Scaling Biomanufacturing with General Biological’s Abhi Godavarthi
Abhi Godavarthi is the CEO and co-founder of General Biological, a startup that has developed a novel biomanufacturing technique to produce specialty chemicals and other products at a massive scale. The following interview has been lightly edited for length and clarity.
Let’s start with the basics: What is biomanufacturing?
I'll start with what the alternative is: petrochemistry. If you take a barrel of crude oil, that black goo that comes out of the ground, about two-thirds of that goes into fuels and the other third goes into chemicals and materials. These processes throw high temperatures, high pressures, and some catalysts at it to convert these hydrocarbons to, say, polypropylene for plastic bags, paints, adhesives, lubricants, and all those sorts of things. All the carbon in those products is coming from crude oil. That is petroleum-based manufacturing.
Biomanufacturing, by contrast, is about getting cells, enzymes, microorganisms—whatever—to make a product in a way that is cheaper and cleaner than petroleum-based manufacturing processes. In biomanufacturing, we’re using carbon from carbohydrates (such as sugar) instead of hydrocarbons, and instead of using dead catalysts like metals, we’re using some living biological thing like an enzyme or cell. The reason you might want to use an enzyme or cell is because, just like you and me, they operate at room temperature, not 800 degrees centigrade. Sugar doesn't explode the way oil explodes. And if you’re looking at “what are things that convert sugar to useful stuff,” living things are the main engines for that. So that’s biomanufacturing at a high level. What comes out the other end – the products – is a different question. It can be antibodies for COVID, mRNA vaccines, lactic acid for skincare, or the stuff that we make—specialty chemicals like succinic acid, which goes into plastic, resins, coatings, and stuff like that.
How did General Biological start?
The ideas behind GB really started in college over shenanigans with one of my best friends, David Sozanski. David and I bonded over a slight distaste for pharma M.O., that there’s this racket of companies and financiers that control the industry. And as a younger person interested in life sciences, it seemed like you couldn't really put a dent in that. So we naturally gravitated towards life science applications outside of novel therapeutics. One of the first interesting things that we came across was manufacturing blood. Only a few countries in the world have great blood banking infrastructure, and blood has…great “product-market-fit”, for lack of a better term. Everyone needs it, there isn’t enough. But we quickly saw that the manufacturing costs would be ridiculously high. Also, blood is still pharma, though it’s not a new drug. Another interesting avenue was cultivated meat. You're probably familiar with cell therapies that are like saving kids with cancer, but if you can drop the manufacturing costs to make cultivated meat dirt cheap, the same underlying technology to grow mammalian cells can be used to drop the cost of life-saving therapies. So this theme, the intersection of biotech and manufacturing for large-volume markets, stuck with us. There are real benefits to scale.
We thought that the interesting problems were all in manufacturing. We believed that the biological design tools were only going to get better and more accessible, but how to scale things up is where most of the neglected problems were. So we focused on solving that. As we got going we brought in our third partner, Kyle Mohler, and we’ve been off to the races since.
What is the limiting factor in scaling biomanufacturing today?
I think if you ask anyone in this space, you will get the same story again and again: the extremely expensive and unpredictable nature of scaling manufacturing.
When we’d go into these biomanufacturing facilities we’d see these giant stainless steel tanks. First, they’re made of stainless steel to protect against all kinds of contamination that can occur in biomanufacturing. If something contaminates your reactors, it will generally ruin your process yields. The way people solve this issue is pretty inefficient: shut down whole facilities and steam sterilize the tanks between production runs, which requires a resistant material like steel. Now second, the reason these tanks have to be so big is because the production rate per unit volume is super low. That’s because most normal laboratory cells eat carbon slowly, which means they make stuff slowly. Thus you need massive tank volumes to hit a given output.
Basically, these companies are investing hundreds of millions of dollars into these gigantic stainless steel tanks, which need to be big because they have slow reactions, and they’re not even using them half the time because they’re busy cleaning them. And on top of it, the bigger the tanks, the more unpredictable your process is – many examples of large scale-up efforts totally collapse. The person writing a $2B check isn’t getting a meaningfully lower risk than the person writing a $2M check. That's what we describe as the perfect storm: massive capital requirements, low utilization, and equal or increasing uncertainty as the checks get bigger. And that’s the technical – and financial – problem we wanted to solve.
We spent a lot of time trying to get to the root cause of why we haven’t tapped into the inherent advantages of biomanufacturing. Fundamentally it comes down to the fact that most companies are using E. coli and yeast for their process. These are great R&D tools, but they grow slowly and are too prone to contamination for industrial use. So we started looking for alternatives. We literally Googled something like “microbes that grow fast and don't get contaminated” and we went through the first four pages of search results, and we found one that looked like it fit the bill for what we were trying to do. It tears through carbon. So instead of needing tanks that are ten times the size, it just needs to be fed carbon at 10 times the rate. You don’t have to shut down the bioreactors because they grow in conditions that other organisms don't like, so your utilization is much higher. And so, instead of building one big tank because you need the economies of scale, we are able to pursue a “scale out” approach, where we copy-and-paste a single, high-output reactor module. And that removes the uncertainty typically associated with scaling – if you de-risk the module, you de-risk the factory.
What is the basic idea behind General Biological’s technology?
Let me start with the broad idea: we have a process that runs with basically no waste, in water, at room temperature. So in theory, you should be able to have a very low cap-ex for biomanufacturing because you don’t need all the equipment to heat things up, cool things down, transport flammable raw materials, deal with waste, and so on.
As I mentioned before, the use of our “non-model” bacteria gives us two huge unlocks: 1) lower CapEx and 2) modular scaling. First, traditionally manufacturing is done in a batched way in stainless steel. Because we don’t need to generate steam to sterilize things (and thus don’t need a tolerant material like steel), we can shift to plastic. That’s a huge reduction in capital costs. Second, because the reaction is faster, we can hit the same output with a smaller reactor – and so we aim to replicate this highly productive “module” instead of building bigger steel tanks. So there is a meaningful risk reduction after the module works. Just to illustrate, our plastic tank has the same output as a stainless steel reactor that is 10-15 times larger and at least 100 times the cost. Right now, our tanks are 100 liters, which is a couple of cubic feet. We’re now scaling our module to 1,000 liters because you can’t realistically copy-paste 100-liter tanks. There’d be too many modules. We think you have to do at least 1,000 liters. And ideally, we see identical performance at this 1,000L scale. Once we do that, it’s just scaling “out.”
And how will General Biological get to scale?
So I think your question is the most important one. This is why the low CapEx unlock with plastic infrastructure is so crucial – it’s a chemical engineer’s approach to biotech. As I mentioned earlier: instead of one giant tank, we have multiple smaller tanks. This seems like a trivial thing, but the beauty in the modular approach is that you have significantly killed the scale risk. You just copy-paste the module that you already know works with given metrics. Again, if you de-risk the module, you de-risk the whole factory. And it’s a game changer in terms of how biomanufacturing is financed. All these things in the past required raising debt from a bank and taking out massive loans that made everyone pretty nervous. Our paradigm is fundamentally different and means you don’t have to raise $200 million to build your first small-scale manufacturing plant – and when the checks do get massive you have taken out a huge part of the scaling risk. Even with a first-of-a-kind technology, you can quickly access favorable debt and start to deploy fast with a small tank that has the same output as a bigger, more expensive infrastructure.
It’s also worth mentioning that the cost of debt for traditional petrochemical infrastructure is not low either. People sometimes refer to them as “hidden costs” but with 40, 50 years of data we now realize how much of a liability these plants are to the local communities, and it’s not really “hidden” in the interest rates they have to pay.
Scalable, modular biomanufacturing has been a dream of the industry since the beginning, but it’s only getting traction now. Something like half the capex of petrochemical facilities is heating things up and cooling things down. The other big part of capex for these facilities is dealing with all the waste. So for every ton of oil, you’re getting like half a ton of waste and half a ton of product. Disposing of all that is a problem. For smaller facilities, it’s a drain on cash and a liability for the community. With our approach, there is less CapEx, less liability for the local community, and of course a lower cost of capital. This implication on financing is a huge factor in how we get to the needed scale.
Why aren’t you concerned that existing biomanufacturers are just going to copy your approach?
We got asked this question a lot when we were fundraising. Everyone wants to know what you know that other people don’t. What’s the secret?
Everyone knows that the cost of DNA sequencing and synthesis is on these exponential downward curves. What we realized is that those costs have everything to do with design and absolutely nothing to do with manufacturing. So why won’t incumbents just copy our approach? Because it’s counterintuitive. The instinct for incumbents is to stick with biomanufacturing in E. coli and yeast, and just edit the genome to get them to make what they want because it’s a tractable problem. But the reality is that it’s cheaper than ever before in history to wrangle a new microorganism that is more suited for manufacturing and edit its genome to make the products you want.
General Biological is taking a clean-sheet approach. We’re throwing out E. coli and using a microorganism that has the right properties for true industrialization and scaling. We don’t use stainless steel bioreactors, we build our own plastic bioreactors. We don’t do batch manufacturing, we do continuous manufacturing. These are critical for getting to scale. And the only way to do these things is to go beyond E. coli. So that’s the bet we made.
Given the drawbacks, why are E. Coli and yeast the default solutions for biomanufacturing?
That’s a good question. The first reason is a technical reason. A large part of the reason for E. coli’s prominent place in biotech is that it was the first microorganism to become domesticated. We figured out how to edit its gene pretty well in the 70s. It also grew sort of fast, so you weren’t sitting around in your lab all day waiting for things to grow.
The second reason is a sociological one. Academia is built on an apprenticeship system so you use things because your mentor uses things. And that carries over to industry.
The last reason is a common story about risk tolerance in old industries. If you’re a pharma company and E. coli works for your clinical products, you’re not really thinking about manufacturing costs. You make like 99% margins. You’re more worried about adding something to your patent lifetime. That's the pharma mentality – manufacturing is mostly an afterthought.
So why do E. coli and yeast have a prominent place they do in biomanufacturing? I think it's chance and people just do things the same way because their mentors did it that way. There are plenty of organisms that have better properties than E. coli in a biomanufacturing context and now we’ve reached a point where it's feasible to wrangle those organisms on a budget.
Does General Biological plan to license its technology to biomanufacturers or is your roadmap to be a chemicals producer?
It is really hard to roll out new manufacturing technologies at scale. Everyone knows this. So we have to vertically integrate: we’re going to be a chemicals business. We’re building our reactors ourselves, manufacturing the chemical products ourselves, and putting the chemicals in people's hands ourselves.
Where we’re headed is essentially building the new-age refinery. Right now we use sugar as the input. But we want to get as close to the waste carbon as possible to reduce the cost of our raw materials. That requires building out a new value chain: you need installations right next to where all the corn scraps are lying around to process them into usable feedstocks, distribution deals on those feedstocks, and financing to put all these projects together. If you want to make use of all the carbon that’s just lying around and convert it into something high-value, you have to be willing to do some of the manufacturing yourself.
All of this is asset-heavy. But this industry will flounder unless someone is willing to put the assets in the ground; I don’t think licensing gets us there in the long term. And ultimately the vision is to put these refineries everywhere – people need to start thinking of the new Standard Oil.
Given the impact that this will have on the petrochemicals industry, do you see this as a climate technology?
My lazy answer is yes, of course, it’s climate technology. But I’m going to give you a longer and more twisted answer. The chemicals industry is one of those things that's everywhere so you don’t notice it. And you wouldn't notice if the carbon in products that you were buying suddenly all came over from sugar instead of oil. But underneath the surface, we’re building entirely new value chains focused on what is lying on our shores. Stuff that’s just lying around. The economic benefits are the most compelling thing about this, but you’re also decarbonizing all these value chains. It’s safer and cleaner. The smells in the air will be gone, these communities are not going to have all this toxic stuff flowing into their water.
But the chemicals industry is in a really weird spot. As I said earlier about two-thirds of every barrel goes to fuels and one-third for chemicals. Demand for fuels is projected to drop because transportation is going electric. But the reason Exxon’s projections have stayed flat is because that ⅓ chemicals fraction is ultimately responsible for the lion’s share of value derived from crude. That’s the high-value petrochemical segment. Profits are expected to stay flat because the oil majors are expanding that one-third rapidly – more of each barrel of oil is being allocated for chemicals. The reason for that is as the world prospers, people need more stuff. There's no real alternative to these materials in the way that there might be renewable energy alternatives. Simultaneously, you have these gigantic agribusinesses with north of $100 billion in annual revenue, and they have a once-in-a-generation strategic opportunity to go from being agribusinesses to everything businesses because their sugar just became good for a hell of a lot more.
So our little biomanufacturing industry is sandwiched between these two giant incumbents with diametrically opposed incentives: one (generally speaking) looking to preserve oil as a profit center and the other one strongly pro-decarbonization, pro-innovation, and pro-technology that is looking to get into this higher value use case for a raw material (sugars).
All of it goes back to the question: where will all the carbon come from? Ultimately what we’re about is taking advantage of the sugar that’s just lying around and demonstrating that this is a structurally better way to do things. It’s not the end of petrochemistry, it’s the future of agribusiness. And like I said: people need to start thinking about the new Standard Oil. I think they’ll realize it looks quite a bit like GB.
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