The Climate Biotech Podcast
Are you fascinated by the power and potential of biotechnology? Do you want to learn about cutting-edge innovations that can address climate change?
The Climate Biotech Podcast explores the most pressing problems at the intersection of climate and biology, and most importantly, how to solve them. Hosted by Dan Goodwin, a neuroscientist turned biotech enthusiast, the podcast features interviews with leading experts diving deep into topics like plant synthetic biology, mitochondrial engineering, gene editing, and more.
This podcast is powered by Homeworld Collective, a non-profit whose mission is to ignite the field of climate biotechnology.
The Climate Biotech Podcast
Reimagining Bioreactors to Solve Manufacturing Bottlenecks with Brian Heligman
Biomanufacturing doesn’t fail for lack of clever biology; it stalls at the factory gate. We sit down with Biosphere CEO Brian Heligman to unpack how a materials scientist’s journey through batteries and perovskites led to a bold thesis for the bioeconomy: change the constraints of the bioreactor and you change everything downstream. Instead of miles of steam lines and fragile commissioning, Biosphere is betting on UV-sterilized stainless systems, modern automation, and a full-stack approach that removes cost, complexity, and fear of contamination at scale.
Brian shares the hard lessons that shaped this strategy. In batteries, volumetric energy density mattered more than academic fashion. In solar, perovskite hype obscured the real blocker—stability. Translate that to biotech and the pattern holds: milligram wins and elegant papers won’t survive a plant with 50% contamination rates and $200 million capex. We walk through why legacy steam sterilization persists, how biopharma escaped into single-use plastics, and why industrial biotech needs a third path that’s cleaner, cheaper, and durable enough for daily production.
We also get tactical. What does it take to prove sterility “100 out of 100” times? How do you stress-test reactors with spore challenges, long sterile holds, and instrumentation that actually supports root-cause analysis? Why start with ag biologics (eg biostimulants and biopesticides) where customers feel the manufacturing bottleneck most acutely? And how can a 20,000-liter demonstration line bridge the gap between pilot and revenue, unlocking offtake and real unit economics without betting the company on a greenfield?
There’s a policy and resilience angle too. With defense and industrial strategy shifting toward domestic capability in vitamins, antibiotics, and specialty inputs, better reactors are not just a cost play, they’re a strategic asset. Over time, once performance is undeniable, even conservative markets like biopharma may follow. Until then, the opportunity is clear: lower the hurdle rate, reduce plastic waste, simplify scale-up, and let product companies focus on what customers actually want.
We felt that the way we could have impact was solving hard technical problems to change the constraints around the bioreactor, commissioning a system and using it to serve customers, and then having that demonstration line be the proof of concept for further commercial scale.
SPEAKER_02:Welcome to the Climate Biotech podcast, where we explore the most important problems at the intersection of climate and biology, and most importantly, how we can solve them. I'm Dan Goodwin, a technologist who spent years transitioning from software and neuroscience to a career in climate biotechnology. As your host, I will interview our sector's most creative voices, from scientists and entrepreneurs to policymakers and investors.
SPEAKER_01:We're thrilled to welcome Brian Heligman, CEO and co-founder of Biosphere for a discussion about climate biotech. Brian trained as a material scientist and engineer, getting his PhD from UT Austin in advanced battery manufacturing before later pivoting into biomanufacturing. Together with his co-founder Ari Lippmann, Biosphere has been built around a simple but radical idea. Replace outdated steam-sterilized fermenters with UV sterilized bioreactors that cut costs and make scaling easier. As you know from talking with Homeworld, we're really into good problem statements. And the journey that Ari and Brian got to finding a very good problem, I think is a gold standard and I hope is inspiring for other entrepreneurs and scientists out there. So without saying anything more, let's just jump right in. So, Brian, who are you? Where did you grow up?
SPEAKER_03:So I actually grew up in a suburb of DC in Maryland, and then went through high school there to University of Maryland, and so spent most of my upbringing kind of right outside DC.
SPEAKER_01:Is this a college park?
SPEAKER_03:Yep.
SPEAKER_01:Awesome. Awesome. Well, did you always know that you'd be a tech first CEO at the front lines of biomanufacturing?
SPEAKER_03:Definitely not. I think I always felt a really strong pull to science, where I remember when I was a kid, I thought I wanted to be a chemist, and then I kind of learned what chemists did and decided that maybe I wanted to be a chemical engineer. And then I learned what chemical engineers did and decided I wanted to be a material scientist. And so that was the journey, especially really trying to focus on how you could apply some of that science and technology for impact. And then it's funny, throughout this venture, I've been pulled back towards the chemical engineering side of the spectrum more recently. So that wasn't something I really thought about. And especially with this more recent project, I really had focused on finding a great team to work with. And after I linked up with Ari and we got to talking, we decided to start Biosphere together. The route to a CEO just ended up being what made sense.
SPEAKER_01:I can't wait to talk more about Biosphere, but I do want to hover a little bit because when I met you, you were still a PhD student, and I thought of you as the battery guy. And you really blew my mind telling me great stories about what that was like. And I think you have some really good anecdotes for where kind of the academia industrial interface falls flat in the context of batteries. And I bet that has some influence in what you are doing for Biosphere. But first, tell me a little bit about this transition of did you know that you were going to do batteries out of College Park?
SPEAKER_03:So at University of Maryland, College Park, I think a really formative experience for me was getting pulled into a medical device research lab, my freshman year. And so just from my engineering 100 professor, he actually ran a program focused on point of care diagnostics, where with a single drop of blood, we could measure what the blood ammonia levels were. And so my first project was actually working on a Theranos competitor at around the same time that was a little bit less ambitious in scope. And it was something that definitely stood out to me in that it was funny. The grad student I was working with just immediately called Theranos out as this big fraud. And then a few years later, that was more of a consensus opinion. And so it was formative in that I got to realize that I was good at this type of applied scientific research. I could make money doing that, and it could help people. And so I really solidified that as the thrust of what I wanted to do with my life in trying to apply science and technology for impact. At around that like 2012 to 2016 time period, I got really interested in clean energy. It was always something that I thought had a ton of potential impact. And I was really excited about some of the applications of solar in low resource environments where you can imagine electrification of the whole world with solar in a way that's pretty exciting. And so during that time period, as I was diving into the space, I had looked at solar cells and batteries as the two types of things I wanted to work on. And it was one of my first places with more disillusionment around some of the academia industry interface. Was I was particularly excited about both at the time. And the real focus in the 2010s in solar cell research is this class of materials called perovskites. Perobskite solar is something that has some really favorable characteristics for a solar cell. It's got potentially really high efficiency, it's super cheap to make, but it also has some drawbacks in that it is made of a water-soluble lead compound, and it is also unstable when exposed to water or light. And so when you hear the solar cell's not stable with light, you're like, that seems like kind of a problem. And the one professor I had talked to for a PhD program had published one great paper on the stability that really had seemed to make strides. And so I asked him, I was like, oh, like what's going on with that? And he was like, oh, we're not really doing that work anymore. And it was just kind of a little bit disillusioning that like the stability seems like the problem here. Like peropskites can have this transformative impact if they can be stabilized, but it wasn't something that was considered a top priority. And that was just because of the nature of their research programs. I do know perobskites have made strides since the 2016 time period, so they are getting pushed along forward. But it was kind of in contrast to the battery program that I had visited, which had actually been built around the inventor of the lithium-ion battery, John Goodenough, who is an amazing guy. He won the Nobel Prize while I was there, and somehow he has invented like every cathode material that has ever been commercially useful, or his labs have. That program was really structured around a decent amount of engagement with industry. And so that was something that given my focus on applying of technology for impact, it was a better fit. And super happy with that, as how it turned out. The program was great, but I think during that time period it was more clean energy that I wanted to focus on. And batteries and solar cells were just kind of the two materials things that seemed like they could have impact.
SPEAKER_01:Two quick questions to hover on this. With the lead profite issue, was it an issue of like a silent death temporarily? Did people just not talk publicly about these? Because I I feel as if I followed it from one step outside, right? I was in the bio department and then read the occasional lead provskite paper, and I read it from the perspective of, oh, could bio precipitate out the lead and try to capture it. But it didn't it wasn't something that wasn't framed to me as like this is the rate limiting step that's stopping lead provskites from taking off. So was it kind of was there an obfuscation that bothered you, or was it just the fact that this guy changed his lab so much?
SPEAKER_03:I think it was just to me the obvious locker for commercial utility. And so doing research into this stability felt like the thing that would be impactful. And I think he just didn't have the funding to do it. I think some of the issues with perobskites are kind of captured by some of the issues with graphene, where like people found out it was easy to make graphene with things like tape. And perovskites are really easy to make in that you just need a spin coder and you can turn out to get a material that has exceptional absorption properties. And so for a thousand bucks of lab equipment, you can publish a paper, and there was a lot of room for some development on that front, and so it's a lot easier to just continue to push up efficiency by playing with formulations of perovskites. You can publish a ton of papers on it, but without more fundamental work on the core stability stuff, it seems like that technology will be limited. And so it has, I think I saw recently that maybe the first commercial cells are getting produced. I don't know if you ever have come across Jenny Chase. She was at like Bloomberg New Energy Finance, she's an analyst who comments a lot about solar cells, and I think her thing on Perovskites for a long time was just like, let me know when I can buy one. There's a lot of research, everyone always asks me about this potentially transformative technology, but it's not really commercialized in a meaningful sense. And the stability and encapsulation, making sure that the water-soluble lead isn't introduced to the environment where lead is pretty bad. So that felt like the high-leverage thing. And I didn't really want to do work just pushing up the efficiency of this technology without getting at the fundamental problem facing it.
SPEAKER_01:I love this point. I a big motif for my PhD was coming making a relationship with scale dependence, right? So in the brain, there's a lot of we talk about scales a lot. In this case of scale, you're talking about a thousand dollar project versus a million-dollar project versus a hundred million dollar project. And I think there's a beautiful reuse of that age-old metaphor of looking for your keys underneath the streetlight, where because it was so cheap to do a bunch of experiments, people are doing a lot of papers around perovskites. But I love your point of that you can do a lot of kind of micro scale projects, but the macro problem isn't going to be solved until people do a more substantial push. I I really like that. And uh, so what did you I you know, I really want to get to biosphere, but I think it's you know what I love about you as a CEO is that you've done this like nitty-gritty hard science, and so it's just fun to see how that you eventually got into biomanufacturing from this. Could you share a few words?
SPEAKER_03:One quick thing that I'll throw in, just so I'm not totally bagging on academia.
SPEAKER_01:I I bag on academia. People can I can be the lightning rod for for negativity, but yeah.
SPEAKER_03:The thing that's I read, I think it was like a blog post talking about the single most compelling reason to do a PhD is you get to spend four to five years working on something the market doesn't value in the short term. And so, like, more so than anything else, it is a much longer time horizon effort that you get to do in that. And so I think that PhDs in academia are unique in enabling that, but I do think fit thinking about the problem that you want to work on really does matter. Where like it should have that kind of bigger perspective, I think. And if you're starting with the end in mind, figuring out what research could be most impactful, it's a really easy to like many people get PhDs that don't meaningfully push things forward. They like learn some ways of designing experiments, they like get trained as scientists. But I do think academia is uniquely positive in that it can let you do some of that longer, more heavier RD.
SPEAKER_01:Yeah, strong agreement there. And then you chose, I mean, I think it showed a lot of early maturity to have chosen to go from batteries from that because from seeing that there's a potential trap, even though it would have been an opportunity to work outside market forces. What did you choose to work on your PhD with and what was an outcome from that?
SPEAKER_03:So I joined a lab that had a pretty heavy focus on a lot of cathode development work. And at the time I was originally really trying to think about storing intermittent solar energy, and that's kind of a thrust that I carried through even taking me to where I am now. So I started out looking at some of the zinc air type approaches and like how could you use low-cost materials. But actually, there was a really brilliant grad student in our lab who ended up showing a V1 prototype of this new type of anode material, and I saw it as something that was just truly different from anything anyone had tried before. He basically was making an alloying anode out of nanostructured metal foil, and so he melted together tin and aluminum. When it cools down, tin and aluminum phase separate like oil and vinegar, so they don't like to mix. And then by casting that ingot and then rolling it into a foil, he would smash down all of the domains in one direction and stretch them out in this other direction. So it was like this interdigitated metal foil that was a nanostructured material. And there were some ways in which that's really different from the way other people have developed electrodes in the past. There are some potential advantages with reducing the capital intensity of manufacturing, you can simplify it and you can push forward energy density. And so that was really the project that I pushed forward for the next five years, first collaborating with him on the first paper and then kind of taking more ownership as I built out the framework. And the thing that was exciting to me was I think another anecdote kind of talking about some of the mismatch between industry and academia that we had talked about before, was there was a seminar at UT where a bunch of academics and industry people came together. And as part of that, I got to have lunch with an executive at Apple who was doing a lot of their developments of batteries, both for the phones, but also that was a time when Apple, I think, was still thinking about a car more explicitly, so there was a lot of stuff going into that. And he voiced in that lunch just the single most important thing is volumetric energy density. It's like how much energy can you fit in a space? The battery field really likes gravimetric energy density. In some ways, it's easier to measure, but it's like how much energy can you fit in a given weight? But like those are the two ways you can think about that. And it was just really jarring because right after that lunch with him, let's say an academic got up and explained how industry didn't care about volumetric energy density and gravimetric was what mattered. And it's like I literally just had lunch with the person who was doing this work, and he said the polar opposite from that. And so the this approach was really good on that front. It could have a lot of impact on volumetric energy density. It could be you could squint at it and see it being commercially useful. And so through the five years, I progressed through some of these first proof of concepts up to the first pouch cell battery, where it's the first kind of real form factor, and ended up looking at commercializing that technology. I had gotten uh DOE SIBR grants to start thinking about spinning it out as a business, but eventually ended up recognizing that the battery industry had matured a lot between when I had started. If you look between 2016 and 2021, the price of batteries had fallen like fivefold. And approaches that made sense in 2016 made a lot less sense taking a more grounded look in 2021. And eventually I saw some of the more shining lights in the space. There's a company called SEAL in Nanotechnologies that has been working on this class of anode material for 10 years. They had been really they raised a large amount of money and finally got first products to market. And you get to see how challenging it is. Where there was some joke I used to make how there's been like zero successful battery startups in history. And as you're starting a battery startup, it's something that's easy to kind of write off that well, I'm gonna be the first, and like everyone else has failed, but we got this. But eventually taking a more grounded look and thinking, should I try to raise outside capital to spend on commercializing a new battery material at that timeline? It didn't make sense to me anymore, and so I ended up shutting that down and thinking about what I wanted to do next.
SPEAKER_01:That's awesome. I mean, really, obviously, you end up in a good place, but so we can do survivorship bias. But I do want to celebrate that, especially the entrepreneur. Part of what we have to do is be irrationally positive, right? And like have a story in our mind. We're gonna make it happen no matter what. But killing things is a huge part of it too. And so selfishly, I'm glad that you killed that battery program because I agree with the decision that you made. There was a great paper that just came out on a Packy McCormick's blog called The Electric Slide with Sam Domico, and it just did this amazing analysis of how all battery costs have dropped, you know, 99% since the 90s. Really, I found that super inspiring. And once again, that would be a very different business from what you're running now. So I I want to kind of move now to I think that's when we met. I think when you and I met years ago, you had just stopped the battery thing, you're in a you're in a big search period. And how did you get into biomanufacturing?
SPEAKER_03:So I had a little bit of background in biology from back when I was doing the medical device work. So, like biological systems were things I interfaced with for a few years. And the one other thing that it's kind of funny, but uh a friend of mine was doing some investment at kind of mid-stage companies and had been looking at an AI protein design company and asked me to help him diligence it when I was in grad school. And when you're in grad school, you don't really have uh you have a lot of free time. So it was interesting to me to just try to understand what was going on here. And one of the big questions that I had was like, it seemed really credible to me that artificial intelligence and advances in understanding protein folding could allow for new enzymes to be developed, but like how would it get manufactured? And is there more of a TSMC for biomanufacturing? Like, how would this company go to market? And during that exploration, I was on Twitter, and that's actually how I connected with Ari the first time when I was just trying to learn about the biomanufacturing space to help my friend out and just give him some perspective. And after that, we just kind of had one call, I think, and that was about it. Fast forward to me having shut down my battery company. At the time, I was really still trying to think about what do you do with cheap intermittent solar energy. And I kind of saw a few paths forward. I'm like, well, I learned two things in grad school. I like learned a lot about battery materials development. I also learned around hard tech entrepreneurship. I'm like, which of these skills is more valuable? It's not immediately obvious, and like you could go work for Tesla, but maybe I should try to think. If I am if I feel that my battery materials company was not a good startup, then what would a good startup be? And at the time, it's funny, there's a handful of people who were all playing with similar ideas on what do you do with the really cheap solar energy in the future. I think they're all brilliant people where like you can see Casey Handmer, who's been super early and vocal to this. I think Austin Vernon, brilliant chemical engineer, amazing blog. He just started something similarly focused. Jacob Brown was a Tesla battery cathode guy who was also thinking about this. I know Tapagosh is a friend of mine in the semiconductor space, but similar, we were all just kind of like batting around ideas and trying to think through what would the ideal low capacity factor industrial process be. And one of the ideas that really resonated with me was this idea of like industrial photosynthesis, where what you should do with the cheap solar energy is make a fuel that could then be upgraded to products throughout the night. That's kind of what the plants do, where they store the energy of sugar and then they use it to make useful things. And it's a pretty technical thing, but uh if you want to transform CO2 into products with electrochemics. Chemistry, you can kind of make two products, which are carbon monoxide and formic acid. And so that's CO or HCO2H. And there are like steric reasons why that is easier electrochemically. And one thing that I was trying to understand is well, what's the deal with formic acid? That's something I don't really think about a ton. What is it used for? What could potentially be an application if you expect formic acid to get cheaper with CO2 electrolysis maturing? And there was a really elegant synthetic metabolism that was developed by a professor in Israel, which basically was a cell that could process formic acid into pyruvate in the core metabolism. And that was pretty cool because I'm like, I expect formic acid to get cheaper with CO2 electrolysis, and maybe this is the ideal industrial process. When it's sunny, you make a big tank of formic acid and then you feed it to genetically engineered microbes to turn it into differentiated products. Because I was doing all of this work with like aluminum smelting, and then you can think about chloralkali process and hydrogen electrolysis, a lot of this stuff as well, like form energy is doing where you like buy the energy now, sell it later. Because I would kind of say that you could do time arbitrage of the energy where you buy it now, sell it later, and that's batteries. You could do spatial arbitrage where you build transmission lines. So you like buy it over here, sell it over there, or you could make stuff with it. That was a place where I just wanted to learn more. And so I actually reconnected with Ari talking about these synthetic formatrophs to see should I work on synthetic formatrophic organisms to try to be well suited for using intermittent energy. And Ari at the time was just laser focused on this manufacturing problem for scaling up products. He was at the time looking at should he buy a facility, establish a manufacturing capacity, and look at building the infrastructure to enable product-focused companies to scale microbial fermented products. And after I did a little bit more digging on the formatrophic stuff, I recognize that's maybe more of a 2030s play. Like solar energy is not quite cheap enough yet. The tech TRLs of the CO2 electrolysis, it's not quite there. But Ari seemed to have identified a really interesting market opportunity, which was a big problem with scaling biological products. Is the manufacturing infrastructure is very capital-intensive commoditized hardware that hasn't really seen much change. And Biosphere effectively started when Ari and I got together and decided to form a technology company innovating on production-scale biomanufacturing systems. Some of the thinking around what makes a good technology startup is I really do think you need to develop new technology. If the there are interesting plays with like private equity roll-ups or manufacturing type plays where it's just about building infrastructure. But if you don't have anything differentiated and defensible, then you're just doing things the same way as other people. And there are other people that generally have access to more capital than you do, or at least as much. And so what we instead focused on was could we identify a technical wedge that's enabled by a why now that could have a meaningful impact on the cost of production scale biomanufacturing infrastructure?
SPEAKER_01:So to take it a kind of the full story that I'm I think when you're talking about the professor, you're talking about the RNB-van papers, right? Or Ron Miller. Yeah. So I mean, if if a person listening to this has not tried to read an REIN paper, I strongly recommend it because you read it and it makes at least me feel like I know nothing. Like I'm not at least feel like I'm not creative, I know nothing about biochemistry, but they're really cool papers, right? They're very theoretical, saying this is how you could go from point A to point B. And so you took from that and kind of like his vision of the formate economy to designing kind of re reimagining the capital expenditures for biomanufacturing. I'm really, I mean, obviously, I'm very intrigued by this. And I think what a lot of people listening to this will ponder is kind of like it's the annoying question of why is biomanufacturing hard in the first place? Because I totally agree with the point that you're putting forward. I think that's pretty intuitive, that anybody can alpha fold up some protein, right, and feel really cool about it. And anyone could probably get, you know, whatever, a milligram or a gram for you know some amount of money, but you're not gonna do anything meaningful at any industrial scale until you start scaling it up. And the scaling it up is something that when you learn biochemistry, or like most people who read the our environment papers don't have an immediate intuition of what the details of actually bringing it up are. And I mean, I think we can be honest, I think we're kind of seeing the death knell of a bunch of companies that were started over optimistically from 2018 to 2022 on a lot of hype cycles on climate, I think for a lot of common reasons, learning that biomanufacturing is really hard. But that's you know, I've never I've never built a manufacturing myself, I've never worked on a tank. So why is it hard to do anything at a scale in biomanufacturing?
SPEAKER_03:It's just a system that's complex enough, and most of the solutions are bespoke enough that it's challenging for a lot of startups to access it. And I think the other problem that at least we saw was a lot of the enabling technologies and breakthroughs have happened on the genetic engineering side. And so that was something where a lot of companies were founded to genetically modify microorganisms to make products. I mean, they started with genetic, but more recently the tooling has gotten a lot better. And then those companies wanted to scale up to have the impact that you're describing. And so the path to scale for them was deploying hundreds of millions of dollars into infrastructure to build the factory. But the problem was it wasn't their core competency or focus. These were a lot of biologists and genetic engineers doing truly innovative work. But then they like would hire out an EPC to build a biomanufacturing line. And I kind of joke that these two startups built similar plants across the street from each other in Brazil that were both like multi-hundred million dollar capital investments. And both of those plants had a lot of challenges with the commissioning and getting it to run effectively. You would hear stories around how like when the plant was commissioned, the contamination rate was 50, 70% or more.
SPEAKER_01:Oh dear. And just so people understand what that means, you're saying three out of four things that you try to grow all has to just get thrown in the trash, right?
SPEAKER_03:Yeah. And there's not a lot of great rework when you have a contaminated batch in those cases. And so what we took from that was the core competencies of building biomanufacturing lines were different than the competencies to develop the products. And the other thing was if you could have a step change to the cost enabled by proprietary technology for the$200 million biomanufacturing facility, it like lowers the hurdle rate. Because you can see successes in the space. And I think there people have scaled a lot of bio-based products. Like you can look, laundry detergent enzymes are huge commercial success. People, I think a company that gave me a lot of and still gives me inspiration, they're around now. It's Genomatica, now Geno. They developed a process for turning sugar into spandex. And last year, a company announced a billion-dollar greenfield plant to establish manufacturing for this bio-based spandex process. It's taken them a long time to get there. But if the hurdle rate is you need a billion dollars of upfront capital investment, it is just going to be harder. Like the and the higher that bar is, where right now the bar for an integrated manufacturing line is kind of in that 200 to 300 million is like a good sized line for some of the more commoditized products. We just saw that reducing that number makes it easier for everyone. And it still would be hard to successfully scale. There are ways you can try to do it with contract manufacturers today, but the challenges associated with capital projects of that level make it a little bit more difficult for new entrants to establish capabilities.
SPEAKER_01:There's an interesting feel of two problems that are somewhat at odds. So one is you know, one answer to why is biomanufacturing hard is that every development is bespoke, right? There's the downstream processing that's different, there's the what growing the bug is different. So there's that, but that's also in conflict with the other tension of it doesn't make sense to have to build your own bespoke plant yourself. I remember when I was first looking into biomanufacturing, I think it was Darren Platt who told me this quote, but I but anyway, he has a the joke is basically to the effect if you want if a biologist was gonna go create an iPhone, they would first go to the sand the beach and dig up sand, right? He's like, that's what biomanufacturing looks like is you're not even dealing with glass yet, you have to go get the sand. So if the challenge is you simultaneously have a bespoke process to actually get your thing working, and you don't want to have to build the capex yourself. Kind of how does how does Biosphere think about the those two balancings?
SPEAKER_03:I think what we have at the start focused on was identifying whatever types of process agnostic innovations we could do, where if you put aside the process, there are some places where processes are bespoke, downstream processing where you're doing the separations are consistent within a product category, but there's a lot of variability across different product categories. We wanted to understand where are the common maladies, and the bioreactor really is one. I think there has been more standardization around two types of bioreactors. I kind of think of a 200,000 liter stirred tank reactor as the workhorse of the industry. It's maybe something that costs like 15 to 20 million all in, which is like a big lift if you're a startup, and that's the industry standard, and usually people want a couple of those. I think that we feel that by developing that technology, it will be stuff that we can trickle through both by commissioning infrastructure ourselves and making it available to partners so that we will build advanced bioreactors that have better price performance enabled by the underlying technology innovations that we've put forth. And then eventually you could imagine evolving into more of a technology licensing model where you provide it to other people. But we at least are technologists that aren't like the way we are trying to solve the problem that is the current path to scale relies on extremely capital-intensive infrastructure, is through technical innovation that reduces the floor of these types of systems.
SPEAKER_01:Got it. So is it right to say that Biosphere is a company that builds next-gen bioreactors and for the short term rents them out?
SPEAKER_03:Yep. And so we realize that given the fact that we want to be fairly aggressive on technical innovation, we'll need to build and operate the first systems ourselves. I think one of the other things is you need so many things to go right to successfully launch a product. Where like the biology is hard, the manufacturing is hard, the securing the commercial offtake is hard, the marketing is hard. You see all of these challenges where it's I think the example I try to give sometimes with makes of like why it's hard is let's say you've developed a new process that makes vanilla. So like the vanilla flavor. You've engineered N. coli to do that. The question is, like, what would the market pay for this product? And so you say, well, today 99% of vanilla is produced from coal tar. Customers don't like coal tar, like the American consumer is wary of some of these synthetic chemicals. And so there's like Madagascaran vanilla, which sells for$2,000 a kig, which is the natural stuff, and then you have the petrochemical stuff that's$15 a kig. And you said, I feel like I should be able to sell it for more than the petrochemical stuff, but people also don't like genetically modified organisms. And so you're like, they don't like them as much as like Madagascarian flowers. So I think that I can sell it for$30 a kilogram or something like that. But until you're manufacturing and selling the products, it's hard to get someone to secure that type of offtake because you don't really have the discovery of going to a big CPG company and saying, wouldn't you like to eliminate say all natural ingredients on your products? I would love to sell you this, which is enabling and does give you a brand advantage, but they want to have the product to sell it to really understand its performance characteristics. And then you need the hundred million bucks to build the plants, or you can try to fit into existing CMs, and there are it's a lot of friction when you have a process trying to go into something that was built as an antibiotics plant in Bulgaria or something. And so the nailing the off-take, the technical scale-up, and the general execution is something that I think there's just a lot of pieces that all need to work. And most companies just can't afford to take risks on the manufacturing infrastructure. Like you've spent all of this time, you've raised your Series B, you kind of have an understanding of the technology platform that exists. And you're not going to do something different on your manufacturing line when you're looking at building it because you've taken all this other technical risk. And so the other piece of this that's maybe worth briefly touching on is the industrial biochemical scale-up, I think, is also shaped by the fact that biopharmaceuticals are the dominant biomanufactured product. And so one of the things that's interesting is there are legacy bioreactor companies. They are not focused on this market, they don't even show up at the conferences. If you are a Sartorius or an Eppendorf, you have a customer that you are effectively serving in the biopharmaceutical producer. And it is a totally different set of requirements versus the person who wants to make this bio-based vanilla product. It's very regulatory constrained, a different host. And so actually, Sartorius, one of the leading bioreactor companies, shut down their stainless steel bioreactor program to focus on a single-use approach, which can basically be thrown away after every run, just because that's a better fit for biopharma. So, in some ways, we think that the much of the innovation is downstream of the advances in genetic engineering, product development, thinking through how you can make products that resonate with customers. And the legacy hardware vendors are just focused on a different market. There's some ways you can try to draw parallels with the legacy space companies versus SpaceX, where it's like serving a different type of customer in the DOD. But all of that is to say, I think that the challenges are very much downstream of the fact that it is a highly complex multi-year scale-up that requires a ton of capital intensity and it's generally underserved by current vendors on the hardware side.
SPEAKER_01:Yeah, totally get it. It makes me uh I mean, I I empathize with kind of all players here. If you are a biomanufacturing vertical, it's kind of nice to go sell something for hundreds of thousands of dollars a gram, right? To do the GMP to go into humans. What I really feel bad for is the companies that are doing kind of like next-gen foods, and then to sell the you know, the person who's considering buying them, say, Yeah, great, can you just give me a five kilograms just so we can test it around? Right, because for them that's nothing. It's like give me five kilograms of your beef, I'll show it to my my cooks, right? But five, you know, five kilograms of a new beef, and I'm just making that up, right, is a lot if you have to build the whole manufacturing process for that. I think it's it's worth going into some specifics here about what you guys chose to be kind of your big innovations because you look at a tank and these things are seven years old, there's probably a lot of things you could have made better. But how did you kind of rank order or you know what what is the defining technology that you guys talk publicly about with with biosphere?
SPEAKER_03:Yep. So when we were in this kind of early exploration phase, you can try to think about what are the characteristics of the bioreactor. The kind of outsider question is how is this different from a normal fermenter? People often say biomanufacturing is like brewing beer, how is it not? And so you can say that bioreactors are aerobic, they're agitated, they are instrumented, and they are aseptic, or like some of the really big ones. We ended up thinking about the aseptic constraint as a pretty interesting one. So you have this big 200,000 liter tank and it needs to be sterile. The microbe you've genetically engineered to make vanilla is not very good at growing anymore. I kind of will give an analogy that it's kind of like when humans bred wolves to become pugs, and pugs are not the greatest at being dogs. And so if biomanufacturing is kind of like a pug farm where you're throwing out steak trying to grow as many pugs as you can. If wolves get into your pug farm, then you don't have a pug farm, you have a wolf farm, and that's a lot worse. And so, right now, the primary approach used by industrial biotech is using a steam sterilization approach. This was developed by Pfizer in the 40s when they were commercializing penicillin. So you can see the modern reactor looks pretty similar to that system. But steam has some undesirable characteristics. It introduces a lot of maintenance burden on seat replacements of valves. You have to have, if you ever have seen some of these systems, there's pictures I show where there's just like 100, 200 valves in a lot of these with miles of stainless steel steam piping, a thousand bucks a foot. And that is one of the things that's pretty different from a normal like microbrewery fermenter. And so one of the interesting things is the biopharma people have actually moved away from steam sterilization. They found it to be too expensive and unreliable to make pharmaceuticals. And so they just use single-use bioreactors they throw away every time. And if it's too expensive and unreliable for pharmaceuticals, it's not really something that is a great fit for some of these other products potentially. And we came up with the approach to use basically UV or non-ionizing radiation to sterilize the inside of a bioreactor. We believed bioreactors are mostly already clean, non-porous surfaces. UV is good at sterilizing clean non-porous surfaces, and a lot of it just seemed like an engineering challenge to develop a bioreactor that could be sterilized with UV radiation. It was something that's not done today, and there was not really any prior art in it. But there was no technical reason why it couldn't work. It wasn't like an open-ended science project. You needed to engineer the system so the radiation hits all of the internal surfaces. And the upside of that is you can substantially simplify the auxiliary process piping. Right now, each of these tanks, it's effectively like a 200,000 liter stainless steel vacuum chamber because you need to be protected in case the steam condenses. And so it just adds a lot of engineering requirements throughout every step of the design process. And it's the reason why you can buy a 20,000 liter fermenter for about 15 grand. And like I said, like a 200,000 liter. Liter startank reactor costs 15 million. And so if you just try to imagine you should get economies of scale as you get bigger, that 15k fermenter is an off-the-shelf thing you could buy, it would show up at your place next week. But it's not sterilizable, and that ends up being one of the real challenges. So we chose that as a first highly differentiated thing that could enable a sustainable cost advantage. And then the other place we've invested in a lot is just trying to think about how you can leverage more frontier approaches to industrial automation to better handle the complexity of bioprocesses. And it's a place where you can see there's been a lot of new developments and more open automation ecosystems, things that are more MQTT-based approaches, which is like a more Internet of Things way of sending data around that we think can be enabling for having well-instrumented automated biomanufacturing lines more cheaply. And so we basically chose to vertically integrate through automation and develop proprietary reactor designs enabled by a different set of engineering constraints and are looking at commissioning a 20,000 liter demonstration line that we can run for customers. We've seen there's kind of some unmet needs at this scale that would be useful for early commercial manufacturing. So if you're trying to do new product introduction and you want to have a cost structure that's reasonable, that 20,000 liter scale is one that we like. And so we felt that the way we could have impact was solving hard technical problems that change the constraints around the bioreactor, commissioning a system and using it to serve customers, and then having that demonstration line be the proof of concept for further commercial scale up.
SPEAKER_01:I think for the entrepreneurs listening to this, your story is a really good one. Because the the discovery of the problem of sterilization is kind of like the the dream problem in some ways, right? Meaning that first of all, you only found like I think it's really easy to take for granted now, like oh, okay, biosphere does better sterilization, blah, blah, blah. But no, to really find that and to see that the state of the art was desveloped in the 40s, you had to dig, dig, dig, dig, dig working backwards from a really big problem. So it just I want to make sure that we appreciate that. Also, I love the idea that I've stared at so many bioreactors and I've never wondered why there's so many tanks and valves. So it's good to know that there's an there's an easily and replaceable answer for this. It reminds me that what for a little time in my undergrad, I was in rockets. Um, and we had a really good engineer from SpaceX who took a little time off, I think, to de-stress to teach. And he had this great quip, which is that he's like, when you build rocket, you measure with a micrometer, you draw with chalk, and you cut with a hatchet. He's like, when you actually launch stuff, it's a lot messier than you think. And I think that's relevant here, right? You design with alpha fold and you get a molecularly precise, and then you shove it full of steam and hope for the best. So I think radiation as a clearance mechanism mechanism is a lot better. How challenging was it to prove that this was good? Like that this was good enough.
SPEAKER_03:That's really been one of the big challenges that we've been grappling with. I do think it's one of the things that you come in from an outsider with a new approach, and then you have to kind of learn a bunch of lessons around why best practices are the way they are and figure out how to move forward. I'd say that it turned out, you know, it's people talk about like how prototyping is easy, manufacturing is hard. Sterilizing the first UV bioreactor, actually, really not that hard. Getting a UV bioreactor that could be sterilized a hundred times out of a hundred in manufacturing environments is much more tricky. I think when you also talk about the kind of big hairy problem aspect, people are terrified of contamination in this industry, and they just throw CapEx against it for good reason because when you make these products, your margins are so thin that if you lose a couple batches, that was all of the profit you were going to make for the year. And so people are very reticent to try anything new in this space. It's also part of the thing pushing us to build the first systems ourselves at a reasonable scale to demonstrate it. And so a lot of it has been trying to do validation of individual components, qualifying them into these systems in a more defined way. Because really, the hard part with dealing with contamination in a plant like that is there's enough complexity that root-cause analysis of like why did it get contaminated? There was some story floating around on LinkedIn about how this one plant had an evil bioreactor that would always get contaminated and they could never figure it out. And there was a crack in the single valve seat that would be hidden when the valve was open, but only would show up when the valve was closed, and it took them like a year and a half of just like tearing their hair out. You hear other people who at some point you're just like, maybe if we just clean it for longer, it'll go away. But given it's like a weakest link in the chain thing, if you like almost sterilize a bioreactor for many products, that is it just I guess it depends on the product category too. Because you hear about some types of products that are run with much more loose acceptance criteria on what goes into them. But it's the validation and ensuring that we can deliver a system where we can guarantee quality has been something that has been front and center in our mind. Because at the same time, if we sell someone a UV biomanufacturing run and it does not sterilize appropriately, they're not gonna give you a second chance. And so a lot of it has been focusing on how we can really aggressively stress test these systems in bench top and pilot environments to gain confidence that at larger scale it's gonna be successful.
SPEAKER_01:I gotta make the joke that if you do actually find some bug that can survive 100 doses of your UV, that might be useful. You might have a little biodiscovery there.
SPEAKER_03:Uh this one of the real questions is you say, well, what is the right challenge? There's actually good literature out of Merck talking about like how do you assess what your worst case soil is when you're validating bioprocessing equipment? Because you can just keep challenging with more and more stuff, and then it'll break eventually, and then figuring out is that the right level. There is one microbe, I think it's called like radiodurons something.
SPEAKER_01:Conan the bacterium.
SPEAKER_03:Yeah. So there like that one, like we test with a lot of spores that are pretty UV resistant. That one, I'm like, let's not keep that one in our lab right now. Like we can use pretty aggressive challenges. I think that like the types of spores we're using are considered to be super UV resistant. So what we do right now, and this was also a learning process, is we like soak all of our reactors in a concentrated spore solution before cleaning them and then returning them to service with a multi-day sterile hold to just validate we can reproducibly return to service from a worst-case event. So I do think we're challenging it pretty hard. But that one microbe, I'm like, we'll just keep that off to the side for now.
SPEAKER_01:Actually, I fell into the hole about why that one is so resistant. And it's really interesting, right? They use melanin and they use you know all these other chemicals, but I think a big one of you know, DNA repair mechanisms, obviously going haywire, but uh you know, it also does the brute force solution of just tons of copies of its genome. So it can it can eat a lot of radiation and and and eat a lot of double strand breaks before it stops working. Moving on though, when you think about kind of what's next, you know, you guys raised a big round, congratulations. And then there's been some really exciting progress in the company. And so it's it's I love that we've gone started from the RN Bar Evan motivations, talked about one of the big first core technologies, and it'd be great to know just kind of where are you now and you know what's got you excited for the next year.
SPEAKER_03:So a big thing for us with a more processed agnostic innovation is trying to find the right market. And so thinking through the commercial strategy has been an ongoing effort at the company. We kind of came with this larger market problem, but what's the right niche? And one of the niches that we've found that has a real unmet need for high quality manufacturing at the scales we're describing is actually in the agricultural space with biostimulants and biopesticides. And there's a lot of really exciting products being developed that can do things like replace a third of the nitrogen used for corn and soybeans. So you don't need synthetic fertilizer. You basically use this and it will fix nitrogen from the air. I also think there is really interesting developments in the biopesticide space where you can use biologically produced products to have hyper-targeted pesticides that have less negative health and environmental effects. And so we've been engaging with a lot of customers in this space to try to get an understanding of their manufacturing needs and what is their road to market. How do they engage with a step change in bioreactor price performance? What could that unlock for their businesses? And I think that's been something that's been really rewarding because it's a product category that is finding meaningful success today. I think that they are launching products and growing quite a bit, and they really feel the more acutely the manufacturing bottleneck, and that a lot of these companies can't like build a bunch of plants themselves to scale up their products. They're finding CMs, but dealing with a lot of the quality issues. And so finding what the right balance of quality, cost, and performances for those types of applications has been great. And most of it has been focused really on what would be the early commercial scale for them. So we've done a lot of conceptual design of this manufacturing line and then the customer engagement to understand the economics of that manufacturing line. We've gotten the core technology to a place where our benchtops are great, our pilot reactor is coming together, but thinking more around the original goal of Biosphere, we always saw ourselves as a next generation biomanufacturing systems company where we didn't want to just make and sell bioreactors. We wanted to own the soup to nuts, thinking about media prep, utilities, bioreactor, and downstream, and figuring out where new technology can impact the overall price performance. And pushing that to actually a test against customers in the market has been the main focus of us right now.
SPEAKER_01:Yeah, it makes sense. I you know, I don't know if it's in your core business, but the fact that there's no plastic uh might actually have some benefits. I don't know if you can ever like kind of steal some effluent from uh from a somebody else's like plastic tank and just see if you can massback that for plastic. I'm sure you do. I'm sure you would. I I mean I know people who work in kind of that kind of GMP manufacturing, and they're like, I really want to work on climate, and then every day I go work on these tons of plastic, I'm gonna throw them away at the end of the day and feel terrible about it. So there is a difference of kind unlock that you're touching on, especially as now you look at the Bayer stock, which is down 75% since acquiring Monsanto and a disastrous deal, right? So there is kind of like the anti-plastics, anti-effed up chemicals going in our food angle that frankly, if it's if it's just steel and light, you know, I'd much rather just chug it from a biosphere reactor.
SPEAKER_03:Yeah, I think it's interesting. One of the market or value propositions that's resonated is the e-waste reduction argument for the biopharmaceutical players, or because they do generate so much plastic waste, that is a thing that moving away from some of the single-use components to more usable things has value to them. Our perspective has been that our technology actually could have a lot of value across the biopharmaceutical sector, but they're not going to be early adopters of new technology, which is why we've looked at some of these more industrial applications. There's like kind of a classic innovator's dilemma type argument you can make where they talk about how the mainframe customers didn't really want personal computers until personal computers got good enough. And like it's because you weren't exactly able to serve the needs of that market with your new approach. But there are other markets that value the performance characteristics upon which you're good. And so the biopharma market, they do care a lot about sterilization and they do have a lot of issues downstream of maintaining sterility. But I think that the fine chemicals and specialty chemical sector are people who feel the pain point more acutely, and I think it's probably a more direct path to market for us to serve them at the outset.
SPEAKER_01:Awesome. And I I know you can't talk too much about it, but I think I saw online that you guys recently did a uh DOD contract, got awarded to you guys, right?
SPEAKER_03:Yeah, we've actually got two DOD contracts. It's interesting that the Department of War now, so it's no longer DOD, they are focused. Yep, the DOW. They are focused on industrial policy again in a way that's a little bit more unique. You can see this downstream of some of the rare earth type decisions and the geopolitical tension there. There are a number of more bio-based products that the geopolitical and strategic rivals control, with things like animal feed vitamins being monopolized by outside parties. Antibiotics are pretty much all produced overseas in certain countries. And the DOW has been continually refining their strategy for how we can maintain technical advantage in biomanufacturing and leverage it to meet the needs of the workfighter. And so we've been working with them on two distinct projects at this point, where they see value in a more streamlined, more performant biomanufacturing system for some pretty interesting applications. So it's something that it's been really a valuable relationship for us and one that we're gonna continue to invest in the future as we balance both our dressing private sector customers and also engaging with the public sector more generally.
SPEAKER_01:That's super exciting. I'm really happy for you guys. So this is where we wrap up. I'm gonna ask you four rapid fire questions, and then at the end, we can ask where people can find you, kind of what kind of teammates you're looking for, you know, how the listeners can help out Biosphere. But first, four questions, and you'll see that they bias pretty strongly towards personal development. So, first rapid fire question. What's a single book, paper, art piece, or idea that blew your mind and shaped your development as a scientist?
SPEAKER_03:I mean, the one that always stands out to me is The Last Question by Isaac Asimov. It's like a short story, it's maybe 10 or 11 pages that takes a pretty high-level perspective on the development of civilization. And I've always loved that. That's been something that has stuck with me for a long time. I recommend it to everyone. I think it's a very fun short read.
SPEAKER_01:Wow, I've read the Foundation series, but not the last question. So okay.
SPEAKER_03:10 pages. You can get it's what's also so accessible. I like short stories because you can get through them in a short period of time. But I would highly recommend it, strongest recommendation to anyone listening.
SPEAKER_01:Fantastic. All right, number two, what's the best advice line that a mentor gave you?
SPEAKER_03:I mean, advice is always a little bit generic, but one thing that stuck with me from my first academic advisor when I was doing the medical device work was he pulled me aside and he said, Focus on one thing, Brian. You're too scattered. You need to focus. And I think that's something where it's always a good idea to focus more than you are. It's easy to get pulled into doing a lot of different things and not doing everything well. And so trying to balance the right level of broad ambition with narrow focus, I think, is something that probably, at least for my own personality, I always need to be trying to strive to focus a little bit more than I am.
SPEAKER_01:Pretty helpful for me to hear that too, right now, actually, to admit just to admit. Okay, number three. If you had a magic wand to get more attention or resources into one part of biotech, what would it be?
SPEAKER_03:One thing that I think is pretty interesting is there are compelling arguments for applying AI and machine learning to microbial fermentation. You can actually see papers of DSM using artificial neural networks to optimize raboflavin manufacturing in like 2002. And it's this highly complex system where you have controlled inputs and directly measurable outputs with the transfer function being extremely complicated with like life inside of it. And as we've been building this advanced infrastructure to try to enable people to do more creative things, like trying to figure out how that can be done well. One thing that was exciting, I just saw recently, a Google team came out of stealth. And so they are focused explicitly on applying AI to microbial fermentation, which I think they have a lot of infrastructure and horsepower, so I'm sure they'll do some interesting work. But really, I think that figuring out what a more performant and flexible reactor can do for bioprocesses such that people don't have to hamstring themselves to extremely simple processes for scale-up, I think is something that would be a super cool and I think a profitable endeavor for the people who take it on.
SPEAKER_01:Great. And the last question what is one aspect of personal development that you think biotechnologists need to spend more time on?
SPEAKER_03:I'm not sure if it's personal development, but I think that like sales and thinking about customers is something that would be a good thing for this industry. I think a lot of technologists focus a lot on the technical side. It's something we talked about a ton today, and it's something that I obviously love as having create a technology company. But something that's resonated with me more and more throughout my journey over the last few years is they talk about like how Jeff Bezos wanted Amazon to be the most customer-focused company ever and like obsession with customer. And the customers really matter. It's the thing that your technology is only useful if you make your five pounds of new beef. Do people want that? And what do they actually want is something that I think it would it's a trap that many technologists, including myself, fall into. But I think that figuring out who you're serving and how you can serve them and help solve their problems is the way that you create value for other people. And I think that's something that we all, at least I feel, is only more important every day.
SPEAKER_01:Fantastic answer. All right, Brian. It's been an absolute pleasure to catch up. Can you tell people where they can find you, what resources you want to point them to, and how they can learn more about you in Biosphere?
SPEAKER_03:Yeah, I think I am I checked my LinkedIn. I used to be very active on Twitter when I was a grad student, but I think the entrepreneurial journey has left me less time for tweeting, but I still do check my Twitter as well. So those are two easy places. You can email me at Brian at biosphere.io. That's another great way to reach me. Nice, easy to find email. I think we're always looking for potential partners who are looking at scaling up new biomanufactured products, engineers, commercial development leaders, people from operations who have thought about biomanufacturing and these types of sectors. And yeah, I mean, anyone who has a lot of interest in what we're doing, I think that the team that we build is really the most important thing. So I think that's both with internal team members and outside collaborators, a place we're always looking to have jets.
SPEAKER_01:Awesome. Brian, congratulations on all the awesome progress. Can't wait to talk again soon. Yeah, thank you so much. Thank you so much for tuning into this episode of the Climate Biotech Podcast. We hope this has been educational, inspirational, and fun for you as you navigate your own journey and bring the best of biotech into planetary scale solutions. We'll be back with another one soon. And in the meantime, stay in touch with Homeworld Collective on LinkedIn, Twitter, or Blue Sky. Links are all on the show notes. Huge thanks to our producer Dave Clark and Operations Lead Paul Himmelstein for making these episodes happen.
SPEAKER_02:Catch you on the next one.