Ryan Graves: Humble Bee Bio, Plant vs Microbial Biofactories, and Rapid Distributed R&D
Ryan Graves is the CTO of Humble Bee Bio, a NZ-based early stage startup developing novel biomaterials to replace plastics.
We talk about
The rapid improvement of synthetic biology
Humble Bee Bio's polymer
How the polymer derives its unusual properties from a solitary Australian bee
Their go to market strategy
Contrasting drop-in and performance materials
Using plants vs microbes as biofactories
Ryan is on a mission and it was a lot of fun to dive into Humble Bee Bio’s approach and challenges as they develop their proof of concept material.
I am late publishing this episode (was meant to be last week) because I was struck down with COVID, and am still recovering.
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Also, apologies for the lack of video from 3:40 onwards because of Zoom issues. Should be fixed for future episodes.
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(03:50) How synthetic biology rapidly improved in the last 20 years
(09:34) How distributed research teams helps Humble Bee Bio move faster
(16:07) Properties of Humble Bee Bio's polymer
(19:26) Why the Australian solitary masked bee makes this unusual material
(28:06) Humble Bee Bio's beachhead market
(33:21) Using plants instead of microbes as biofactories
(41:13) Contrasting drop-in materials with better materials
(43:10) Vision for Humble Bee Bio
Tsung: This is a conversation with Ryan Graves. Ryan is the CTO of humble Bee Bio, a new Zealand based startup developing novel biomaterials to replace plastics. Previously he cofounded and managed operations for a drug discovery startup for multiple sclerosis, and had worked in various labs in pharma and academia in both New Zealand and the UK. Ryan has a PhD in neuroscience with foundations in molecular biology.
In this conversation we cover Humble Bee Bio's polymer, and how it derives is unusual properties from a solitary Australian Bee, their go to market strategy and we contrast a drop in and performance materials, and Ryan talks about using plants versus microbes as biofactories.
I'm Tsung Xu and this is Materially Better. This podcast is a series of conversations about new performance materials and their applications. For the first time in generations, I believe that new materials will play a big role in unlocking innovation and solving pressing problems.
And now here's Ryan Graves.
What is Humble Bee Bio and what is your role as CTO there?
Ryan: Humble Bee Bio's a, a biotech company based in New Zealand. And we are developing novel biomaterials, to improve planetary health. And by planetary health, that's got a direct impact on human health. So both those things are really core to our mission. The company was inspired, largely by the problem of plastic pollutions, plastic pollution, but also forever chemical pollution as well.
So that was the problem that the founder, the founder of Veronica Stevenson, she had wrestled with this problem for a long time. And she decided to just go hunting for a solution, solution that she found came in a kind of an interesting, place, and it was, inspired by a solitary bee.
And the solitary bee doesn't live in a hive. It lives by itself in it, and it makes a nest and it lines it nesting with this nest, with a nesting material that it, that implants its larvae, and the larvae kind of grows in this beautiful nesting material and then eats its way out. And we have a new, new bee for the world.
But when she pulled the nesting material out, and sent it all to some chemistry labs, they were pretty stunned by its properties. And so the idea came about, how can we create what nature's already designed and how can we kinda recreate that in a laboratory setting and then scale that to an industrial setting, and actually start pushing up products that will be a solution to the current plastics, problem that we have right now.
And so my role as CTO within the company, is to drive the R&D program, to take what is, a very challenging place to start with and try and develop stuff that's gonna be, superior performance to petrochemical based plastics. And then also to try and scale that so that we can actually get a, commercially viable business proposition, that we can compete on cost of goods and, and the like.
Tsung: Yeah, I really want to dig into more, of course, a lot more about Humble Bee Bio. And one thing you didn't mention during that intro, which I have to shout out, is that it's an Australian, masked bee, right? So just wanted to give that shout out for Australia and, making quite a unique species of bee.
What led to you interest in synthetic biology and biomanufacturing?
Ryan: I was, I got really excited about, molecular biology way back when I was an undergraduate, and I still remember the lecturer, the lecture, that, sparked all of this interest. And I had a professor, Professor Warren Tate, who was the one who just, man, he just, really lit the fire in our imaginations of what you could do with these different tools.
Most of this was orientated towards using genetic, tools to make monoclonal antibodies and other, biotherapeutics, for, for the biopharmaceutical world. And then, I used these tools throughout my career in various different ways in the lab and the rest of it.
How synthetic biology rapidly changed in the last 20 years
Ryan: But then when I got to know Veronica Stevenson and, and Humble Bee Bio came onto my radar, I was quite blown away by what was happening in synthetic biology. And suddenly these same tools that we used sort of 20 years ago and even before that, had suddenly become industrialized. And so we were able to just synthesize DNA at such an affordable cost, much longer gene fragments, sequence very hard dna, and, and push this all into a biomanufacturing, setting. Huge fermenters and make tons of, different materials. And and it seemed like it was always, science fiction 20 years ago. And then suddenly you've got companies that are actually doing it, that they're actually producing tons of these materials.
Some are even doing it at profit now. And So, suddenly the whole world opens up and of possibilities. So I guess that was, that's where my interest came from this. And and I've always just, I've just loved how nature can design genetic elements, and push those out, manufacture them into proteins, and then the proteins become these functional entities that make things go around, and so how can we translate that and shift our manufacturing to the advancements of what a, a cell's been doing for billions of years?
Tsung: Yeah. That's great. And it must be really good to, see that and, as a practitioner, as a, as an operator in the industry for decades in a sense, and at least be close to that for decades and being able to see that trajectory and, 20 years is not a long time. In, in, in historically speaking. And so to see that level of progress must be pretty, pretty amazing. In your experiences too, across many sectors, what do you think helps, and from what you've learned has actually helped you to be more effective in what you're doing now at Humble Bee?
Ryan: There's quite a f I guess there's quite a few things. I The scientific understanding is the fundamentals. Understanding the, genetic elements, the how cells operate, the different chassis that are available to engineer, structural biology. And how these proteins, fold and do all their thing.
And then how you can turn those into biomaterials and biofabricate. There's, everything we do is pinned into those fundamentals. Science really. That's the core of it. I think there's a bunch of things that have happened around us that, that have made things possible, especially, forming a company here in New Zealand, at a, essentially a corner of the world.
The globalization of the world has certainly helped. Even things like, the Covid pandemic, it just in some ways brought the world much closer together. Jumping on Zoom calls, and, and contracting, companies on the other side of the world became really easy. We've formed a partnership with Ginko Bioworks, last year.
And, and you and those interactions were so easy and seamless to get that deal up and running and to work with that, that, that team, that I don't think that would've been possible, even 10 years ago. I It was definitely possible, but you had to get on a plane, right? And, and get on a plane often.
And, that just costs time and money, that small companies don't usually have. So the globalization certainly helped. And yeah, even sourcing talent and advice. You, we've got a sets of advisory groups that are all around the world and the only barrier is usually is their time and time zones.
And what questions we ask them. But again, we can get access to all of these amazing advisors are keen to help. And things like the technology that we are speaking on right now has certainly enabled that. Those are probably the, the main things. Hum operates as a virtual company and so we, we contract out all our work to, to labs around the world that are, that can do this.
So in some ways, we can go and access the best talent around the world and their labs and their setups without having to build them, and without having to draw the talent here or grow it up within our own company. And so they all become part of our, our company in some ways. And so we, we love the model.
It's got its challenges, but it's, it's certainly a really fast way to do very difficult things and to scale quite rapidly.
Tsung: That's a really fascinating aspect of what you've told me previously about Humble Bee and is just that distributed model, which, I've come across in the context of cloud labs, which is obviously somewhat different. But, and just, having worked in semi distributed teams before myself.
How distributed research teams helps Humble Bee Bio move faster
Tsung: What was the thinking for your, for Humble Bee with starting with distributed teams? And you already touched on the benefits, but yeah, curious how you think about some of those tradeoffs.
Ryan: Yeah, largely it was. The model came because we were so capital constrained. Raising capital is difficult. It's difficult for the sector. It's certainly difficult in a, in New Zealand who are, a little bit more conservative around this deep tech, science and, long, long R&D cycles to before you get to market.
So we, we operated on hundreds of thousands of dollars and so when you do that, you just don't have the capital to build out a lab or to recruit people with the right expertise and, and drag them to New Zealand, nice place and all, but it's still expensive to do that. And so it, it more just came out of, out, out of need more than want, and it's worked incredibly well. We're certainly not the first company to do this. I know certainly in the drug discovery world, but virtual biotech companies have operated for, a couple of decades using this similar model. But yeah, with a few hundred thousand dollars, we managed to, like I say access talent around the world, access their labs, get them to do the things that they were super, super good at doing.
Almost exploit their niches in a way. And, and they were always excited to work on a very challenging project like what we had. So that, that was kinda the main driver. But then when we sat back and looked at the model, it's got a lot positives about it, particularly the speed that we can move at with, with established labs.
They already have the instrumentation, they have the setups, they, they have the expertise to execute what they're very good at. And so you can plug a problem to them and they can do it very fast. So we don't need to upskill our own team internally to do that type of work.
So yeah, that's been the main be benefit of this. And we have teams in, in, in Melbourne, at Deacon University. We have teams in Queensland and Brisbane, in Auckland and here in New Zealand. And, we've accessed, teams in San Francisco and as I mentioned for Ginkgo Bioworks, in and Boston.
Yeah, that's been, incredible for a company like ours just to rapidly scale, and build, essentially build a team up.
Tsung: Yeah. No, it's amazing. And obviously seems like a very, asset light and capital light approach to, to, to scale in the early days as you've said. I wanted to back up a little bit just to talk a bit about what led you to join in the early days when you talked about the Veronica and her founding, but yeah, what led you to join initially?
Ryan: It was more just to think around the excitement around. What could be done? I shared a similar kind of passion for the problem. I'm, I've got a strong passion for both, human health, but also planetary health. As a kid I was always trying to clean up the environment and jump into nature and all that sort of thing.
The in, now I've got young kids and stuff as well. You can certainly see the problems that are coming. Planet Earth, and how that is gonna really affect both our biodiversity, and also our human health. And, so it was quite easy to jump on board on in terms of a mission.
And then the second part of all is just, I guess the excitement, and possibilities to really build out a technology and, and a company. So yeah, it was quite a, quite an easy decision to join, and join in with the excitement of what's happening with synthetic biology. There, there's probably a lot to be said around timing as well.
I think 10 years ago this was a very, would've been a very difficult proposition to get excitement around it. But I think when you glance at some of the other companies and see what they're doing, a lot were mentioned in your brilliant article, you see what Sulgen's doing and Lanzatech and, Checkerspot, Bolt Threads, AMSilk, and you want to you wanna be a part of that journey, that trajectory of these explosive, technologies that are gonna seriously change how the planet, is and how humans can interact. Whilst, whilst not severely changing how we generally live. And, and that was a probably a thread that Veronica and I both shared.
This thread of, everybody knows that a lot of the stuff we do is not good for the world. We all buy plastics, we all buy clothes that are detrimental to the environment. We all know it. And. But it's, at the end of the day, it's actually, it's not really a consumer's fault because we walk into shops, we need stuff and there's, there is no options.
Like you walk into a clothing shop, there is no environmentally friendly options. Cotton has huge issues even though it's a natural, natural and textile. And then you've got all your synthetic polymers. So it's not it's not like we're making bad choices. There's actually very limited choice.
We have to drive in cars. It's, all these things that, that kind of help our society, continue on its trajectory. I'm all for that. But, what I, what we wanna offer is that consumers can walk into, into shops and that sort of thing and actually be able to select things based on what their values are.
So we really want to create things and give them that option.
Tsung: Yeah. No, that's great. And I think, Yeah, progress is really good in so many ways. And I think you really frame it well, right? Like just there is limited choice and, how can you give them more choice for better products that they will actually want to buy, that also happen to be sustainable by default.
Properties of Humble Bee Bio's polymer
Tsung: And so maybe we can jump a bit more into Humble Bee Bio and the material specifically. What is the, the biopolymer that you already touched on briefly, but what is that, that you're developing? Can you talk a bit more about it?
Ryan: Yeah, sure. The. The natural wildness material, had some Xu, has some extraordinary properties that really blew us away, blew away the chemists that were working on it. Some of these properties is that it's, it's, it's got flame retardancy properties, which is quite remarkable for a natural compound.
It's resistant to solvents such as toluene, resistant to acid and bases, one molar HCl, doesn't degrade it, which is quite phenomenal. And so the idea sparked on the back of that was, we can, this is a mall malleable, material that can be put through industrial processes, and we can shape it how we want and push it into products.
And so that's of where it started. The challenges started straight after that, though.
And then the idea was how do we do this? Can we use a chemistry route? And that was attempted and actually we found it was too difficult. And so we switched over to using a synthetic biology route. And that's when I came on board the company. We sequenced the genome of the bee, we identified the gene, that codes for this nesting material. And now we've sought to recreate that. So we've pushed that gene into various different chassis, such as e coli and Pichia pastoris. And we express the protein, purify it.
And then we've got a team of biomaterial scientists that take that pure protein, push it into various different formats, and then create biomaterials from that protein. So it's essentially a pure protein that gets pushed into films. Fibers, coatings, and then we test those for the, for its various properties to, with the ultimate goal to actually make a bunch of, proof of concept, biomaterials.
Tsung: Yeah, And we've talked a little bit about these, mature properties before I just, on those, you mentioned flame retardancy, you mentioned, acid, resistance to dissolving in acid and bases. I I'm curious if, just how you think about is that the combination of those that makes this somewhat unique?
Are there specific things that it just simply does better than most polymers out there? I'm curious how you think about the performance comparison versus what you it would be competing against in the market.
Ryan: Yeah, look, the, what that's competing against in the market is actually, it's, it's pretty wide at the stage and, and it's in some ways plastics are an incredible, material. They're so incredibly versatile and hence why we use them in everyday life. The main issue is just with their degradation properties.
They just, they degrade to a certain extent and then they sit around an environment for, up to 500 years plus, which is obviously gonna cause so many problems from, from an environmental point of view. Think I, I think I read recently that there's, that the mass of all plastics on the surface of the earth now outweighs the mass of all the mammals on earth.
Which is just extraordinary. And it's pushes towards this dystopian sort of, future view of, of where planet earth is going. And probably the scariest part of all that is most of that has been produced in the last 20 years. So you only gotta push forward into sort of when our kids are growing up and, grandkids come along, what the world's gonna look like. It's gonna be, since you're covered in microplastics and, and other pollutants. That's the main driver and the main, concern around the current versatility of the plastics we use, today.
Why the Australian solitary masked bee makes this unusual material
Ryan: But going back to what the nesting material does, we've done a bit of work in trying to understand what the bee is looking for in its nesting material and why it has evolved, towards this nesting material.
So essentially the bee Australian bee, in Queensland is, it's exposed to a number of different, environmental, pressures. Quite extreme pressures, it needs to keep its saliva moist to a certain extent, and it's gonna be in some pretty arid conditions. And how does it form a material that can both have breathability but also keep, keep some moisture inside, but also when it does rain and, the seasons that you have in Queensland, it's, it's either raining pretty hard or it's really dry.
How does it keep the water out too? And then obviously you've got the issue with bush fires and. Potentially the flame retardancy properties. And be's been evolving for, when we look back at the, the phylogeny, it's, it's got millions of years of evolution, to develop these different types of nesting materials.
And it's developed, a material that can do all of these things. And so it's very much about, how can we recreate that in the lab? Because that's an extraordinary set of properties to have in a single material.
But probably the key thing in terms of us wanting to advance this is its biodegradation properties. And be completely fair, we don't fully understand how this biodegrades, but all we know is that it doesn't, because we can't, it's very hard to find this nesting environment despite there being a decent population of bees around who are making this every, make it, twice a year and they lay larvae.
So it degrades in some manner. Otherwise it'll be really easy to find. So we do believe it biodegrades, but that's, that's a piece of work that we have to do at some point to fully characterize that and understand what it's biodegradation properties are. But I think that's probably the most exciting part of this material.
Tsung: Yep. Yeah, for sure. For the end of life. And the environmental benefits of that.
Matching or going beyond the properties in the natural material
Tsung: To what extent are you using the, the properties from the, from the bees nest, the nesting material as a baseline, as something that you could go beyond?
And to what extent are you looking at that as like the goal in terms of the properties you're trying to hit?
Ryan: Yeah, that's a really good question. So yeah, ideally we are using the nesting material as guidance. It's actually really difficult to recreate the nesting material. Exactly. And we've certainly looked into that and it's, there's, although we've had all these advances in synthetic biology, we're still so limited.
These, These insects are just remarkable in terms of what they can do, from both, their genetic code to moving to protein, to moving, to making a nesting material. They can combine certain different, combinations together. They've got machinery within their glands that, are far more advanced than the most advanced microfluidics that we have today, accessible today.
And that can combine this all in a perfect sequence to produce something that's, that's quite incredible. And so we can only recreate parts of that at the moment, just with the technologies that we have. And so we are very much using the nesting materials, a guidance set, of what we think is possible, and then trying to remake that and see what we can come up with.
So that's the principle thing of what we're trying to do with the proof of concept.
We've made that, then we're gonna go back to the site, the synthetic biology principles, where you have this, design, build, test, learn cycle, where we can start making random and systematic changes to the genetic code.
And it, this is just the beauty of it. It's entirely possible with the budgets that we have these days that we can do that. And then we can see. The different properties, of those changes can make. And so from that very nature with the, again, like I say like the design, build, test, learn cycle, the learn part is actually, can we start tuning the properties to this?
And so if we really want something that's hydrophobic, can we alter a whole lot of the underlying chemistry and drive it to being something that is super hydrophobic? We think it's possible, but we obviously need to try and do that. So yeah, a bit of both sort of guidance and inspiration for men nesting material, but then actually using the tools and the robotics that we, that the world now has and the bioinformatics and machine learning tools, and actually see whether we can do this on a, using those tools as.
Tsung: Yep. No, that's fascinating. To, it touches on, what you talked about before about how things just wouldn't have been possible 10 years ago, in a sense to, to do some of these things or certainly at this speed. And to this extent perhaps in terms of some of the genetic edits, can you walk through the high level processes, for making the biopolymer and making that proof of concept today?
Ryan: Yeah, I can walk through some of it's proprietary, but, I'll see what I, how I can navigate this. Yeah, so I essentially, essentially it's, we are using precision fermentation. So it is very much about engineering a cell, and the cell being, most, one of the most advanced machines we have on planet earth.
And we feed it a different code, a genetic code. And so this is fairly standard molecular biology in some ways. And then we use precision fermentation to. To scale that up into scales of grams and then kilograms. And from that we can purify the protein, which, has actually been extremely tricky with this particular protein.
But we've certainly, had to experiment with that and figure out novel ways to do that. And then once we get that pure protein, the biomaterial scientists have a number of tricks up their sleeve, both using different, green chemistry, so different sort of green solvents. And then a bunch of different, physical techniques, to make biomaterials.
Some of these techniques are wet, spinning, electro spinning, and then just casting films and different coat techniques, to, to see what, biomaterials they can.
Tsung: Yeah, there's a couple of follow ups there. So in terms of the, materials that you, targeting to make and to fabricate from the proteins, do you, can you give a sense of what sort of, first, first target materials that, that you have in mind? And then just the additional piece there is, how do you, how's the degree of difficulty in comparison with, with both the upstream piece of it, the synthetic biology piece of the process versus the downstream, fabrication piece?
Once you've got the purified protein,
Ryan: Yes. No, that sounds, I can definitely answer that. Remind me what the first question was again?
Tsung: Yeah. Yeah. Sorry.
Humble Bee Bio's beachhead market
Tsung: So just, in terms of what the first, material, is that you're looking to fabricate from the purified protein.
Ryan: Yeah, we have a, our beachhead market will be in, is into textiles, and textile finishings. And this has largely been driven by the market need or the market pull. Our company gets approached on a, every second week by some big brand, looking for solutions, for their textiles.
And some of these textiles are within cars, some of them are clothing, and various other different iterations of that. So we definitely get a sense that there's a big market need out there. A lot of the forever chemicals, and other, and other, petrochemical based. Compounds are starting to be regulated out.
So regulation's a driver, but also consumer. A lot of this has been consumer pushed as well. So yeah, we see a big market need in textiles. And that's probably one of our primary markets.
Tsung: Would it be coatings that you're looking at first or just generally? It could be textiles and or textile codings.
Ryan: Yeah, like the, textile finishings. So a type of coding, I and again, this is some of it's driven by market need. Things like your DWRs, which are your durable water repellants. The use of polyfluorinated compounds that are being regulated out. So again, there's quite a strong market, pull, for, high performance, but sustainable, biomaterials to replace those.
And that kind of almost fits with some of the other challenges that we see going forward with scaling. So initially when we scale, our cost of goods are gonna be relatively high. So things like finishings is using a much lower volume of our biomaterial. So hence why the two things click together and fit.
Fiber is a bit more challenging just because it consumes a lot more raw material. And the raw material, until we scale to a very large amount, will struggle to compete. Cost, by cost of goods with polyester or the other different fibers that are out there.
Tsung: Yep. Makes a ton of sense. And I just wanted to clarify that because, yeah, the second piece, to that question previously was just around, so take finishings then, as your end product. Is the, is it just, is it a higher degree of difficulty to synthesize the protein, and bio manufacture the protein?
Or is it kinda like the actual There's more challenge in actually, fabricating the finishing
Ryan: I think it's, I think that the challenge for us to date has certainly been in the front end about how we work with this gene, and express the protein and produce the protein. That has certainly been our challenges to date.
But my feeling is that will hopefully be more straightforward. But yeah, there's certainly been a lot of challenges and like I say in the gene expressing this gene and purifying it out. And and I think a lot of that has to do with just the fact that this is so incredibly novel.
No one's really worked on a protein like this before, so it's just had all its challenges. Yeah, the biofabrication is, it's certainly gonna have, its have its challenges, but we don't see them being incredibly insurmountable. Probably the bigger challenge that we foresee is how we're gonna scale.
And, do you know, I think the whole industry's kind of concerned about this. How do you really scale biomanufacturing, with the current infrastructure around that we have and the cost of goods, challenges that we have.
Tsung: Yeah. How do you think about that today, then scaling
The future once you a proof concept? yeah.
Ryan: Yeah. Proof of concept comes first and scaling and cost is gonna be a secondary concern. We certainly don't wanna be distracted by that at the moment. We've got enough technical challenges, to drive through at the moment. This. The scaling was interesting and we both attended that Built With Biology conference, a brilliant conference in Oakland earlier this year.
And there was certainly so much chatter around that conference around how we scale. Precision fermentation is the obvious way to go with this. And then literally scaling to, the more you scale, the more your cost of goods come down. This is certainly how the petrochemical industry works, through, we compare and contrast against what it costs for polyester per kilogram and it's, we all of go, Oh, how on earth do we compete with that?
But then when you break it down, that industry has had. Operates on an enormous scale, and hence they get the, they get the, the economies of scale in that very, by that very nature, they've also had government subsidies for the last sort of, what 60, 80 plus years that have helped build that in infrastructure.
When we as a new industry are looking to try and compete, cost of goods wise, it's it's on a very unbalanced grounding. And so we certainly are. Some things in industry that are trying to rebalance that. With, the Biden administration putting out, wanting to inject 2 billion into the buy economy is certainly a really good seed to see, this sort of, hopefully gonna germinate in many ways.
But yeah, we see that as a big problem. The other thing that has very much surprised me and very much excites me is around the alternatives to precision fermentation. Can we scale using algae? Can Can we scale using photosynthetic, organisms, cyanobacteria, microalgae.
And this is certainly a lot of technology was developed through the biofuels era that we saw. And then even pushing on from that, can we scale using plants? And again, the, some model organism plants have certainly gained traction in recent years. Technically it's more complex, but the scaling story is, is so much more, Exciting, to grow fields or greenhouses or vertical, farming of plants that are producing, a very high value protein is, is an incredible story.
And we are really keen to attempt that at some point, and run the cost of goods numbers to see what we can do in terms of a, a process around that. And, and we're starting to talk to people who, who do life cycle analyses and compare and contrast the two different modes.
Fermentation is still got its challenges around not just cost, but so carbon. We really want to be a carbon absorbing industry. And so there's work to be done within fermentation to make sure that we. capture carbon, push it into the biomaterials. We make it, send those out to society and essentially capture carbon from atmosphere and push it into our everyday goods.
And hopefully some of those goods stick around in our houses and in our cars for 20, 30 plus years. And so it's almost a carbon capture, a useful carbon.
Using plants instead of microbes as biofactories
Ryan: Is fermentation the best way of doing that or is photosynthesis a better way of doing that? And I think, most people lean towards saying photosynthesis would be, so can we grow biomass and extract, 15% of that as being our protein of interest and then use that biomass for other, other sectors of the economy, and build that into our life cycle analyses.
So yeah, that's some of the more exciting stuff that we have planned to come next year, which I think, that certainly excites me. Cuz we do see the challenges of fermentation and building cities of stainless steel.
Tsung: Yeah, sure. In terms of those bioreactors and plants, specifically biomanufacturing plants, not plants to as shay as you said, how, I've had a couple of conversations, brief conversation about this recently. How do you think about the limitations at least today in terms of using plants as strategies and plants as the enabling, bio mass to actually grow these proteins. Are there just limits to how complex the molecules are that they can make?
Ryan: Yeah, look, I'm not a plant molecular biologist expert by any stretch. I've always worked at mammalian in bacteria. But when we've been looking into this, I the challenges with plants is that plants are incredibly complex from a genetic point of view. They're genomes are three times larger than mammals are.
Which comes with all sorts of challenges about how do we insert the gene of interest into these and get these plants to express them. And, and need, and the techniques are coming on now. You can push them into the chloroplasts and get the chloroplasts, which, for those, out there that, the chloroplast is the part of the, the plant.
That makes, that is green. That gives us the plant, it's green color. But it's almost a separate little engine that has its separate little, genome, that, that may is a place where we can insert a gene much more easily than where we can insert it in the genome of the entire plant.
So I've heard that the, and read that the, that the chloroplast engineering is, is a way to go. We are seeing this with tobacco. The first biopharmaceuticals are being, produced in tobacco now. The first one was approved early this year by the fda. So we, and I think it's a vaccine actually, so we can produce a vaccine compound in tobacco and extract that.
And that's now going into humans, which is an incredible story. Whereas previously everything's been made in VAs and bacteria or, or other, different fermentation avenues. So yeah, the plant technology is coming along. The other challenge, there's a couple of other challenges that I foresee.
One is around just the genetic engineering story. Society, I don't think we still, we have yet a full social license to use genetic engineering. And so the genetic engineering in, in most places, store has to be in a very contained environment. And obviously with plants that limits it. So it would have to be contained, greenhouses and large parts of the world.
Some other parts of the world are definitely, more progressive about this technology and have enabled a genetic. Modified food, genetically modified, plants to be out in fields, and grown. So there's, societal limitations on this as well. And probably the last part is the bio processing.
So the downstream bio processing, extracting proteins out of, bacteria, particularly if they've been secreted in a fermentation. System is very well studied. There's a lot of engineering that's gone into this over the, the last few decades. And the downstream processing costs are usually about, 40 or 50%, sometimes even higher than the actual fermentation costs.
So that really needs to be an important part in the cost of goods model. Plants, it's likely to be even higher. So there's certainly challenges around that, to make sure that the downstream processing of extraction is, is gonna be, fast and cheap. So yeah, those are the three main, issues.
I see. Just the technical getting the plants actually express it the way we want. The issues around genetic modification and organisms in society and then the downstream processing.
Tsung: Yep. No, that makes a ton of sense. And Yeah, it's a really fascinating take.
Contrasting drop-in materials with better materials
Tsung: Some people say that compared with drop-ins, differentiated performance, in a material will accelerate demand, for biomaterials. What do you think about that?
Ryan: That's a really interesting question and a really strategic question for all companies who are in this space right now. There's, I think there's examples of both, and I think the industry's gonna be doing both. Particularly at the outset, the drop-ins just enable much faster speed to market, which can get revenue streams up much earlier.
And there's a lot of examples around these drop-ins, Lanzatech and Solugen, are the two main examples, Lantech are making ethanol and ethylene and, and, and other things that are, plugging straight into the existing infrastructure now. You look at AMSilk and they've got silk proteins that are going into skincare, products and those skincare products.
It's essentially replacing out a petrochemical based, product. The ones that give that silky feel. Then there's now a biological silk in there, which has got much better degradation prop. Properties. So the drop-ins are definitely, part of the mixture. Ultimately though, I think the high value comes from, making buyer better higher performance, materials than what is currently out there in the industry.
And it's, I think it's at that stage where we can actually start, pushing up the, the value proposition for us as a company. But they're, they require a lot more, Engineering to get to that point. A lot more r and d. And also, the manufacturing, getting them up into manufacturing and stuff will take longer.
Vision for Humble Bee Bio
Tsung: If Humble Bee Bio is, wildly successful, what have you achieved and what are the products and services that you'll make, and what do they look like in 15 years?
Ryan: Yeah, so I mean our little solitary bee has certainly given us a really interesting, protein to start working off. And we wanna almost see that as a its own little mini platform of which we are hoping to make a number of different products in a number of different applications. So that's the first, the first part of our pipeline, the second thing is that, we are gonna, we're starting to look out for other examples of, of societal need or market problems, and then look in nature to find solutions, very much about how we did it the first time round. The first time round is always really tough. We want to capture that knowledge and those processes and start repeating it for a second, third, fourth, fifth, six, different, little product, platforms.
So it is very much looking, for those societal problems and then using the skills that we have, looking at insects, looking at fungi, for the solutions that we desire. Going in, into the sequencing the genomes, extracting the genes, recreating those, materials, and then seeing if they, and then product test and developing proof of concept, products and making them.
But yeah, I think the world's, the world's hugely in need of these new products. I don't think we, we will be short of demand. It's more just about what can be limited by imaginations, in terms of what we can, what we can take from nature and learn. And, I think someone phrased the term co-design with nature.
And I think it's a wonderful phrase and a wonderful, way of thinking about how we can develop novel materials for the.
Tsung: Yeah, I really like that. And Max, who had been on the show, just very recently, said as well, that, yeah, there's this code co-development process with nature, which is basically what you're speaking to here as well. Yeah, super fascinating just to see all the different startups and Humble Bee obviously has, you've started off with a different platform, if you will, a platform molecule, different starting point. And so it'll be fascinating to see how yeah, your learnings, your, and how that informs sort of the direction that you decide to take there.
How would you like help, and who would you like to hear from?
Ryan: Yeah, that's a interesting question. Again, at the Built With Biology conference, it was, it's such a collaborative industry right now. And I hope that continues. I think we all see the problems and challenges of a, of, both that we've talked about during this podcast, that we're all of binding together and really helping each other out.
Which I, which is just amazing. And I hope that, I really hope that continues. The things that I think we as a company, are gonna need help in the future with is largely around scaling. And, not just scaling and fermentation. It's actually probably exploring the idea of can we scale and plants, can we scale an algi?
Can we scale and sign a bacteria? What other chassis are out there to scale with? I think that's probably one of the. Core issues we have. And then probably the other one is about, how do we build these, these big variant libraries and actually really drive the design and build test learn cycles.
We've certainly are developing that talent and house to a certain extent. But particularly with the, the bioinformatics and, and machine learning and, and really building out that stack if you like. Those are, that's another, big one where, there's other companies that are way more advanced at doing this, and we certainly wanna learn from how they're doing that and how they can benefit, the future really in terms of, producing high performance, bio.
Tsung: No, that's great. And it's also really good to see you doing that in New Zealand. Obviously Lanzatech, has strong presence out there too, but that's really great to see. Anything else we should have covered and any parting words for listeners?
Ryan: Probably the only other thing to say is more just around, around talent. I think there's certainly a lot of very well trained molecular biologists, bioengineers, biomaterial scientists, who are in the industry right now getting excited. A lot of coming out of academia and into biotech companies as they grow and, the people wanna really make impact.
And I think that's really exciting. But again, when you of project forward and a lot of people have done this, Eric Schmidt and his, his group have certainly pushed forward about how, projecting the future, about how large this industry's gonna grow and actually what do we see as the bottlenecks and, developing talent is gonna be one of the huge ones.
of Reaching out to anybody on this podcast who's, at university level or even at school level, or even, at, at, who's, who's 10 years old at this stage. The industry is gonna and is gonna be bright. Get into stem, get into learning about biology, get into learning about engineering, machine learning, bioinformatics.
This, certainly the future is definitely gonna be bright for those types of people and the industry and the industry certainly needs it. Society certainly needs that talent to come through. We need, we're gonna need just, huge numbers of, of, of future talent to run these biomanufacturing plants and keep co-designing with nature and keep improving what we're doing.
Tsung: Love it. Great message for those up and coming engineers and builders looking to make an impact in synthetic biology and biomaterials. Final thing is how can listeners connect with you, Ryan?
Ryan: Yeah. I'm personally active and so is our company Humble Bee Bio. We're active on Twitter, and on LinkedIn. Those are probably the two best avenues. We've got a beautiful website as well, and it's got a contact page for that. Www.humblebee.co.nz. That's another avenue.
Yeah. We're always open ears and, keen to connect with, any of the listeners out there and, particularly with other companies, that are building, or talent who wanna build with us.
Tsung: Fantastic. I'll link to all of those in the episode description. Ryan, this has been a lot of fun. And yeah, look forward to the next time we speak, but, for now, yeah, I really appreciate you coming on the pod and yeah, I'm excited to see the progress with the proof of concept.
Ryan: Yeah, it's been an absolute privilege to be able to speak with you. I'm certainly a huge admirer and supporter of the work that you do. So yeah, keep up the great work of, of disseminating the cool ideas within this industry and driving excitement up. It's, it's awesome. You do great work too.
Yeah. Thank you for inviting us on this, on this podcast.
Tsung: Appreciate that a ton. Thanks Ryan.