168. Biomanufacturing 101: Rebuilding the Modern World with Biology

Erum [00:00:00] AI's role, the architect or the intern,

Karl the CEO. Every day.

Erum Oh, snap.

Erum Hey Carl, how's it going?

Karl There's so much going on, Erum. It's all good. I wanna welcome our listeners to the Grow Everything podcast where we talk about how biology is changing all industries. What's up with you?

Erum Oh, man. Yes. Very busy over here. just been trying to maintain. If you've been watching the podcast, you might notice that I've got a little haircut, try to freshen up my look a little bit, but that's.

Erum Halfway done. I might color my hair. So for those that care, I'm sorry for, for those that don't care, I apologize. I'm talking about it. but yeah, that, and just trying to exercise, I did a Pilates burn class and I don't know, I mean, I don't. Really keep New Year's resolutions or think about it. But I think I'm doing it subconsciously. I'm like, why am I doing all this stuff?

Karl So it's always an [00:01:00] interesting time of the year if you're a gym rat because the gym fills up with new people and they're all pretty much gone by the end of February. but you'd started, So I will encourage you to continue the habit. I think it's a very important habit to,

Erum okay, hold me accountable. Hold me accountable.

Karl Yeah. Yeah. So let me just jump into a couple things before we get into the episode. I wanted to mention this over $1 billion deal that Eli Lilly did with a German therapeutics company called Seamless. It's a gene therapy deal that's focused on hearing loss. And this deal struck me because you wouldn't think that you could do gene editing to take care of hearing, but there's a lot of diseases out there that are genetic, and this is one that apparently is worth a lot of money. So if you could imagine being able to program mutation that people have that are related to hearing loss or blindness or other diseases that people have. This is a great example of this. And Lilly is already [00:02:00] making tons of money from their GLP ones, so I'm very excited about this. What do you think, Erum?

Erum Yeah, I I need to look into it, but I'm curious.

Erum Is this gene editing on somatic cells or like sex cells? Like the gametes, like, so the, then the future children will not have. hearing loss.

Karl so I am looking at a Bloomberg article and what's interesting is. Lily has a hearing loss portfolio back in 2022, bought a company called Kuo for $500 million, and that really helped them get into this area of treating hearing loss caused by genetic mutations.

Karl The example that they give is two years later. So in 2024, they did an early stage trial and they, used these drugs on an 11-year-old boy who was able to hear for the first time in his life. So that particular drug from kus is now to phase three trials and Seamless is a different kind of technology platform. But to answer your question, I dunno. And this article doesn't say, [00:03:00] exactly how this works. I can't wait to read more about this. And I think it's, you know, we talk about bio manufacturing and bio industrials on this podcast but when I see these kinds of news stories, I get very excited because it just shows how quickly biotech is advancing and really treating things that matter.

Erum Yeah, I mean, on the flip side, some people might argue that it's moving very slowly because gene editing has been around for quite some time and there's still a lot of controversy around it. why I asked about the. Somatic cells versus the sex cells because it's like, okay, well is that the stepping stone to design our babies? regardless, gene editing is a tool. It's actually more precise than other drugs to help alleviate, I don't wanna say disorders 'cause Some people that do have hearing loss are fine. they're okay. And I, I just feel like there's maybe some that are like, you know what, I'm okay living my life without hearing things.

Karl yeah, it's, uh, just as a interesting aside, or a New York City experience, is taking [00:04:00] the subway down from the Upper East side. At of the school day. and ending up on a subway car with children who are coming from probably an, there's. The train cart is silent except for the sounds outside of you. And what you're seeing is a bunch of people signing at and with each other, and it's really an amazing thing to see and to experience because you, I think generally we don't think about how many people are affected by hearing loss, but when you are seeing that many people together in one place, particularly children and teenagers, it's pretty striking.

Erum Yeah. Yeah, I can imagine. And of course when you're on the train, we listen to podcasts and for our listeners, I don't just listen to our podcasts, you know, we do make it, I listen to different types of podcasts. And there was one that was recommended to me recently by our friend, Ginger Dosier founder of Bio Mason, and founder of the Biome Consortia, and she does amazing things with biology. Kind of the [00:05:00] big thing Bio Mason does is make cement out of microbes, which. We'll talk about in today's episode. So you've been friends with Ginger for some time. We've had on the podcast and I've caught up with her and she recommended this podcast called Long Now, which is the institute for people to think on very long timescales.

Erum And there's one episode which we have to put in the show notes. It's really almost like a TED Talk. And then there's q and a afterwards. So this was a beautiful explanation of how biology can solve a lot of problems. So we need to have Dr. Lynn Rothschild of NASA on, so Dr. Lynn Rothschild is a scientist, astrobiologist, an evolutionary biologist synthetic biologist, has all the expertise of someone that we must feature on our podcast.

Karl God, we gotta get her on.

Erum Yes. Yes. And so, a lot of, her work focuses on the, origin of life on earth and what's going on in space, and [00:06:00] then of course, pioneering the use of synthetic biology to enable space exploration. And then of course, a lot of what she talks about is, well, there's so many things you can do with synthetic biology, of course that would have applications here on earth. So, that's the kind of the nuance story of space exploration where people feel like, oh, why are we focusing on space when there's a lot of problems here on earth? It's a win-win if you create a technology that could enable both, let's focus on innovation rather than, speculate on who is it being used for, but it was a great episode.

Karl I love the Long Now Foundation. I love what they stand for, and I'm gonna have to check out this podcast. Going to the Long Now Cafe in San Francisco is one of my favorite things to do when I'm there. It's really a magical place. But, I definitely wanna check this out and yeah, we, I think what we've, we maybe have had Lynn Rothchild on our list, so we've gotta just reach out to her. and speaking of space exploration and synthetic biology, [00:07:00] you put down pluribus and we've talked about it a couple times. The show that is on Apple tv, created by the same people that created Breaking Bad. Now that we both have watched it and the first season is over, what do you think?

Erum I'm like, when's the second season coming out?

Karl Right. It did kind of end suddenly.

Erum Yeah. Yeah. Yeah. It was amazing. And again, no spoiler alerts, but it is, about this collective consciousness that takes over most of the human population. And then there's a few people that aren't a part of the collective consciousness. they're still living their lives as they were before this collectiveness started happening and it's like, what is that a commentary for? Right. 'cause of this collective conscious, like all of a sudden you have most of the world's population, it thinks the same way. Like they're part of the same mind and it absorbed everyone's thinking. So everyone now is an expert in a field. They just can tap into everyone's storylines, their expertise, and to me. I saw it as, [00:08:00] allegory to obviously the internet and AI and that we can all access it and use it. so it was like, okay, is there a moment in time where we'll just all have access to all the same information? And it does make things better for the individual because that's a part of the narrative, is that this collective consciousness is trying to convince some of the people that didn't get into it to come into it and saying that it's a very beautiful experience. But of course, as an individual, you wanna hold onto identity so closely, so tight. It's you. And if you go into this collective consciousness, is it death? And then all of a sudden you're reborn. I don't know. What do you think?

Karl Yeah. What do you lose by being. part of the collective consciousness. I think that, I like using the allegory of ai, like the collective consciousness is ai. but the challenge there is everybody gets that collective consciousness without requesting it. And it is like a [00:09:00] genetic story from the beginning. So there is some biotech related things going on. But if you don't have the free will to choose whether you wanna be a part of the collective consciousness, I think that that's really the question there. there has been in the past talk of how the internet and how even AI create this collective consciousness that is greater than all of us individually. And I think there's a lot of truth to that. But I just think that, there's pros and cons to free will.

Erum Okay. Yeah, that's really great. Can't wait for season two. Um, again, love how there's. Biotech or biology being portrayed in different ways in media to help spark people's imaginations. And I think this was a really good one. if you really wanna think very deeply about what is biology and what can we do with it in a very philosophical way, our episode with Michael Levin, I cannot stress enough, is a great one. So I think we should just keep that episode in our show notes in perpetuity.

Karl we're gonna talk about Biomanufacturing [00:10:00] and since we're talking about media, I just wanna mention to the second season of Drops of God, which is about the wine industry and really understanding wine and it's such a beautiful... season one was so beautiful, so well done. I thought it was just gonna be like a limited series and it would just be that first. Season, which is apparently based on a manga, but they just dropped a new season, which is just as interesting and I'm only three episodes in, and I think it's just lovely. I love it. It's, it moves very slowly, but if you're into wine and you're into bio manufacturing, great show

Erum wine or flavor, you know what I mean? Just really it's about flavor and earth and being able to taste the, fruits of our planet in like, in, its, like natural form I guess you can say. And obviously fermentation doesn't just happen naturally. I means in some areas, it does in a really like gross way, which is like rotting fruit. but then it's like this [00:11:00] beautiful, combination of all right, nature does bring a lot of flavor to plants and herbs and grapes, of course, and then humans take it and to the next level in cooking and fermentation.

Erum And, and that is really a great segue to talk about what we're talking about in today's episode, which is biomanufacturing, how do we take biological matter and make something incredible useful for humanity.

Karl Exactly. So we are approaching this episode as a Biomanufacturing 1 0 1. We think it's gonna be analogous to the episode that we did around DeSci I, it's gonna be a little different in that IAM and I are gonna talk, but we're gonna bring in quotes from different people who we've had on the podcast to talk around specific areas, related to Biomanufacturing.

Karl So if you don't know what Biomanufacturing is or if you really need a refresher, this is the episode for you, Erum. Let's get started. What's going on or Why Biomanufacturing? Why does it [00:12:00] matter?

Erum All right? Yeah. So here we are talking about biomanufacturing 101.

Erum And one of the ways that we wanted to frame it, we wanted to borrow from our friend Joshua Lachter, who just had on the podcast, he's of a company's synonym that focuses on buying manufacturing tools.

Erum and so what he wrote about was the great reformulation. And what is that about? So a lot of our products that we use every day that we find everywhere, I mean the things that we consume on a daily basis, furniture, materials. a lot of things that we use are made through petro chemistry.

Erum So we think of things that are plastic, food dye, a lot of artificial flavors and fragrances and. it's so tremendous when you take a look at all the products, just pick up something in your house and look at what ingredients it's made out of. especially when you're looking at laundry detergent or shampoo, personal care and beauty products. And you're like, [00:13:00] why? And there's a lot of reasons why, especially when you consider how and why the petrochemical industry started.

Karl I would just add to that you're probably wearing something that has some synthetic molecule in it. you might have a pair of underwear that have a stretchy band that's probably made from oil.

Karl you know, you might be wearing a pair of yoga pants. I'm not today, but I do wear, a tracksuit sometimes. And that is definitely polyester. And polyester is made from, oil. even the ones that are made from recycled materials are typically made from oil. So this idea of, why do we need biomanufacturing? Well, we need an alternative to the creation of all these products from oil and, that's what biomanufacturing is.

Erum and so this idea of using petrochemicals actually when it first started was a green technology. We were very dependent on using trees for making a lot different products, especially when it came to fuel to make fire, to heat our homes. [00:14:00] But then all of a sudden people discovered petro chemistry or petrol or oil and were able to make kerosene and other types of fuel and instead of chopping down trees, we finally have this other way of making heat that technically is greener. 'cause you don't have to chop down the trees. And so that's one aspect.

Erum Another aspect I like to think about when it comes to, how we became so dependent on petrochemicals is of course there's the oil industry and they're producing this raw material that we can make and we then we have all these chemists that became, very interested in how to transmute, I guess you can say transmute petro chemistry into different types of products for different types. Of, experiences or functions you can say. And there was of course, during these world Wars where a lot of chemists were then, asked to make different weapons, chemical weapons, and they made different things that were used, in warfare [00:15:00] unfortunately. But then they had to set up a manufacturing process for that, and then they had it after the war was over and they're like, well, we can make this stuff what can we now use this infrastructure and these processes that leverage petro chemistry, what can we make out of it?

Erum Oh, well, you know what? We can make, some laundry detergent or we can make, plastics or coatings which is, coatings is a whole like, invisible world that is everywhere. Everything's coated in, in some type of petro chemistry based coating, like a clothes, for example. look, we can't vilify petro chemistry because it really helped us, kind of get away from chopping down trees and made the modern world but then of course now we're in this place where we overdid it,and I hate to laugh at it, but it's just like, wow, wow. That we kind of came this far and now we see, of course, all the environmental effects. we all know this, right? and chemistry isn't the only way to make products and this is when, we wanna talk about biomanufacturing

Karl So what is biomanufacturing? A [00:16:00] simple definition is the use of biology, microbes, cells, enzymes to make things that we currently use, and that could be anything from beer or wine and yogurt to chemicals, materials, and products. Let's let Doug Friedman of bio give us his take on what bio manufacturing is.

Doug in reality is is actually quite simple until you get into the details. And that is, manufacturing chemicals, materials, or other products using biological systems. And sometimes it's easier to compare and contrast. So how do we get chemicals, materials and other non biological or non health related products today? Primarily through chemical manufacturing. Chemical manufacturing is primarily taking typically a petroleum based feedstock using chemical processes is.

Doug To then turn it into something that is useful for people in biomanufacturing, we're essentially doing the same thing. You could use a petroleum feedstock. You can use a gas feedstock. You can use a lot of other feedstocks. from other [00:17:00] renewable sources, corn, corn stover, sugar beets, et cetera, and convert that now using a microorganism like E.

Doug coli or yeast or many, many others, typically using fermentation, just like brewing beer to ultimately get the exact same products or in some of the more exciting cases, new products you can really only make with biology.

Karl So what's the opportunity when we move from, just using petrochemicals to using biotechnology? In the past, we've referenced this report from a coalition known as the Advanced Biotech for Sustainability Coalition and we've also referenced a McKinsey report, from a several years ago. And according to those reports. Biotech could remove something like three to four gigatons of carbon from the atmosphere. But what does that really mean? That's like basically taking every car in the United States and in Europe off the road and bio manufacturing could unlock a trillion dollar market by [00:18:00] 2040. to put that into context, a trillion dollars is every plastic bottle, every polyester jacket that you're wearing. Most building materials. Every detergent, every ingredient that goes into cosmetics. All of the stuff that is made from petroleum or that is derived from petroleum is remade with biology.

Karl That's a trillion dollar market.

Erum And speaking of reports, one of the reports that we talked about extensively on this podcast is one by the consulting firm, Capgemini, and they did a lot of work talking to executives from all the top companies in the world to understand what they think of bio manufacturing the use of biology when it comes to transforming their industries, their products, and the way they operate. And it turns out, when they were talking to these executives, 95% of them are pursuing BioSolutions. They're not just talking about it. They're really actively looking for it. And there are lots of [00:19:00] reasons why they're either going ahead slowly or they don't. And that's something that we wanna talk a little bit more about. What is slowing things down or stopping the pursuit of BioSolutions?

Erum And so what we're doing in this episode is, yes, biomanufacturing 1 0 1, what is it? How does it work? Why it failed and why things are different now. So let's talk about the most basic type of bio manufacturing Yes. So the most basic type of biomanufacturing is fermentation. So a lot of you are familiar with fermentation, of course, because during COVID we all became sourdough focaccia makers, and of course yogurt is made through fermentation, beer, wine, and it's been going for thousands and thousands of years. So. That is the foundational, I was gonna say platform, but that's too technical and I think we wanna honor that. Fermentation is a biological process,

Karl and then what's happened really over the [00:20:00] last, 5,000 years is. Fermentation has become much more precise. And one of the things that happens is we've gone from precision fermentation, to continuous fermentation. when you're brewing beer, that's called batch fermentation. You fill the vat with your ingredients. you ferment in there, you remove your beer and you start over again.

Karl Precision fermentation is where you you've engineered a microbe to make something very specific, not just alcohol, a medicine or a material or a chemical. continuous fermentation, which is where you have fermentation that just happens continuously. You're feeding the microbes or producing product. You're moving the product out of the vat.

Karl And a person that talked a lot about this was Michelle Stansfield, who she called this hyper fermentation. So let's let Michelle talk about what hyper fermentation is.

Michele So hyper fermentation is a continuous fermentation technology. And ultimately, if you think of any manufacturing [00:21:00] method, when you go from piece by piece assembly to an entire assembly line or moving assembling line, it ultimately drives up productivity. You get more product, which then drives down cost of goods, because it's getting more product per energy unit that you expend in the manufacture. So continuous fermentation really changes the way that we move and we manufacture, through biology.

Michele So, when you think about incumbent technology, what they do is a big stainless steel that they had sugar and microbe and a couple of little. and of a broca or a couple of vitamins and they grow those, microbes until basically they're senescent until they're older and they've eaten all the sugar.

Michele What we can do with continuous fermentation is we can feed them in a manner that keeps them at a certain age. So We all know that teenagers are a lot more productive than old people. So we, can tailor, manufacture. So it, keeps the yeast at a specific, very productive age. And we can do that for a very long period of time.

Michele We don't have to stop the fermenters and clean them every time. [00:22:00] We can just keep going.

Erum So the key insight there is that continuous fermentation can really help unlock costs, which is one of the biggest things when it comes to replacing products. with continuous batch fermentation, you can continuously make the product versus having to take all the stuff out and clean it, wait and then do it all over again. That downtime is very expensive. But thanks to Cauldron and other companies, we are excited to see that okay, we can continuously make product. and there's another type of manufacturing that would enable that cost to come down because you're able to make product continuously.

Erum Do you wanna talk about another type of manufacturing?

Karl Sure. I mean, we've had a couple people on the podcast who've talked about cell-free manufacturing. And what that means is they're taking cells, breaking them open and removing the machinery that does all the chemistry that enables fermentation. And this could be done by taking those [00:23:00] enzymes and adhering them to a wall and then passing. A broth through, this fermentation tank and having chemicals come out on the other end. The reason you would wanna do this is because cells get sick. Or they waste energy, you have to feed them. And when you take the cell out of the equation and you really only have the enzymes that are doing the chemical processing, you can create something that is much more efficient without the biological baggage,

Erum we also spoke to Alex Rosay about cell-free manufacturing and what that is according to his perspective.

Alex Really the idea of cell free is to take this assembly line inside of microbes, which inside of microbes is alongside Hundreds, thousands of other assembly lines reactions going on. It's chaotic environment, but taking that assembly line that you care so much about that's doing all the work and just isolating it and focusing on that.

Alex you get with that is higher purity of the product you're creating and a number of other benefits, such as moving [00:24:00] to more continuous flows, allowing you to get better yields, dropping the cost down of doing the reaction

Erum but there are other ways to do biomanufacturing.

Erum It's a very broad spectrum, and once you start going down that rabbit hole, you realize we just scratched the surface of how we can do biomanufacturing. what we've been talking about is fermentation, using a microbe to make a molecule.

Erum But you can also, of course, use plants, insects, mushrooms.

Karl So let's listen to Ilan Sobel, talk about how they grow plant cells, and use them as bioreactors.

Ilan we've developed a platform technology where we can take pretty much any plant in the plant kingdom. We take the plant once we understand exactly where inside the plant are the cells that produce the critical phytonutrients or phyto medicinal compounds. we take those cells and we conduct hundreds if not thousands of experiments where we change the food, that we feed the cells, [00:25:00] we change the temperature, we change, lighting and a number of other variables at this stage we focus on getting these cells.

Ilan To do two things. One, to grow the exact mirror of the phytonutrients that are found in the plant. two, focus on one or two molecules that we look to increase by an order of magnitude versus what's found in the plant.

Ilan We're just changing the environment. We're optimizing the environment for the cells to do what we want them to do.

Ilan In a industrial scale bioreactor, we're talking north of a thousand liters, these are cells in liquid suspension. So you're taking from Petri dish in solid media to liquid suspension in large industrial scale. Bioreactors and we figured out how Condition the cell to be able to, in a way, toughen it up, make it stronger so that it can go into this liquid [00:26:00] environment, can deal with all the challenges of sheer forces can multiply many times, and in 18 to 21 days, the cells grow and they elicit those critical phyto medicinal compounds. then we harvest the cells and we are left with an amazingly soluble bioavailable end compound.

Erum And then finally, you don't necessarily need a tank or a vat, or it's a liquid medium to make products using bio manufacturing. there's also ways to use mycelium to make products. And it doesn't have to be in a vat, doesn't pour things out. You can just grow mycelium to make products. And our friend Eben Bayer of Ecovative and My Forest Foods does a wonderful job of explaining how they make products using mycelium.

Eben the journey for us the past four years has been scaling up what is a very novel, solid state fermentation process that can be done existing farms.

Eben this is truly an. Explored way to grow mushroom mycelium. The aerial slab of meat that forms across this a [00:27:00] hundred foot long bed, is just an unknown way of doing it.

Eben , and a lot of the things we had to figure out at scale, and that means putting. 80,000 pounds of wet wood chips from a tractor trailer load on conveyor belts into these farms growing the product.

Eben And really dialing in operational consistency based on all the work we've done at lab scale, pilot scale, quarter farm scale. But every time we do this, we're creating these giant boxes, these thermodynamic boxes, It's a complex generative pattern where the mycelium responds to the environment.

Karl So why does this all matter? Well, as we talked about, we wanna be competitive when it comes to a price point, particularly if you're competing against chemicals that are being made through petro chemistry. And if you're competing against those synthetic chemicals or petrochemical produced products, you need to have price parity. In addition, we're looking at these technologies because regulations are changing around the world and people are looking for new ingredients because of the way those regulations are changing.

Karl And then finally, a great reason to be looking at [00:28:00] fermentation and by manufacturing is to create new products that have never been made before, that people will be excited. To spend money on or to use. So those are all reasons why, biomanufacturing matters.

Erum Okay, so now let's talk about why it's hard and what needs to happen in order to make it easier for us. So there's been a lot of companies that have been using biomanufacturing or fermentation and all the different ways that we just talked about, and when it comes to price, price is a funny thing because it's a framework in which you have to produce products and create value so that when people purchase the product, everyone wins, right? And so what's been happening is between companies creating products and being able to commercialize those products and getting into the market, there's been what we call the valley of Death. So. If the technology works, why isn't everything already biobased?

Karl So it's complicated. Let's just [00:29:00] put it that way. and I think it's worth putting some historical perspective on this story in terms of like why it's a challenge and, really between the year 2002 to 2023, the entire bioindustrial industry learn some really hard and expensive lessons that have really informed where we're today. First being the biofuels bust, which is really a tale of companies ignoring scientific companies, ignoring economics. The original pitch was, Hey, let's produce petroleum fuels using fermentation, but it was super expensive and you're going up against a commodity that is heavily subsidized, that is oil At the time of the biofuels boom, oil was very expensive. But then the, cost of oil crashed and biofuels were too expensive to produce and they couldn't compete.

Erum Yeah, I mean the biofuels bust, I would say is the first thing that people point to when you talk about biomanufacturing and commercializing bio made [00:30:00] products

Karl at a large scale.

Erum At a large scale, yes. And they're like, oh, well biofuels failed. And for all the reasons you just mentioned, they failed for very specific reasons. but there are other companies that have employed Biomanufacturing to make other types of ingredients or molecules, that are fundamental ingredients to make, let's say cosmetics and personal care and beauty products and textiles. And those companies have also failed for similar reasons. They're really trying to go after large markets. they're competing against cheaper products friend of the podcast, Veronica Breckenridge, a First Bite Ventures and her team wrote an incredible report called The Graveyard Report that analyzes over 60 failed companies when it came to using biomanufacturing.

Erum And how 80% of them were targeting biofuels or platform chemicals. So let's let Veronica Breckenridge talk to us about

Erum The lessons learned

Veronica I think the biggest pattern I have to say, and, unfortunately, [00:31:00] I feel like this gets repeated every time. It is people who don't understand how, they introduce technology, , which is to go after the biggest and most commoditized market. I mean, biofuel was that way.

Veronica Right? and a lot of big ideas. and we talk a little bit about Silicon Valley playbook and software. They keep talking about the biggest market, but you know what? The biggest market is not your best market. The biggest market tend to be commoditized. It's extremely cost competitive because consumers are extremely cost sensitive and , there's existing structures that already optimize the manufacturing to get to that kind of efficiency and cost.

Veronica New technology rarely gets there, right? Apple didn't introduce a hundred dollars phone, which is when Apple introduced iPhone. That was the average. Phone cost. apple introduced a six phone, right? Tesla's first car is a $200,000 roaster. and it's the [00:32:00] same thing actually. If you look at the ev, there's, , you know, lots of EVs started with like bolt started with cheap cars.

Veronica That isn't never the right strategy. Introducing a new, technology and new manufacturing that requires. A lot of experiment experi, and which means you wanna find lucrative markets and higher price market. which is why, biomanufacturing in pharma or drug production has been successful is actually being more and more adopted.

Karl And I think to add to what Veronica said, let's talk about the challenges in infrastructure. It's very unclear what infrastructure is available for biomanufacturing and synonym.

Karl We've had on the podcast twice has done some work in mapping global capacity. If you don't have a place to produce your product, it's kind of like finding a server.

Karl Before that was Amazon Web Services. There is no shared infrastructure for piloting, but China has announced plans to support [00:33:00] pilot biomanufacturing plants across 47 companies by 2027. So in a year and. Veronica among others has been talking about pilot facilities here in the United States and in Europe you can't prototype at scale unless you have access to facilities. So let's have Edward Shivi of synonym and talk about the need for capacity.

Edward on different levels, people saying, that they need capacity on the pilot scale, and they need more of it. But what I realized after is that it's not that that capacity doesn't exist. There's just a lot of friction and getting to it. and, same demo scale and, same obviously with industrial scale and industrial scale. We definitely don't have enough capacity, but we also don't have, enough, mature science. is a capacity gap, but, at this point, it's a perceived, fermentation capacity gap, there's a lot that needs to happen for that gap to become real on the, science side, on the engineering side and also on the, offtake side.

Edward So the markets need to be as ready as the science [00:34:00] and, the capacity to produce, needs to reflect, the state of the market.

Erum amazing. So we talked about a lot of why biomanufacturing has failed for certain companies, but let's talk about some of the solutions that are coming online. What's the new strategy and what's a new infrastructure? And what we talk about a lot is the consumer and how oftentimes when you're introducing a new ingredient or molecule, there's the performance over sustainability solution. Well, you're not just chasing commodity pricing, you're chasing specialty, high value products. So of course. Here at Messaging Lab, we love to talk about K 18 hair. a company that we've worked with from day one and K 18 wasn't just talking about sustainable hair care, it was talking about a biotech or biomedic peptide that can repair hair in four minutes.

Erum And this performance is what drove their [00:35:00] acquisition by Unilever and. This is one of the great entryways of validating biomanufacturing because people will buy products that work for them.

Karl Not only will they buy them, but they'll also pay a premium for them because the K18 products are not by any means cheap compared to other haircare products on the market.

Karl And part of the reason why people will buy those products is because they deliver on the functionality that they promised. And let's let Suveen talk about K 18.

Suveen So your K peptide was not just about finding an natural molecule and then applying it to hair. It was exactly about taking that molecule, reassembling it, optimizing it to serve the needs that nature had not intended for your hair

Suveen It simply intended to keep your hair healthy. But when you talk about harsh chemistry, you're talking about heat styling and everything else. How do you create that molecule from the nature which is optimized to service that need? And that's where biotechnology checks all the boxes, [00:36:00] purity, sustainability by compatibility and innovation that we seek from the beauty industry.

Karl So we talked about how innovators have gotten their products to the market and it's by no easy feat. This requires a lot of collaboration across different types of people. we like to call along the value chain. So you're talking about people that are manufacturing, people that are distributing, people that are marketing, and.

Erum This brings us to the next solution in Biomanufacturing, which is Orchestration Beats invention.

Karl This is something that we've talked about a fair amount here on the Grow Everything Podcast, and we recently interviewed Phil Morle of main sequence ventures talking about orchestration.

Karl That means connecting the scientists, the company, the manufacturer, the brand, the waste manager, everybody simultaneously and creating an entire ecosystem.

Karl Let's let Phil Morle talk about how Samsara has done this.

Phil the sort of first [00:37:00] principle of orchestration. We did not, find a great founder, exclusively and then just put them to work to build a company on their own, in their own isolated environment. We knew that we needed to understand exactly how the supply chain works and we knew we needed pull from a customer that would actually set the momentum very early on, in the company's life.

Phil so we created this company under a model we have here at Main Sequence, which we call venture science. We call it venture science because when we talk to a research organization, we say, this is how venture causes great science to be created inside your organization. And then we co-found companies with founders that bring advantage from the first day.

Erum so we just heard from Phil Morrell about orchestration of a value chain, In today's world, supply chains are global. They're vast, and usually there are certain chains that are in [00:38:00] one location distributing to many locations. But this brings us to solution number three, distributed by a manufacturing.

Erum What does that mean? It means that we could buy a manufacturer having the tanks, having the whole factory regional close to where the products are being sold. Carl, I know that this is one of your favorite topics. What do you think?

Karl So, when I think of distributed biomanufacturing, I think of smaller facilities that could be located on site next to a big company, but not necessarily. And these manufacturing facilities can be located anywhere in the world. And given that they would be connected digitally, you could have different strains of microbes available to produce different products. you could basically turn the. Facility on to produce peptides one minute and produce hydroxy acids the next minute, depending on what the customers to the facility need.

Karl And instead of having one massive factory [00:39:00] that is shipping ingredients or products all over the world, you have many smaller units located near feedstocks or near the factories that are the end consumers. Two examples that we've had on the podcast are materials and locate at waste sites. Let's let Molly Morse of Mango Materials talk about what Mango materials is doing,

Molly we partner with the wastewater treatment plant to have access to the site and have access to the methane feedstock.

Molly We have a pipe that comes directly off that. we take that pipe and feed it into a tall, deep tank, , that's full of water and where our bacteria live and the bacteria, like me or you if we're to eat a lot of. Chocolate or something.

Molly We would get fat because bacteria instead of eating chocolate, they eat methane gas. It's their carbon source. , their carbon feedstock. They eat the methane and they convert it to their carbon storage mechanism, which is a PHA. It stands for poly hydroxy aloid. It's this naturally occurring bio polyester [00:40:00] that's inside their cell walls.

Molly It's how they've evolved to survive famines, similar to us getting fat. It's similar. Process. Process. And so they've accumulated this biopolymer inside their cell walls. We harvest that biopolymer, comes out looking like a white fluffy powder. And that's one of the key ingredients for the pellets that we then sell onto the market.

Molly instead of having this methane, which is a potent greenhouse gas, instead of having it be flared or vented in some instances, we feed it to our bacteria, to make materials.

Erum and the vision for both being able to turn waste into products.

Erum And also the idea of distributed manufacturing is shared by another guest of ours gave Tavas of symmetry wood, who talks about fab cities and what that could look like in the future. So let's let Gabe take it away.

Gabe there is this whole idea of fab cities where basically you have as many of your products as possible made locally from waste, especially.

Gabe [00:41:00] then you have information shared globally. So ways how to make new biomaterials or make new products, become a bit more open source.

Karl And then finally another approach that I've mentioned a few times on the podcast and we've had listeners write to us about, is kind of a more dirty biology approach where we move away from sterile, tanks. Moving away from this pharmaceutical grade, stainless steel tanks towards more robust microbial, consortia that can operate in non-sterile environments. Think of agriculture where you plant a seed in the ground and the seed is surrounded by hundreds of millions of microbes and fungi that are helping it grow. Or a wastewater containment plant where the water is being treated and purified, and there's a lot of different microbes at play there. Let's let Ginger Dosier talk about growing cement bricks as an example of dirty biology.

Ginger We're actually creating an environment that's similar to [00:42:00] seawater so that you have, right amount of nutrients and the right amount of calcium and carbon sources for calcium carbonate or, Crystallization to start to form. So that became a very easy way to explain it. of course we had to home on like, what do you mean grow?

Ginger How does it know to stop, there was a lot of, very quick ways of explaining, well, you're taking aggregate and you're inoculating it with bacteria and then By doing that and activating the microorganisms that starts a reaction and in the presence of calcium and carbon and nutrient, you start to get the build out of calcium carbonate and it just starts to grow around the individual bacteria and then that bacteria connects to the other bacteria and then those biofilms connect to the aggregate particles.

Ginger So you're essentially gluing and stitching everything together and making it more dense. It's not growing outward like bread, it's essentially becoming more dense.

Erum Amazing. So now we learned about different types of [00:43:00] solutions, the new strategy and the new infrastructure for Biomanufacturing.

Erum But once we make the thing, where does it go? So now it's time to talk about the market and what is the buy a better reality for the consumer.

Karl So on the one hand, as we've talked about performance over sustainability, meaning that consumers. In some cases are willing to pay a premium for a product as long as it performs, but the product has to be better. the example that we just mentioned was K18. K18 products are premium priced. and consumers buy the products even though the products are very sustainable. Kte doesn't sell on sustainability. They sell on performance. IRA, you and I just talked about different green products that we buy, and some work and some don't.

Erum Yeah, yeah. For example, I use compost bags 'cause I. I like the compost and not trying to be high and mighty that, oh, look at me, I'm composting me something. That New York City has set up infrastructure, at least in Brooklyn, to be able to compost [00:44:00] in a way that is manageable.

Erum And the way I do it is I, put my compost in a compost bag and then I put it into the compost bin provided by New York City. And the thing is, though, the compost bags that I had originally purchased. At a premium weren't very good. Kind of fell apart a little bit. And I'm just like, oh my God,

Erum These are like ripping. And this was like when I bought 'em, like, earlier. And then now I bought a new version of it and it actually was cheaper and actually works better. So,

Erum I wanted to bring up the compost bags and you know, you mentioned laundry detergent, is that oftentimes we hear that no one's going to pay a premium for products. We have to get the cost down.

Erum And I think a lot of that depends on the context Maybe people won't pay more money on laundry detergent, let's say, but there are people that will, and so you do see both products on the market. Still to this day, it's not like, you know, we tried green premium and it didn't work.

Erum It still is working, is we're just [00:45:00] taking more time to adopt and as long as it, it outperforms and performance, of course can mean so many different things. It could mean, for example, a world of laundry detergent, being able to clean clothes better, like getting all your stains out while also maintaining the, texture and the, performance of the fabric that you're washing in cold temperatures.

Erum So there's a lot of levels of performance. And then of course. Having perfumes that don't irritate your skin. So there's like not only a green premium, but there's a health premium. People I personally, and this is maybe my, PHI, my personal health information is that I get a, a skin irritation.

Erum So I have to have fragrance free products, but I do like fragrance. So once we start seeing fragrances that don't cause skin irritation. I'm buying it.

Karl Yeah. And I personally am also willing to pay a little premium for products that have superior performance [00:46:00] characteristics. And I am a huge fan of laundry sheets, laundry detergent sheets. I didn't think I would be when I first saw them, but, to me they make a lot of sense. they are more expensive depending on who you're buying them from, but I find that they do perform as well as a liquid detergent. So I'm a big fan But on the other side of this, biobetter reality is what is the CPG side? What do the really big companies say about performance or bio better? Let's let Amy Trau of p and g tell us what they're looking for when it comes to Biomanufacturing,

Amy Trejo there's one thing that really defines what makes something stick, and it's pretty basic. It's about performance, right? And so in order for a consumer to. Use and to love your product over time, it has to perform for her. Right?

Amy Trejo that's the real advantage that we have with biotech going forward and where we will see things that do better.

Amy Trejo In the marketplace and are successful, we'll be driven by the [00:47:00] performance that it provides to the consumer.

Amy Trejo And if you can deliver on that. Then they're going to become loyal to you and to your products. Right? But it has, to deliver.

Amy Trejo And I think that biotech technology can be a really huge enabler of that going forward because there is a lot of potential there to provide performance. Exceeds the incumbent materials that we have today and provide better delight and, improved product, performance than, where some of the materials today have been.

Karl So the big challenge for dealing with very large CPG companies is they need consistency, price, parity, and proven supply chains before they're willing to reformulate their products.

Erum where do consumers and big CPG meet? Well, consumers want performance, but they also want products that are economical. That they can afford. CPG companies need scale and they need reliability.

Karl They also need performance. Biology or bio-based products have to deliver both to win. And biology [00:48:00] can do this. We're seeing it over and over again, and we're seeing it more and more. The companies that are succeeding now understand the intersection between consumers and big companies. They're not selling sustainability. They're selling true solutions. Sometimes those are better performing solutions. Sometimes they're equivalent solutions, but they are selling solutions and that is what matters today.

Erum And that's what we talk about here on the Grow Everything Podcast. And for those that are tuning in for the first time, please listen to all our episodes because that is where you're gonna get into the nitty gritty of the different products that are being made through Biomanufacturing.

Erum And for those that are listening, hope you got a nice review and refresher of all the things that we've talked about when it comes to Biomanufacturing and it doesn't stop there, we wanted to be able to still talk about what's the next level of biomanufacturing.

Karl Why does this matter now? Well, there's

Karl three forces converging. Technology costs continue to drop exponentially. And we've seen this in gene synthesis [00:49:00] and, gene sequencing where the price drop even more extreme than Moore's Law, Which is the law that people use to talk about how the price of computation drops every 18 months while the performance continues to increase As Iran mentioned at the start of this episode, 95% of executives. Interviewed in this Capgemini report say they are pursuing BioSolutions and consumer performance expectations continue to rise. And then finally, infrastructure is being built. Synonym has mentioned this. We've had a number of guests on the podcast come and talk about what they're doing to build the infrastructure. And these distributed biological manufacturing models that we mentioned earlier are coming to fruition. These are becoming reality.

Erum we can't mention technology without mentioning ai, of course. And to be able to harness all information that we have a human population and being able to understand the [00:50:00] patterns, understand the reasoning, understand how to be able to make bio enabled solutions, how to set up biomanufacturing.

Erum In a way, way to make exceptional products. And again, it ranges. It's everything. Of course. It's what we talk about in the podcast and that I personally think is going to unlock some novel molecules, some novel products, things that we couldn't even imagine and I like to point to. Let's get wild. Let's get a little wild here, Carl.

Erum What could be made through Biomanufacturing if we know how to harness it? I like to talk about bioluminescent products and hair dye being one of them. Being able to have bioluminescent paint, stickers. I mean, I know there's going in the dark stickers, but other types of ways to leverage bioluminescence, I think is going to be an exciting product that's manufactured.

Erum Let's let Andy of CellSense talk about talk about bioluminescence

Andy Just [00:51:00] imagining, how can we use nature in our consumer lives? and I saw bioluminescence in the ocean for the first time And Was like, can I make a living light out of that

Andy along that path, people were asking wow, this is really interesting, what does it eat? how does it grow? And we taught, well, it eats sunshine. It photosynthesizes like plants and it grows by cell division.

Andy And we realized wow, this is a gateway into the world of biology for inquisitive minds.

Karl So to close the Saudi room, what do you think? Where are we going with Biomanufacturing?

Erum Well, I would say that there's a big opportunity here if we're going to take a look at all of the molecules and ingredients and products and materials that are made with petro chemistry and how by manufacturing.

Erum Could replace some of those, not all of 'em. Petro chemistry, again, as we said, is not a horrible thing. it does a good job. It did a great job for when it first came out, we kind of overdid it with it. But if if you do the [00:52:00] exercise of looking at what petro chemistry is making today and how Biomanufacturing can change that, you're going to find a world of opportunities that are very lucrative.

Karl Yes. Biology is the most advanced manufacturing technology we have on the planet. It's been doing research and development for more than 3 billion years. And our job is just to build the hardware, to harness it and learn from what nature has given us.

Erum Amazing, amazing. And since it was just us two kind of giving these perspectives. Reintroducing our guests from the podcast to give their perspective. We figured let's just have a little fun towards the end. And so for this part of the quickfire questions, what I'm gonna do, Carl, is I'm gonna ask you a couple questions, then you ask me a couple questions, and then we can both answer questions that I have listed here.

Erum Okay. Carl. Stainless steel or dirty bio.

Karl I'm the big dirty bio fan.

Erum Amazing. Why?

Karl That's another episode.

Erum who would you [00:53:00] have fix a startup? Rick Rubin or Tim Cook?

Karl I think Rick Rubin,

Erum especially in today's environment.

Erum I hear

Karl you. Yeah. Alrighty, rum. Let me ask you a couple questions. Terraform, Mars, cyanobacteria or mycelium?

Erum So cyana bacteria for sure.

Karl Okay. I, um, space travel. One way ticket,

Erum not for me, but for some people. I would highly recommend it. I'll leave it at that. Keep it diplomatic.

Karl So now let's, ask each other these, okay. I'll ask the first one around 2035. Bioeconomy luxury goods or commodities.

Erum I'm gonna say luxury goods and if luxury, if luxury goods means also skincare products and beauty and personal care products, overall hair care.

Erum things that are a little bit more pricey than what's, available today. Only because people will pay for novel experience and I believe that buy manufacturing can provide that. What about you?

Karl I'm gonna say commodities. I [00:54:00] think we're seeing some really interesting signals right now, and I think the, commodities produced by Biomanufacturing is gonna accelerate and really be in a very nice place in 2035.

Karl Okay. Number two, funding. Wall Street or Dow?

Erum Oh, yeah. I want to say DAOs. Which are distributed autonomous organizations look it up. We talk about it a lot. And really why I'm picking DAOs is because it enables more citizen science enables value being generated and shared amongst people that participate in creating products.

Erum And I hope that that is the future of funding. And I think it's a beautiful way once you get it right, to be able to have DAOs fund products.

Karl I would say Dow for innovators and for specific point solutions and Wall Street for infrastructure growth.

Erum Okay.

Erum And then finally, I'll ask you this question, but I'll answer too. AI's [00:55:00] role, the architect or the intern,

Karl the CEO. Every day.

Erum Oh, snap.

Karl Yeah, we're gonna be working for the ai.

Erum Oh man. Yeah. You know what? I guess you're right, but hey, as long as I can, you know, be in Hawaii having my drink on the beaches, I guess it's fine.

Erum You know, I mean, if it's doing all the work, but I still think there's a place for humans to be the creative drivers of all of this. But hey, look, we could be the board members. And AI can be the CEO and it can report up to us. So if that's the way we're saying it, I love it.

Karl All right. So this has been a special episode of the Grow Everything podcast.

Karl We hope you've enjoyed our take on.

Karl Biomanufacturing.

Erum Thank you so much for listening to the Grow Everything Podcast. Find us on all streaming channels. People text us, ask us questions. We do answer. We do actually also have a phone number. So we would love for you to give us a call and let be able to hear your voice.

Erum All the information can be found in our show notes, and of course we have to say subscribe to our substack and make sure you watch us on YouTube. So thank you so much again for listening. I hope that you continue to grow. Key Quotes "Biology is the most advanced manufacturing technology we have on the planet. It's been doing research and development for more than 3 billion years." - Karl "In order for a consumer to use and to love your product over time, it has to perform for her." - Amy Trejo, P&G "95% of executives interviewed say they are pursuing BioSolutions and consumer performance expectations continue to rise." - Karl "The companies that are succeeding now understand the intersection between consumers and big companies. They're not selling sustainability. They're selling true solutions." - Karl "Technology costs continue to drop exponentially... the price drop even more extreme than Moore's Law." - Karl "AI is going to unlock some novel molecules, some novel products, things that we couldn't even imagine." - Erum "The big challenge for dealing with very large CPG companies is they need consistency, price, parity, and proven supply chains before they're willing to reformulate their products." - Karl "Biotech technology can be a really huge enabler... there is a lot of potential there to provide performance that exceeds the incumbent materials." - Amy Trejo, P&G "DAOs enable more citizen science, enable value being generated and shared amongst people that participate in creating products." - Erum "Our job is just to build the hardware, to harness it and learn from what nature has given us." - Karl