean in here? This is crazy."

Eswar Iyer - 00:25:36: I didn't want to bring my shoes that came with dust because who knows how it might impact things. So they kind of appreciated that. I didn't realize that, but I heard later they appreciated it. But they were very, very welcoming and kind, and I got to learn a lot from Ginny. And this relationship later helped me in a different way.

Eswar Iyer - 00:25:56: And then I worked there for six months, and then I was looking... I still hadn't quite figured out the right lab. This lab was still pretty mature and large, but I wanted to work with someone who could spend some more time and give me some space. And, fortunately, I saw someone present in one of the meetings, and this person was called Daniel Cox. He was a new professor. He came from California. He was wearing his baseball hat and some shorts, and he was working on Drosophila. And I thought to myself, "Who works on Drosophila? Is there any relevance to that in life? Why would somebody work on Drosophila?" I was so wrong. That was my ignorance at its peak.

Eswar Iyer - 00:26:47: And then I went and spoke to him. Someone said, "Hey, he's really good," and I spoke to him. After I spoke to him—and that conversation ended up being a couple of hours—I knew that he was the person. He showed me around the lab. And besides all the things, he opened a drawer and said, "You know..." and it had a bunch of tools in there, small tools for tinkering. I was like, "Okay. This is perfect. This is my place. It feels like home." I can do science. There are tools. And we did such amazing science just with Drosophila. You can get down to some very basic neuroscience questions in such a precise manner that this became a foundation for a lot of the inspiration that I got for things later.

Eswar Iyer - 00:27:31: So I was very fortunate to find Dan Cox. He was relatively new in his tenure. He just joined, and he spent a lot of time mentoring and giving me the space to do what I wanted. And I was just very happy being in that lab. I think one of the things that I remember telling him was, "I'm not worried about how long the PhD takes. I just want to do some good work." Again, I was just very naive, and I just wanted to get down and do things. I was not thinking of how to finish my PhD fast; I just wanted to do something that was meaningful. And he gave the environment, he nurtured it, so that I was able to thrive there, and he supported that really well. So many people are miserable in their PhDs. I cannot even tell you. This is luck. You just never know. And I was very fortunate that I worked with Professor Daniel Cox, who's done very well for his career. But, yeah, that was how I found my lab.

Jon Chee - 00:27:58: That's really cool. And I've heard a story where you kind of have to just put yourself out there and get that exposure. It's kind of like knowing what was not a good fit. It really is a combination of luck, but also just trial and error. You don't know until you actually get into it, and you're just like, "Oh my god, this is not a fit for me." And sometimes people just slug it out and grit their teeth and get through it. But I think I love that you were able to find that space for you that really, again, is leaning into your strength: giving me the space to just explore and think about problems and tap into this curiosity. And I love that he just embraced that. And it sounds like this lab was pretty brand new. How big was this lab? You almost had a startup experience in a PhD academic setting.

Eswar Iyer - 00:28:47: That's a great way to put it. It's amazing how you're articulating that. It was like a startup experience. Now that you mention it, it seems very obvious, though I may not have naturally put it that way. But, yeah, I was his second graduate student.

Jon Chee - 00:29:00: Okay.

Eswar Iyer - 00:29:01: There was a graduate student before me, Mykola Sokolskyy, and essentially, it was just the two of us in a pretty open space. We had to do a lot of things from scratch. There were some cool gadgets that were available that we could play with. There was not a lot of money, so we had to do everything by hand. So it taught me hard work, humility, curiosity, and building, all of those things at the same time.

Jon Chee - 00:29:22: Oh, yeah.

Eswar Iyer - 00:29:23: So it was like a startup experience. You have to be resourceful. Oh, yeah. That resourcefulness... I think a lot of opportunities came. For example, one of the processes they were doing, which was very important for the lab, was very inefficient. You had to take tissues and put them on a glass slide and process them, and 70-80% of the tissues would fall away. And you would have spent days doing this, and you lost them. And one day I was teaching this to someone, and I felt like, "That's silly. I should just improve this." So I made a device that retained them almost 100% of the time, and that became my first patent. Someone said, "Hey, you should file..." So sometimes these opportunities are created by being in a space that is welcoming and open. And yet, too many resources are not always conducive to creativity because you're always thinking, "What can I buy that'll solve this?" I'm not saying it's a bad thing. Sometimes just being pushed into a corner and saying, "You need to be really better. You have limited resources, and you need to do this 10x better. Go figure." And those skills definitely play out when you're doing startups and other things.

Jon Chee - 00:30:27: Yeah. No, spot on. That was the exact... I mean, that's the reason why I started Excedr. I've had experiences in well-funded labs and experiences in not-so-well-funded labs. But the spark for Excedr came from the not-so-well-funded lab. And I think I've told the story, but I was tasked with running samples up to the flow core. You're on the Berkeley campus, so you know Stanley Hall has the flow core at the top of the hill. I was down at PMB, so almost down by Shattuck.

Eswar Iyer - 00:30:55: Wow.

Jon Chee - 00:30:56: And so every day, I'm just running up that hill. And there was a waiting list. You sign up for the waiting list, and you're like, "This is how high-performing labs operate, where you're running samples up to the flow core and just waiting." "I need to come back," and it just took forever. So it's kind of this thing where we couldn't afford to have our own flow cytometer, but I was trying to figure out how we could create a financial product to enable folks to get the tools that they need. But it all came from the constraint. It all came from the constraint of not being able to afford it. I was like, "We've got to figure out a way to afford this thing."

Eswar Iyer - 00:31:31: Thanks for sharing. I guess it's not always as obvious. Sometimes the worst challenges that you have are seeds for opportunities. Exactly. Because you'll never be creative and figure things out otherwise.

Jon Chee - 00:31:42: Yeah. You'll never, because it's kind of like if you have $100,000, you just throw it at the problem. You're just going to try to make it go away, and that's not very creative. But there's something to be said about if you can harness that creativity that constraint imposes on you and then have resources but maintain that creativity, you can really start doing crazy things and incredible things. But I found that constraint is oftentimes where innovation bubbles up. Because, again, there are probably other labs out there or people who are in a similar constrained situation. And if you're feeling it, they might also be feeling it. Kind of like you said, "Maybe I should just patent this, and it could be used by other people. This might actually be useful." So I love that. And so it sounds like you were basically leading a startup academic laboratory. Could you tell us a little bit more, as this lab started to grow, what were some pivotal challenges and triumphs for you during this PhD?

Eswar Iyer - 00:32:42: As the lab grew, we applied for more grants, and Dr. Cox was very resourceful in getting funding. This lab got pretty reasonably well funded. We went from the first year having very low resources, almost nothing, to being able to afford pretty good experiments as we evolved. So that was a really good growth to see. I guess the first pivotal moment was me figuring out a solution for a common problem and inventing that.

Eswar Iyer - 00:33:07: And I have to say, there's another professor who influenced me quite a bit in the same ecosystem, Dr. Ancha Baranova. She was a professor who was teaching one of the courses in biotechnology. And that's when I was starting to understand, okay, there's biotechnology, there are companies that do things, and there's academia. But typically, academia makes you feel like biotechnology is this dry place where you just do things. But she was very resourceful. I learned a lot. And when I mentioned to her once that I had made this device, she said, "Hey, you should patent it." And she immediately set up a meeting with the patent office. That really helped me. That is how I basically got started with my first patent. If she had not promoted it and my PhD adviser had not supported me, I wouldn't have perhaps even had my first patent. I didn't think it was worthy of patenting, personally. I just thought it was a thing that I would just whip up in two hours. I mean, that's not so important, right? But somebody else saw the value. So that was one pivotal moment—to see, okay, I can create something that's interesting.

Eswar Iyer - 00:34:11: The second was an important challenge. Everybody was trying to study cells at a tissue level, but this new technology of isolating single cells from my rotation in the laser capture microdissection lab... My PhD adviser was interested to see, "Can we isolate single cells and do profiling of them?" I have to highlight and say this was quite ahead of its time. Single-cell and spatial is becoming a thing now. Now I realize how valuable that was. It doesn't matter. It might have been in a school that might not be Harvard, but they were doing some cutting-edge science. And he could see that spatial reasoning is super important. And so he kind of—he knew that I like these hard problems—and he said, "Do you want to try this out?"

Eswar Iyer - 00:34:55: So that was perfect. I could go to my previous lab where I had interned. They were kind enough to give me access to a new instrument, which was very expensive. They trusted me with that. My task was to figure out how to cut single cells that are single types of neurons, isolate their transcriptome, and amplify them without bias. And doing a microarray was the thing back then. Next-gen sequencing had not come out yet or was just barely getting innovated. I learned so much fundamentally from that space. I could talk a lot about that, but it was really challenging.

Eswar Iyer - 00:35:21: In fact, once I was doing this technique, it seemed to work the first time, and everybody got excited. "Let's do more." And once I started doing more, it never worked again.

Jon Chee - 00:35:28: Yeah.

Eswar Iyer - 00:35:29: And it was really, really embarrassing. I knew it worked the first time, and I could get it to work. I could cut the cells. And then after two months or so, I was starting to think, "What's happening here?" Luckily, I had made detailed notes of everything, and I went and looked at every parameter. And then, late one evening, I was working and got really frustrated, and I needed to take a break. And I went outside because it had started to work, and then it stopped working again. And I went outside, and I realized that it was fogging up, and the humidity was increasing. It could be something to do with the humidity. Then I ran, and the next day, I got a humidity meter, kept it in the lab, and I realized it was correlated with the humidity—when it worked versus when it didn't. I was able to crack the problem.

Outro - 00:36:13: Thanks for listening to this episode of the Biotech Startups Podcast with Eswar Iyer. In part two, you'll hear how Eswar's time in grad school shaped his identity as a builder, whether he was automating image analysis by hand, machining custom lab parts, or designing tools to accelerate research at scale. He also shares how a cold email and a few lucky coincidences led him to the Wyss Institute at Harvard and why that experience changed the way he thought about science, translation, and technology. If you're enjoying the series, be sure to subscribe, leave a review, and share it with a friend. Thanks for listening. 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.

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