Jeremy’s Got Knowhow
Our “Got Knowhow” campaign features individuals who have such deep subject matter expertise on tactile (hands-based) skills that they’re effectively able to solve pressing issues with creativity and ingenuity.
The future of food will never not be a relevant and pressing topic. With this in mind, we turned to Dr. Jeremy Chignell, a scientist and engineer now living and working in Denmark, to help us understand the potential impact of precision fermentation on both our foodways and environment.
“I think people forget that it’s not like a flux capacitor. You can’t just throw anything in and get something really valuable out.”
Can you give me your textbook definition of precision fermentation?
Precision fermentation is an interesting field because it comes out of traditional, oral, and community-based knowledge of ways to store food, as well as science and engineering. Every culture has a rich tradition of fermented foods. But then in the 19th and 20th centuries, the discovery of microorganisms showed that it's not mysterious forces that are making foods go bad, but actually small living creatures that are everywhere – in food, on food, on us, and everything else. These two idea streams combined and created this new field of precision fermentation, that’s now no longer confined to food products.
It was also somewhat motivated by less admirable circumstances. Before World War I, a chemist named Chaim Weizmann created a procedure to make acetone, which was an ingredient in the synthesis of munitions, using microorganisms instead of traditional chemical methods. Even back then, they knew a lot about chemical catalysis,so they were able to develop a cost-effective process to make a munitions ingredient using microorganisms. And with that, it was off to the races. The field of industrial fermentation took off, and in the mid-twentieth century the questions were around what else we could make. With the development of a precision fermentation process to create synthetic insulin, the industry turned to Pharma, which took it to the next level through super sterile environments and very precise, highly engineered organisms that make really high value molecules.
There was also a push to make ethanol on the biggest scale possible, which is the reason for the huge ethanol plants in Iowa and across the middle of the U.S., and why we can put ten, fifteen percent ethanol into our gasoline. That’s also fermentation. So we’re seeing it in pharmaceuticals, fuel and commodity chemicals, and food.
How did you get into the field?
I was into bioenergy when I was in grad school, but afterwards I made a hard pivot into food because the question of the future of food was always going to be constant and relevant. And fermentation has a lot to offer because of its rich traditional roots in food fermentation. I liked it because it has such a strong connection to human history. Fermentation to prevent food spoilage is really the first example of human biotechnology. If you get the fundamentals of how precision fermentation works – how you can go from corn sugar to a product of interest, whatever that product is – you find that there are just so many applications. It’s really just variations on the same theme. You have inputs, you have your microorganisms, and you have your outputs.
You could be making a pharmaceutical, a biofuel, a bioplastic, food, or something else entirely, but it’s variations on the same theme. So you learn: what is your organism’s metabolism like? What’s the yield, the rate, the process? It can take six months to get used to a new process, and then you can start improving on it. So I liked that it has a strong historical element as well as a promising future, and it’s a cool marriage of ancient traditions and hard core biology, chemistry, and engineering. There’s never a dull moment, probably because of the biology. Biology always keeps you guessing.
It seems like precision fermentation is more relevant today than ever, given the impact our modern food production system has on the environment.
It has a role to play, but I think it’s been over-promised over the past few years. There’s been a bit too much press, too many promises made, with articles on how it was going to save the world and everything. But hype cycles are almost irrelevant because we’ve been doing this for 100 years and we’re going to keep doing it. There’s a lot of promise, but you have to be careful about how much you’re promising.
That makes sense. That tracks with our cultural tendency to over-promise or make totalizing claims. I saw a headline today that said “This prominent psychologist says happiness comes down to one word.” Really? One word? Milk is another thing that comes up quite a bit on YouTube with the subject of precision fermentation. Why is that?
You’re talking about milk in terms of alternative protein, right? When Perfect Day launched, it kind of blew the doors open as far as mainstream knowledge of this process is concerned. But you could also argue that it’s been used for a long time, it’s just that this particular company figured out a way to get a yeast to make a whey protein. When you have a method for making a dairy protein that involves no cows whatsoever, that gets people excited. Our food system has gotten really good at making milk, but it’s a hugely inefficient system with some ungodly percentage of waste. Precision fermentation methods also use a lot of water and energy and sugar, but cows use many times more. It’s shockingly more.
The problem is, we’ve gotten so good at making whey with cows that it’s tough to compete because it’s a commoditized protein - a food protein. In the marketplace, we can make it technically more efficient in terms of water and energy. But from an actual production perspective, making things in big tanks, it takes quite a lot of effort, a lot of R&D, infrastructure, and capital.The economics are difficult when you’re competing with a fully commoditized food protein that’s so overproduced, subsidized, and the market price is so low. It’s difficult for any company, especially one at the beginning stages, to make money with that kind of target molecule.
Is there a different case study or example that gets you excited?
Yes, there are many interesting molecules already being made. The other high-profile case study from the past few years is hemoglobin. Like Perfect Day, Impossible Foods was an early first mover in the field when they set out to make veggie burgers that actually taste like meat instead of, you know, corn and beans that just weren’t that appetizing. Their goal was to appeal to a broader audience to reduce animal consumption. They put all this work into making their burgers look like meat, smell like meat, and taste like meat. They were succeeding, with the exception of one ingredient, and that was blood. Or more specifically, the iron that’s in the hemoglobin of an animal.
Human beings have billions of years of evolution leading us to want protein and iron. I’ve been mostly vegetarian for decades, but there have been times when I've had red meat and I’m looking for that iron, that undeniably meaty quality. What Impossible Foods did was find a similar hemoglobin protein from soy (called soy leghemoglobin), which also contains iron and binds to iron. It does exactly the same thing in animal cells as hemoglobin does in animal cells. It transports oxygen by binding oxygen to the iron complex in the hemoglobin molecule. So Impossible took that soy protein and figured out how to get a microorganism to make it, so they genetically modified the organism to be able to spit out this protein with the iron, and it’s red.
It’s naturally red?
It’s actually red. Or rather, it’s what makes blood red. It’s naturally produced by soy plants at a minuscule level, so what they did was take the gene from the soy plant that codes for the creation of that protein, put it into a yeast, and exponentially over-produce it in large tanks like the kind you’d use to make beer, which you can see pictures of. They pump it out of the tank, separate out the yeast cells (which are now useless because they’ve done their job), and use different downstream processing methods to recover that blood protein. Then they mix it in with their veggie burgers and it actually works, if you can believe it. You cook it up and it has that meaty flavor that people crave when they eat meat.
So in theory, it can be whey protein, soy leghemoglobin, or any protein, and it has that same workflow. You find that protein, usually in nature, find the gene responsible for making the protein, and then take that gene and put it into your yeast or other microorganism, grow it up in a big tank, and find a way to recover it afterward. Then you have this functional ingredient for food, cosmetics, or even textiles as coloring agents. It’s mixing and matching which gene you want, which organism you’re going to put it into to overexpress it as it grows in big tanks, and then how you’re going to recover it in the downstream.
What is your day-to-day like?
The company I work for now in Denmark is a little more niche, so it’s a bit different. But in my previous job where I was last doing precision fermentation, it was about 60% in the lab setting up small scale reactors and 30% data analysis and writing. If you’re more on the biology side, you might do some molecular biology to be engineering strains, like a strain of yeast. Your job is usually: Okay, I have this yeast. My job is to get this DNA into the yeast and see how well it actually produces my target protein. And even further upstream, you would have computational biologists who are using a lot of bioinformatics tools and computational tools to actually figure out what the gene looks like, how to modify the gene or the protein sequence to be expressed more efficiently, etc. How can you best modify the gene to make a protein perform even more efficiently?
The molecular biologist then hands the strain to people like me. I take the tube or vessel with the GMO yeast or bacterium in it, put it into a small scale reactor, grow it lots of times in reactors, and quantify how well it’s making the protein that I want it to make. Then I do various things like change its feed, the reactor design, or its parameters for growth. That’s where the engineering comes in because up to that point it’s pretty much all biology. With me it becomes a weird mix of both.
My job usually ends after I’ve successfully scaled it up to maybe a 10,000 liter scale, and then it’s ready to go into commercial production. You take that technology, you take it to a commercial facility, and they make it really big scale. Then a manufacturing engineer would continuously improve the process of production at full scale.
How much room do you have for experimentation?
It depends on the company. A bigger company might have less room unless you’re at a higher level like a principal scientist, but a smaller startup is more likely to say, “Yeah, go try your crazy idea because we need the big win, right?”. On the other hand, smaller companies have less infrastructure, financing, or time than larger companies (and often shorter timelines), which are natural constraints on how much experimentation you can really accomplish.
If you could choose, what would be the problem you’d solve now?
What I think is really impressive and important is actually making food (not just food ingredients) with precision fermentation. The examples I gave was making food ingredients, like a protein or you could imagine a coloring agent or a texturizing enzyme. There are a number of companies making mycelium, filamentous fungi, which means they are actually growing food in a big tank. It’s like tofu in composition, and being used to make alternative chicken nuggets that you see in stores. You grow fungus in a big tank, and instead of recovering a particular protein and throwing the rest of the yeast away like you do in precision fermentation, the whole organism is the product. You separate out the water, and you’re left with something that looks like tuna fish. It’s basically pure protein, like 80% mass protein, that you can use in various ways. It's a mature technology that was developed by the company later called Quorn, in the 1960s, I believe.
It’s a really efficient way to make a lot of food that’s relatively low water-consuming. You can do it anywhere. You can set it up in the middle of the UAE, which is what they’re doing now. The Middle East is where a lot of research funding is coming from now, where they’re water stressed and want technologies to make their own food without having to rely on arable land.
Do you see any risks in this space?
It’s going back to managing expectations. Back in 2021, with so much money sloshing around and people wanting more sustainable solutions, precision fermentation was kind of rediscovered and positioned as this mature technology that could save the world. I remember reading a couple of things that were basically promising to break the second law of thermodynamics. Like, all you have to do is throw in water and sugar into a tank and you come out with this perfect protein at the back end! No, that’s impossible.
I think people forget that it’s not like a flux capacitor. You can’t just throw anything in and get something really valuable out. There’s a lot of design that goes into the ingredients that go into the reactor, and design in how to manage the environment of the organism. And if the components aren’t right, and in the right ratios, then the organism will not make what you wanted it to. There’s a risk to not recognizing how much design there really is. Information has to be included in the process in the form of design, medium design, and recovery.
Fortunately, we’ve been doing it for a long time, so we know a lot about how to do it. But from a food ingredient perspective, we haven’t gotten to the point where we can deliver on bulk foods with precision fermentation. Depending on the market value of the product, in order to make the process economically viable, the titer (for example, the grams of whey protein per liter of liquid) often has to be very high. Every liter of water you’re pumping through your system takes a lot of energy. The more of your product you have per liter, the more money you’re making for every liter you’re processing. I fear the titers are not there for some of these technologies. There are expectations and projections, some more reasonable than others, but the data lags.
There is a risk of pushing a tech development cycle mindset onto biotech. Tech development cycles may be more tightly correlated with labor hours, more predictable and faster, but biology doesn’t necessarily always cooperate.
I also see huge potential risks in infrastructure capacity. Developing the best strains and most functional ingredients is less impactful if the large tanks and facilities to make them don't exist. Which they don't currently, at least not at the scale that we would need in order to make precision fermentation a core technology for food and bioproduct manufacture. Companies like Synonym and Liberation Labs are actively addressing this gap by designing and building new infrastructure assets, but building physical assets takes time and a lot of capital. So the risk I see in the future is a situation in which the upstream technologies are mature enough to start making precision fermentation products at meaningful scales but the manufacturing capacity just doesn't exist. It does seem that in the past two or three years more companies (and governments) are starting to address this problem with industry-government partnerships and direct investment.
On the topic of risk and scale, how does teaching or training factor in?
There’s definitely a learning factor when it comes to any biomanufacturing operation. Training operators (and scientists) can take months, and there often is a lot of turnover because these are difficult jobs. When you have time-intensive training and lots of turnover, there is always the risk of institutional amnesia or drift of procedures because of the 'telephone game' when training new people and because attention spans are always getting shorter. The risk comes because, in a fermentation environment, you're often dealing with processes that use high pressure steam or high temperature, so there is safety risk. There is also the risk of batch-to-batch variability, due to changes in attentiveness of certain crews or team members. There are usually no personal devices (phones, etc) allowed in a production facility, which helps a huge amount with the attention span issue.
