You might be familiar with plant-based alternatives to animal products — things like the Impossible Burger or Beyond Meat. And maybe you’ve heard of places trying to grow fish or meat cells in a dish to make sushi or steak without a fish or cow. But in today’s episode we’ll cover an old technology that’s bringing us some new foods: precision fermentation. With precision fermentation, many everyday products including dairy-free milk, insulin, and the collagen in lotions are now being made by microbes. How did we turn microbes into teeny tiny production factories for so many different products, and where’s the limit when it comes to what we can use them to create?
Transcript of this Episode
Alex Dainis: It’s 6am, and you roll out of bed. You wash your face, put on a little moisturizer, and head to the kitchen. Let’s say you’re diabetic. You take your insulin, pour milk into your cereal, and scroll through some videos as you eat. Then you pick out an outfit for the day, a breezy polyester dress, and head out the door by 7am.
Within the first hour of your day, in a year not too far into the future, you might have touched four separate products that all used ingredients made by microbes: the collagen in your moisturizer, your insulin, the protein in your cow-free-but-still-dairy milk, and the material of your dress.
Sam Jones: And in fact, those first three are all products on the market right now, that you could be using without ever knowing they come from tiny microorganisms. How did we turn microbes into teeny tiny production factories for so many different products, and where’s the limit when it comes to what we can use them to create?
Welcome to Tiny Matters. I’m Sam Jones and I’m joined by a guest co-host today, science communicator and video producer Alex Dainis. Hi, Alex! I’m so psyched to have you on Tiny Matters with me today.
Alex: Hello Sam! I’m so excited to be here! We’re talking today about one of my favorite things: new foods brought to you by science. You might be familiar with plant-based alternatives to animal products — things like the Impossible Burger or Beyond meat. And maybe you’ve heard of places trying to grow fish or meat cells in a dish to make a steak without a cow. But today I want to talk about an old technology that’s bringing us some new foods: precision fermentation.
Sam: We’ve used fermentation to make foods from bread to beer to kombucha for thousands of years. At its core, fermentation is the use of microorganisms like bacteria and yeast to break down one substance, something like the sugars in grain, and turn it into another substance that we want instead, like the alcohol in beer. And if you’ve ever been to a craft brewery, you’ve likely seen the big steel tanks that this kind of fermentation happens in.
Alex: In these forms of fermentation, you’re typically consuming or using the entire end product. Maybe your beer goes through a small amount of filtering before you drink it, but in general, you’re consuming the whole output. But some fermentation processes select just one specific molecule as their output instead.
Beth Conerty: We've commandeered the term precision fermentation. We are adjusting the organism to not just produce ethanol or a food product, but we can actually tailor the biology to produce this huge array of high value end products.
Alex: That’s Beth Conerty. She’s the Regional Innovation Officer for the Illinois Fermentation Agriculture Biomanufacturing, or iFAB, Tech Hub. In precision fermentation, you use the metabolic pathways of organisms like yeast and bacteria to create a product. Usually, you do this by inserting the gene that codes for the molecule you want to produce into that microorganism. A popular one right now is casein, the main protein found in dairy products. So you insert the gene that codes for casein into your microorganism, add it to one of your big steel fermentation tanks and let them start to grow.
Beth Conerty: And what they're growing on is a mixture of water, a sugar, and that's usually corn dextrose right now. And then usually, minimal amount of like salts and minerals basically just the compounds that every cell, ours included, need to, to grow and, and expand. So then they all go into the tank, the cells grow for somewhere from 24 hours to seven days, kind of depending on the organism. And at the end of it, we take out this soupy mixture of fermentation broth and we start doing solid liquid separations. We remove the cell mass. Typically we start, filtering out whatever salts remain. If there is sugar there still, we filter all of that out to get to just the final molecule or protein. Your case was a protein. So we're, we're just targeting that individual molecule at the end.
Alex: I chose casein as my example case because precision fermentation casein is already on the market here in the U.S. A brand called “Bored Cow” sells flavored milks and yogurts that are made with casein that comes from a tank, not a cow. “Brave Robot” has also been on the market for a while, selling animal-free, dairy ice cream!
Sam: And while this might all sound like a new technology advance, precision fermentation has been used to make specific molecules for decades. It just hasn’t always had such a flashy name. One of the most common precision fermentation products is insulin. Between the 1920s and the 1980s, insulin used to treat diabetes came from the pancreases of cows and pigs. Not only did this require a really big number of animals to keep up with demand, but it also required high levels of purification and standardization to reach a high enough quality to be a medicine.
Alex: Then in the 1980s, scientists figured out how to make insulin in bacteria instead. They took the gene that encodes the instructions for making insulin and put it into bacteria. They grew that bacteria up in big steel tanks with sugars, let it ferment, and used the resulting insulin as medicine. We’ve been using this method to make life saving drugs for decades. But now, we’re able to use it for other things we might need due to a couple of key advances.
Beth Conerty: So certainly the cost of synthetic biology dropping. The margins on pharmaceutical products are enormous. But if you're trying to feed people, you don't you don't want to gouge them on price. You have to meet price parity with traditional sources. And so those prices of the biology, the upfront innovation, the upfront processes had to come down. Another one is sustainability. A lot of those traditional manufacturing processes have a pretty steep environmental impact. And while I am not here to say that precision fermentation is a perfect solution for sustainability, it is taking a step toward decarbonizing manufacturing and to replacing petroleum processes with more biological methods.
Alex: Sustainability can mean different things for different products. Sometimes you’re looking at the total energy consumption to make a product. Other times you’re looking at carbon dioxide emissions from the production process. But you could also be measuring things like water usage, or waste reduction. When researchers look at the sustainability of precision fermentation, they often compare replacing a portion of proteins or fats from animals with identical precision fermented molecules instead. One study found that replacing meat from animals like cows with precision fermented proteins instead could reduce deforestation and related emissions by 50%.
Sam: And there are other ingredients, like palm oil, that are found in countless food and beauty products, whose traditional production is pretty terrible for the environment. The practice of growing and harvesting oil palms is a huge industry that, in trying to keep up with ever growing demand, can result in deforestation, habitat destruction and carbon emissions. Replacing a portion of the demand for palm oil with precision fermented palm oil could help mitigate carbon emissions and encroaching deforestation.
Beth Conerty: And so these have come together, and now people are very excited about exploring fermentation’s potential for a much broader industry and a much broader set of, of products.
Alex: While my special interest here is food, as Beth mentioned, we can use precision fermentation to make lots of different things, from pharmaceuticals to animal proteins to the polymers that make up clothing! Not only that, but sugar doesn’t need to be the only input food. There are companies using carbon dioxide gas, which could be captured from our atmosphere, as input for these fermentation reactions too.
Beth Conerty: Lanzatech, based out of Skokie, Illinois, uses gas fed fermentations, and they have a deal with ZARA, the fashion brand, to make a dress. So make polyester, you know, make textiles from upgraded carbon dioxide. So they use a strain that can use these gasses and convert it into products. And instead of the sugar, there's still carbon there. That's the C in the CO2, so there’s still carbon there that the cells can eat and upgrade to a higher value or a different molecule.
Sam: Precision fermentation could be a way to “upcycle” waste products from more traditional manufacturing processes too.
Beth Conerty: So, for example, in the dairy manufacturing industry, I think a lot of people have heard about this, but yogurt processing produces a lot of waste water, and there is still a lot of sugar, called lactose, in that dairy waste water. There are cells that can use lactose instead and eat the lactose and convert it.
Alex: This means that the lactose itself could be food for the microorganisms, which would then turn it into a desired end product. Another exciting sustainability innovation in the space is the idea that we could create polymers that make up things like clothing and plastics from biological sources rather than from petroleum.
Beth Conerty: I feel like it is becoming increasingly limitless. I used to think that it really needed to be a biologically found compound or chemical, to be able to make it through a biological pathway. I'm being proven wrong increasingly on that front, which is kind of exciting. There's a company called Checkers Spot who is making performance materials, and I think that they're doing materials for, like, skis and outdoor gear and outdoor wear. And the precursors to all of that they're doing through precision fermentation. So it is even these really high, high value and high functionality products. Are there things that are too complicated for, for cells right now? Yes, I'm sure that there are. But I don't know what those are right now, and I'm pretty excited about that.
Sam: But, the story doesn’t end with all of our foods and clothing and skis suddenly being made by microbes. There are a couple of big hurdles for any product that wants to go from small scale lab project to commercially distributed product, and for precision fermentation one of the biggest is the “steel in the ground” problem. If you’ve been to a craft beer brewery before and seen those fermentation tanks, you know that even if you’re just brewing a few select flavors, the tanks are big. Really big. A company trying to make a precision fermentation product is going to need small scale testing labs, then medium sized pilot plants, then a manufacturing plant orders of magnitude bigger to make a commercial product, and there just aren’t many of those in the world right now.
Beth Conerty: And so it doesn't make sense for every single company to be investing in that very expensive stainless steel in those very expensive facilities. So the facility I help run at the University of Illinois is trying to address this, right? We're a pilot scale. But once they get done with that, there are no microbreweries for other fermented products. Or if they are in other parts of the world, primarily Europe and China. And so that's really tough on the companies. That's really tough on trying to find initial customers because they're having to, you know, jump back and forth halfway around the world to do those development cycles. So I think that if the United States could invest and address each one of those steps and have multi-user facilities where companies can prove that out without taking a nine figure risk, I think we would see a lot more successes in this space.
Alex: The other consideration for these products is consumer acceptance.
Beth Conerty: People are very, very emotional about their food. So consumer adoption for alternative proteins in the food industry is not a guarantee.
Alex: For a product to be successful, people need to want to buy it! Getting someone to try a new product can be difficult, and getting people to try a product that also has a technology that might feel new can be even harder. You have to convince people that it’s going to be good: either for them, in terms of taste, enjoyability, and health benefits, or for the world, in terms of things like sustainability.
Marija Banovic: We are all consumers. Because when we make our purchases it is mostly, think, automatic. You buy something that you like, that you prefer, that you know. That's already there. So that's the first thing that could influence the consumer acceptance of these products, from this technology because, you know, habits are something kind of ingrained in us.
Sam: That’s Marija Banovic, an associate professor of consumer behavior at Aarhus University in Denmark. Marija studies how consumers react to new food products, and what kinds of messaging and sentiments can or can’t change their minds.
Marija Banovic: If you think again, as a consumer, and how the consumers buy products, you don't think about the technology. You go to the supermarket or whatever and you pick up the product. Do you think how they milk the cow, whatever ingredients are inside, are they genetically modified, some you have labeling then you can see it. But if you know you usually think about the product itself. And then how do I kind of feel about it and then how will I experience it? For a consumer is also the experience, the sensory part, how it will taste.
Sam: Sentiment and perception are huge when it comes to accepting a new food product into your diet, and it’s not always technological concerns that make people wary!
Marija Banovic: I tell my students as well, he's like, if we think about potatoes, potatoes are like a staple thing, people think like, you eat potatoes. You cannot imagine your diet without French fries and all this space. And they came quite late. Like, this is like the 16th century, I think, in Europe. And then if you kind of think about Denmark, first they were feeding it to the animals because they thought this is something that we shouldn't eat. It's not good for us humans. And then, then we kind of started eating potatoes all the time.
Alex: When we’re confronted with a new food product, we often try and find something in our experiences to compare it to to figure out if we’ll like it or not. For example, if you’ve never had blueberry ice cream before, but you know that you like strawberry ice cream, you might make a comparison in your brain and reason that since you like one berry ice cream, you might like the other. The opposite could also be true: if you know you hate mint chocolate chip, you might be less likely to try coffee chocolate chip.
Marija Banovic: When we are confronted with something new, we usually kind of, I have to find in my mind, consumers find in their mind something that is, what could be representative of that, similar category and so on. So if I cannot relate it to something I already know, that's problematic, then it would induce more fear, more skepticism, more misconceptions, and so on.
Alex: Marija’s research looks at how people react to precision fermentation when presented with different framing options. In one of her studies, one group of participants was presented with precision fermentation using framing that suggested it was sustainable and good for the planet. The other group was presented with framing that suggested it was more natural, something that’s much harder to quantify but often evokes feelings of perceived health benefits.
Marija Banovic: We thought about, we should look at the sustainable because precision fermentation technology is often described as sustainable. And then we thought, should we look at it is natural because on the other hand, we are using microorganisms to produce. And that's very similar to the traditional fermentation.
Alex: People who were presented with the more natural framing were more likely to rank precision fermentation favorably versus people presented with the sustainability angle. But when people were presented with a comparison of precision fermentation to traditional fermentation, giving them something known to compare the precision fermentation to, that natural advantage disappeared, and people overall felt more favorably towards precision fermentation.
Marija Banovic: Because it taps into the oh, it's kind of similar to the traditional fermentation. By using this kind of representative heuristics in this case, what we saw in both studies kind of demystifies completely the process of the technology, you know, and then brings them back to the level of the product and that’s what you want.
Sam: Alex, we’re getting a little meta here, talking about how framing information around precision fermentation affects how that message is perceived in a podcast that is delivering information around precision fermentation.
Alex: I know, I know. But you and I are both science communicators and so I know that I like to nerd out on the more social science of communication and messaging sometimes too. And I think it’s really important and interesting that there are people out there like Marija studying how scientific and technical information is perceived by the public.
Beth Conerty: I think that all of the companies we're working with are very acutely aware of the consumer acceptance. I think that the GMO conversation, you know, whatever, 30 years ago kind of took people by surprise. But because most of these founders experienced that and lived through the GMO debate, they are acutely aware of consumer acceptance.
Alex: Beth tells us that consumer adoption of alternative proteins is never a guarantee. Niche markets may be seeking out these kinds of products, but getting a consumer to swap from what they already know and enjoy is tough.
Beth Conerty: I do think that there are other markets that are much more approachable to consumers. So there is a face lotion on the market. I can walk into Sephora, I can pay for it, and I can walk out with it. And the collagen-like protein in there is not made from pigs. It is made from a fermentation process, so it is more compatible with humans. And there is no animal product in there. And again, so I, I'll eat either, but I don't need a pig product in my cosmetics. And so I think that there are other markets that are maybe just more approachable for people to start thinking about, precision fermentation as a tool and as a manufacturing option.
Alex: Do we get to do the tiny show and tell now?
Sam: We do. Do you want to do the honors? You want to go first?
Alex: I do, I do want to go first. My tiny show and tell is a paper that just came out recently in Nature Geoscience, which is not a journal that I typically read, but it was a really cool study that came out from some researchers who were looking originally to see how much oxygen organisms at the seafloor bottom consume. They sent down a bunch of sensors to look at the amount of oxygen at the bottom of the seafloor, and they actually thought that their sensors were broken because they kept showing oxygen levels rise as they got closer to the bottom, which is different from what they expected. They assumed that the farther they went down, it was going to get lower and lower in oxygen. And they actually tried to recalibrate their sensors. They sent them back to the manufacturer, and they finally just discarded them overall because they figured something was broken and it wasn't working. But a couple years later, they went back on a different study, and again they found that the oxygen levels were rising as they got closer to the seafloor bottom.
Sam: They called the manufacturer and were like, "Sorry about that."
Alex: Yeah, I hope so. I hope they called them up and apologized. They actually did say after a while that they were kicking themselves because what they realized was that there was something different but really cool happening here; that the seafloor was covered in these nodules that kind of looked like lumps of coal somewhere in that potato size range. These nodules were actually formed of layers upon layers of metal deposits. And what they figured out was that these were working like batteries at the bottom of the seafloor. And they had a voltage running across them that they think is actually splitting water into hydrogen gas and oxygen gas. There's actually these little, natural batteries hanging out at the bottom of the seafloor that might be doing electrolysis and creating oxygen.
Sam: Whoa.
Alex: Yeah, it's so cool that they found a new source of oxygen because basically when we think of oxygen creation on earth, we only think of photosynthesis. That is the method we think of; it is just photosynthesis. And so they might have just found a new way that oxygen is being created in the ocean, which blows my mind. I think that is so cool.
And they were saying too that there are some big implications here. One is that this is a fascinating scientific process, and that's always fun. But there are deep sea mining companies that are looking at mining these areas for those metal deposits because they could be important things in all the batteries that we need to power all of our electronics these days. The researchers are saying that now they want to figure out more about what's going on here because they want to make sure that if that mining does happen, it's not disrupting these ecosystems that depend on this oxygen.
But there was also a note by a scientist in one of the new stories I found about this that said, "This might also affect how we look for life on other planets," because typically we think that if we see oxygen occurring in the atmosphere of another planet, that's probably indicative of life, but it could also now be indicative of these other kinds of processes. It's something we want to think about as we're looking out at other planets of is this a way that oxygen is being produced out there? Which could be incredibly cool.
Sam: I love the really unexpected discoveries, the ones where the scientist says, "Nah, that can't be right. Forget it. Something's broken. Something's not calibrated correctly." And then they come back and, like you said, are kicking themselves and realize not only is it not a calibration issue, but it could have all of these huge implications. I think that's just so cool. It's amazing.
Alex: It's fascinating.
Sam: I love it.
Alex: I love it. And I too, that's so something I would do, be like, "Oh no, the sensor's broken." And I would do that for eight years and finally be like, "Wait, maybe it's not."
Sam: My tiny show and tell.
Alex: I'm excited.
Sam: Because you are a genetics person, I found a tiny show and tell that I think you'll find interesting. There was a study that recently came out showing that a single celled parasitic organism in the Amoebidium genus, these single-celled parasitic organisms, they have these ancient viruses that seem to be woven into their genomes. And these are big viruses.
Researchers at Queen Mary University of London analyzed the genome of this unicellular parasite, which is really common in freshwater environments apparently, and they found that a huge chunk of its DNA originated from some of the largest viruses ever known. These viral sequences then appeared to be heavily methylated, meaning that methyl groups were added to those portions, to the viral portions of their DNA. And so a methyl group being added to a portion of DNA typically means that those genes are not going to be transcribed into RNA; not always, but typically. And that means that then they're not going to make it to protein either. What does all this mean? Why does it matter? What's the point? The researchers think that these viral insertions into this organism's genome may be an example of how viruses played a role in the evolution of more complex organisms by providing them with new genes, but then through methylation, the potentially harmful genes could be silenced.
Alex: That's so cool.
Sam: I know. And so the research group then wondered how widespread is this? Of course, they're not going to just look at one of these unicellular organisms and say, "Yeah, this is what's going on." What they did was they actually looked at the genomes of a bunch of different Amoebidium organisms, and they found really big variations, actually, in the amount of viral DNA, which does indicate, they think, that this viral integration and silencing is pretty dynamic, which is also really fascinating. These are the kinds of things that you can learn from unicellular organisms or prokaryotes with super short life cycles that are just constantly dividing, dying; new ones are coming up. You can actually learn what is genetically fixed, what is not.
And so that's cool in itself, but also this is a reminder that humans and other mammals, we also have remnants of ancient viruses that are integrated into our DNA. And I guess for a very long time, it was considered inactive and, quote, "junk DNA." There's a lot of stuff that people used to call, quote, "junk DNA" where, no, actually, it plays a pretty big important role.
But now with this as well, people are thinking it could be way more beneficial. I don't know for us how much of that viral DNA might be methylated or... I don't know the exact comparison with this unicellular organism. I don't know if people have checked. I feel like people probably have. I have not checked. Yeah, us and viruses, we go a ways, ways back. And same within unicellular organisms too. They don't just infect us, they're also part of us, which I think is creepy and fascinating and cool.
Alex: I think that's so cool. And I think it's really interesting too because you said these viruses are really big, and so they're holding onto a lot of information. And even if it's turned off, there is a cost to copying that information, bringing it from generation to generation. I do wonder if it's doing something in there that we just haven't figured out yet. Even if the actual RNA itself is silenced and the gene isn't turned on, there's got to be a reason why it has hung around for so long. That's so cool that they found that.
Sam: What's also fascinating is in humans, we do have ancient viruses that are integrated into our DNA, but not a ton. And with these unicellular organisms, so much of their DNA is just from viruses, so it's even more surprising. For us, it's a very small amount so you wonder how important is it really now? Is it just going to stick around there because it's not stuff that's harmful anymore? Who knows? But yeah, these are tiny organisms, and they're like, "Oh, let's just keep most of our genome virus."
Alex: The thing I always think of when I think of viral DNA in our genomes is that... And some of my friends are going to get so mad at me because they worked in this lab, and I don't remember all the details, but there's a big component of placental development that is driven by some of those viral genes that have stuck around in our genome for millennia.
Sam: Really?
Alex: Yeah. And so there's a whole interplay between the viral DNA and the placenta. And again, I don't remember all the details at the moment, but I think it's really fascinating that they can have super important roles in our bodies. And so I do wonder, what are they doing in those? Do you say Amoebidium?
Sam: Amoebidium, A-M-O-E-B-I-D-I-U-M. That's it. That's my tiny show and tell. I had to make it genome-themed for you.
Alex: I appreciate that. That's super fun.
Thanks for tuning in to this week’s episode of Tiny Matters, a production of the American Chemical Society. This week’s script was written by me, Alex Dainis, and was edited by Michael David and by Sam Jones, who is also the show’s exec producer. It was fact-checked by Michelle Boucher. The Tiny Matters theme and episode sound design is by Michael Simonelli and the Charts & Leisure team.
Sam: Thanks so much to Beth Conerty and Marija Banovic for joining us. To be featured in our bonus series, “Tiny Show and Tell Us,” write in to tinymatters@acs.org with science news you’re itching to share, a science factoid you love telling friends about, or maybe even a personal science story. We want to hear about it! And while you’re at it, subscribe to our newsletter! I’ve put links in the episode description. See ya next time!
;void(0);){kind=link}