The Future Of Drug Discovery Is 4 Billion Years Old (Viswa Colluru, Founder & CEO at Enveda)

[00:00] Medicines are a hope. The way to make patients feel powerful is to put great medicines in their hands, which means both discovery and ultimately delivery. There's really only one problem in biotech. It's drugs that work in the lab don't work in people. And because my job was to create landscapes of where the industry was evolving and where Recursion's technology platform sat within that view, I made a striking observation that 100% of our collective human effort to solve that gap [00:30] in the biology bucket. Most often, we tend to complain innovation and novelty.

But if I look around, most things that have changed the fabric of our lived experience were actually not new when they did so. And so if you make the calculation that most ideas that change the trajectory of human life are actually old, then you're increasing your odds that you are on the inflection. Even LLMs, when they changed the world, were like by AI terms, fairly old, nearly a decade. [01:04] A third of all drugs ever approved by the FDA owe their origins to a molecule first found in nature. [01:11] Aspirin from willow bark.

[01:13] Morphine from poppies. [01:15] met formin from a plant called goat's root. [01:18] Despite that, at some point the pharmaceutical industry walked away. [01:22] moved in a different direction, convinced [01:25] that synthetic chemistry and rational drug design were the future. [01:28] Viswa Kaluru thinks that was a catastrophic mistake. [01:33] His company, Invada Biosciences, [01:35] has raised over $500 million [01:38] to build a search engine for nature's chemistry. [01:41] using AI to decode the millions of molecules [01:44] that evolution, [01:45] spent four billion years perfecting. [01:48] Since its founding in 2019, [01:50] and VEDA has identified 18 candidate drugs, with three in trials.

[01:54] pioneering a radically more efficient and economical model in the process. [02:00] In our conversation, [02:01] This one I discuss the deeply personal reason [02:04] He got into drug discovery, [02:06] What competitive table tennis [02:08] taught him about managing a company [02:10] and why he believes the pharmaceutical industry's biggest breakthroughs [02:14] might come from the oldest laboratory on Earth. [02:18] I'm Mario. [02:18] And this is The Generalist. [02:20] This episode is brought to you by Brex. If you're a founder, the hardest part isn't the idea. It's scaling fast without getting buried in back office work.

That's where Brex comes in. Brex is the intelligent finance platform for founders. [02:35] With Brex, you get high-limit corporate cards, easy banking, and high-yield treasury [02:39] plus a team of AI agents [02:41] that handle manual finance tasks for you. [02:44] They take care of things like expenses, [02:46] all according to your rules, so you can move faster while staying in full control. [02:52] One in three startups in the S. already runs on Brex. You can, too, at com slash Mario. [03:00] This episode is brought to you by Ahrefs Brand Radar.

If you've tried searching for your brand in ChatGPT or Google's AI results, [03:07] you've probably noticed something. It's not always clear why certain brands get mentioned, [03:12] or why yours doesn't. [03:14] That's the problem Ahrefs Brand Radar solves. It helps you see how your brand shows up across AI-powered answers. [03:21] Not just in search engines, but also on platforms like Reddit and YouTube. Instead of guessing, you get real data based on millions of actual user prompts. You can quickly check your share of voice, find out which websites or sources are influencing those answers, and see where competitors are getting ahead of you.

What makes it different is that it doesn't rely on simulations or small samples. It's built on large-scale, real-world data. So you're seeing what people are actually asking AI. [03:49] There's no complicated setup either. Just enter your brand and start exploring. Visit com slash generalist to learn more about Brand Radar. [03:59] This was... [04:00] We had such a fun, interesting conversation when we met for the first time last fall, and... [04:07] It made me really want to go a lot deeper with you. So thanks so much for being here. Thank you for having me.

Long time listener, first time caller, as they say. Well, thank you so much. In researching a little bit of your story, one of the things that stood out to me was that your father was a pharmacist. He was. He actually inherited my city's first pharmacy called Vizag Medical Stores. And I come from a city named Vizag. [04:30] or Vishakhapatnam, and I grew up around medicines. And from what I could tell, you know, it has such interesting links to what you're doing now. There was sort of a mix of both sort of what one might call sort of traditional Western medicine and then more sort of Ayurvedic, not homeopathic.

How would you describe the sort of two types? I think the oldest form of medicine, which is from the radical act of observation of what happens when you consume something that occurs naturally, [04:57] and you've been taught and cultured to consume for a very long time. I think on my way over, I'm battling a bad bout of nausea, and the thing that still works for me is ginger. [05:08] And I think, you know, Dramamine natural is nothing but ginger. Yes. [05:13] Yes. [05:13] So you grew up seeing all of this, you know, all of the different types of medicines on offer.

Absolutely. And I think that, as I can see you're laying the breadcrumbs, was one of the key influencing factors in me having maybe both the right amount of skepticism and belief. [05:31] But having both of those from a place where I figured that there was a marriage made in heaven that we weren't yet seeing. What do you remember about? [05:41] that place because it seems like [05:44] probably a big part of your childhood. [05:45] You know, I would accompany my parents to the pharmacy because they were both, you know, essentially helping run the house.

And my first memory was looking at two different drugs. [06:00] and asking why one was priced at a tenth. [06:03] and learning what generics meant at age seven. [06:07] My other memory, which is very distinct, is recognizing that two drugs, [06:13] where one of them had like chloride or a salt ion next to it was the same thing. And the active principle was effectively equivalent. [06:24] and how the healthcare journey, at least in India, depended a lot on people being able to access and afford medicine. [06:36] And also, there are some, I realize that there are just some afflictions where you went to the doctor, [06:42] but they didn't really have a medicine for you.

[06:45] And what's interesting is that, you know, these patients would come over and they would seek advice effectively with the pharmacist as a second doctor. And all of these things left, you know, a very clear impact that medicines meant hope and that when you are ill, you want nothing but to feel better. [07:06] Was that... [07:08] how you saw your life path from a very early age? Did you expect to be a pharmacist, be a doctor? Absolutely not. I thought it was all interesting, but I was dead set on becoming a computer scientist that worked in Silicon Valley, like any good middle class South Indian boy born in the 1990s.

[07:28] But of course, life had other plans. How did that... [07:31] even come onto your consciousness? You say like every boy in South India in the 90s, but were there sort of key inflection points where you became really fascinated by technology? I think it was the first time where early adopting relatives were... [07:47] able to afford personal computers, and were able to do things that my dad's accountant or his typewriter, you know, assistant took so many months to do. And then they were definitely neighborhood kids that had come to America, studied engineering, and come back with really cool toys.

And also glimpses of what seemed like a magical future life, where technology was [08:17] from the other side of the curtain. [08:19] And I think the fact that today, [08:22] you have folks spawn maybe between 75 and 95 in Silicon Valley. [08:29] being a vast majority of [08:32] South Indians, including large tech CEOs. And I think it was very much a product [08:38] of the culture and crucible of the society we grew up in at that time. [08:42] Were you the kids sort of trying to build websites yourself or programs yourself?

Or how did that manifest for you? Oh, it manifested for me really by choosing to study computer science instead of commerce and economics, which was one of the first electives in middle school. Oh, wow. Falling in love with programming, the logic of writing an algorithm. I still think that [09:04] Today, I try to map things out in steps independent of the language, whether it's English for a pitch deck. Yes. Right. Or whether it's Python, even though I don't code, I might get back into it. Thanks to Claude, we can all not worry about compiling or syntaxes.

But I think it influenced how I break down problems and how I thought about how the underlying structure of any argument must be made. And you had a sort of key moment in your childhood, which seems to have really... [09:33] changed that path, which is your mother got very sick. What was it that afflicted her and how did that sort of impact the way that you thought about the rest of your life, really? [09:43] Yeah, I think that was the moment that defined my childhood and ultimately, I think, put me on the path that has me sitting on this couch here today.

And it was my mother's diagnosis in the late 90s. So I was, you know, eight or nine years old. And after being sick for a few months and not getting the help that she needed, we went and saw, you know, a super specialist that just did a lot of tests. [10:13] which I would go on to find out very soon, thanks to our own personal computer and the internet, as chronic myeloid leukemia. It is when your bone marrow produces, you know, undifferentiated cells, too many white blood cells, and they start to kill your marrow and other organs.

[10:31] And at that time, it was effectively a death sentence. [10:36] They told her she had about five years to live and that she was ineligible, perhaps on the aid side, and we were on the financial side to receive a bone marrow transplant. [10:47] which was really your only hope at that time, we were told, well, you know, if you had the money to go travel to the United States and you could get this done at Sloan Kettering, you know, they could probably deal with the conditioning regimens. So the things that you need to wipe out the previous marrow and yet keep the patient alive in that very, very precarious state.

[11:06] So that was not an option for us. And then we would go on to find out in the coming weeks that even to give her those five years, we would have to somehow marshal about four times my dad's annual income every year. So it very much became the precipitating moment of focus for our family, purpose for us. And also, I think, [11:30] where I learned the meaning of courage from my mother who showed up after that moment. Actually, [11:36] Not a single day asking, "Why me?" [11:40] or in any way insinuating that life had treated her unfairly.

She jumped into action. She used to help my dad at the pharmacy and so on, but she launched multiple small home-based businesses to supplement her income, keep her busy, challenge her to grow. [11:55] And what started off as, you know, a tiny spare bedroom effort to arrange dry flowers and decorate people's homes or create small gifts grew into, I think, one of the most exciting homegrown businesses in about four or five years and about 48 hours before she died. [12:17] She was adamant that my father go finish an assignment that she had accepted from a hotel nearby to decorate the hotel for Christmas Eve.

[12:28] And to this day, my sister and I talk about the sheer resolve that she must have had in that moment of excruciating pain. And, you know, taught us that courage isn't about not feeling fear. It's about moving forward despite it. How old were you when that all happened? [12:44] I was about 13 or 14 years old, and I think old enough to recognize that my life would never be the same again, but young enough to not be cynical about it. Yes. [12:54] And I realized... [12:56] If I look back and reflect on her journey, the piece that gave her the most power, [13:02] was the creation and approval of a new medicine called Imatinib, more famously known as Gleevec from Novartis.

[13:11] And when she couldn't access it after, you know, the first few bottles, because it was $2,200, I still remember the exact number per month. [13:20] and that was several times my family's combined annual income, I realized that the second real piece was [13:31] her getting access via a foundation that Novartis set up with in partnership with someone else. And so for me, it became medicines are a hope. The way to make patients feel powerful is to put great medicines in their hands, which means both discovery. [13:46] and ultimately delivery.

[13:48] And that's a big part of what would go on to influence some decisions I've made. And I've not really talked about publicly about choosing to work on small molecules or medicines that you can take and distribute in pill form cheaply and where you can reliably turn them into generics. [14:04] Right? [14:05] So yes, that [14:07] period of life was effectively when I'd say the [14:11] quadrants of my compass were set. You saw the hope, but also clearly you saw the limitations of this paradigm and can't help but [14:21] but change who you are in some really fundamental ways, right?

Yes. [14:24] And so then... [14:26] You go and study... [14:28] in the S. Well, first in India and then go to the S. for a D. That's correct. What was the sort of... [14:36] shape you had in your mind of the way that you wanted to help at that point. [14:39] Yeah. [14:40] I wasn't quite sure exactly what form that will take, but I wanted to be involved in the discovery of medicines and maybe their production or delivery. And I ended up studying a major that was essentially a marriage between biology and chemical engineering.

It was literally called biotechnology. So I have a bachelor's in technology in biotechnology. I love that. And that was a very eye-opening time. I realized I had a penchant for... [15:09] research, even though we didn't do much fundamental research in college, and ended up choosing the biology side of things. And by that time, I had gone from maybe a B-minus [15:22] depending on the year student, to someone that was obsessed with this problem. [15:27] And I would prep for about two and a half years my GRE applications in order to find a place at a good graduate school in the

S. [15:38] And as fate would so have it, you know, my deep, extensive preparations and [15:45] five or six backup schools that I applied to all rejected me. [15:49] But my number one choice was the University of Wisconsin at Madison. Two of my favorite textbooks in college were written by professors there. And somehow by the skin of my teeth, including when Daylight Savings Time moved the interview by an hour and I didn't realize it because no one else changes their clocks, I somehow managed to make the interview and then make it through the interview to get into the cellular and molecular biology program as one of 13 kids that year.

[16:19] And this was in 2011. And so I moved from sunny South India to sunny Madison, Wisconsin. [16:24] Yes, I wondered about that. As a culture shock, it feels like that's about as steep as it gets. What was that like? It was actually very interesting. The first shock I experienced was the cold. [16:38] My first winter there, I think the temperatures hit minus 40. [16:43] Which fun fact for you is the same temperature in either scale? [16:47] So minus 40 Celsius is minus 40 Fahrenheit. Wow, that is a fun fact.

And it's also the temperature at which instantly your nose hair will freeze if you go outside. So I found out both of those things, but really fell in love with the spirit of inquiry. [17:02] at a top tier American university, the lack of hierarchy, [17:08] And I think my first taste of what makes America uniquely special is that, as far as I can tell, it is the purest form of meritocracy that we have. [17:20] where who you are or where you come from matters less than what you can do and how you think.

[17:26] And I found that to be deeply infectious. And it was when my love story with this great country started. I think I'm right in saying that [17:35] Satya Nadella also went to Wisconsin, maybe. And I remember him in one of his, it must be in Hit Refresh, his book talking about how it was responsible for him stopping smoking because it was so cold outside that he was like, I can't do this. That's right. So, you know, that's a well-trodden path. It is a well-trodden path, indeed. Maybe we can talk a little bit about what you were studying at the University of Wisconsin.

You'd sort of, [18:00] You can tell me how clear the steps were when you began, but you really started to get interested in immunotherapy, which... [18:09] had gone through, you know, really a fall from grace, from interest. Several times. Several times. So, yeah, how did that, like, appear on your radar, and why did you think it was worth spending time on? You know, the two textbooks I mentioned, one of them was a book called The World of the Cell, [18:27] by Professor Wayne Becker, who had gone emeritus by the time I came on campus.

But one of the later chapters in the book was about cancer. And it was very interesting because, you know, 95% of the book was about fundamental cell biology, but he's got this one chapter on, you know, cancer as a fundamentally cellular disease. [18:47] And that lens allowed him to look beyond genetics of cancer and ask what are interesting ideas that haven't yet come to fruition that may hold tremendous unfulfilled potential. And this last [19:01] paragraph or two talked about this concept of engendering an immune response against cancer. And this for me was really interesting because like all cancer patients, my mother had gone through a remission relapse cycle, actually multiple.

And as she was treated with toxic chemotherapies early on in her journey, she probably accumulated mutations and her cancer [19:27] you know, effectively mutated into lymphoma at some point, which she also then beat. And so I started asking the questions of her doctors, well, why did this happen? And they said, well, you know, there's a few hypotheses. Your cancer can become stem cell-like and come back in another form, or maybe your original cancer, which she ultimately ended up succumbing to, you know, was never really removed by the medicines we gave her.

And they call these [19:57] the end of the day, what makes cancer lethal is its ability to spread. If it stayed in one place, it would just be called a tumor and a benign tumor, and you can go and surgically remove it. [20:06] And so this was very interesting to me because it was essentially an antidote at the cellular level. [20:13] And so you can escape a chemical because of vasculature or genetics or mutations. But if you truly allow and create the ability of immune cell to recognize a cancer cell, [20:24] you get rid of every last virus in your body after you get the flu, right?

And you recover. So that was very interesting to me purely on a first principles basis. At that time, I had not realized its storied history. And over the course of the coming years, as I was studying it, I would appreciate that [20:41] old ideas are actually where a lot of latent potential lies in a way that would, you know, more often than not go on to change the world. Yes, I certainly agree with that. I was, you know, trying to do just a bit of research in advance of this, and it was fascinating to me [20:57] how far back versions of immunotherapy have gone, you know, even to, you know, even in treating cancer and, you know, 1800s, there are people trying to do versions of this.

I wonder what it [21:11] sort of predisposed to look so deeply [21:15] at something that other people are overlooking or that you feel that people are overlooking. Does that just sort of seem to be part of your innate makeup? Did something teach you to do that? [21:24] You know, I think I've reflected a lot on this because we'll come back to courage, I think, as a central theme for how you can build great companies and change the world. [21:36] And it is not something I've ever felt [21:40] compelled to [21:42] against in a way that I think most of [21:45] my peers or other people I've known feel the pressure.

And I don't know where that comes from, [21:53] But I think the same thing that forces you to conform to a particular manner of like dressing or speaking is what forces you into the current zeitgeist of thinking, because you want to feel comfortable. [22:09] validated. [22:11] You want to feel smart. [22:12] And I'm going to borrow this from our mutual colleague, Pablo, who told me that one of his metrics that he looks for when he was finding founders for Hummingbird. [22:23] is the ability to accept low status for a long time.

Yes. And I think that is a very interesting lens through which to evaluate effectively an equivalent of the marshmallow test. [22:37] I but. [22:38] I think what's interesting, and I'm very grateful for this because I didn't make the part of me that is like this, is I never felt like low status was something I had to accept. [22:47] I was just okay with it. I realized early on, you know, I grew up in a very wealthy neighborhood through sheer chance, even though we weren't wealthy. [22:58] and that most people spend time thinking about themselves.

[23:04] And I would realize I spent a lot of time thinking about myself. [23:08] Which means that most people aren't thinking about you. Yes. True. Even as a kid, you know, I had that realization one day. And I think that sort of released the pressure to look a certain way. [23:19] And that, by extension, I think, untethered me from the moors of, oh, you have to research [23:26] You know, if I was starting my PhD in 2011, it was all about oncogenes and, you know, small molecule inhibitors to RAS proteins, which are, you know, effectively what advanced chemotherapy was.

No one was joining immunotherapy labs at that time. [23:41] And that theme, I think, would hold me in good stead through the arc of my career. [23:47] and put me on this seat. Yes. There's a great blog post called The Moat of Low Status, which I think does a great job of talking about what Pablo names there. And for folks' context, Pablo was an investor at Hummingbird and then upgraded to Invada. The challenge of picking one of these companies [24:07] overlooked ideas is that they can really go dormant for an extremely long time, right?

Like, you know, there's, [24:15] Examples of... [24:16] The ancient Greeks even knowing... [24:19] some of the core mechanics that would make the steam engine happen, but they were used as toys, you know. And so you can go centuries or, you know, so, so long without these things coming into fruition. [24:29] What gave you confidence that [24:32] Hey. [24:32] My life isn't going to be wasted if I spend it in this area because there maybe was an inflection that you were seeing or some signals that... [24:40] this wasn't going to be just a, [24:43] You know, 200 years away, let's say.

You know, I actually flipped it in my head. [24:48] And I said, most often we tend to conflate innovation and novelty. But if I look around, most things that have changed the fabric of our lived experience were actually not new when they did so. [25:02] Steam engine, yes, initially toys and then to power water wells and then ultimately locomotion in water, actually, before the railroad. I love that you know this so much better than I do. I brought it up, but you've gone deeper. And that same thing is true for electric cars, neural networks, alternating current, the Internet.

[25:25] transistor, rockets, flight. And I was like, wait a minute, that's also true for statins, morphine, rapamycin, transplant medicine. And this for me was interesting because if you made the bet that most often, even LLMs, you know, when they changed the world were like by AI terms, fairly old, nearly a decade. Totally. And so if you make the calculation that most ideas that change [25:54] then you're increasing your odds that you are on the inflection. If you just pick an idea that's old enough, [26:03] where you also feel like both the constraints that restricted its potential [26:08] are clear?

[26:09] And that the world in ancillary technologies has developed enough that the idea could be revisited. Right. So those are the two things you have to evaluate. So one of the big leaps I'd make from my time in graduate school is to actually leave immunotherapy, which had then been rechristened to immuno-oncology, which held a lot more sway and budgetary power than immunotherapy, [26:39] I thought that the story was far from done. The idea had gone through many troughs of disillusionment. [26:47] But computers and processing power and our ability to store and move data had been increasing exponentially.

[26:54] And so I said, wait, you know, this is an unfinished idea that I think deserves attention. And so I found myself in AI drug discovery, what, like nearly a decade before it became cool and half a decade before the term even was coined. [27:08] Before we get to that, you know, in looking at the work you did at University of Wisconsin, you know, it's full of, [27:15] all of these terms that I can't pretend to understand. You have working on new vaccination methods, new... [27:21] DNA, novel DNA vectors. And, you know, looking at your LinkedIn, you have all of this.

And then you also have that you are part of the University of Wisconsin Table Tennis Club. It made me wonder why that is in there and what that meant to you. Like, was that the way that you blew off steam during this period? Was that where you made your friends? So what's funny is I always grew up really wanting to play tennis. [27:46] And I still remember watching Roger Federer beat Pete Sampras on a... [27:52] 16-inch CRT TV that we all used to have back in the day that you needed to give a solid whack once in a while because the antenna wasn't perfect.

And I went up to my dad and I said, dad, I really want to play tennis. He's like, great, let's go check some places out. And we go check them out. And effectively, they're about, in that time, in the mid-90s, about $100 a month. Oh, wow. US. And my dad was like, yeah, no, we're not doing this. And instead, he's like, [28:22] Let me go buy you a table tennis. [28:25] paddle, racket, and find you a good coach. And so we found an academy that was subsidized by the government. [28:33] for one dollar a month.

[28:35] And so I went to play table tennis every day instead of tennis and fell in love with how fast the sport was, how it demanded flexibility. And that became my thing. So I would go on to actually choke in every tournament in high school. Oh, wow. No way. Learn a lot about myself and how I dealt with pressure to perform because I didn't feel that in any other domain. [29:00] But I felt that because I felt like I had to win because I was only one of the few kids that had coaching and overcame that partly and would go on to be on the table tennis team at the University of Wisconsin, which is really Indian and Chinese kids.

And it was also overwhelmingly undergraduate. So college students, not graduate students. And so it was this really insane, beautiful window into American life. [29:30] through the lens of an immigrant in a competitive sport that was viewed as a drinking game. And I fell in love with the intercultural mix, competitive play. I would go on to be, even though not the best player, captain the team and even coach the team as a retired player for a year or two and made some of my best friends that way. I don't think we ever did spectacularly

[30:00] the country, but we did beat Harvard at the Nationals. [30:04] And I was like, that's good. I'm going to keep that in my back pocket. I bet that, you know, that would have made your family very proud, right? Absolutely. It was great. [30:12] You know, there are plenty of... [30:14] I think of someone like David Foster Wallace who talks so much about [30:17] and write so interestingly about the parallels between tennis and life and writing and creativity and all these sort of things. [30:24] and math. Are there any sort of observations that you have about the way that table tennis or those lessons feed into your daily life?

[30:32] I think this is true of any sport, but the biggest observation I made that I perhaps drew parallels and lessons from is that competitive sport is really about winning one match at a time. [30:48] and each match is its own journey. [30:51] and is one equally, I would say, in mind and strategy, as opposed to skill and practice. [30:59] which is why I think I got picked to be [31:03] captain and coach is because I would see these extremely talented kids that could beat me left handed, blindfolded, not kidding.

And I had a teammate who was so good, she could hear the spin [31:17] so she could receive a serve from just the sound. [31:20] And all they really needed was a dispassionate but interested observer. [31:26] that [31:27] taught them in the matter of a few points. [31:31] you know, I wouldn't say teach, maybe guided them towards [31:35] with the particular dynamics of that matchup. And so it was really about winning one match at a time, which is a metaphor that I really like. And each match, as you might imagine, is not about rankings or numbers.

It's really about what happens on that day and your ability to win in the mind as much as it is winning with your body. And that for me is, I think, a lesson I still take to this day. [32:02] David versus Goliath is not as lopsided as it seems ever. And so you bring those lessons from... [32:10] the table to... [32:12] Life at Recursion Bio. [32:14] which sort of had this [32:16] These two sort of this tech and this bio component coming together and riding this new exponential wave that you sort of mentioned.

How did that specifically become the place where you decided to spend your time? I imagine there weren't maybe that many companies even that fit that bill. Not at all. And it was actually a wavered LinkedIn ad. [32:36] That caught my attention. And of course, as highly skilled immigrants that enjoyed taxpayer subsidies for advanced degree, you only have 60 days to find a job. [32:47] or else you have to leave the United States. So like everything else I'd been doing since my time becoming someone obsessed with trying to be successful in this domain, I spent a lot of time researching companies and jobs.

And I think somewhat ironically, this one fell in my lap. [33:05] It had the most interesting story. [33:07] And I would go on to Marvel, continue to hold my fascination for technology during this time, which had taken the form of, you know, smartphones, which were half a decade ahead of my life in India at that time. That's no longer true, but it was back in the day. And my Samsung Galaxy, whatever, S13. Yes. Had a facial recognition program. [33:31] that was actually not bad for that time. And with no pre-training on my face, you know, and just a couple of photos, half the times it unlocked my phone.

And I recognize that that belie a deep improvement in processing and algorithms, specifically of visual data. [33:50] and pixels. And what recursion was doing was effectively facial recognition for cells. [33:56] And I could grasp that very early on in even, you know, their job ad and the videos that Chris and others had on YouTube. [34:04] And I said, wait a minute, this sounds really cool, because the way that the industry was at that time obsessed with treating disease, and to some extent still is, is by mapping out molecular underpinnings and figuring out what genes may be causing a particular disease.

[34:34] biology that were not driven by a priori theoretical explanation. [34:40] And that for me was very interesting. And the way that, you know, recursion in its original form wanted to use that technology was also very, very elegant, which is normally you have this massive body of literature that develops over decades to that reaches a tipping point about how you think a disease works. [35:01] And then you create a drug for it by trying to manipulate one node or another. But rare disease patients and rare diseases, which are in the thousands, so there's about 5,000 to 7,000 diseases that are caused by mutations in a single gene.

And they're rare, like teleologically they're rare because most genes are conserved for a reason. And if you lose their function entirely or if you gain too much of it, then it becomes toxic in utero. [35:29] But there are small, like about a fourth of the genome, where you can have some loss of function or gain of function, where you can still be born. And you can be usually somewhere between sick and very sick. [35:44] And these diseases, while the genetic cause is known, there's not enough of a body of literature that's been built up because the interest and the funding isn't there for you to take an approach and say, you know, I'm actually going to study this one pathway that I think is dysregulated because of this gene.

And so this ability to shortcut disease. [36:04] through facial recognition of cells, the study of rare diseases [36:08] in a way that can be directly applied to drug discovery, felt deeply intellectually satisfying and impactful to me. Because those patients most go through a very long journey to even be diagnosed. [36:21] only to be told there aren't medicines. [36:24] And so it was a very easy bet. And I would be the first hire that I think Chris claimed at that time that he didn't personally interview. [36:34] And so I'm very glad that, you know, he found me up to the mark after he came and saw me.

He was away traveling at that time. [36:41] Not just up to the mark, because he writes such a phenomenal parting post when you left a few years later. I think that says more about him than me. Well, I don't know if I've really ever seen that happen before. So it says something about both of you, probably, that, you know, a CEO goes to the trouble to write about what it was, a departing outstanding employee or something like that. Yeah, I think I'm happy. I'm happy that I was on the ride at that time.

Yeah. [37:08] He's an incredible, incredible founder, CEO. What did you learn from him? Are there things that you take from the recursion time into your operating today? Absolutely. And I wrote a [37:19] unpublished letter in response to that and shared that with my colleagues at that time. And I think I made [37:26] A few salient points then, but two that stick out to me today here on this couch. [37:32] One is I saw the way [37:34] that [37:35] Chris operated with a sense of urgency. You know, for example, we had, I think, a partner visiting a tiny office, which was about twice the size of the studio at that time.

Or we had a bunch of new employees joining the next day and all the desk needed to be rearranged. So he just, you know, came back to the office after five o'clock and he was like, hey, whoever's here, we're just going to [38:05] I was like a week into my job. Yes. And I didn't know what corporate life was, you know, how a CEO was supposed to behave. And thanks to Chris, I never picked up any bad habits. Yeah. You know, I'm still happy doing everything from the now famous Jensen quote of cleaning toilets to like moving, you know, furniture, which I actually saw Chris do.

So that was maybe one thing is this bias towards action and the action being urgent by default. [38:31] The second is, I think we was very clear that not only the application of AI, but this unbiased, [38:41] discovery of new hypotheses that may not be treading well-erected goalposts was very different from how the industry thought. [38:56] And it required a lot of courage. [38:58] And I would spend my first part of my career there really trying to sell the recursion approach as the first [39:06] platform product manager, probably first product manager in tech bio at that time, which I dubbed as connecting the creators to the customers, right?

Selling that to Pharma. [39:18] and being essentially the victim of many blank stares. [39:23] And I think this idea that, you know, if you believe in something from first principles, it is completely OK being misunderstood was maybe something, another dimension of courage relative to what my mother showed me that I picked up at that time. [39:53] need to adapt just as fast. [39:56] Persona helps secure some of the Internet's largest and most trusted platforms with identity verification. [40:01] If you're building a product where trust matters, identity should be a priority.

[40:06] you've probably already experienced Persona without realizing it. [40:09] verifying your LinkedIn profile, signing up for Etsy, [40:12] or renting a scooter with lime. [40:14] trusted by leading companies like Square, Brex, and Twilio. [40:18] Persona gives you the building blocks to create identity flows that adapt to your customers, risk tolerance, and locales you operate in. [40:25] Whether you're verifying age, onboarding businesses, [40:28] or automating KYC. [40:30] It's fully configurable, so you can launch in days, not quarters. [40:34] Want to see for yourself? Generalist listeners get a free year of the starter plan.

Head to com slash generalist and check it out. [40:44] How did you know it was the right time to leave? Had the idea for your own company visited you at that point? Yeah, I mean, I was having the time of my life at Recursion. I would go on to make incredible friends, many of whom are now at Enveda, luckily, and I did not want to leave at all. Yeah. [41:06] I realized during my time at Recursion that there's really only one problem in biotech. [41:12] It's drugs that work in the lab don't work in people.

[41:16] And because my job was to create landscapes of where the industry was evolving and where Recursion's technology platforms sat within that view, I made a striking observation that 100% of our collective human effort to solve that gap, [41:35] lie in the biology bucket. And this was interesting to me because we had medicines before we had biology labs. [41:44] and before we even had molecular biology as a formal scientific field. [41:48] And that was simply by focusing on interesting chemistry. Our ancestors walked the Silk Road, [41:55] drank the milk of the poppy, realized that that soothed their ankles and their feet, and that they could sleep a good night's rest after drinking that.

That allowed us to discover opioid biology, gave us morphine, understand how pain works, and till today, have really the only solution for breakaway pain. [42:16] And for me, that was interesting going back to my roots, where as a South Indian boy, I had my friends, family, mother, grandmother give me herbs whenever I was ill, you know, like that ginger I had this morning. [42:33] And it struck me that there were many other [42:37] morphines, aspirins, artemasonins to be found, Nobel Prize winning, disease busting, you know, billion people treating medicines that where a large section of society somewhere on this planet [42:52] would be unsurprised by that discovery.

[42:54] And so I started asking the simple question, if things that work in the lab don't work in people, [43:00] And hundreds of millions of people believe in something working in people. Doesn't that warrant a second look? [43:07] I didn't know it at that time fully, but I would go on to recognize that that was how the industry started. [43:14] And this was an unfinished idea. Well, like immunotherapy, like AI drug discovery, it was an unfinished idea. And I just didn't quite know at that time how unfinished, but I knew enough to know that, you know, I knew of several plants just off the top of my head where I've experienced, you know, their effects.

And I know that millions of people would be unsurprised. [43:37] if there was a modern medicine found, but we weren't paying any attention to it. [43:41] So that became the precipitating, I would say, realization, and maybe the observation that no one was doing it. [43:50] Not only was no one doing it, [43:52] When I tried to find out why no one was doing it, [43:56] I uncovered a tremendous amount of stigma, [43:59] And that stigma was rooted in past failure, which I was actually leaning towards, not away from. And that stigma was essentially misconstruing [44:10] absence of evidence as evidence of absence.

And, you know, it would have perhaps discouraged me, if not for the fact that around that time, as I was thinking through this idea, there was a company called GW Pharmaceuticals that had gotten the first approved, first novel anti-seizure medication [44:29] approved in a very long time. And it was nothing but a purified form of the cannabis extract with essentially one compound called cannabidiol. It was non-psychoactive, but it was tremendously neuroactive. And if you trace the origins of the cannabis plant, I think there's a 2000-year history [44:47] of treating symptoms of what we now recognize to be seizures.

[44:52] And so there was this massive section of the world that was like, of course, [44:57] And that company would go on to get bought for $7 billion. [45:01] And they didn't even change anything. [45:05] All they did was they generated the evidence. And so I said, given my background, [45:11] given my [45:12] training and naivete, given my roots and my desires. [45:16] that I was perhaps the best champion for this idea [45:21] Because I couldn't find another one. Yes. And I said, if I don't do this, I'm going to regret it for the rest of my life.

[45:28] And I didn't quite frame it as elegantly as Jeff Bezos, but I knew that if I let that moment pass, I may never do it again. I never have the opportunity to do it again. And that may end up being one of my biggest regrets. [45:41] You mentioned that, you know, all of this energy is focused on on the biology and that, you know, maybe the industry didn't start that way, but that's where it was when you found it. [45:51] For folks that aren't familiar, like why did it evolve in that direction and why has it found, you know, why has it been so hard to move it away from that?

[45:59] You know, I think the scientific method in general biases towards breaking things down, [46:06] and simultaneously calling them fundamental. For example, I think if you go visit CERN, [46:12] The word fundamental is thrown around almost on every billboard inside the museum, and even formal writing explaining science to you, because they think that they're studying things that are so small that they make up everything. And I think biology has been a victim of that broader scientific movement. [46:31] And I think anyone that lives life and observes it recognizes that almost everything that matters is emergent.

[46:40] consciousness, your lived experience, disease, even obesity, something that's simply the accumulation of fat is as much a disease of fat tissue as it is a disease of the brain and the gut. And I think that broader movement edged the currents of biology, number one. The second is at the turn of the millennium, the molecular biology revolution had reached its zenith, [47:08] So our ability to sequence genes, [47:11] and all of a sudden correlate mutations in genes. These were called massive GWAS studies, genome-wide association studies. [47:19] And if you look, you know, at papers in the 2000s, that was what the most exciting labs were doing.

And it was for the first time sequencing, you know, hundreds and then thousands of people and saying, oh, look, you know, this gene here has a number of mutations that either protects from or predisposes you to this other disease. [47:49] I think, complex diseases that can be either treated or ameliorated by a single effector. And this became sort of the dominant way of thinking. But I do think that is also a result of technology. We invented a sequencer. [48:07] for genetics. [48:09] And so that became the most voluminous form of data.

[48:13] And this data, I think, both became highly amenable to the scientific zeitgeist of trying to reduce problems down to really simple things, and I think the human predisposition towards correlation. [48:27] We love our brains were wired for correlation, not truth. [48:33] We're like, "Oh, I see a pattern behind the bushes that must be a tiger." [48:37] Right. And so I think these two things made it so that we said, oh, wait, most disease, [48:43] can and should be caused. [48:45] and if not caused, at least treated by a single chemical or now other modalities like RNA that allow me to tweak this one protein, which is expressed in this one tissue or is expressed in the diseased tissue of interest in order to cause this [49:03] balance between benefit and risk.

[49:05] And if you think about it from an evolutionary perspective, going back to genetic diseases, the lesson lies right there that [49:12] Most of these genes and proteins exist for a reason. So perhaps completely ablating their function is walking a very tight rope physiologically, which is what we go on to find out. And because so much of life is emergent, life exists essentially to turn your breakfast into you. [49:32] to make energy cycle and matter flow, or the other way around. And all of that happens through a deeply coordinated symphony.

And so symphonies are rarely one-protein shows, right, or one-musician shows. [49:46] And I think those are the things that are driving some of the low success rates that we see today. [49:53] So we have a, I think, a, [49:55] a rich shape of the problem here of, you know, all of this energy directed through one paradigm, uh, [50:02] stigma where people, you know, are, are sort of maybe looking down at saying, take ginger for this or take willow bark for this. And then, you know, this, this evidence of, or this absent evidence [50:13] Did you have a shape in your mind of a solution at that point?

For me, it was very simple. As Charlie Munger says, you know, take a simple idea, but then treat it seriously. I just wanted to say, look, if there's hidden chemistry, that's interesting. It is not the first time that chemistry would teach us biology. So you mentioned the willow bark. [50:33] which gave us the molecule that would go on to become aspirin. We didn't find aspirin because we studied inflammation through and through. In fact, [50:42] The study of aspirin taught us about inflammation. And that same pattern holds true for rapamycin, teaching us about metabolism and then eventually immunity and aging.

It also holds true for warfarin, which comes from the University of Wisconsin, stands for Wisconsin Alumni Research Foundation, WARF, where a Wisconsin farmer made observations that would give us a blood clotting medicine that was the mainstay till about half a decade ago, where warfarin taught us about the [51:12] the first time that we learn biology through chemistry, [51:16] Because this chemical pool that nature has made is deeply evolutionarily selected for activity. And so there's a reason that molecule exists in that shape and form. [51:29] And understanding how it mediates its function in a biological system has, on average, given us a Nobel Prize every other year.

We make a big deal of the AlphaFold Nobel Prize and a big deal of the CRISPR one. But, you know, discovering vitamin D, for example, which was, you know, the active form was discovered at the University of Wisconsin, you know, led to a Nobel Prize. Discovering cholesterol led to a Nobel Prize. [51:59] that biosynthetic pathway, I think, was another prize. So this for me was very interesting. Going back to things that work in the lab don't work in people. Let's just start with things that work in people. That requires us to put chemistry, not biology, back at the center of the process.

Those were maybe like the three legs of the stool. [52:17] Okay. And so you set out to do this new business yourself. I think you raise a very small pre-seed round to do something this ambitious. $225,000, right? That's right. And the first check-in was mine, which was the entirety of my life savings, which was $55,000, which felt like a tremendous amount of money. By that time, I had out-earned my father his entire career. So it did feel like an incredible amount of money. But yes, [52:47] How did you get to the stage that you needed to get to to get this off the ground?

Winning one match at a time. Yeah. It was very clear to me that, you know, I was just going to always have to out execute what people would expect in order to get the capital needed to brandish an old idea. You know, new ideas are hard to sell, but old ones even harder.