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
Redirecting the Microbiome: Rethinking Copper Mining with Sasha Milshteyn
What happens when a structural biochemist turns his attention to mountains of rock? Dr. Sasha Milshteyn takes us on a remarkable journey from studying tiny molecular movements in proteins to revolutionizing how we extract copper from massive mine heaps.
The mining industry faces a critical challenge - we've depleted most easily-processed oxide copper ores, leaving behind harder-to-extract sulfides that typically yield just 30-50% recovery using conventional methods. This creates a significant bottleneck for the clean energy transition, which demands unprecedented quantities of copper. For decades, miners have attempted to improve extraction by growing iron and sulfur oxidizing microbes in labs and inoculating heaps with them, but these introduced microbes rarely thrive against established native communities.
Sasha's breakthrough insight came from recognizing that every ore heap already contains a complex ecosystem of extremophiles - acid-loving microbes that derive energy from "eating rock." Rather than fighting against these established communities by introducing foreign organisms, Transition Biomining analyzes the native microbiome and identifies what's limiting its performance. They then develop custom "prebiotics" that enhance the function of these specialized microbes, potentially boosting recovery by 25-30 percentage points.
What makes this approach particularly powerful is how it integrates with existing mining infrastructure. A medium-sized mine moves approximately 100,000 tons of rock daily - the equivalent of 1,000 train cars. By working within established processes rather than requiring entirely new systems, Transition offers a practical path forward for an industry traditionally, and understandably, resistant to change.
Beyond mining, Sasha shares valuable insights for all scientists and entrepreneurs: understand what happens at scale before designing bench experiments, question assumptions in established protocols, and recognize how little we truly know about biological systems.
Linkedin: https://www.linkedin.com/in/amilshteyn/
Website: transition.bio
And that's kind of what the industry has been doing for the past 40 years, right, growing the known sulfur and iron oxidizers and inoculating the heaps. That's been the standard approach. That has never really worked well enough, and so what we're doing is actually finding the problem within the biology that's already there and fixing it.
Speaker 2: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. We're thrilled to welcome Dr Sascha Milstein, a biochemist turned entrepreneur and the founder of Transition Biomining. After a career studying the microscopic machinery of life, Sascha now sets his sights on one of the biggest climate bottlenecks around.
Speaker 2:Working through mountains of rock that we call copper mines. His team is harnessing the power of native microbes living in ore heaps, which we'll learn more about, which is essentially turning whole mine sites into giant bioreactors to pull out more metal with far less waste. We'll dig into how he made that leap from a lab bench in structural biology into the mine pit and what it takes to steer microbial ecosystems in the real world in very complex environments. And also, just on the personal note, Sasha is a very compelling scientist and entrepreneur and I'm really looking forward to this conversation. So, Sasha, let's just jump right into it. Who are you? Where did you grow up?
Speaker 1:Thanks, daniel, and thanks for an introduction. Who am I? So I was born in Ukraine and grew up in St Petersburg. So up until I was just about 14 years old, grew up under communism in Russia and effectively as a free range child. My family immigrated to US in 94. So I was right at the end of eighth grade, and so I had all of my high school, college, grad school, educational in the US. And who am I? You know? Very often people ask me what I do, and my typical answer is well, I'm a scientist. And then the next question is inevitably well, what kind of a scientist are you? That's a question that always stumps me a little bit, because I see science as really more a way of thinking, and then every kind of sub in science is just a set of semantics and rules, right, and so once you learn to think about science, it's really not so much what kind of a scientist are you, right, but what problem are you working on?
Speaker 2:I love that. Yeah Well, and let's go through the details a little bit. So did you always know that you'd be a structural biologist who's now working in mining?
Speaker 1:No, I had no idea. In fact, you know, in high school my plan was to go to college, get a pre-med degree or something similar to that, and go to medical school and become a surgeon. I even did an internship at a hospital when I was in 11th grade, spending 40 hours in the emergency room shadowing the art doctors which actually ended up being 80 hours until they figured out that I wasn't supposed to be there anymore and kicked me out. I really wanted to be a surgeon. That was a particularly attractive direction for me because it always seemed very mechanical, almost where you can physically fix problems. But then when I started looking at colleges and looking at pre-med programs, I realized that the pre-med programs were mostly designed to kind of get you through with a high GPA so you could get into the math school. And what I learned in high school was that if I weren't at least slightly overwhelmed by a course, I just lost interest in it. I took AP courses just to learn something and be interested in it. And so when I went to college I ended up declaring a biochemistry major because I figured that was still on path for medical school.
Speaker 1:I had a couple amazing chemistry professors. I took chemistry for chemistry majors, just for fun. I had a couple of really amazing professors who every couple of weeks brought a faculty member to talk about their research, and so that course did two things for me. One, it got me excited about chemistry and you know, being me, I added a chemistry major, thinking that it wasn't going to be much extra work. Thinking that it wasn't going to be much extra work. And then, halfway through my freshman year, I also got really excited about research that one of the faculty members was doing and went to her office and said hey, can I come work in your lab? I started working in the lab halfway through my freshman year in college and never looked back, got stuck into the world of research and trying to understand how things work on the molecular level.
Speaker 2:Wow, this is a big trend I've actually seen with people on this podcast is that they all tend to get into research really early with very similar arcs of. I was doing this because I thought it was awesome. So at some point in the arc that I know you were in, structural biology became the thing, and then that turned into neuro. Was that undergrad or was this now your grad work?
Speaker 1:That was now in grad school, so as an undergrad I did my chemistry and biochemistry majors. I ended up working in three different labs over the course of my undergrad, ranging from biophysical chemistry looking at protein folding problem, which was a really hot problem at the time, and then I took a semester off and did a co-op at Pfizer doing organic synthetic chemistry and drug discovery. And then I came back and did another stint at a lab on campus doing bioanalytical chemistry, looking at gas phase ligand binding of various metals what happens effectively in aqueous environment.
Speaker 2:Wow.
Speaker 1:Overachiever of the year? I don't see it as overachieving. I think what I really found fascinating is just learning all of the different techniques and tools for studying both biology and chemistry and the world around us. I really see my education as mostly building a toolbox. I never had that one burning problem that I had to solve. It jumped from space to space, kind of looking to build out this tool set that you can then apply to any problem.
Speaker 2:As in machine learning, we would call it steering into the steepest gradient. But you know and I think people listening to this one you're thinking let's get to the rocks. But I think it's like the fact that you end up doing work in neuro through the lens of some structural biology at least for me like really hits the cord as well, as you know, the way you're always pushing yourself to the max also hits a chord. But my PhD was in neuro economics, but from also a different perspective. So how, what was this arc of you? What? What made you choose to do a PhD in the first place?
Speaker 1:PhD seemed like the logical next step if I wanted to continue doing research. All right, so if I wasn't going to medical school, phd was was the next step. And so I actually applied to programs ranging from biophysics to chemical oceanography, to medicinal chemistry, dr Justin Marchegiani, again, you know there was a breadth of kind of interest. And so the biophysics program at Brandeis University ended up being kind of my favorite choice. And how I ended up in neurosciences. I was working in a structural biology lab that was studying structure function relationship and enzyme. So relationship between the structure dynamics and the function of enzymes. So relationship between the structure dynamics and the function of enzymes. So how do motions of the proteins affect their function?
Speaker 1:And while I was trying to figure out my PhD project, we had an incoming kind of request from a neuroscience lab at Johns Hopkins that had a model for regulation of a metabotropic glutamate receptor, that's on addiction pathways. So they found that if they disrupted the function of that receptor they also disrupted cocaine addiction in mice. But it had an unintended consequence of disrupting short-term associative memory. What they were really interested in is understanding the full molecular mechanism of this receptor regulation to see if there was a way to uncouple those two effects. So they built a model in mice and they discovered that there was an enzyme, pin1-peptidylprolyl isomerase, that all it does is it catalyzes the rotation of the peptide bond between a proline and a serine, or proline and threonine, where that serine or threonine is phosphorylated, and so the proline bonds have a high energy barrier for rotation, so they tend to exist in distinct conformations. And so there was this enzyme that all it does is accelerate the rotation around that bond and has a huge effect in the regulation of those receptors.
Speaker 1:So it was kind of an interesting question of how does it do it? What is the mechanism? So this lab came up with a model for how this works and they came to my PhD advisor, dorothy Kern, with an ask to do a quick experiment to confirm just one aspect of this pathway, to really strengthen their hypothesis. And I volunteered to do that experiment, to really strengthen their hypothesis. And I volunteered to do that experiment and three months later the results indicated that it did not work as they had predicted. And so that turned into my PhD project of figuring out exactly what's going on there. Wow, that's a two-week experiment that ended up taking about seven years of my life.
Speaker 2:Yeah, I mean that's a good arc, right, when you get pulled into something, and you know so I think. Also, I mean, I love neuro. Once again, that's my background too, and you know Paul Reginato, co-founder of Homeworld, has this great phrase that he said you know, when I worked on the brain, he said we work on things that are too small to see, and when I work, I'm working on something that's too big to see, and I think that they I love that phrase and that's such a good step into beginning to think about mining, Cause that's exactly kind of your arc, right. You were talking about you know what, like rotating bonds on single enzymes, and now you're dealing with these tons of rock, and so we'd love to just hear this arc of what made you even begin to start thinking about mining. How do you go from dealing with the Angstrom scale to the tens of tons scale?
Speaker 1:Right. So in between those two steps I did a postdoc. So when I completed my PhD I realized that, as much fun as it is to kind of dig into these tiny scale problems and really understand the underlying mechanisms behind things, what I wanted to do was do something that's a little more practical and has kind of bigger real-world applications.
Speaker 2:And.
Speaker 1:I switched fields again when I did my postdoc and I shifted into metagenomics and synthetic biology space, looking at how do you apply knowledge of microbial genomics and elements that microbes encode to real-world problems. The lab was working on drug discovery from metagenomes, so taking the whole collection of DNA from a given environment we were mostly working with soil because that's the most microbially diverse environment, right and then you know how do you identify chunks of DNA that encode for these drug-like molecules and then how do you heterologously express them to make that molecule in an organism that you can actually grow in the lab. So the really important learning at that stage was that there are so many more microbes in the environment than we're aware of. For every microbe that we can grow in the lab, there are about a hundred that we can't because we don't know what they need to grow in the lab, and part of it is because they exist in an ecosystem, right and so they rely on other microbes in their ecosystem to provide critical elements for them to thrive.
Speaker 1:This is where I learned about the community dynamics and learned about limitations that we have with cultured microbes and how they just really skim the surface of what's out there in the environment surface of what's out there in the environment. That postdoc led me directly into a job at Zymogen, which was a big synthetic biology company in the Bay area. There I continued working in the metagenomics group and applying these methods of taking microbial, environmental microbial DNA, using it to solve problems in industrial biotech everything from drug discovery to crop protection agents, to building blocks for novel materials and while I was there, I ended up working on a project with a copper mine, and that was really the point. That kind of got me to where I am now.
Speaker 2:It's the John Lennon walking by a guitar store moment.
Speaker 1:Yeah, exactly.
Speaker 1:And you know, interestingly, when that project first came to me, my initial reaction was like, why would we want to work with a mining industry I'm at a company that is focused on replacing petrochemicals with biologically produced molecules.
Speaker 1:Right, and mining is this incredibly destructive, incredibly dirty industry that does not have the best reputation for wanting to do things sustainably. And like, why would we even engage with that? Interestingly enough, I couldn't exactly say no, and I was curious to learn more, and so, through the process of, you know, talking to the people at the mine, kind of looking at the problem that they were having, what they wanted us to do, I realized a number of things actually. So one is that microbes play an incredibly important role, especially in copper mining. I got to go to the mine and see the operations and take a gold card tour of the mine site, which is, I think, about 10 square miles, and so just seeing the size of those operations and just thinking about biology at that scale, it was a little bit mind-boggling but also got me wondering how do you get the biology to work at that scale?
Speaker 2:Yeah, you know, I want to just kind of hover on this, this moment of going on the golf cart tour and obviously we want to talk about when you decide you were going to start transition. But you know a lot of people that we engage with at Homeworld say oh, you know, I can engineer proteins, I can liberate lithium. Obviously I've got, got a company. And then the first question I was asked was have you ever been to a mine? The answer to most people is no and it's not a knock on them, it's that it's pretty hard. You can't just walk onto a mine and then there's got to be that shock when you are a structural biologist thinking about working in very ethanol-sanitized benches to this place with gigantic 10-foot wheel trucks. And I would love to, just to the extent that you can, because we know that the mines like we're obviously not naming the mine or anything like that, but just kind of what was the experience, being a biologist for the first time going on a mine site?
Speaker 1:that was a little inspiring, right? Because you, just you look at this scale of operations and if you've never thought about it, it's really quite impressive. So you have mines decent size mine will move a hundred thousand tons of rock per day, I agree. Simply, you got the pity to kind of try to visualize what that means in like real world terms. Doing some math, it's equivalent to about a thousand standard container train cars. That's a good one. Think, 365,000 train cars per year is a volume of ore that a decent sized mine will move.
Speaker 2:And then you have to drive by all the parts of the mine that aren't relevant to you and there's going to be, you know, the big trucks and then the big pile, and so do they just kind of drive you to the point and they're like okay, here, biologist, here's your sandbox.
Speaker 1:So the question that we're looking to answer, uh, was really what are the biological drivers of overproduction and some of their heaps?
Speaker 1:So this is a mine that did a lot of heap leaching.
Speaker 1:Obviously, this is kind of how I got into this space and this is one of a few mines that has already been leaching sulfides for some time and has some experience, and they had some of the heaps that were producing well above what they were expecting and this overproduction was ascribed to biology going right and this is something that the mining industry has been trying to achieve for the past 40 years at least is to get that biology to work efficiently.
Speaker 1:But there's still very little understanding of what's actually happening at that scale and mines have very limited tools to look at the biology that's happening in the heap and yeah, so the project was really to understand the microbial drivers of overproduction and for that we had the mine drill core samples from heaps that had just come off from under leach. So they just removed the irrigation system on top of the heap and drilled core samples for multiple lifts. So lift the stacks of ore, so they will stack a lift, they will leach it and then they will remove the irrigation system and then build another lift on top of it right, and then continue leaching through that growing pile of rock, and some of those heaps can get to over a thousand feet tall like it's a I'm imagining a pyramid.
Speaker 2:Is that the right mental model?
Speaker 1:yeah, each higher lift is a little bit smaller than the one below it to maintain stability. So you can kind of think of the not the egyptian pyramids, but maybe the Inca pyramids right. Wow.
Speaker 2:I think that's a really beautiful thing. There's these moments where I'm really bullish on bio and mining, right, and then every so often I just have these moments of what are we doing, right, and when you just imagine a thousand foot tall pyramid but they're spraying stuff on these heaps, right. So presumably you do some sort of integration with an existing infrastructure.
Speaker 1:That's right, yeah, so they set up a drip irrigation system and they drip, dilute sulfuric acid through these heaps to catalyze the dissolution of copper from the minerals. So historically that's been used on oxide ores, and oxide ores don't actually need biology, they're readily acid soluble and you get very good recoveries. You can approach a hundred percent recovery from oxides with heat bleaching. But the problem in the industry is that the oxide resources have effectively been exhausted at this point. There are mines that still have some oxides, but 90% of the remaining copper in the global resource reserves, that's in the sulfide mineralogy right, and so sulfides would traditionally be processed using concentration circuit and then the concentrate would be tipped off to smelters, which at this point China has 53% of global smelting capacity and continuing to grow 53% of global smelting capacity and continuing to grow. So in addition to exp and for pyrometallurgy, you have to grind the rock into really fine powder to then make the concentrate. So you're expending huge amounts of energy to grind the rock into powder and 150 micron and belong below size.
Speaker 2:Got it Well, okay. To powder in 150 micron and below size. Got it Well, okay. And so to kind of zoom out from micron size but not go to full thousand foot tall pile of rock size, let's talk about company size. So what was the point that you realized? Oh, my God, I'm going to start my own company about this.
Speaker 1:Honestly, there wasn't exactly a point. So that project got me interested in biology. Right, effective, efficient biological processes can really increase the recovery of copper by 25, 30 percentage points, which is very significant, because for sulfides, typically your recoveries are in 30 to 50% range. Right, so you're leaving more than half of copper behind, and that was the problem that really stood out to me, and the ability of the biology to really improve on those recoveries. That's what got me thinking about the problem. What actually got me to start the problem? What actually got me to start? The company had nothing to do with that. Necessarily there was another. So after that project was done, I was stuck on this problem. I kept thinking about it and thinking about you know. So the one thing that happens when you we actually went and supervised for drilling to make sure that our samples weren't getting contaminated, to make sure that we knew exactly how they were collected, because if you're trying to understand the biology and environment, you have to take a lot of care to preserve what's there rather than what gets added to it after you've collected the sample and so going on this heap and looking at it and thinking about you know my background in synthetic biology and the challenges of scaling. We can do a lot at the bench right, so we can. We think we can do just about anything right, and yes, we can do it at the bench. But then the big challenge in biotech industry has been translating from bench to scale right. And so when you're standing on this heat that you know, maybe a square kilometer in surface area and 40 feet deep right, what occurs to you is well, how the hell do you get biology in here? Because traditionally the mining industry has relied on culturing specific iron and sulfur oxidizers and adding them to the heaps to try to drive that those catalytic processes. But kind of everything in my background was screaming like this is never going to work and so, post that project. I kept kind of going back to thinking about what can you do at that scale? It's not like what can we do at the bench, but what can you actually do at that scale? It's not like what can we do at the bench, but what can you actually do at that scale.
Speaker 1:And so after I left Zymergen, I was hanging around looking for the next interesting thing to do and a friend of mine, who was at an IndieBio funded company at the time, just happened to mention to one of the partners there that she knew somebody was thinking about upper bio leaching and they said hey, introduce us. Famous last words exactly. And so for me that was great. Sure, I'll talk to them, I have no plans on doing anything, but they have a couple biomining companies in their portfolio and halfway through a conversation, pay woo. The partner at indibio here in San Francisco goes why don't we find you to start your own company?
Speaker 1:I hadn't really thought about it before then, right, not that I haven't thought about it, I thought about it, but I was like I don't know the first thing about this.
Speaker 1:And so it's an overwhelming challenge that I wasn't necessarily ready for. And you know, my initial response was something like I don't know why would you? And we continued talking, and IndieBio was really convinced that the idea that I had was worth trying, and so we worked out an arrangement where and I'm eternally grateful to them they gave me a latitude, they gave me the first tranche of funding and basically said go figure it out, spend all of your time on figuring out whether this is legs. And I spent the first six, seven months just really going to all the conferences talking to the people in the industry and trying to understand both whether the way that I was thinking about the problem was viable, but also, you know, how do you actually get innovation into the mining industry? Because it is from my experience working with the mining company before. I already saw how slow things can move and how challenging it is to bring a new technology to mind.
Speaker 2:Yeah, I mean you can empathize with them why they have to be the way. They are right when you're moving enormous machines and the cost of a false positive could sink a company.
Speaker 1:Well, they're also doing their planning on decades to hundreds of years scale, so you really do have to respect that. They have real limitations on kind of what they can do and what they can try.
Speaker 2:Yeah, my experience is always that there's an interest. They're like you know how hard this stuff is. Do you know how? Hard, it is to actually get this thing pushed, and I think one of my favorite phrases I've heard is that when somebody adopts a new technology, they're putting their job on the line. They really have to trust you and that and the technology, and so I have empathy that it's a long sales cycle.
Speaker 1:That's right? Yeah, absolutely. But having said that, there are ways to kind of get through. That may not seem very obvious, but really they are. Seem very obvious, but really they are. And that's you really have to fit in within kind of the existing systems and in the industry, right this?
Speaker 1:is not an industry where you can be disruptor, and I had this conversation with somebody just a few days ago that what we're doing is not disruptive. We're not displacing a technology. We're not displacing a technology. We're not displacing a process. We're working within the existing process to make it work more efficiently. And the way that I've been thinking about what we're doing has really started with not what can we do at the bench and then translate, but what does it need to look like in the end state to actually work and to actually get implemented?
Speaker 2:Yeah, let's actually unpack that, because the end point that you're at makes total sense, but I think it's worth people understanding what you're not doing, cause I think that's one of the big things you have to choose as a company, just like when you're doing stuff in a lab. You have to choose what you're not doing and you're not making your own mind, right, right, but it's, I think you know, at least for me. Sometimes I think about that. How could you just set up your own minds and put robots with?
Speaker 1:you know, sell free on the back or whatever. You know, I do have a little bit of a dream of at some point building kind of the mind of the future that integrates a lot of the technologies that I've come across kind of over the past couple of years building this company, the technologies that I've come across kind of over the past couple of years building this company, you know, to really have a small demonstration mind to really show what you can do if you combine all of these kind of cutting edge technologies to fully optimize everything from scratch right and rethink how it's done, instead of kind of incremental small changes that don't risk somebody losing a job, but actually building it from scratch to implement all of the possible improvements.
Speaker 2:Oh, I love this. Yeah, it's kind of to make the sandbox. The drum I beat on this is low capex mining. You know what does it look like to, instead of having one billion dollar factory, if you had 110 million dollar machines that are reusable or and I won't say I've never been to a mine, so my opinion doesn't matter yeah just the thing I would push well.
Speaker 1:so, yeah, that gets challenging because if you think about the trucks that move the ore at the mine right so they have about a 300, I think, 325 ton load capacity those trucks cost something like five to $6 million.
Speaker 2:This is the hopelessness I'm talking about, that's incredible.
Speaker 1:Yeah, so having low capex mining is is a really tall order, but can you make it a lot more efficient? Yes, I think that's entirely possible.
Speaker 2:Got it, got it. And I think you know in this conversation we have to be sensitive, that you're a young company and so we don't want to dive into too many details. But we can riff about what you've said out already and I'll kind of just kind of shake your tree of knowledge on this.
Speaker 2:One thing that we learned, paul Reginato and I, when we were at MIT, going into what does it look like to deploy real biology out in the real world, and I think we talked to the Ian Powers lab that was doing carbon capture and they were creating inoculants in the lab, putting it into mining, mine tailings, and I think it's in one of the sup figs that they showed us is that the inoculant that they create in the lab disappears very quickly, right, like within two days, 24 hours. You know like it's gone. But then what was also weird is that there's still some measurable effect, and I remember that was one of those moments where I walked away, another one of those like flashes of hopelessness oh, I have no idea what you would do. And so I think that's the idea of don't do the inoculant right, find something in the space and make it better. Seems to be kind of what you say you're doing right, and it seems like that approach is intuitive to me.
Speaker 1:Yeah, actually, my computational biogeochemist the other day put it really well in the conversation that we were having the way that people typically approach these problems is you find a solution and you add it in right. And that's kind of what the industry has been doing for the past 40 years right, growing the known sulfur and iron oxidizers and inoculating the heaps right. That's been the standard approach. That has never really worked well enough, and so the industry is a little bit soured on bio in part because of that. And so what we're doing is actually finding the problem within the biology that's already there and fixing it. So that's kind of a you know, you flip the problem on its head. And the reason why we took this approach is because, kind of in the work that I've done with a mine, what really stood out to me was that they're not necessarily single or even a couple species that dominate heaps, that especially the heaps that were overproducing right.
Speaker 1:Those actually had quite diverse communities with well over 90% of microbes that were capable of iron and sulfur oxidation never being having been seen before they get assigned to their closest relative. But if you actually put it on a phylogenetic tree, that closest relative is not very close and it's also one of the biggest undersampled spaces in the microbial diversity that we know. Right, if you look at the NCBI database, I think at this point it's somewhere around 200,000 sequenced microbial species, but there's still less. Around 200,000 sequenced microbial species, but there's still less than 10,000 of them that are these kinds of extremophiles that thrive in acidic environment, very low nutrient, you know, have learned to derive energy from actively eating rock, right?
Speaker 2:Growing in behind fenced walls where they don't. The owners of the mine have a vested interest in not putting those genomes out there.
Speaker 1:Well, it's not even that, but it's just, it's a very limited subset. So what the kind of existing approaches for bioleaching have really focused on are the microbes that they've been able to culture from the environments, from the acid mine drainage, from the microbes that are washing out from the heaps that are overproducing or producing really well, and the focus has really been on things that you can grow in the lab, and what we know is that's a tiny sliver of what's actually in the environment. Part of it is because those microbes thrive in communities and there's interdependency between them, and so when you grow those microbes in a bioreactor and we've gotten pretty good at growing single microbes in the bioreactors, but if you also want to grow a consortium, having that stable consortium in a bioreactor is damn near impossible, and so if you talk to people in the mining industry who've done this, they will tell you that you can start with a culture, but by the time that culture is growing up in a bioreactor and gets to the heap, you actually have no idea what's in it.
Speaker 2:All right. So what you're saying is an agar plate is not a good simulation of a heap leach, got it?
Speaker 1:Absolutely Right.
Speaker 1:And the other thing that really struck me about biomining research is that effectively all of the research has been done in shake flasks, right?
Speaker 1:So you have a slurry of ore and liquid media and you're expecting that the results that you see in that flask are going to translate when you go to a column or a heap environment where you're not in liquid media, right, and your microbes need to be making biofilms on the ore.
Speaker 1:And the way that mining industry monitors the microbes that are added is usually by looking for them in leachate flowing out of the heap, which to me screams hey, these microbes are the brain solution. Are they the ones that are doing the work? So that's raised a lot of questions for me about the wisdom of inoculating microbes. And then you also have to think about them competing with the native microbes that are already there, because microbes are in every environment, right, and even in the mining environment, what you will see is you will have a broad community in that dry ore, but then, as you start leaching, as you acidify it, you start selecting for the acidophiles and then ultimately down selected microbes that can derive energy from the processes that are involved in leaching, and so those microbes, by and large, are already there.
Speaker 1:I think it's a very rare case where you don't have microbes capable of these processes that are already present in the ore, and so that became my focus. How do you make the biology that's already there work better?
Speaker 2:Yeah, I like the way you're critiquing the way we've been doing it. It's giving me flashbacks to my PhD, where my advisor would yell at me frankly, to list the assumptions, right. Right, and when you do stuff as complex in bio and you can't view everything like you would, software, right you have to be really clear with your assumptions. And it's totally true that there's these things you do that you just assume is going to be fair. So, yeah, like throwing it on like a circulator flask. Oh yeah, this is totally how you culture things.
Speaker 2:And then, you're right, it doesn't look at all like that. How does this? You know, and to the degree that we can explore this, you know, it would be fun just to explore what this looks like to sell, right, because you're you know, one of my favorite questions I've ever been asked as a startup founder is are you harvesting demand or generating demand? And what's interesting about the way you're describing it is it sounded at first like you're harvesting demand of people saying we need this to be better. We're already spraying stuff on it. Please make it better.
Speaker 2:But there's also kind of a generation of demand here, like creating demand, saying that we're thinking about this in a different way and we need you to want to take these experiments with us. And I'm curious, you know, as the CEO and founder of this company, what does that look like to you?
Speaker 1:Honestly, it's a little bit of both. Right? So I think of what we're doing as complimentary to things that minds may already be doing. Right. So, if they're already inoculating, what we're able to do is evaluate whether what they're adding is doing what they're expecting. Right. So our focus is really on being able to tie what we're doing to how the biology changes and then tie that biology change to improvement and productivity of the heat. We're not.
Speaker 1:You know, a lot of the experiments in the industry have been especially with things like nutrient supplementation have been really, hey, let's try to titrate this in, and then we see that if we titrate this in, we get some improvement in yield, and then, if we put too much in, we see the decrease in yield. But there is no connection between that and why is it actually working, and that is the reason why we're seeing this really prevents you from translating those learnings to another heap or another mine site. Right? Because one thing that you'll hear from the industry over and over again when you come to them with a solution is well, how do you know it will work on?
Speaker 1:Our ore is completely different from the ore that you tested this on, and so the way that we approach what we're doing is it's not a one size fits all solution. It's really custom tailored to a specific ore and the specific microbiome that's present in that ore. It's really based on understanding. You know. What is that microbiome, how does it interact with that mineralogy and solution chemistry when you start leaching, and what is keeping it from performing better? Right, how do you reshape that microbiome so you can think of it? The analogy that we often use is we're designing custom prebiotics to really improve the function of that community.
Speaker 2:Prebiotics is. You know, some people would call it biostimulants.
Speaker 1:Right, Biostimulants, prebiotics or precision fertilizer. I mean it's another analogy that people connect with.
Speaker 2:You could also rebrand it as not sugar.
Speaker 1:Not sugar. It is certainly not sugar.
Speaker 2:Here's a solution for bio mining Co-locate with a sugarcane plant. Done yeah exactly.
Speaker 1:What's really interesting is that you really have to tailor that solution to the community, and this is something that we've seen in our experiments. We've tried a few experiments where we just did kind of general nutrient supplementation right, because mining is a very nutrient limited environment, right? So what happens if you remove those nutrient limitations? Can you get way more biomass? Can it be effective? And what we saw is that, yeah, you get a ton more biomass and you get a very diverse community and it does absolutely nothing for metal extraction.
Speaker 1:The way that we think about it is what we are doing up front sounds extremely complicated and it's really a function of kind of the breadth of my own personal experience across different disciplines and so kind of having that toolbox not to think about, oh, here's a hammer and like how do I turn this problem into a nail, but looking at the problem and being like, okay, what tools do I have to solve it? And then just really rethinking the entire approach and going backwards from, instead of going from, this is what we can do at the bench. How will it scale? Will it scale? Asking the question of what do we need to do at scale? And then how do we create our experimental systems to really represent that, so that when we do something at the bench we can be reasonably confident that it will translate to scale with relatively minimal adjustments.
Speaker 2:And once again, without trying to probe more than is good in the conversation, do you ever do co-locate with the lab, the mines? Do you imagine working in a shipping container, or is that a TBD?
Speaker 1:It's a TBD, so one of the visions for kind of how we work, right.
Speaker 1:So we designed that initial product to get the heap jump started.
Speaker 1:But the ore and the microbiome also evolve over time because you're removing material from the heap and you have seasonal changes, you have various weather events that can affect what's happening in the heap, and so we envision ongoing monitoring process that allows us to.
Speaker 1:So in our lab setup we can identify some leading indicators in solution chemistry that track to microbial health in the heap right. And so we envision the system where we are monitoring the heap, and so that would require, you know, some of the same sampling that mines already do. It would just require a stream of data and then we would occasionally go out and sample the microbiome and that would give us the data that we need to adjust the formulation along the way to really maintain the performance throughout the leach cycle. And so this is again the difference from kind of a continuous you build one solution and you're applying it continuously regardless of what's happening to really tailoring it and adjusting it as needed along the way. So I don't think we will be operating in a lab container at the mine site, but we will certainly be getting samples and analyzing them in the lab.
Speaker 2:Yeah, I mean, that makes a ton of sense, and the way you frame this also makes a ton of sense. So this is where we have to move to the wrap-up and we get to explore a couple of rapid-fire questions. But I just want to throw the editorial that I love the way you explain this. It sounds awesome and I think there's a lot of subtlety in the way you frame it, and a lot of it is what you're not doing, right, cause I think someone can listen to this and, oh yeah, everything you said makes total obvious sense, right. But then there's tons and tons of hands-on learning there, to be specific, of what you do. At the end we want to hear how people find you and what's next and how people help you guys. But this is the first time, because this is my favorite part, so we have four rapid fire questions at the end. So the first question, sasha, is what's a single book, paper, art piece or just idea that blew your mind and shaped your development as a scientist?
Speaker 1:Yeah, I'm not sure how much it shaped my development as a scientist, but there was a paper that came out a couple of years ago on how impurities in sodium phosphate used for media preparation for E coli change how that microbe behave and the reason it blew my mind. Because E coli is the most studied microbe in the world. We do everything with it and you would imagine that by now we know it so well that we can control it precisely. And then you find out that, hey, actually to have reproducibility you need to be so incredibly careful about who do you buy your reagents from. And we've known this in structural biology space for a while, especially if you look at crystallography, you know media components can make a difference between a protein that crystallizes and a protein that doesn't, and the source of the component. Wow.
Speaker 2:I'm pretty sure some PhD student is going to listen to that and have their anxiety level is going to go up another 50% and not sleep.
Speaker 1:Yeah, and I think the most important thing that I've learned as a scientist and the most important thing that I learned in my PhD was how much we don't know, and that's something that I come back to over and over again. It's incredibly important to keep in mind that you think that you know how things work, but really you probably don't.
Speaker 2:Wow, you could just use the wrong buffer and stuff. Oh yeah, I think it's beautiful. All right, on a positive note now, or not? What's one of the best advice lines that a mentor gave you?
Speaker 1:That's a tough one. I think that goes back to my undergrad days and I had a couple of professors lab professors that really hammered it into us that you don't just need to read through the steps of a protocol and understand what it's asking you to do, but you really need to think about what happens at every step of the protocol.
Speaker 1:Like what is the reagent that you're adding doing. Why is it doing it? Is it really necessary? And it's actually kind of fun because a lot of the protocols and biochemistry and protein science are just passed down through generations in the labs and very often will have extraneous things that do absolutely nothing or may even harm the process because somebody just didn't think about. Why is this here?
Speaker 2:I love it.
Speaker 1:I got heart palpitations in my PhD because I kept skipping a step and everything failed and it took me six months to realize why I had a really fun experiment experience with inorganic chemistry lab where we were using tinfoil as one of the reagents, and every time I did the experiment I got this black crud and what was supposed to be happening was not happening. I was beating my head against it for probably a week and coming back and redoing the lab and still just getting black crud. And you know what it turned out to be Doritos. No, so tinfoil. We talk about tinfoil, but really most of the foil that we use these days is aluminum foil, so I was grabbing aluminum foil, not thinking about it.
Speaker 2:Oh, that's so good. Moving on from Supperfest stories and our trading days, if you got a magic wand to get more attention and resources into one part of biology, what would it be?
Speaker 1:Yeah, I think really systematically looking at the interactions of microbes with their environments. So this is something that we're super interested in as a company, right, and this is the data that just doesn't exist. You know, my original idea for the company was like hey, we can do a lot of this computationally and do all sorts of predictions, but there is no data to do it on, right, and we're building that data set in the process.
Speaker 2:Wow.
Speaker 1:But these multimodal experiments where you are looking at all the different ways that the microbes interact with their environment and especially within communities, that would be really nice to have cool.
Speaker 2:And then the fourth one is you run a company, you're training people, you're creating people's careers. So what is one aspect of personal development that you think biotechnologists need to spend more time on?
Speaker 1:yeah, I think, for industrial biotechnologists in particular, it's really thinking about how do you translate things to scale? Will they scale? Because I think, as scientists, we get trained to work at very small scales on the bench, right, and we don't learn to think about what happens when you try to translate this process to thousands of leaders or hundreds of thousands of funds, right, and so I think that's a huge stumbling block for a lot of biotechnologists and that's where people need to put a little more thought in.
Speaker 2:Well, that's four questions and we are out of time. Sasha, it's an absolute pleasure to geek out with you and learn about all the work you've done. I admire the journey so much and for people who leave this thing like, wow, Sasha's really cool. I want to learn more about him and transition. Where would you send people to?
Speaker 1:Well, to learn about transition at high level, you can go to our website, transitionbio. You can also reach us through the contact us form on that website and you can find me on LinkedIn. And the one thing that I will ask is, if you do find me on LinkedIn, please tell me why you're reaching out to me, because and that's the general advice for anyone reaching out to anybody on LinkedIn that they're not directly connected with Cause. It really helps first, and you will unlikely to get a response from me If you don't tell me why you want to talk to me, why you want to connect.
Speaker 2:Tell me you're popular without telling me you're popular.
Speaker 1:Yes.
Speaker 2:Sasha, it's been an absolute pleasure, my friend, thank you so much, Likewise Daniel.
Speaker 2: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 in the show notes. Huge thanks to our producer, dave Clark, and operations lead, paul Himmelstein, for making these episodes happen. Catch you on the next one.