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Fellowship Podcast Series - Andrew Stout

Andrew Stout is a New Harvest Research Fellow at Tufts University researching how to nutritionally engineer cultured meat products and bioprocesses. In this episode, Alex interviews Andrew about his experience working in Dr. Mark Post's lab and whether cultivated meat could be engineered to reduce the carcinogenicity of red meat. Transcript is below. 

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Transcript

Alex (00:04):

Thanks for joining us on the Cultured Meat and Future Food podcast. This episode is part of the New Harvest Fellowship series. We're excited to welcome Andrew Stout to the show. Andrew is a third year PhD candidate in Dr. Kaplan's biomedical engineering lab at Tufts University. There he studies how synthetic biology and metabolic engineering can be applied to cultured meat with a particular focus on nutritional and functional enhancements of cultured meat products and bioprocesses. Before Tufts, Andrew obtained a BS in Material Science from Rice University. He was a researcher in the lab of Dr. Mark Post at Maastricht University, where he studied scaffolding materials for cultured meat. He worked as a research associate at Geltor in San Leandro, California, where he worked on a team engineering microbial strains for the production of animal free collagen. Let's jump right in. Andrew, I'm excited to welcome you to the Cultured Meat and Future Food show. 

Andrew (01:03):

I'm excited to be here. Thank you for having me, Alex. 

Alex (01:06):

Andrew, tell us a little bit about your background, when you started your research and, actually, when you first heard about New Harvest. 

Andrew (01:14):

Yeah. My background is in material science, that was my undergrad degree at Rice University in Houston, Texas, but I actually heard about cultured meat first before then. It was my senior year of high school, I guess, in 2011 to put a date on it. And I had this class that was a food journalism class, and we read a New Yorker article called the test tube burger, which was about Mark Post's endeavors to grow meat in a lab. And we had a debate assignment in that class. I was put on the side of debating against the technology of cultured meat. And I did a pretty bad job in that debate, but it was a pretty cool topic. So that was kind of my first exposure. And then once I got to college, I was interested in finding ways to get involved in the research. I guess my freshman year of college, I reached out to Mark and asked if it would be possible to come one summer and do research with him in the Netherlands in Maastricht. 

Andrew (02:16):

And he said that if I could kind of make it work and all of that sort of stuff, find funding and things like that, then it would be possible and he'd be happy to have me. So I managed to do that the summer of 2013, which was a really cool summer to be in Mark's lab because it was the summer that they produced that first burger and everything. And I wasn't involved in the production of that burger, but it was really cool to be in the lab while they were working on that. So I worked there in 2013, got really interested in the biomedical engineering side of things. Back at Rice for sort of the rest of my tenure there, I worked in a bioengineering lab that was working on heart valve tissue engineering, and kind of try to build those skills. 

Andrew (02:59):

I went back to Mark's lab after graduating, so in 2015, for another six month period and worked on a scaffolding project related to cultured meat with his group. And that's actually the first time that I heard about New Harvest, was at the first conference that Mark's lab hosted, which would have been in 2016. And I heard about it because I was seated next to Isha at the dinner table one night. And then let's see, after that finished my time with Mark's group. And then I worked at Geltor for a year in 2016 and 2017 working on their strain engineering team for producing recombinant collagen proteins, and then applied to the New Harvest Fellowship. And I'm on my third year of my PhD at Tufts. 

Alex (03:49):

Wow. Okay, cool. And there's some name dropping in there, right? Mark Post, Isha, Geltor. That's really fascinating. How was that first conference? Because that was the, I believe you said 2015, the Scientific International Conference for Cultured Meat, right? 

Andrew (04:05):

Yeah. Yeah. It was awesome. I was really sort of eyeopening for me because I had a been there in 2013 and I was really interested in the topic and the people in the lab were really interested and invested in the topic. And there was clearly a fair amount of press coverage and things like that, but kind of the whole time that I was there, I thought, I think in 2013, somewhat correctly, that Mark's group at that moment was really sort of the only group working on this. And I kind of kept that impression until the conference. And that was the first time that I was really exposed to all of these other people who were working on the same stuff and approaching the same problems from all these cool angles and that there was an organization like New Harvest that was working on accelerating this kind of technology. So it was kind of a path changing conference for me because before it, I had kind of been projecting a career path in my life, I was interested in medical school. And then I was interested in kind of keeping cultured meat as something sort of in the back of my mind that I could maybe get back into later in my life if things picked up or if I saw opportunities. And it was this eye-opener that the opportunities were really present and really there and that I could kind of dive head first into them. 

Alex (05:20):

Wow, very cool. And then when you first started working with Mark Post in 2013, was that before or after that big London showcase? 

Andrew (05:28):

It was before. So it was the summer before I worked there for, I guess maybe two months before the showcase, two or two and a half months. And then my, basically my flight out back to the U.S. Was a few days adjacent to the showcase. So I actually traveled to London, got to go to the showcase and then fly back to the U.S. from that London showcase. 

Alex (05:52):

Okay. So you were at the showcase? 

Andrew (05:54):

I was there. Yeah. 

Alex (05:55):

Wow. We might need more than an hour. Haha, no, no, joking, joking! So tell me, what was that experience like? Was it like what you expected and, you know, you did mention that before working in Mark's lab, you kind of felt like it wasn't that big of a topic that people were researching. Did the showcase change your mind and how was the showcase? 

Andrew (06:17):

Yeah, yeah, it was cool. And it was pretty surreal. I mean, I think how it goes, I would have been 19 or 20 and so I think I was pretty shy and looking back, I kind of wish I had talked to more people and introduce myself and stuff. I sort of just hung out with people from the lab who were great people. So it was, it was nice, but I did feel, I think part of the reason that I was sort of shy there was that I was just pretty shocked by the size of the interest and the number of people who were there and what those people kind of said they did. I can specifically remember one person. It was an audience member asking a question and basically they said, I'm with a group in the U.S. That's working on this same problem. And that just floored me. I had no idea that anybody else was working on this at the time. And I didn't go to introduce myself to them because I couldn't find them later. But yeah, it was pretty wild. Another, I think very telling indication of the times was that there were a lot of people wearing Google Glass, which I don't know if that was just a sign of the times, or if it was an homage to Sergey Brin, the funder of that project, but it's an image that stuck in my mind. 

Alex (07:24):

I guess those forward thinkers that were wearing Glass, they would probably also be forward thinking and thinking about the future of meat. And I think one thing that I have noticed is that, you know, the industry does anchor a lot of things around that 2013 event, specifically the London event, but at the same time, Mark and Mosa Meat in general is very accessible and welcoming. And I think that if you reach out and there is an opportunity to work with either him and the team in the lab or otherwise, I think they're very open to that. And I think that openness has actually been very good for the industry. 

Andrew (08:03):

Yeah. 

Alex (08:04):

So that's definitely awesome. And of course going back, it makes you think like, did you know it was going to be such a pivotal event? 

Andrew (08:12):

No. Yeah. I've definitely been surprised at how quickly it has exploded from that event. And I think a lot of people have been surprised how quickly it's exploded. I think that one of the reasons it's such an anchor point and one of the reasons that prototype demonstrations continue to be these really big anchor points for the field, I think it's because it's an inherently tangible product, you know, it needs to be big enough to see and feel and taste and things like that. And so I think that, you know, something abstract, like the ability to get a cell density in a bioreactor to something crazy like a hundred million cells per ml or 200 million cells per ml, or the ability to scale up to a hundred thousand liter bioreactor or something like, those would probably be sort of more scientifically important milestones in this path. But I think that the narrative always has been and is always going to kind of be grounded in these products that you can feel and see and touch, and that are clearly to everybody watching identifiable as the meat product that they're recapitulating or replacing or whatever you want to call it. 

Alex (09:16):

One of our team members, Yuri, he always reminds us of the saying, 'seeing is believing', and that is definitely true here too. 

Andrew (09:24):

Yeah. Yeah, exactly. 

Alex (09:25):

So I want to transition into your current research. Can you tell us about what you're working on now and why it's important to culture meat? 

Andrew (09:34):

Yeah, so currently I'm whole-hog in the genetic engineering side of things. I've sold my soul to that side of the world, I guess, with my current endeavors. But what I'm specifically working on now, and what I've been working on most recently is basically genetic engineering, synthetic biology, metabolic engineering, whatever you want to call it, with the goal of enhancing a cultured meat product. So basically trying to sort of demonstrate a proof of concept that with these genetic tools, you can use cultured meat as a platform to have a meat product that has enhanced nutritional features, different nutritional features, potentially different bioactivities, different sensory features, kind of a whole host of options. And so specifically the most recent and our first, I guess, demonstration of this was pretty simple, but it was engineering cow muscle cells to produce enzymes that convert a native compound into beta carotene, which is a pro vitamin. So it's what our bodies use to make vitamin A, and it's not found in high levels in beef and it's not natively produced by any beef cells. The cow genome, it doesn't contain any of the genes for the enzymes that are responsible for that pathway. So the question was, can you get these cow muscle cells to produce these plant nutrients, these phytonutrients, and sort of impart those nutritional benefits on a cultured meat product in a way that you probably couldn't do through animal transgenics or with conventional meat production. 

Alex (11:05):

And so ultimately this would allow us to create a meat product that has extra nutritious factors. Is that right? 

Andrew (11:13):

Yeah. Yeah, exactly. Basically it's all motivated by just trying to stray away from needing to eat my greens. Been a 27 year old battle with my mom and I feel like I'm finally taking the technological route. 

Alex (11:26):

So let's break this down a little bit in kind of like, explain it like I'm five, when you mentioned nutrition, what does that mean when it comes to food? 

Alex (11:35):

Yeah, that's a good question. And I think it's a murky question cause it's a pretty controversial sort of field, just nutrition science in general. But basically, I mean, at its most basic level, nutrition is those compounds and molecules, et cetera, that you consume that your body uses for some purpose or another, that could be that your body needs proteins and then breaks those proteins up into their constituent amino acids. And then your cells use those amino acids to produce the proteins that your cells need to survive. Alternately, a lot of, for example, vitamins or micronutrients are really important cofactors in different biological processes. So if we think about vitamin A to use the beta carotene example, there are a lot of biological processes that need vitamin A as a cofactor or vitamin B as a cofactor to help facilitate, maybe metabolic processes that your cells are doing, or to facilitate transport processes that your cells are doing. 

Andrew (12:35):

And then I guess the third, and maybe this should have been the first angle, is when you consume things that are comprised of sugars, your body uses those, breaks those down, basically turns them for the most part into glucose and uses that glucose to generate energy. So, I mean, nutrition is all of the energy that your body uses to do the things that it does. It's all of the constituent parts that your body can't make for itself in which it needs to do those things that the energy is propelling it to do. And then it's all of the cofactors that your body needs to kind of help along those processes. And then I guess one other sort of side that I'll mention is a lot of it is also just sort of regulation of different states that your body can be in and that cells can have. I mentioned that because I think it's pretty relevant to the beta carotene side of things, but we can dive into that later if you want, but is that a good sort of wide angle view on it? 

Alex (13:32):

Absolutely. I think one question I have is that you mentioned that there's a little bit of controversy in this topic. What is the controversy in the community? 

Andrew (13:41):

Yeah, I mean, it's, I think that the controversy is just that nutrition science is a really sticky beast and because it's a science that the public has a lot of interest in, i's a science that there's a lot of incentive to simplify things for. And so from the vegetarian side of things or the plant-based side of things, there's a lot of incentive to try to basically tell this narrative of 'meat is bad, meat is bad, meat is bad'. From the meat producer side of things, there's a lot of incentive to tell this narrative that 'meat is great, meat is great'. Because of sort of the general population's active interest in the answers to these questions, I think that there's not a lot of incentive to present really nuanced takes about 'this could be good for some people and bad for others'. It's really hard to know who it's going to be good for, who it's going to be bad for. 

Andrew (14:30):

There are all of these cofactors involved. And I think another thing that has been hard from the nutrition science standpoint is that you're sort of inherently always sort of running human trials. There was basically a saying I've heard is that the dietary guidelines for Americans has proved to be the largest unapproved human trial in scientific history, right? Because it's basically changing patterns and habits for a ton of people with potentially not really knowing what those patterns are going to do and who it's going to affect. So I sort of say it's controversial in part to shield myself because I think a lot of people who really do understand things and do do the science get up in arms when a lot of people like me who have a very limited understanding of hardcore nutrition science start kind of infringing on their field. 

Alex (15:21):

And I think this might be the reason why my mom tells me to stop drinking coffee one week and then next week tells me it's totally fine, actually, you should drink wine instead. 

Andrew (15:32):

Yeah, yeah, exactly. 

Alex (15:34):

So let's talk about beta carotene. So what is it and how is it related to vitamin A and why is it important? 

Andrew (15:42):

Yes, it's a class of chemical, which is called the carotinoids. There are a number of them, a lot of which are dietarily important. It's also a pigmented compound. So it's orange pigmented. It's what makes carrots orange, for example. And if you've ever heard of carotenemia, if you eat enough carrots, your hands will start to take on sort of an orange tinge, and that's not really dangerous, but it's an over accumulation of beta carotene. There was a magic school bus episode about it once. It's related to vitamin A, in that, it's what our bodies use to make vitamin A. So we consume beta carotene in our diet through things like carrots, tomatoes have a lot of carotinoids, various plants have these. We consume the beta carotene, we turn it into vitamin A, and then there's a bunch of processes that vitamin A is important for a pretty well known. 

Andrew (16:32):

One is that it's important for your retinal health. So it's important for your eye health and your vision strength. And so that's why people always say, eat your carrots to help your vision. And another reason that it's really dietarily important, and I think sort of the story that dovetails best into this whole cultured meat story, is that it's an antioxidant. So basically what an antioxidant is, is it's a compound that scavenges reactive oxygen species. So when we eat red meat, for example, the heat of cooking, our digestive enzymes, a bunch of processes start to break down the fats that's in that meat and the proteins that's in that meat through oxidative processes. And to dive into a little bit of the biochemistry here, you have your bonds between these atoms say carbon atoms in a fat. And what happens is that these bonds are made by two electrons that are shared between those atoms. 

Andrew (17:33):

And then when the bond breaks, sometimes that fatty acid will be left with a single, basically free floating, electron. And that species that, that free floating electron is really reactive. So what that'll do is that'll find another fat and it will basically break that fat in half leaving another free floating electron. And then that is kind of like a chain reaction where you basically have a really reactive thing that can react with a bunch of things and continually propagate the formation of these really reactive things. And ultimately that can be dangerous because as those reactive oxygen species find their way to your colon, for example, one of the things that they can react with is that they can start reacting with cells in really damaging ways. And they can react with cell's DNA, and damage a cells DNA. And then upon that cell repairing its DNA, it might make a mistake. 

Andrew (18:28):

So it used to be an A base and it changes it to a C base when it repairs and that's a mutation. If you have a mutation in the right or I guess the wrong spot, that can lead to cancerous cells. So basically these reactive oxygen species, when cells are exposed to a lot of these, those cells can become cancerous. And that's one of the big sort of proposed mechanistic links between red meat consumption and diseases such as colorectal cancer. And so what an antioxidant does, is it basically quenches that reactive species. So it'll see that free-floating electron and it'll basically steal it and incorporate it into itself. And so that compound can no longer go and continue this cycle of reactive oxygen species generation and reaction. So antioxidants can act to quell this sort of snowballing process that can ultimately lead to pretty harmful things happening in the body. And so from a dietary perspective, eating antioxidants can kind of 

help with that process. And that's part of, I'm sure that everybody's heard, that if you're going to eat your steak, you should also drink red wine at the same time. And that's because red wine has a lot of antioxidants. And it's also because I think that's a nutrition narrative that people certainly want to get on board with. Does that track? I know that was a long... 

Alex (19:51):

No, no, that was great. And I've actually never thought about food in such a deep level and it's actually kind of awesome. 

Andrew (20:00):

Yeah, yeah. 

Alex (20:01):

That is cool. And that is actually making me think two things. One, you do have to be careful what you eat because of all the things that do happen after you eat something versus something else. And two that makes me think that meat might actually become a super food like kale and all these other green stuff. 

Andrew (20:20):

Yeah. Yeah. I guess one caveat I'll say, and this, I think hopefully kind of colors in the lines about why this nutrition science can be so controversial is that you also don't want too little oxidation. So oxidation in cells is also an important process. And so if you were to have just totally swarm yourselves and swamp yourselves in antioxidants, that would also mess up a lot of processes. So I think that with everything, even superfoods, there's real reason why people say you can have too much of a good thing when it comes to kind of nutrition, biochemistry. 

Alex (20:53):

Right. It's all about the balance. 

Andrew (20:55):

Yeah. 

Alex (20:56):

So we briefly touched on kind of cancerous cells. And I think one very interesting aspect of cancerous cells is that they are multiplying at a very fast rate. You know, one of the biggest concerns that does come up when discussing the limitations of cultured meat is media development and really bringing costs down with a serum free media. But one thing that doesn't come up a lot when we're discussing limitations is cell growth and doubling, and how many times these cells can double. Have you come across any aspects of this? Is this a limitation for the industry? Do we feel like we can proliferate cells over and over and over? How many times can they double, what are the limitations here? Any thoughts on this general area? 

Andrew (21:41):

Yeah. Yeah, definitely. That's a really, really good question and a really important question for the field. I'll try to approach it from sort of a few angles. So one on the number of times cells can divide. So, if I were to take a muscle cell from a cow, there is a theoretical limit to the number of times that that cell can divide in human cells. It's been characterized and that's called the Hayflick limit. I think it's 52 times that a human somatic - so just from the body, not a germline stem cell or something like that - can divide is 52 times. So a few things on that. One, if you get a single cell and divide it 52 times, or really it becomes two and then two become four and then four becomes eight, that is a ton of material. If you ride that Hayflick all the way perfectly, you have a huge, huge, huge, mass of cells. 

Andrew (22:33):

And one of the CAOS (Cellular Agriculture Online Symposium), the online symposium that you're involved in, somebody from Mosa Meat did some sort of napkin math from a single biopsy, what you could theoretically get from a cell mass in 20 doublings or 30 doublings or something like that. And I think it's really easy to lose sight or just to not intuitively always perceive the power of doubling, but once you really kind of run out the math, it's really powerful. So that's the first thing I'll say is that this limit technically does exist, but at a theoretically sort of perfect realization of that limit, I don't think it is actually limiting from a production standpoint. 

Andrew (23:09):

The second thing I'll say is that that's all assuming that you hit that theoretical perfection, which of course is not going to happen. So it could be that in a large bioreactor, these cells are seeing more sheer stress than they normally would in the body. And so maybe they really can't double as many times. Maybe they can double 25 times at best. And maybe your doubling rate is kind of reduced because you have cell death and things like this. I think that while the theoretical limit isn't a limit, it still has yet to be seen kind of how close we can get to that theoretical limit. And I think that there is point where it starts to become a problem. The second thing that I'll say is that that is wiped out if you think about immortalizing cells, that worry I guess, or at least it's really subdued if you think about immortalizing cells, either spontaneously or through a genetic engineering process, because you basically lose that limit. Those cells are then theoretically able to indefinitely divide. And I think that there's a lot of value to that one because you don't have that theoretical limit anymore. 

Andrew (24:14):

And two, because you can imagine that if you have to go back to a biopsy, even if you can say run a year of your process on a single biopsy from account, and you can produce a ton of meat from a single biopsy, I think that there's a reasonable argument to be made that when you go back to a different cow, it just might not act the exact same under the exact same parameters as you have been operating for a whole year. And I think that that could prove to be a really big hurdle in terms of just consistency in terms of sort of needing to start from the ground up on your whole scale-up process, your characterization, your validation of your cell lines, all of that sort of stuff. 

Andrew (24:54):

And then the last bit, I've tried to save the best for last, which is that I think that it's a really good point about the doubling time. And I think sort of a useful way to think about it is to steal a metric from pharma. And so if you think about antibody production in cells, or if you think about sort of any drug production that uses yeast or bacteria or mammalian cells, the category defining metric is often titer, which is T I T E R. That's basically your grams per liter per hour. So that's a single metric that ties in a lot of different things. In the biopharma standpoint, it's how much of the product you're producing. For cultured meat. If we're going to kind of adopt the term, your product is the cells. So your 'grams' is how many cells you're growing, your 'per liter' is the density at which you can grow those cells, and then your 'per hour' is the speed at which you can grow those cells. And so the nice thing is that there are three ways to impact that metric. 

Andrew (25:54):

You can increase the number of cells that you're growing, or the mass of a single cell or something like that, if you want to start thinking a little strangely about it. You can increase the cell density, so decrease that per liter metric, or you can increase the growth rate, so decrease that per hour metric. And I think that there are limits to the degree that you can play with all of those. And so it becomes kind of this act of balancing your optimization between those three things. 

Andrew (26:21):

On the dividing time side of things, I think that is a big hurdle for cultured meat, because if we think about sort of a bacterial process or something, there are producing strains of microbes that divide in like an hour, 10 minutes, really, really short time spans. And mammalian cells tend to divide in like 24 to 48 hours. And so I think it is a really important hurdle for the industry. I think that there are, again, sort of genetic techniques or non-genetic techniques that groups have taken to increase that growth rate and kind of keep trying to ratchet your doubling time down in cells like these producing cells like Chinese Hamster Ovary cells. And so I think the cultured meat could really benefit by taking a page out of the book of groups that have worked to decrease the doubling time. But I also can see it being an area where even alongside taking a page out of those group's books, cultured meat needs to put a lot of energy. I think it's a really powerful metric in that if you think of that titer as your real sort of measure of productivity. 

Alex (27:33):

And now that a lot of companies are starting to talk about scale, maybe we will see more of that come up as well. 

Andrew (27:39):

Yeah, yeah, definitely. 

Alex (27:41):

As we make our way closer to commercialization, going back to your research and what we're doing with beta carotene, how could this affect the larger scale production? And I mean, that in kind of like a final product way. So if you were to imagine your research ending up on either plates at the dinner table or even at the grocery store, how would that look like? 

Andrew (28:06):

That's a good question. I think that one of the benefits I guess, of academia is that we sort of have the ability to look maybe one step removed from kind of the next product. And so I think if I was running one of these companies, I don't think that I would necessarily put all of my chips into the beta carotene basket right now. You know, there, I think that there are real rate-limiting hurdles to address, but I think that as those hurdles are addressed, then having something like a nutritionally enhanced product where you can really kind of tell this story about why it might be nutritionally superior, I think that that could help bridge some price gaps for consumers. And beta carotene is just one example. There are a loads of different targets that can be addressed if a culture, meat product is going to hit the market at twice the cost of a conventional meat product, I think there's a degree to which novelty will help it limp along in a market. I think there's a subset of people who would happily consume that pretty continually, but ultimately it's all about both bringing the price closer to what the average consumer is interested in paying and bringing the average consumer closer to being interested in paying for a cultured meat product. And so I think a nutritionally enhanced product kind of addresses one of those angles. And then potentially you could have sort of meet in the middle at a, at a happy price point, happy consumers. And then of course continually try to work the price down in terms of a production standpoint. 

Andrew (29:36):

I think it is tricky because while it's not guaranteed that these engineered metabolic processes will really change a production process in terms of like you were saying cell doubling time or things like that, it would be pretty irresponsible to say that they definitely won't. Right? And so beta carotene production could affect the doubling time of cells. And I think from a really large scale production standpoint, any change to any of those metrics could really force you to rethink your process. And so at scale, I think I'm still pretty naive to the inertia that exists in that sort of a situation. But I would imagine that it's a pretty substantial inertia. And so I think that it would not be something that a company could just one day show up and say, 'Oh, we're going to start out in beta carotene' and everything's gonna run the same. I think it would need to be a really sort of deliberate act. But once you figure out the deliberate act and once you establish your production process for that, then it's not hard to, you know, continue that production process for a long time. 

Andrew (30:37):

The, I guess, beneficial caveat that I'll say here is that in certain cell types, something like an antioxidant has been shown to increase cell growth rate. And so we have a paper coming out, hopefully soon, about this. And one of the cool things is that we use both C2C12 and bovine satellite cells and got them to produce this beta carotene. And in the bovine satellite cells, which are a primary cell line, we saw a decrease in growth rate with the production of these antioxidants. And we kind of talk about why we would think that might be, but basically this engineering is a pretty hard ask on primary cells. They're pretty fragile cells. And we think that we were sort of beating them up throughout this entire process and they were getting us back by growing less quickly. But in the immortalized cells, which can take a licking and then keep on ticking, we saw that the production of these compounds actually increased the growth rate. It's also interconnected. And I think one target can have these ripple effects in so many different ways. It can affect flavor, it can affect growth rate, it can affect nutrition, et cetera, et cetera. And I think that there definitely are targets out there that can be these kind of triple threat targets, where you increase the nutrition, you increase the growth rate and you improve the sensory characteristics of a product. And I think that those offer really, really, really cool opportunities because sort of no matter how you look at it and no matter which angle you look at it from, it's potentially beneficial with the large caveat of it involving genetic engineering, which I know some people would sort of write off from the get-go. 

Alex (32:05):

We have a question from one of our listeners, go ahead, Bianca. 

Bianca (32:09):

Hi, this is Bianca from Australia. And I was wondering if cultivated meat could be engineered to reduce the carcinogenicity of red meat. And if so, how? 

Andrew (32:19):

Yeah, that's a great question, Bianca, and I love it because it's so relevant to this beta carotene stuff. So I think one answer is that the engineering of these cells can be performed to increase something like the antioxidant levels of these meats. And so for example, with beta carotene, we saw a reduction in lipid oxidation levels when we cooked basically a little small cell pellet of these cells, when they were expressing and producing this beta carotene. And because that lipid oxidation is one of the key mechanistic proposals for red and processed meats links to diseases such as colorectal cancer. I think that there's a pretty compelling argument to be made that this could potentially reduce that risk. I think there are also non genetic ways to approach the same thing, so you can potentially add any oxidants to the media, cells might incorporate those, and you would just sort of change that oxidation level of the cells. And then also I think tied to that, a sort of sub mechanism of the production of that lipid oxidation that's been proposed, is that high levels of heme iron, iron that's bound to heme proteins such as myoglobin or hemoglobin, is involved in those oxidative processes. And so red meat has a lot of heme- bound iron. And so that could be kind of why red meat shows higher levels of lipid oxidation and potential carcinogenicity than say, white meats or fish or things like that. And so cultured meat is inherently absent of hemoglobin unless it's added. And it's probably safe to say that it will be potentially deficient in myoglobin, at least at the start. I think that groups will work pretty hard to change that. But those two, I think, are sort of arguments to say that it could kind of inherently offer reduced oxidative pressure upon consumption. The big caveat on that heme iron standpoint is that heme iron is really important from a sensory perspective. That's why impossible foods adds a heme protein to their burger, cause that does a lot of lifting for red meat flavor and red meat, sensory qualities. So I think that one's a target that would kind of need a bit of a finer balancing game. 

Alex (34:34):

Great. And as we start to wrap up, what are your plans after you conduct your research? Are you interested in starting a cultured meat company, potentially joining one, continuing research in a different direction? What are your plans afterwards? 

Andrew (34:50):

Yeah, so that's a toughie, and I think about a lot but seem to not make any headway on. I feel like it's a bit of a cop out answer, but I think the honest truth is all of them. I have really, really liked the academic environment that I've been in so far. And so I do not scoff at the idea of academia as a potential longterm route. I do sort of tremble at the idea of academia as a long term route, cause it's a tough row to hoe, but I think that it offers so much freedom to ask questions and try things that are interesting to you that I find it really promising. But also at the end of the day, this is an effort that's aimed at an applied approach. You know, the goal is to produce products that people will consume. And so I think that that is kind of a big pull towards industry in whatever form. I think that in the short term, I'm pretty interested in trying to go wherever I can continue kind of learning the most because I think that that's been a big bonus of my PhD is that I feel like I've learned a lot really quickly and I'd like to continue the speed of learning, but then longterm, it's hard to say. 

Alex (36:00):

You can get in touch with Andrew on LinkedIn and learn more about New Harvest at www.new- harvest.org. Andrew, do you have any last insights for our listeners today? 

Andrew (36:12): 

I think that looking kind of back at my time, sort of watching this space and stuff, one of the things that's really struck me as pretty interesting is the degree to which nuance has been added to the field's perception of itself. And in that, I mean, back in the day, nobody was talking about hybrid products of plant based meat supplemented with animal fats or, you know, people would kind of joke about the idea of like tiger meat or things like that, but VOW is now sort of actively working on producing these really cool, unique types of meat with their kangaroo meat, et cetera. So I think that my takeaway would be for people to continue just trying to think really outside of the box about what's possible with this technology. I think there's so much value obviously in recapitulating meat products, but there's so much maybe just more fun to envision kind of a weird products and if anybody's has access to or can buy or can read the In Vitro Meat Cookbook, it's this art project that some Dutch artists did around, I think around the 2013 release. And it basically presents all of these crazy product ideas. Like they have a meat product that basically like twitches and crawls its way into your mouth. And we can think about how to potentially do that. You know, optogenetics exists and people have used them to shine light on artificial muscles and have those muscles twitch and things like that. And so I think it's always valuable to sort of, of course try to look at things with some realism, but occasionally step back and look with those blinders of realism completely removed and sort of just get excited about it and how weird it can all get again. 

Alex (37:46):

Andrew, thank you so much for being with us today on the Cultured Meat and Future Food show. 

Andrew (37:51):

Thank you so much for having me, Alex. It was a blast. 

Alex (37:54):

This is your host, Alex, and we look forward to seeing you on our next episode.


Transcribed by New Harvest volunteer Bianca Le. 

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