The future of cell-free biotechnology
Michael Jewett is a pioneer of cell-free biotechnology.
Instead of using living microbes as factories, he uses their internal molecular machinery to make valuable proteins, medicines, diagnostics, and other chemicals. Jewett recently used the technique for vaccine production in an approach that could produce up to 150,000 doses from one liter. He believes cell-free biotech could democratize the production of essential medicines, improve water safety, and help convert atmospheric carbon into useful products, among other promising possibilities. “It’s just-add-water biotechnology,” Jewett tells host Russ Altman on this episode of Stanford Engineering’s The Future of Everything podcast.
Transcript
[00:00:00] Russ Altman: This is Stanford Engineering's The Future of Everything, and I'm your host Russ Altman. Since we started this show eight years ago, it's become an archive of amazing and impactful work by my Stanford colleagues. Research is not something that just happens in the lab, and as you'll hear on this show, the research at Stanford can impact areas like health, technology, law, and business, and many other topics that can affect everyday life. We hope you'll tune in to learn more about how research has the potential to help your life and to help the lives of people you care about in your family and your community.
[00:00:32] Mike Jewett: You can kind of think of DNA like a cookbook. It stores the instructions. We transcribe that information into a temporary copy, like a grandma's recipe card, and then you translate that into proteins, which as you said, they're the doers of the self. What's so special about these cell-free systems is they have all of the processes of biology going on, in fact, like energy metabolism to support how we make proteins, but we can produce those proteins outside of the living organism, so that can allow us to make things like medicines when and where they're needed.
[00:01:08] Russ Altman: This is Stanford Engineering. It's The Future of Everything, and I'm your host, Russ Altman. If you're enjoying the show, please share it with people you like, people you love. We'd love to have them on board. We'd love to share with them The Future of Everything. Personal recommendations are the best way to go. Today, Mike Jewett will tell us that you can get better medicines, better vaccines, better biofuels by using biological systems where we strip away the cells and we just use the guts of the cells to do useful things. It's the future of cell-free biotechnology. Today we're continuing our feature, the Future In a Minute. At the end of my interview with Mike, I will ask him some rapid-fire questions and he'll give us his rapid-fire answers in the Future In a Minute.
[00:01:51] And also, before we get started, remember to tell your friends and family about the show, especially if you're enjoying it. We'd love to have them on board. So biotechnology is one of the great things that has developed over the last 50 years. We can use living tissue yet living cells to create medicines, to create vaccines, to create biofuels, to run cars, engines, and many other applications, including things that will help for sustainability. There are even bacteria that can eat. Toxic materials and turn them into non-toxic materials. Well, the problem with that technology is it relies very heavily on cultivating and growing large numbers of cells in huge vats the size of a swimming pool, in order to get enough materials to then do all this useful stuff.
[00:02:44] Well, it's possible that we can break open the cells and take the pieces inside the cells that do that work, isolate them, and make much more effective and efficient little machines, biological machines, to create these very same medicines, vaccines and biofuels, without having to keep those cells growing. Mike Deit is a professor of bioengineering and chemical engineering at Stanford University, and he's an expert on these so-called cell-free bio technologies. He'll tell us how they work and how they're starting to change how the biotechnology and bioeconomy might look like in the future.
[00:03:23] Mike, you study cell-free biotechnology. What's cell-free biotechnology?
[00:03:30] Mike Jewett: Hey Russ, that's a great question. So, you know, biotechnology is all around us. Um, you know, we've used this to make medicines for decades, and generally speaking, people use, uh, microorganisms, living cells to make those types of products like an anti-cancer drug. My lab does something different, which is called cell-free biotechnology. So rather than using living organisms ourselves to make stuff we actually use the components of cells to make those types of products. So what we do is we take cells, we rip off their cell walls and we collect the insides, and then we use the insides as a molecular factory to produce everything from medicines to chemicals, to diagnostics. Um, I guess you can kind of think of it like taking a car and lifting the hood up and pulling the engine out. It's like using the engine, but without the constraints of the car chassis.
[00:04:20] Russ Altman: Gotcha. Okay. So far free be it for me to like question the wisdom of this, but let me just ask a couple of questions. It seems to me that cells, the good part of the cells is that they're living and they do things like repair stuff that's broken. So like you said, cars, and that's a fair analogy, but cars don't fix themselves, whereas to some degree cells fix themselves, like if they have an injury or a problem going on, they have some sensors. So are you throwing out the so-called, uh, baby with the bath water, when you give up the intact cell and all of its kind of amazing biological capabilities that we actually don't really fully understand yet.
[00:04:57] Mike Jewett: Yeah, so that's actually the totally surprising part. We're not actually throwing the baby out with the bath water. In this case, we're actually just getting rid of the evolutionary baggage of the cell. So I'm an engineer, um, Russ. And so what I try to do is, is, you know, take biology and use that to, you know, let's say, um, create better access to medicines or convert carbon oxides into the atmosphere, into, you know, sustainable chemicals. And one of the challenges as an engineer is that those cells that repair themselves and grow and have all these kind of great features, that's terrific if you're a cell living and in the environment and you're trying to adapt and live and survive.
[00:05:37] That's actually not necessarily what I want as an engineer. And so oftentimes there's a tug of war that exists between what cells want to do, um, let's say live and survive, and what I might want them to do as an engineer, which is to produce a medicine. And so the advantage of our approach is that we kind of get the best of all worlds. We get the capacities of biological processes, like how do we convert inexpensive substrates into things like medicines and chemicals, but without the constraints of that living evolutionary baggage that oftentimes is totally fighting what I want to do as an engineer.
[00:06:13] Russ Altman: So that actually is, that's a great answer. I knew you would have a great answer. I didn't know what it was. Uh, so let me ask you, tell me about this evolutionary baggage, like that's a very interesting idea. Tell me about the things that like cells tend to do that can, uh, like mess up your engineering goals.
[00:06:29] Mike Jewett: Uh, yeah. So, um, so cells are like finely tuned in terms of their ability to, let's say, keep the processes that they need going alive. So, um, one of the major ones is how a cell uses, let's say, energy to support its growth. So we oftentimes use the components of microbial cells, like bacteria or yeast, and those cells as they're growing, oftentimes like 50 to 70% of the energy of the cell is going towards a process called protein synthesis. And it's to support that process of protein synthesis so that those cells can replicate and divide and be happy.
[00:07:09] And so one of the challenges is when I, as a bio technologist, might give those cells an engineering objective and code it at the level of DNA. And I realize we just jumped through a lot of topics, but maybe we can come back to those. It's, um, the cell might not want to take its energy and resources to support my objective. It would rather actually keep itself growing and make more of the components it needs for, let's say, protein synthesis. And so that's kind of this, this tension that we have oftentimes as engineers for those that use kind of cells as factories.
[00:07:41] Russ Altman: Gotcha. Okay. Okay, good. So, so we've established that the cells have amazing properties, but they also have some features that make them not so perfect for your engineering. And as you said, you bust them open, forgive my, uh, like course language and, and, and then that you to take the pieces like the engine, you, you pointed out, uh, and you can use that then to do things. So what are the big wins that accrue when you take this approach? I'm guessing that, for example, we've all seen these pictures of these huge industrial vats where they're growing huge amounts of bacteria, trying to coax the bacteria to do all these things. Maybe, um. I, it, it occurs to me that maybe one of the advantages is scale, that maybe you can do this on a larger scale. So tell me what the advantages are.
[00:08:24] Mike Jewett: Yeah, so good question. So, um, some of the advantages are actually, um, that instead of maybe having to do things at these massive scales, we might open up opportunities in let's say distributed manufacturing or decentralized manufacturing. So, I can you give you an example. Um, if you're a large pharmaceutical company and you wanna produce a medicine, um, we do, we, we grow these organisms in let's say 50,000 liters or a hundred thousand liter tanks. That's like an Olympic swimming pool, right? And so, um, that when we build the manufacturing plants for those products, it's expensive.
[00:08:58] It can cost hundreds of millions of dollars to a billion dollars or more. Um, and that creates risk. And so the consequence is that there are oftentimes many types of products from biology and biotechnology that can never reach the customer. Because the risk is too great that maybe something changes and maybe the customer doesn't need that process. Uh, the cell-free protein synthesis systems or biotechnology systems that we use kind of flip that on its head. Um, and we opened this chance to use biology maybe at lower scales. So I'll give you an example with vaccines, 'cause you asked like, what's a big win, right?
[00:09:33] Russ Altman: Yeah, yeah,
[00:09:33] Mike Jewett: Um, so, you know, one of the things that terrifies me is, um, something known as antibiotic resistant bacteria. So in fact, um, it's now projected by like 2050, um, the possibility is that there will be more lives threatened by antibiotic resistant bacteria than by cancer today. Um, and that's scary because, um, you know, it can lead to, uh, many people, uh, you know, potentially getting sick or, or even worse. Um, and so myself and many others are trying to think about ways to, um, develop new approaches to, uh, create medicines maybe more quickly at scales that could be distributed, and certainly also reach kind of global locations. So in fact, like, you know, 30% of the world's population lacks access to essential medicines.
[00:10:20] And so what we can do with these cell-free systems is we can grow up ourselves and our cell-free systems. We can lyse these cells and we've got like this engine, we feed this a piece of DNA and now it can produce a medicine. What's neat about our system is that it can be freeze dried. So you kind of think of it like astronaut ice cream or, or freeze dried fruit. And so you have this dried powder and what's neat is we can just add water to kind of make this medicine. So a big win is we created a just add water biotechnology. In the case of these medicines for antibiotic resistant bacteria or pathogenic bacteria, we can produce about 150,000 doses of, of vaccine to prevent infection by bacteria in about a liter. So you can think of that like a carton of milk.
[00:11:02] Russ Altman: Okay, so this is great. And so actually I asked a good question, but I had the wrong answer in mind. I was thinking you would tell me, you can scale up and do huge vats of things, but actually you're scaling in the opposite direction to create almost a, uh, a more manageable deliverable, uh, technology. Add water, get your antibiotic, and, um, this, this bypasses amazing things like we don't need to have a cold chain of refrigerators everywhere from, you know, wherever it's manufactured to, wherever it's being taken. And that, that refrigeration can be a huge issue for, as you know, very well for living cells and all kinds of tissues. Um, so that's a great example.
[00:11:40] Um, what, what, what about, um, so I've read about recently the work that you've done and one of the things that you guys focus on is creating proteins. Uh, and proteins as, as many people may, will remember from their, uh, high school biology proteins are the things that do stuff in, in living systems. The DNA that we always hear about encodes for proteins, which are these beautiful three-dimensional structures. They, uh, contract in your muscles to make force. They are in your eyes and they bend light to make a focused, uh, focused vision. Uh, they digest your food. Um, you're able to make these proteins outside of the cell.
[00:12:19] Mike Jewett: That's right. And, uh, to kind of understand that process, you're, you're totally right, you kind of need to understand a little bit about how the biology works, right? At, at the heart of biology, you know, we're programming instructions at the level of DNA. You can kind of think of DNA, like a cookbook. It stores the instructions, right? We transcribe that information into a temporary copy, like a grandma's recipe card, and then you translate that into proteins, which, as you said, they're the doers of the cell. What's so special about kind of these cell-free systems is they have all of the processes of biology going on. In fact, like energy metabolism to support how we make proteins, but we can produce those proteins outside of the living organism, so that can allow us to make things like medicines when and where they're needed, like we just talked about.
[00:13:03] It also can allow us to explore the landscape of protein sequence and protein function generally. So actually there's been a complete wave of innovation in biotechnology and medicine over the last, even just handful of years, with something known as AlphaFold, which allows us to take kind of this protein sequence encoded by DNA and, and define what the structure's gonna be ahead of time, right? It led to the Nobel Prize in 2024. And like the, the big interesting opportunity for the future, um, and a real frontier of science now is, right, how do we get to protein function? And these cell-free systems allow us to express proteins, uh, very rapidly and, um, kind of explore that functional protein space, um, even more than before.
[00:13:49] Russ Altman: Yes, and, and one of the things that I, I think you're doing is in the area of biosensors, uh, and this is, and I believe that some of these are, at least, are proteins. And can you tell me about what a biosensor is and, and, and how, how that's looking in the context of cell-free technologies?
[00:14:05] Mike Jewett: We're using, uh, biosensors, um, you can think of it like diagnostic or even like a light switch. Um, you know, and so what the biosensor is going to do is it's gonna tell me the presence of a molecule that I might care about. And one of these key advantages of cell-free systems in the context of diagnostics is I can create something like a COVID test, but for something else that we might care about. And you're right, our lab has been looking at, um, these particular sensors involved in kind of water and environmental sampling. So, you know, you're probably aware, um, more than 2 billion people on the planet lack access to clean water. And so being able to understand kind of when and where water is safe to drink is an increasingly, um, challenging and important problem.
[00:14:48] Biology, of course, senses things all the time, right? If you put your hand on, you know, a hot plate, you know, you realize it's a hot temperature. Um, microorganisms are sensing their environment to say, aha, there's food. I'm gonna swim that direction because I'm hungry. And, you know, in this case there are lots of biosensors that even detect like contaminants, like lead in drinking water. And so our lab has been super interested trying to develop, you can kind of think of it like a pregnancy test for water or a COVID test for water to tell us when and where our water is safe to drink. That's tricky because actually contaminants in water, oftentimes you can't see them.
[00:15:23] You can't taste them, you can't smell them. Um, but these biosensors that we use are proteins that, like a light switch, tell us whether or not the, um, the contaminant is in the water. Um, how that process works is leveraging the information flow of biology where we use something known as a transcription factor, so that's the biosensor that we're using. For lead it's something called PbrR. Um, this biosensor, when it's in the presence of lead, will allow for that information and coding of DNA to be transcribed and translated into a visual protein that we can see, like a green fluorescent protein from a jellyfish or, um, you could imagine making a, a small enzyme that can take a substrate and turn it into something that's color metric that you can visually see with your eyes.
[00:16:10] Russ Altman: So that's really cool. So if I'm, so if there's lead in the water, the water's gonna turn green, basically.
[00:16:15] Mike Jewett: Yeah, totally. And, and the hard part.
[00:16:17] Russ Altman: So that's very cool.
[00:16:18] Mike Jewett: The, the hard part, of course is like getting it to like work so that I can see it in a timescale that I care about and the, you know, like I wanna see it in 15 minutes. We all got used to that.
[00:16:28] Russ Altman: Because you're thirsty. You're thirsty.
[00:16:30] Mike Jewett: Right. That's right. Um, totally. And the other thing of course is, um, it turns out that biology doesn't need to sense lead at the legal limit approved by the FDA, which is five parts per billion, right. So biology, of course, it needs to know that it has lead around or other metals because it needs metals for its enzymes or other proteins, but it doesn't need it at the human specified performance characteristic, right? And so in our instance, what we had to do is we had to teach the transcription factor, this biosensor protein, to read lead at the legal limit, which was a really fun problem.
[00:17:05] Russ Altman: That's, so I was just gonna go there and you've already brought us there, which is you're taking these natural proteins, which might be very good at something, but you might need them to be better or different at that same thing. So in this case, I guess you're trying to make it even more sensitive. Is that the right, is that, was that the direction you were going? Like it was too happy with high lead levels and you needed to tell it, hey, I need you to detect lower lead, lead levels.
[00:17:29] Mike Jewett: That's right. So we want this sensor to turn on at like the lowest level of lead possible. We want the light switch to turn on, right? It's, we use a genetic circuit, see, but you can kind of think about like the circuit of your light switch and we need it to turn on at super low levels. And so that was one thing we had to solve for with this particular lead sensor. But the other thing we had to solve for is we wanted the sensor to only turn on in the presence of lead, but let's say not other atoms that might, or other elements, that might be in your water, like zinc. And so it's something called selectivity as well. We needed to address both the sensitivity problem, but also the selectivity problem, right? I want the light in my room to turn on only when I'm doing it, not when my child runs around the corner and flips it on and I don't see them. And so, um, so anyways, that's kind of one of the challenges.
[00:18:14] Russ Altman: So in addition to taking these natural molecules, a key part of your research is, um, basically, uh, engineering them, evolving them, if you, if you will, to have slightly different properties that are better fit to your, to your use case. Um, so that gets you into the, you, you're creating entirely novel proteins in many cases.
[00:18:33] Mike Jewett: So we're creating both novel proteins, new to nature proteins, or just tuning a natural protein to make it into something that we want. In the context of like this lead sensor, if we just stick with this story for a second, the way we did that is a, a protein is made up of many amino acids. There are 20 amino acids in biological systems. Those, those amino acids are arranged in different orders, and it's that sequence of amino acids that leads to the protein structure and the protein function. We don't know how to necessarily change the sequence of amino acids a priori to predict the human specified function.
[00:19:09] And so that's what we iterate on, right? So what my lab would do is we make mutations or changes in that sequence of amino acids, probably around where like that protein would bind lead, or where the protein in this case might bind to DNA, because it's modifying essentially how the process is transcribed. And then we would just iterate quickly through many different sequence changes till we find something that worked. And, and that can be an arduous process in, in some contexts. Um, what's neat is in today's world, we're trying to use machine learning algorithms to accelerate that process.
[00:19:43] Russ Altman: You're listening to The Future of Everything. I'm Russ Altman, and we'll have more with Mike Jewett next. Welcome back to The Future of Everything. I'm Russ Altman and I'm speaking with Mike Jewett from Stanford University. In the first segment, Mike described what he means by cell-free bio technologies and why they're so useful and why they can lead to biotechnology in powder form. Just add water. In this segment, I'm gonna ask him about sustainability, I'm gonna ask him about how he uses AI, and a little bit about education. Don't forget, at the end of our conversation, I'm gonna ask Mike a few quick questions as part of our segment called the Future In a Minute, Mike will then give me some quick answers.
[00:20:33] At the very end of the last segment, Mike, you mentioned that you had used some machine learning to kind of supercharge your design of new proteins that had these special lead binding, uh, capacity that you needed for your sensors. Um, is AI playing a big role in your work?
[00:20:50] Mike Jewett: Definitely AI is playing a big role in our work, and I think everyone's, and actually, um, you know, one of the key things and the only way we solve this problem with the lead biosensor. So we didn't get really to the, to the end of it, but actually we were able to engineer this transcription factor, um, PbrR to read out lead at the legal limit, and in the absence of zinc. So actually to get a little more specific, one of the challenges with trying to identify lead as zinc is they're both like plus two cations. So they have different orbitals and different geometries. So if we think about the chemistry, but they're kind of similar, right?
[00:21:22] Russ Altman: They're positively charged metals.
[00:21:24] Mike Jewett: And, and so, and so as we look at, as we look at like how to discriminate between those two, we had to teach this transcription factor and the shape of the active side of this transcription factor to recognize one but not the other. And so in order to do that, we generated a lot of data and we said, hey, let's use machine learning based models to try to guide iterations of this design. You might have, you know, just kind of back to the previous segment, we were changing the amino acid sequence to get better designs and so we actually used the machine learning model to predict for us what sequence changes we should make so that we could read out at the level of lead, but not at zinc.
[00:22:04] Because actually the first time we tried to engineer the lead sensor, um, it was terrible. Um, 'cause basically we made a better sensitive lead sensor, we, we could actually report out on lead at the legal limit, but it turned on in the presence of the zinc. So it's actually a totally useless, uh, sensor. Um, and actually the machine learning model allowed us to predict and identify sequence changes that could do both, but only in the presence of large quantities of positive and negative data. And so we, and many others, are of course using large, you know, data sets to guide design. And I think it's gonna continue to be really an impactful, important area, um, in bioengineering research.
[00:22:42] Russ Altman: That's super exciting and, and, and it makes, it makes sense that you could use the AI to learn the subtle differences between zinc and lead and say, hey, let's focus on the lead and let's try to not to be misled by the zinc, which is actually not only, not toxic, it's required for life. So you, it's a big difference between zinc and lead.
[00:23:00] Mike Jewett: That's right. You know, it's funny, we found that like, like when we were just trying to stare at the data we had, we couldn't find the right patterns. And I know that's not new, right? For those of us that have been looking at AI and machine learning. But, but it was really, of course, helpful to use this model guided by kind of large evolutionary trees of enzymes and proteins that exist in nature, um, to guide us.
[00:23:22] Russ Altman: So I know one of the big application areas, and you mentioned it briefly in the, in the first segment, but I want to go back to it, is sustainability. That, that you see that these cell-free bio technologies have a special opportunity to contribute to sustainability, and play that out for me.
[00:23:38] Mike Jewett: Yeah. So, um, look, uh, being able to sustainably produce all the stuff that we need every day is really, really important. And at the heart of that are proteins or even ensembles of proteins, um, you know, right now most of the things around us, from paint to toothbrushes to shoes, are all created from carbon-based chemicals that we get from petroleum. And so we, and many others are super interested in this idea of are there different ways to get the carbon that we need to produce the products that we use on a planetary scale? Um, and so, you know, if you think about that a little bit and you look to the atmosphere, um, there's a lot of carbon in our atmosphere and carbon oxides, um, form a form, so it's carbon dioxide, for example, carbon monoxide. And so what our group's really been interested in is how can we take above ground carbon and pull it out of the air to transform pollution into the stuff that we use every day.
[00:24:37] Russ Altman: This is kind of what trees do, right?
[00:24:40] Mike Jewett: That's totally right. Except for trees are using it to grow and get bigger. We're trying to use the proteins of, you know, biology and cells to take that carbon and then molecularly transform it into, let's say, a sustainable aviation fuel or polyacrylic glass, um, or, you know, a disinfectant that you might use in your house. And so, um, in, in many respects, we've been trying to kind of write instructions in DNA to kind of build protein ensembles, um, that, you know, not, don't necessarily take the carbon to grow like a tree or a plant, but take that carbon to produce these chemicals that we might be interested in sustainably. And the, the key thing is to be able to do this in something that we call carbon negative manufacturing.
[00:25:23] And what I mean by that is instead of kind of like canonical petroleum-based processes that produce chemicals that oftentimes emit carbon, carbon dioxide or carbon oxide into the atmosphere, can we invert that and, and basically in a carbon negative way, take carbon from the atmosphere and put it into the products that we need? Now we've gotta translate this concept into new to nature pathways and one of the more recent studies that we had that we just published on, we actually tried to create something that combines electro bio catalysis or electrochemistry and biology. So it's kinda like taking the best of both worlds. Can you take the best of chemistry and biology? So we're using chemistry to take carbon dioxide from the atmosphere and turn it into a one carbon molecule called formate. And then we created a completely de novo biosynthetic pathway, or ensemble of proteins to go from formate to the entry molecule to many biotechnology products called acetyl-CoA.
[00:26:18] Russ Altman: So this is great, and I just want to go back to my tree idea. So, um, you, you spent in the first segment you told us you can break open these cells and you can take the engines that are useful. Are there any useful engines in plants that you could break open those cells and grab to help advance this agenda? Or is the way the tree doing it just not useful for getting to this acetyl-CoA or, or the other kind of building blocks of, um, of carbon based matter that you're trying to generate?
[00:26:45] Mike Jewett: So 100% the tree is useful. Um, so just, just to stick with that, um, of course trees are one of the largest carbon sinks that we have. And of course we, we take wood and all kinds of products from trees. Trees of course have biosynthetic processes that make all kinds of molecules. One really interesting class is called isoprenoids, and those can be used for medicine. Like if you think of plants, um, and trees, they could be used for making medicines that help, you know, fend off, uh, disease, but also, uh, chemicals like, um, uh, cyclic molecules or molecules that we, it can even use as like, uh, sustainable aviation fuels. Um, and so what we oftentimes will do is try to, uh, take those ensembles of proteins from the plants and then repurpose them outside of the plant. And the reason why is the plants that turns out grow slowly, right? So if, if we take a tree, right, we've got something that kind of grows slowly and unfortunately those processes oftentimes don't, don't meet the rate or kind of the, the, the time space yield we might need as engineers to get products to,
[00:27:50] Russ Altman: No, that's a very fair question.
[00:27:51] Mike Jewett: Plant on a planetary scale fast enough to matter, you know?
[00:27:54] Russ Altman: Very fair answer, 'cause I have watched trees at length and they don't seem to change very much. And I can imagine that you would want those processes that, that they're doing to just move faster. Now, of course, maybe your AI magic could speed them up in the way that you, you improved the lead. But I get that it, it, it would be a big, it would be a big challenge. So what, just to, just a final, the final step. You said that there's this one molecule, I think you said, acetyl-CoA, that is a very early precursor for lots of different materials. Just for those of us who don't follow the chemistry carefully, what kind of materials could stem from a large collection of biologically produced CoA, acetyl-CoA.
[00:28:33] Mike Jewett: Yeah. So acetyl-CoA is like this central hub. It'd be like being in the middle of like a London tube stop, right? And you can go anywhere in London from, you know, from like the central station, but in this case that acetyl-CoA enzyme, uh, the acetyl-CoA molecule can go towards, you know, a material, towards a polymer that might, you know, be something that you can weave into clothing to, you know, even kind of, uh, fuels or. Things like plastics, like biodegradable plastics. And so, um,
[00:29:02] Russ Altman: Okay, this is huge. This is huge.
[00:29:04] Mike Jewett: So it can really go into a lot of different directions. And actually one of the advantages of like our cell-free approach that, that we're really excited about is that, and tying this to the rate question that you mentioned a second ago, which was like, well, okay, I get it. We wanna go faster. One of the challenges historically with biotechnology in living organisms is that the rate at which we produce products, coming back to our Olympic sized swimming pools, means that we need these large Olympic-sized swing pools to, to produce these products. Because we typically make molecules, let's say on the order of like a gram per liter, per hour. And so I need a hundred thousand liter fermentor of a cell growing.
[00:29:41] If we could use either biosynthetic pathways and the, the capacity of enzymes to go faster, let's say a hundred grams per liter, per hour, so a hundred X it, can we, can we a hundred X the physical performance of cells by using a cell-free system, which is theoretically possible and actually might be supercharged by AI and protein design. Now all of a sudden, I, I could do something in a meter cube. Well, instead of a hundred thousand liters, you know, that's a thousand liters. Well, I, I could buy compost, you know, in, in a meter cube, and, and that might just change the game enough to open up access to biotechnology products for sustainability in ways we've never been able to see before. So, so that's kind of, you know, I'm just trying to draw the line to what we were talking about earlier too, but something that we're certainly excited about.
[00:30:27] Russ Altman: No, no, I can see that, that, that, that actually is great 'cause I have heard criticisms that, um, old fashioned bio technologies, in terms of creating fuels, first of all, they take too much energy and second of all, they don't produce enough to really move the needle and the, and the, and the future that you just described does move the needle because of basically orders of magnitude of more efficiency in the use of space and in the use of biological material.
[00:30:51] Well, before we end it, I, I did wanna ask you about education. 'Cause I know you think, well, of, of course you're a professor and you're educating people constantly, but you've also thought about educating more broadly the public and even going down into grade school. What, what is your pitch about, um, how biotechnology should be understood by a young learner?
[00:31:11] Mike Jewett: Well, you know, the truth is we, we all like, all of our lives have been changed by that one experience in a classroom or by a teacher that like spurred your imagination or creativity or just excitement about, hey, I wanna go learn more about this, right? And oftentimes biotechnology research is one of those things that's harder to access mainly because it all, it requires large equipment, you need like sterile technique. We probably, you know, maybe remember being like a kid and you like stamped your hand on like agar and you got to see like all the things that grew on that, you know, agar plate, you washed your hands and you found out that actually all the things still grew 'cause you didn't wash your hands well enough.
[00:31:48] But, you know, the way I tend to think about it is we all know how to read and write. We all increasingly know how to read and write in a computer code, or at least for using agentic AI systems at this stage. And we're learning how to figure that process out. And I think it's equally important that we know how to read and write at the level of biology. And that means we need to understand how to program at the level of DNA and go through that process of DNA, going to RNA, going to protein. And so we've actually created these educational kits as a way to open access to just how do you do biotechnology? And what's cool about them is they are freeze dried educational kits. They just add water. So in the same way I was mentioning, we can just add water and make a vaccine.
[00:32:28] Russ Altman: This is your magic trick.
[00:32:30] Mike Jewett: That's right. It is a magic trick.
[00:32:30] Russ Altman: You're just add water guy.
[00:32:32] Mike Jewett: And, and, and honestly like, it, it, you can kind of create like a light bright, but for, you know, biotechnology and you can create artwork or like a periodic table of chemicals or rainbow or whatever, you know, your high school mascot, um, when we initially pitched this, but it puts in, in the hands of students, you know, the ability to learn how biology works. And we've done this with things like just how to make a protein, like we've talked about here, but many people have learned about CRISPR systems. So I've worked with a colleague at Stanford here, Stanley Qi, working on a CRISPR kit. But the idea is how do you develop biotechnology in a way that puts it in the hands of people so they can have those experiential learning opportunities.
[00:33:12] Russ Altman: And we know that those could be transformative. And you know, we were talking about how we could do the freeze dried thing in order to send things to far away lands, but you could also send them down the street to the local grammar school. And so that's a great vision for how to make biotech accessible and available in grade schools. Well, before we finish up, I wanna move to our segment that we call the Future In a Minute, where I ask you, uh, several questions kind of rapid-fire, and you do your best to give me rapid-fire answers. So are you ready for those questions, Mike?
[00:33:42] Mike Jewett: Absolutely not.
[00:33:44] Russ Altman: Okay, great. Here they are. What is one thing that gives you the most hope about the future?
[00:33:48] Mike Jewett: Well, I probably can't do one, but I'll say, you know, human innovation, creativity, and curiosity is, is one of those things that I think makes me optimistic for the future. And of course my kids, right, the youth.
[00:33:59] Russ Altman: What's one thing you want people to walk away from this episode remembering?
[00:34:04] Mike Jewett: You know, I think we're at a critical moment for potentially redefining the future of biotechnology, and what I hope people learn here is there's this new approach called cell-free biotechnology that allows us to access biology at its most intimate level to maybe create, just add water systems that allow us to make medicines, sustainable chemicals, educational kits in a more accessible and equitable way.
[00:34:27] Russ Altman: Aside from money, what is the one thing you need to succeed in your research?
[00:34:33] Mike Jewett: Collaborators. So the best science, Russ, happens at the intersection of disciplines, and so I love being able to work with others to kind of find that space where we can innovate together. And of course time.
[00:34:46] Russ Altman: If all goes well, what does the future look like?
[00:34:50] Mike Jewett: Well, you know, I'd love to be in a space where, you know, biology's already all around us, so how are we using bio technologies to meet local problems? Everything from transforming carbon monoxides into the air, to sustainable chemicals, to being able to have on-demand manufacturing and medicines when and where we need them. So being able to know whether or not you're water's safe to drink because you've been empowered locally as a part of a 21st century biotechnology and bioeconomy to use biotechnology yourself.
[00:35:17] Russ Altman: If you were starting over again and you needed to get your degree or certification in a different discipline, what would it be?
[00:35:24] Mike Jewett: You know, I'm still partial to being an engineer, Russ, I love building stuff and I love building with biology, but it would have to be music.
[00:35:32] Russ Altman: Thanks to Mike jut that was the future of cell-free biotechnology. Thank you for listening and don't forget, if you wanna help shape future episodes, rate the show. We'd like a 5.0 if we deserve it, but also put in some comments. Put in some ideas. We read them, we'll see what we can do. Don't forget that with more than 300 episodes in our back catalog, you can listen to a wide range of conversations on the future of just about anything. You can connect with me on many social media platforms including LinkedIn, Bluesky, Mastodon, and Threads, where I'm @RBAltman or @RussBAltman. You can also follow the Stanford School of Engineering @StanfordSchoolOfEngineering or @StanfordENG.
