Breaking Moore's Law: The Multiplexing Revolution | Eswar Iyer (2/4)

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.

In our last episode, Eswar Iyer shared how growing up in India sparked a deep curiosity about science and how key moments—from backyard experiments to a transformative high school summer camp—shaped his early path. If you missed it, check out part one. In part two, Eswar talks about his time in graduate school and how it 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 breaks led him to the Wyss Institute at Harvard and why that experience changed the way he thought about science, translation, and technology.

Jon Chee - 00:01:17: I love that. I have similar experiences like that too. It wasn't humidity, but it was the electrical currents in the building that I was referring to. I was in this old building called Tolman Hall, which is not there anymore because it wasn't seismically retrofitted, so they had to knock it down. My lab doesn't exist anymore, but the electricity wasn't solid in that building. So sometimes, the electricity just wasn't consistent. I was like, what is going on? Everything in the method is the same. Why is everything—I love that. You go outside and you're just like, "Oh, it could be an environmental thing." Sometimes, because you're so heads-down, you're triple-checking everything, but it's just something external. It's hard to consider. So, stepping out from these problems, changing the context, or just changing your frame of reference is always important. I love that.

Eswar Iyer - 00:02:14: Totally. Totally. But that was very pivotal because that helped me now get single cells, crack the problem, do profiling, and then I developed another method to profile these cells. Now we were able to profile them and understand what's happening inside. That opened up a lot of data; suddenly, I had to learn how to do data analysis at a scale that was much larger than I had ever done. It opened a lot of theses and a lot of projects for other people. So it became a pretty important moment for me and others. That was one moment.

And then the other was, we profiled them and we found that there are a lot of transcription factors expressed in one type of cell. Nobody had seen so many transcription factors being expressed. You usually think each cell has one type of transcription factor that turns it on or off, but there were hundreds of transcription factors expressed at different levels, so it was almost hard to believe. No one wanted to publish the paper. The only way to prove it was to knock it down or turn it off one at a time and then see if the neuron's phenotype changed. That was a massive undertaking because you had to do all the screening and so on. That process was not scalable because you again had to do this artisanal cutting of the tissue, staining it for a couple of days, and then imaging it.

So that made me think, "Hey, can I not take a live animal that's expressing GFP, put it in a confocal, and image it?" It didn't seem viable at the time because animals move. There are a lot of issues. But I figured that if I could anesthetize the animals with chloroform and some mixture of imaging oil—if I mixed it, the larvae are alive and I'm able to image them with almost perfect signal-to-noise. It was too good. That was another pivotal moment that helped me crack that, and I was able to now get almost 100 times more data than I would have gotten by other methods. I got all these tons of images, and that was a big moment.

But then I was like, "Okay, how do I quantify these?" I didn't have any tool to quantify. Typically, you have to quantify these neurons by hand. You trace them, and it takes a couple of hours to trace each neuron, and then you ask how many dendrites have increased or decreased and so on. That forced me to then think about how I could solve this with image processing. I dabbled with ImageJ and I figured out and wrote a series of pipelines that could actually quantify this as well as humans. So that was another major pivot point. That improved the throughput by almost a thousandfold. What would take four hours now took maybe six seconds or so. It was such a joyous moment just to see what was taking me four hours, and I could just sit in front of a computer splashing every second. It was so pleasurable.

Jon Chee - 00:04:49: That's amazing. I'm just thinking about these kinds of experiences in the lab, and I always talk to my parents about it. They weren't in the lab, but they just assume everything's super efficient in laboratories. But what you're describing, there's a lot of things that are still done by hand. It is far less efficient than what it might seem. The fact that we actually get medicine approved when there are still all these manual processes to get there is just like, "How? This is like a miracle." I love that. I've always been fired up about finding efficiency gains within the lab because, at the end of the day, the patients can't wait. Time is of the essence. So what can we do to make these very manual processes far more efficient? So I love that you're working on that. I mean, you have multiple—did you patent this too? No? Okay.

Eswar Iyer - 00:05:46: I just wanted to solve a problem that was deeply bothering me.

Jon Chee - 00:05:50: Yeah, yeah, yeah. I was gonna say, you're just building a patent portfolio in this PhD program. Very cool. And so as you're wrapping up your PhD program, did you know what was next for you? What were you thinking?

Eswar Iyer - 00:06:02: Yeah. It was a very interesting and important time, I would say, because as I was finishing up my PhD, it was a lot of deep science, but I knew by this time that I was better at building tools. I also wanted to build tools that accelerated perhaps 100 people rather than just be very good at one science or biology because I knew the context changes so much. In engineering, what Newton discovered still holds true. But in biology, whatever someone discovered a couple of years back may or may not be true. So I really wanted to be more engineering-focused, which accelerated things. That pushed me to ask how I could go in that space.

I did a few things that were sort of crazy. Of course, I tried to reach out to a bunch of people. I wanted to learn more about machining. There was another problem that we had. We had to grow all these animals, and you had to time it precisely to collect the eggs, then you have to heat them and cool them, and then you get these larvae. So I started building an automation to do this. I had no idea how to build an automation, but I found an inventor's club. They had a machine shop. I made friends with the person running the machine shop, and I made a deal. I said I'll help him clean the machine shop if he can teach me how to machine things. He was a very talented machinist. His name was Sandor. He took a liking to me, and he started teaching me. He said, "Let me teach you how to make a hole first." I thought, "I know how to make a hole. Come on." "No. Do you know how to make a hole that's a thousandth of an inch in precision and then three holes that are a thousandth of an inch in precision from each other?" I was like, "Oh, no." He started with that, and then started teaching me all the things about lathes and mills and other things.

So I really learned a lot. That way, when I was working on a microscope, if I needed a part like a microscope camera adapter, I could just look at it, and within a couple of hours, I could go build it on the lathe with some very crude measurements, come back, and it would fit really well. Whoa! Right? Otherwise, you don't have parts. You can't buy these custom parts. So I was starting to become good at prototyping my own ideas rapidly with microfluidics or some imaging image-based analysis and all these things. But I knew that biology was not the thing, so I just didn't know what would happen. By this time, I thought, "Hey, I think I should be applying for a job, you know?"

Jon Chee - 00:08:17: Yeah.

Eswar Iyer - 00:08:18: I applied to a few jobs, but maybe the biotech market was not great or maybe I didn't apply well. I didn't really get a lot of traction. But I did that just so that I ticked that box for saying I applied to some jobs. But really, my heart was at the place of developing more tools and doing something more challenging. Like, "Okay, I've already failed. Everything else is a bonus now. If you are not fearful, what is something that you could do? If you're not worried about just publications or things, you could really spend a few years. What could you do?"

As I was dreaming about that aspect, I thought, "Wouldn't it be great if I could build a human brain-like tissue on a microfluidic chip for drug discovery?" I knew a lot of large pharma companies were backing out from neuroscience because you test these drugs on animals and they don't always pan out. Animals can be fine. They can drink sewage water and mice or rats would be fine. We will not be, even though we are pretty similar. So there are differences in how we process things, metabolize things, and so on. It was very compelling for me to think about this.

I also learned about a place called the Wyss Institute at Harvard. The way I learned about it was I bumped into somebody in the corridor at the Krasnow Institute, which is where we were at George Mason. This person was talking about a lot of people, and he said, "There's this person called George Whitesides, and he's brilliant. You should look him up." So I looked up George Whitesides, and later found he's the most cited living chemist ever and has created companies worth billions of dollars. But what appealed to me was that some of the ideas were so simple. He talked about an egg beater as a centrifuge in resource-poor areas or using microfluidics on tissue paper just by printing some channels with some lipid. I thought that was very appealing. Rather than being stuck in academic circles where you're thinking about only the hard problem, which may take long to translate, you're doing that, but at the same time, working hard to translate that. I really wanted whatever I did to translate rapidly.

So I learned about the Wyss Institute, and I wrote to the director of the Wyss Institute, Dr. Don Ingber, saying, "Hey, I want to build a human brain on a chip, and I have some ideas." I didn't expect him to write back to me. Here's again where I got very, very lucky, and this is where you never know how connections work. I wrote to him. I never expected to hear back, but I went to my old lab by a twist of fate, which is a long story. I went to the old lab that I interned, where the person who had invented laser capture microdissection worked. I went and said hi to my old mentor, Virginia Espina. I told her, "Hey, I'm doing this and applying places." She said, "Oh, go speak with Lance Liotta. He's the lab head, and he might give you some ideas." She was able to pull him and make him talk to me. After I described everything, he said, "You know what? The perfect person for you is Don Ingber." I was like, "Okay." I was like, "You know him?" He was like, "Yeah." He was very kind enough to give a strong referral, which I think made them look at my application, and that basically landed me a job at the Wyss Institute.

Jon Chee - 00:11:25: That's so cool.

Eswar Iyer - 00:11:26: You never know how these connections work, but again, I didn't expect anything to come out of this small few months internship. But I was very fortunate, again, thanks to the people taking faith in you sometimes. So there at the Wyss Institute, I joined the Harvard School of Engineering first. I was at Professor Kevin Kit Parker's lab for about a year, and I was building the human brain on a chip. Actually, I was trying to build a human amygdala on a chip. So I learned a lot of engineering tools: How do you nanofabricate things or microfabricate things? That naturally led to the evolution of my thought and saying, "Okay, engineering..." I learned a lot about how you read and write into the biological system: growing neurons on microelectrode arrays, constructing your own cell culture chambers by going to the fabrication facility. I learned a lot more machining there. I got certified by the Harvard machine shop on using their equipment, laser cutting, 3D printing, just rapid prototyping things. All of that really helped me prototype a few things. But, yeah, then I moved into Professor George Church's lab. That's a different story in itself.

Jon Chee - 00:12:30: Okay. I guess there are a couple of things that really, really stood out to me. One, you were commenting about how you just never know how people know other people and these connections. It's like, there's that six degrees of Kevin Bacon. There's a certain amount of separation where you'll eventually get connected to Kevin Bacon, but it's kind of this thing where the scientific community is pretty small. And, you know, you talk about how you're just like, "I just wanna learn. I'll do the cleaning in the machine shop, in early labs." That's what it takes, and people are really willing to embrace you and teach you. It's kind of like, "I'll do the laundry. I'll take the trash out," whatever it may be. And people are like, "Awesome, because I don't wanna do that. But let me show you some things." It's a good trade. You don't have anything else to contribute. But I think if you're willing to roll up your sleeves and show that willingness to do it, you will just be surprised at how much people are willing to show you the ropes.

And I love that, one, there's also an element of this, like, put good out there and just don't make it a transactional thing. Just put good out there, do hard work, be curious, contribute where you can, and then ultimately, the universe pays you back. Right? You can't predict it, and you don't know when or how or whatever, but just if you put good out into the universe, eventually, the universe pays you back. I think that's my philosophy, and it seems to have kind of unfolded that way for you.

Eswar Iyer - 00:13:55: Yeah. I think you've said it so beautifully. That's really my philosophy as well. Whenever I have done things without any transactional interest in mind, not expecting a result or outcome and just doing it because it is the right thing, typically, sometimes after five, six, seven, eight, ten years, it's come back much more. There are so many stories I can share, but that's my belief too.

And part of this willingness also came—I can't really say I'm such a humble person that it just comes naturally. Failure, early failures, when you're trying everything but still perhaps not exceptional in one aspect, but some other aspects come naturally to you where you're significantly above average. Because you failed so much, you know that you can't take things for granted. You kind of know you're good at some things, but not very good, and you're also grateful for the opportunities people are giving. So that makes you more willing to learn. Yeah.

Jon Chee - 00:14:51: Yeah. Absolutely. There is a certain amount of gratitude. So you're just like, "Oh, man. I suck. Please. Please. Anything here, it's only up from here. It's only up." And it goes back to your early ninth grade. It goes all the way back. You're just like, "I've experienced rock bottom. It can only get better here. All I need to do is just put in the work."

Eswar Iyer - 00:15:14: And all I can even say for that is you're just so lucky. There are so many people who are smarter than you and can do better in things. Again, just being grateful that you have the opportunity. Here's the thing that I realized, I guess, that I can articulate better now than then. I could feel it then, but I can articulate it better now. Life does not really guarantee anything when you're born. There are so many kids without any opportunity. Sometimes without a limb, without parents, without things. We are seeing war everywhere. If you get certain basic things, you're super lucky. You can't have a sense of entitlement that "I'm here, so I need a, b, c, d."

So being very flexible is a very important aspect of my philosophy because everything can be gone in a minute, and you just have to be grateful. You're here for a very short time. That helps me see things in a slightly different perspective, and my experience has always been aligned. My experience has shown that, and now I'm able to see it with that philosophical mindset as well. So, yeah, put good in the universe and don't expect it, and sometimes—sometimes you do have to be transactional. I'm not saying you cannot be, but the best outcomes have been when it's not been transactional.

Jon Chee - 00:16:20: I couldn't agree more. And I think you said it really eloquently. It's kind of like, yeah, you're here for a short time. Life is comprised of these moments in time. And having that gratitude for what you have is so critically important. Exactly what you said: just keeping in perspective, there are so many others who are not as lucky and always remembering that and not feeling that entitlement. "I deserve this." Because exactly as you said, the universe can also, in addition to bringing awesome things to you, bring terrible things that are out of your control. You live by the sword, you die by the sword. It kind of goes both ways.

Eswar Iyer - 00:16:54: When good things come, we never say, "Why did I get a good thing?" But when bad things come, we say, "Why did it happen to me?" Yeah. Perhaps, in some way, none of us are special. Perhaps, we're all very special. The fact that we are living on this small planet, in this life, in this biochemistry that's all happening is very special, and not very special in the sense that anything can happen to you as much as the probability for anybody. So being appreciative of that is important. And also not being too harsh in judgment toward others. You know, in a coin flip, we could swap places.

I think being aware of that—I'm not saying that's true in every sense. We have willpower. You can exert that, and you can take actions. You do make choices, and you have consequences. That's a fact. But there's another element to it which may not be in your hands. But we mostly like to judge people based on that angle. That may be a force multiplier that can be sometimes as much as 100%, where you know exactly if you went and picked up a cup, you're going to get the cup. And sometimes we have almost zero control. You can't stop the sun and moon from rising. At least not yet. Right? We are getting better and better. So somewhere in there, for every opportunity, your will can make a small difference. You have will because you're made up of the same elements as the universe, and you get to exert that. But being aware of that and knowing that there are other forces at play that may not be—it could be so many other people. There's someone who might have just been nice to you and taken a bet. You may not even have known this. I think that perspective is important. That's very important for me to function.

Jon Chee - 00:18:21: Yeah. Absolutely. And something too is giving people grace. I try my best to remind myself that there's always something else going on in someone else's life that you're just not privy to, that there's a bunch of external things, and just give people grace. If an interaction isn't how you like it to be, I just try my best to assume there might be something that I am not aware of on the other side, and it's okay. We'll try again another time. We'll try again another time when, hopefully, things might be better. And rather than just, "Oh, they're trying to attack me" or whatever it may be. Just try to give a little bit of grace because it's always a good reminder, remembering that as much as the universe can be nice, it can also be cruel. If you understand that and try to remind yourself, it kind of puts it into perspective.

Eswar Iyer - 00:19:07: Totally. Someone I respect said, "Every good has a little bit of bad. Every bad has a little bit of good."

Jon Chee - 00:19:13: Yeah. That's spot on. And so this first role at Harvard, you know, you're doing your brain tissue engineering, and then you mentioned that there's another story of heading to George Church's lab. When did you know it was time to leave that current lab, and how did the George Church opportunity arise?

Eswar Iyer - 00:19:31: I was working at this lab, and internally, I knew after some time that perhaps it was not the best fit. It was not how I expected it. It was great to learn all the engineering tools, but the key insight I had was biology is self-assembled, whereas engineering, in some ways, the mindset is to 3D-print it into something. I'm not saying that's a bad idea and so on. But to me, I found the idea of self-assembly more elegant. So I started thinking about what the minimal set of conditions are by which I can grow a brain into its structure or an organism, coming from a developmental biology background. So I liked the tools, but I was philosophically finding that. That was sort of happening where I couldn't see myself fitting as well in that. I'm trying to build a human amygdala by printing these cells and so on. There are a lot of other things going on. Technically, it was extremely complex.

But I was in the streets, actually walking in Kendall Square, when I saw George Church walking by. It was very serendipitous that I started talking to him. It ended up being a thing. Actually, there's a backstory to this. I admire George Church a lot. I had heard his talk, but it was very different. Synthetic biology was not really my space deeply at the time. Something I hadn't mentioned is that my wife also did her PhD at George Mason.

Jon Chee - 00:20:54: Oh, she went to George Mason as well?

Eswar Iyer - 00:20:56: George Mason.

Jon Chee - 00:20:57: Oh, so your sister was there. Your wife was there.

Eswar Iyer - 00:21:00: So we went to undergrad together, and she ended up joining the same lab, and we ended up marrying after some time. So we actually worked together for some time. But she noticed, and she said, "You know what? George Church would be the perfect person for you." And I said, "Yeah, I like him, but I don't really know a lot about synthetic biology. That's a very different space." And his talk also was so high-level that I was not sure if I really appreciated all the details. But she said, "Look, you're curious, and no matter what you do, you're going to find it interesting after a few conversations." I thought it was very interesting. So she actually was very instrumental in saying, "Hey, George Church is your person."

So I had this in mind, and I was walking through the streets in Kendall Square, and I saw George walking by. I recognized him by his large beard. I went to him and I started talking. I shook his hand, said, "I'm Eswar," and so on. I told him, "I'm really passionate about technology development, and I wanna build this human brain on a chip." And he was extremely kind and receptive. One thing about George is how humble and how down-to-earth, how comfortable he can make you feel. So we ended up walking for a long time. And one of the things that he told me that impressed upon me was he too failed his ninth grade, which my wife said, "Do not tell anyone in your interview that you failed your ninth grade. That's not a good way to start your interview." But I mentioned it to him, and he said, "Oh, you know what? I too failed my ninth grade. That's okay."

Jon Chee - 00:22:18: Wow. That's amazing.

Eswar Iyer - 00:22:20: So it was really—you know, sometimes having good role models is valuable. And then he said, "You know, if you're trying to develop technology, that's not really fancy right now." Now it's gotten a lot more, but perhaps there was a feeling that only if you do deep science that's meaningful. Technology development is not that deep. There were some pockets perhaps in leading places that didn't feel that way, but in general, there was a feeling that deep science is the thing, and then technology development is sort of superficial. But I kind of resonated, and having somebody like George say, "You know, that's pretty important," I wanted to work with him or Ed Boyden or both of them, ideally. He said, "I work with Ed, and you should send me a resume."

So I kind of thought, "Oh, wow. That was a really good conversation," but I didn't send him a resume that day. I thought, "I'm not sure if he's serious enough." And I met him two days later. My wife had purchased a ticket to a conference because George Church was going to be speaking there and spent $150. She said, "Go be there. Talk to him." But I fortunately met him two days before. So there too, I just went because I'd paid this money, and I saw George and he said, "Why didn't you send me a resume? I thought you were going to send it to me." And I was like, "Oh, no. Okay. You're serious." So I sent my resume, and that ended up being an opportunity to work in his lab, which became one of the most amazing, pivotal times for me.

Really, I ended up pushing myself to the limit, learning so much that I cannot—I literally just went exponential from wherever I'd learned some basic science. I was thinking about exponential technologies, multiplex technologies, but he was the leader in multiplexing. His lab was doing so many things. They had artists, bioethicists. You could think about very different things. There were people who were inventing the next generation of—you know, CRISPR was one of the tools that came out of the lab. There were so many tools that were available, and they're thinking about it so divergently that there was no limit. It was a blessing and a curse because the blessing was it was amazing. But because I had set such a high bar for myself, every day felt like I was on the verge of failure. Just because I had imagined all the other people around me were stalwarts. I was looking at it, and I was trying to push myself every single day, and it almost felt like if I didn't make progress that one day, I had slipped back quite a bit. That exertion made things much easier later. But that was really exertion from mind, heart, soul, physically, in every which way. It was a very, very intense time. And the interesting thing is George never pushed you to do things.

Jon Chee - 00:24:52: Yeah.

Eswar Iyer - 00:24:52: It was a very open, clean lab. He was just very supportive, kind, open, and that made you work 10 times harder. Because you know that you are the biggest rate-limiting step, and you have no excuse. So that was a very interesting experience there.

Jon Chee - 00:25:07: I love that. And, one, props to your wife for just kind of nudging you. "Just go do it. Go do it. You're gonna pay $150. Now you have to do it." There's money behind it. You have to now. I love that. And sometimes, you know, another important thing is picking your partner, and your partner is along for the journey and can have these inflection points. You just never know where it would take you, and you ended up crossing paths with George Church. And I love that description. I tend to see that when leaders are just supportive, you don't wanna disappoint them. You're just like, "I wanna make sure I live up to this excellence," and then everyone else in the org is also very excellent. And you're like, "Oh my god. I need to..." and no one has to put their thumb on you and try to pressure you into doing the hard work. It just comes from within. You're just like, "Oh goodness. I can't be behind or last in this organization."

So I appreciate that, but I know it's also a lot of exertion. My co-founder was my first experience of seeing excellence. I was kind of rough around the edges when I was younger, but working with my co-founder and seeing excellence, I was like, "Oh, gotta take it up a level." And also just coming to Berkeley, it was like, "Oh, you gotta take it up. This is what smart is. You gotta take it up a level." And then all that hard work gets seared into you. So when you leave that environment—and I imagine that drive from George Church's lab you probably still carry with you to a certain extent to this day. I felt the same way. Even when I was out of the lab, even when I'm not in the same room as my co-founder, it's just baked in. The bar is risen. But yeah, so talk a little bit about being in George Church's lab. I've never been. I've only heard legends. Aside from George Church, were there other colleagues, mentors in there that had a really big impact on you? What were the challenges and triumphs of being in that lab? Obviously, exertion being one of them, but talk to me about that.

Eswar Iyer - 00:27:10: Yeah. That's a great question. That lab has a legendary status, and I think almost a mystical status, and there's a reason for it. Perhaps there's some truth to it as well. George's mind is so vast in so many spaces. You could almost talk to him about anything, and he has pretty deep knowledge of it. A lot of people can talk at a high level, but you go three layers deep and they don't. George had such diversity of space and depth of space in all of those that he could engage anybody to a very detailed level.

To give one example, when I was deep doing my analysis for my sequencing work and so on, I thought I had made this table that only I knew how to work. I spoke to George. George had asked me, "Do you have these tables? These are the columns. Send me the data. Let me do the base calling for you." He was so busy, but he could envision the data structure, asked me, and basically, he actually said, "Hey, actually, that looks fine," even when all this CRISPR stuff was happening in the background and so on. His level of depth and breadth are amazing. Very few people that I met can do that. He remembers a lot too, and combined with—I think he promotes—he brings people on. His interview style is very interesting. Sometimes he brings people he says are very nice, but also talented. Someway, he's picking for something interesting, but it sort of works itself out. Many times, people wonder why they were picked, and then it really blends itself in a different way.

So that lab had an eclectic collection of very interesting, neurodiverse people. There was a bioethicist, which I had never heard of, but I could see why that was valuable. There was an artist, a very famous artist, Joe Davis, who I became close friends with and still am and sort of influenced my thinking to some extent. Of course, the bioethicist as well. Then we had several eclectic people. You know, everyone from the whole spectrum of neurodiversity, perhaps people who are introverted, extroverted with dyslexia or synesthesia and so on. So you start respecting the neurodiverse. You see it as a strength rather than treating somebody as weird. You're actually looking for that 0.1% that is different. You know, when you're looking for gold, you're sieving through a ton to get a gram of gold. Most people focus on the ton of dirt, and they miss that gram of gold. But I think here it was focusing on the gram of gold and trying to put all of this together.

So I really found myself very much at home in that place, and I felt like it was the first place where I felt like this was my tribe. My PhD lab also felt very much at home, but for my interests and all the things I wanted to do, it felt again like a tribe. So the experience was very interesting. You come up with your own ideas. Sometimes George may give them, but I preferred coming up with some of these ideas and tracking them. It was very much a startup experience because you had to go convince people, and then if the idea was good, it would evolve. If it was not good, it would die itself out. It was almost like an evolutionary process. There are almost 100 people.

Jon Chee - 00:30:15: There were 100 people at the time? Oh my God.

Eswar Iyer - 00:30:16: And nobody really understood all the things that were ever happening. There were always news articles that were coming every week, one or two news articles. It was just so much happening. Everything from woolly mammoths to data storage in DNA to space to CRISPR. Nobody could understand how one lab could actually do all of these things. It was because of all these interesting people that were coming together, forming almost organic connections and evolving and then doing things. So it was a very interesting experience. It felt like running my own startup. I could recruit people. I could find ways to pay them. George would support them. I built my own automation with the help of a team that I had built. I could work on the biochemistry, the software. I could find all these interesting people, and I could start working with them without worrying about boundaries. That was a very, very powerful experience.

So one thing that influenced me a lot: the cost of sequencing was following Moore's law. Moore's law is that every two years, the cost halves, or around that. The sequencing cost was hundreds of millions of dollars for the first genome. It was following Moore's law. Something happened around 2006, and it broke Moore's law. Within six years, it became a thousand-dollar genome, what was expected to take sixty years. So I became obsessed. I thought Moore's law was a thing. "Everything follows Moore's law, doesn't it?" And here's an example of something breaking Moore's law. George and his lab were very instrumental in helping break Moore's law. In 1984, George published the first work on multiplexing. Now, multiplexing had been done in electronics and differently, but for DNA sequencing, he thought of multiplexing, and he really pioneered a lot of that multiplexed work. That evolved over decades into all these different technologies that led to the human genome being massively parallel sequenced and breaking Moore's law. So I became obsessed about, "If I'm in this lab, if I don't understand this one phenomenon, I'm wasting my time. I really need to understand this and apply this to everything I do."

That obsession led to realizations that are not obvious. It took me a while to get this, but the key understanding was three things. Three things happened for Moore's law to be broken. One is, of course, miniaturization. Things are smaller. Second is parallelization. You do things in parallel. But the third thing is multiplexing. You do a billion reactions in the same volume versus one reaction, and that's how Illumina and other flow cells were able to reduce the cost. That was a big breakthrough moment. Now I started thinking with all the ways I could multiplex, and I took an oath that I will not work on any technology that didn't have this potential. Right? Because why would you when you can really change the arc of evolution in such a powerful manner? That was my key take-home from there, scientifically. All the work that I did there led to highly multiplexed things. I had a patent that was licensed with Genentech. All the things that I was working on were validated into very useful technologies later.

But, personally, there's one thing that I learned about from George. He's very graceful with everything. He was always very respectful, always had a sense of calmness and awareness, and I think he took a lot of faith. He had a lot of faith in people. We think faith is for religion and things. But in science too, one of the things I learned from him is you have faith in science and the people that have generated results and faith in just people. There is a very important aspect that I have to highlight about that lab. I think there was a reason why he was able to sometimes hire people on a very short notice, just seeing them on the street for a short amount of time or so and being able to make the judgment call. I have had many stories of people who did well there later telling how they basically came and gave a chalk talk and they got hired and so on. I think there's something about that that helps people push to their limits. It's one of those intangible things that is the essence of what that place is like, but it's important to understand human behavior.

Outro - 00:34:13: Thanks for listening to this episode of The Biotech Startups Podcast with Eswar Iyer. In part three, you'll hear how Eswar helped shape a groundbreaking spatial biology platform at 10x Genomics, from early prototyping to full product launch. He shares what it was like to drive innovation inside a fast-scaling company and how he learned to navigate manufacturing, IP, and team building along the way. If you're enjoying the series, be sure to subscribe, leave a review, and share it with a friend.

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