Henry Markarian is the founder and CEO of Integrated Dynamics, a company using advanced fermentation technology to transform organic substrates into sustainable value chemicals.
Tell us about yourself and what Integrated Dynamics does?
My name is Henry Markarian and I’m the CEO and co-founder of Integrated Dynamics. I went to UIUC to pursue a degree in computer engineering and technology entrepreneurship, so I knew I was going to get involved with a startup at one point, but I didn’t expect it to happen almost immediately. On the first day of classes in 2019, in a gen-ed about Ukrainian history and culture, I sat down next to a kid named Alex who would not stop talking about batteries. I proceeded to harass him over the course of the year until he let me join his startup, Natrion, which develops polymer-ceramic electrolytes and advanced components for battery systems.
I was the first engineer on the team so I got to spend my nights and weekends working end-to-end bringing projects from ideation to real life, then pitching them as solutions to public and private partners. It was a lot of fun, but it also really showed me that the underlying engineering process doesn’t change between “disciplines,” it’s all the same work with different tools and languages.
About 14 months later I left to focus more on my studies, and in the last semester of college got the chance to fly out to the Bay Area with some other students to meet UIUC alum founders and executives. One of the site visits we had near the end of the trip was to a company that was making hydrogen fuel cells at the time. They were telling us about how hydrogen is the future, how hydrogen buses, cars, and so on were only years away, and I was inspired for a moment. But I had amassed some experience building an electrolyzer in my basement as a teenager, so I was intimately aware of how much of a pain working with hydrogen is. After some inquiry, I realized that billions of dollars had been raised across the hydrogen-use industry without much attention to the fact that hydrogen was still virtually impossible to produce, transport, or store economically.
I went back to campus in early January 2023 with the idea that modern means of producing hydrogen and its critical derivative fuels and chemicals are fundamentally flawed. Some preliminary research showed that while renewable solutions work for niche use cases, they generally aren’t water-, energy-, or CAPEX efficient enough to scale nor outcompete oil-based incumbents. I started digging into literature on proposed alternatives, found some articles outlining how certain microbes can digest organic feedstocks into hydrogen, carbon dioxide, and certain value chemicals, and ended up in a rat’s nest of papers talking about rare high-temperature metabolic pathways in the middle of the night. By morning I had built conviction that a certain high-temperature microbe could become an E. coli-like platform for commodity biomanufacturing, and thus Integrated Dynamics was born.
In short, Integrated Dynamics is developing a novel biomanufacturing platform that leverages engineered, high-temperature microbes to produce value chemicals from low-cost organic feedstocks using existing ethanol infrastructure and supply chains. We’re targeting woody and cellulosic biomass as inputs and have already engineered our microbes to produce ethanol and acetone at ~90ºC alongside their native hydrogen and carbon dioxide capabilities. You can read more about our synthetic biology team’s work on our Substack.
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How does that kind of process work and what makes it a competitive solution?
I’ll contrast this to the simplest but most widely used form of fermentation, which is yeast fermentation. If you drive in the United States, there’s a good chance you have about 10% ethanol in your gas tank, the vast majority of which is made through fermentation of corn by engineered yeasts. This process happens around 35ºC, which is comparable to a warm shower. In contrast, our process runs near the boiling point of water, more specifically >85ºC.
One of the most apparent differences here is metabolic rate; as a general rule of thumb, the hotter that a biochemical process runs, the faster it runs as well. Compared to standard ethanol fermentation where yeast can take 48 to 72 hours to grow, our >50ºC hotter process can hit growth times as low as 24 hours. In large-scale commodity production, equipment utilization is an important factor in lowering CAPEX and increasing margins; a process which can run twice as fast uses half the equipment and thus half the CAPEX of a similarly-scaled competitor.
Yeast-based fermentation also suffers from contamination issues, because at lower temperatures there isn’t really a great way to control which microbes grow and which don’t. On any given speck of dust there’s perhaps hundreds of different types of microbes that are just hanging out, and they all love what’s going on in that fermenter. The same conditions which cultivate yeast for ethanol production are also optimal for environmental contaminants, which either inhibit or entirely prevent the desired fermentation process from occurring. In comparison, processes that run as hot as ours innately exclude contaminants and greatly reduce the need for high-touch hygiene practices like UV or steam cleaning. No microbe that you would reasonably expect to encounter outside our reactor could survive within it.
Many common fermentation products like ethanol will also inhibit cell metabolism, which drives down process efficiency and limits the system to batch fermentation. A standard ethanol producer is forced to sequentially feed, grow, distill, dry, then reset their fermenters within a ~60-hour span to ensure their yeast doesn’t die off due to ethanol poisoning, but the high temperatures we operate at allow volatiles like isopropanol, ethanol, and acetone to simply vaporize out of solution as they’re produced. We can just keep feeding and keep distilling without concern of reaching inhibitory levels, which reduces the total equipment needed and greatly increases equipment utilization again.
Finally, when one engineers yeasts and other relevant microbes for the purpose of making something, they often have to peel back these cells’ abilities to actually survive. The yeast that’s life mission is to make as much ethanol as possible is going to have a hard time withstanding the slightest exposure to bacterial toxins: there’s always a balance between how resilient your microbe is and how good it is at effectively doing what you want it to do. The second-order effect of growing microbes in an exclusionary environment is freedom in metabolic engineering, since there’s no chance your microbes will ever encounter a biological contaminant to compete with.
How are government regulations and policies right now affecting where you and your industry as a whole?
There are virtually no regulations on industrial biotechnology for commodity chemical and fuel production. Especially when compared to a therapeutic, where I’m taking something made by a recombinant microbe, or compared to a food, where I’m outright consuming a recombinant microbe, there’s very little contact between biochemicals and humans or animals. There’s obviously nuance here, but putting GMO ethanol in your car doesn’t really affect anyone from a health or safety perspective.
You’re saying that there are some applications in the same field that have heavy regulations, like working with microbes to create antibiotics. But you’re working with the same toys and tools as it were, and you’re not facing similar regulations?
Absolutely. Regulations exist on biotechnology to protect people and animals, but if we’re making the same molecule as another non-GMO product and our engineered microbe is not a part of the product itself, there’s many fewer regulations that apply. There’s no genetic engineering that ever touches a human in this process.
On the support side, this is a great time for industrial biomanufacturing. We make about 15 billion bushels of corn in the United States on a yearly basis, which is so much corn that if we were to force farmers to only sell it for food, the price of corn and the price of a lot of associated products might actually go negative. It’s crazy how efficient we are, so we should look at biomanufacturing as a conduit with which to establish our dominance in the global scale by doubling down on our existing advantages.
Early technologies dominated simple pathways like corn-to-ethanol, and next generation technologies like ours will expand the market horizons towards commodities like hydrogen and carbon dioxide for SAF, ketones, higher alcohols, and even bio-SAF feedstocks. Building out a diversified agro-chemical domestic supply chain is critically important for our foreign policy position as a country, especially in volatile markets like we’re experiencing now. Some days our allies need food exports, and others we need domestic production of critical chemicals, but at the root of both are efficient farmers stimulated by strong private markets for agricultural products.
Fantastic. We ask this question at the end to everybody: How do you define deep tech?
Anything where the underlying technology has been proven for the first time. There are some really great investors that we had talked to previously who segment the type of risk that all startups deal with into technology risk, engineering risk, and then market risk. I would say non-deep-tech startups are the ones where there’s not really any sort of technology risk.
If you’re building a dating app these days, there’s not often any new underlying science. How you implement it and how it’s marketed are more important than whether there’s some sort of new science behind it.