Serum-Free Media for Cell-Based Seafood

March 10, 2021

New Harvest Fellow Cameron Semper is a postdoctoral fellow at the University of Calgary. In this episode, Alex Shirazi interviews Cameron about using microbes to produce growth factors that can then be used to improve the outcomes of fish cell culture, fungal secondary metabolism, and structural biology. Transcript is below.


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Alex (00:04):

Thanks for joining us on the Cultured Meat and Future Food show. We’re excited to have Cameron Semper on the guests for today’s episode. This episode is part of the New Harvest Fellowship series. Cameron is a postdoctoral fellow at the University of Calgary. His research seeks to leverage protein biochemistry for the advancement of cellular agriculture. Cameron’s work involves using microbes to produce growth factors that could then be used to improve the outcomes of fish cell culture. His other research interests include fungal secondary metabolism and structural biology. Let’s jump right in. Thanks for joining us on the Cultured Meat and Future Food show. We’re excited to have Cameron Semper as the guest. Cameron, I’d like to welcome you to the Cultured Meat and Future Food show.

Cameron (00:51):

Hi Alex. Thank you so much for having me. It’s a pleasure to be with you today.

Alex (00:54):

Cameron, tell us a little bit about your background and when you first, actually, when you first heard about cellular agriculture.

Cameron (01:01):

Yeah. So I’m a postdoctoral fellow at the University of Calgary. I first learned about cellular agriculture when I was in graduate school. So around that time I started getting more concerned with sustainability and animal welfare and being a little bit more cognizant of the choices that I was making, eating food. And actually what really started off was my spouse sent me a bunch of pictures of this social media pig called Esther the Wonder Pig, super cute animal, and really quickly, it was just like, yeah, I can’t eat these animals. They’re sentient, they clearly feel pain. That sort of thing. So my interest in cellular agriculture was driven largely out of self-interest because I didn’t want to feel guilty while eating meat, but I was really unsatisfied with a lot of the kinds of alternatives that were available at the time. So like many people, my first true introduction to cellular agriculture was the Mark Post’s cell cultured hamburger. So I remember hearing reports about that and also hearing about the costs of that. And I remember thinking I better start saving if I want to eat hamburgers again in the future. That was really when I first got introduced to cellular agriculture. And at that time I was doing my PhD in RNA biochemistry. I didn’t really think that I had a role to play in cellular agriculture. I was just happy to view it as a spectator, as an interested bystander. But then as my career progressed, I started to recognize that there were some ways that I was able to contribute and that’s how I became enrolled in the New Harvest fellow program. And that’s how I became involved as a scientist and not just a fan, so to speak.

Alex (02:28):

Great. And so Esther, the wonder pig was that a children’s book that you saw? Cause I’ve, I think I’ve heard of that as a children’s book or was it something else?

Cameron (02:36):

You’re right. So it is a children’s book now, but it actually started with just a Facebook page. So it was just, it’s a pretty funny story. These two guys, they loved animals. Someone said, Hey, I have this mini pig that needs a home. Can you guys take it in? So they said, okay, yeah, sure. It’s a mini pig. How big can it get? I think she’s now over 600 pounds. Wasn’t quite as miniature of a pig as they were expecting. But during that time they really fell in love with her personality. And then they started posting pictures of her to social media. So I was following the page way back when she was still a piglet and got to see her grow up and they would post videos of her and she loves watermelons. So it was always really hilarious to watch her eat watermelon on these videos. So right away it was just like, yeah, I can’t really make the decision to be eating pork products, that kind of thing. And then because their social media page has attracted such a following. They bought a whole farm sanctuary, they have children’s books and I think they actually have a movie in the works. So you’ll probably be hearing more of Esther, the wonder pig in the future.

Alex (03:31):

Wow. That is really insane. It seems like it grew quite a bit, not only the pig itself, but the brand. I have heard that there is no such thing as mini pigs, they all start off small, but then they always get big. Let’s shift gears and go back a little bit towards your research area. And before we even touch that, let’s talk about the fish industry. So we often hear about why the fish industry needs change like a really radical change. Can you tell us what the problem is with aquaculture?

Cameron (04:04):

Two main aspects of seafood’s kind of fishing industry there’s wild catch and aquaculture. Wild catch, there’s a number of problems. Fishery collapse is a really big one. And I remember actually, when I was in elementary school, we were told this classic story about the kind of explorers from Europe coming to Canada. And they were on the East coast of Canada. And I have this distinct memory of this, the story about how they’d read written in their journals, that when they got off their boat, there were just so many fish in the ocean that like you couldn’t look anywhere without seeing a fish that you could just grab one with your hand. And now there’s not nearly as an abundance of fish. So that there’s an issue with a wild fishery because over fishing can lead to collapse and huge problems in trophic cascade, that sort of thing.

Cameron (04:44):

And aquaculture is a completely different animal, but there’s a number of issues associated with that. So one really big one is disease outbreak. And then that’s where the colony or the community of fish can be afflicted with viral infection commonly. But then there’s also a lot of environmental concerns with aquaculture as well. So eutrophication is a really big problem. That’s where the nutrients that they use to feed the fish bleed into the water and then algae will spawn and take over. There’s also habitat encroachment. So many of these agriculture operations are taking place off the coast or in a portion of a river and freshwater cases. And so they’re really changing the natural environment to facilitate aquaculture and they’re growing the fish species in quantities and concentrations that are very high because they’re trying to maximize yield. And there are obviously many consequences with that. The waste produced by aquaculture can then be really concentrated and get into the sediment and that can have downstream effects as well on the microbial communities and the nutrient balance and all that kind of thing. So there’s a number of issues aside from just the ethical standpoint as well, right? Growing that many animals in that high concentration as is the case of aquaculture. I can’t imagine that would be a great existence for those animals. There’s environmental concerns, there’s ethical concerns. So yeah, it’s definitely an industry that seems prime for a better approach. And I definitely think that cellular agriculture has the potential to offer a solution in this instance.

Alex (06:04):

Definitely seems pretty urgent. But in terms of urgency, what would you say is like a breaking point to where we have to stop having fish the way that we’re currently capturing and consuming fish? Is it something that we might see in the next five years, or is it something that over time is just going to get worse and worse?

Cameron (06:25):

Obviously the natural world is very resilient. As much as human activity can have a drastic impact, we do see some resiliency, so I’m not sure that we’re going to run out of fish in the next five years. But I think what you’ll just see is you’ll see continued decrease in diversity of these aquatic communities. And in some cases, especially for species that can be caught really in mass, right? So these are the ones that are caught by these big nets that kind of go along the sea floor. And there you have the issue of bycatch, I think in those cases. Yeah, we’re really at risk of, of almost completely depleting our resources. But I think, yeah, you’re just going to see continued decrease in diversity. I think that you will see price increases for a lot of species that are traditionally wild-caught and that as a consequence, I think you’ll see increased reliance on aquaculture, which will then have this kind of other negative effects. So that I was talking about earlier where there’s eutrophication and the habitat encroachment. So I think as the ability for wild caught fisheries to be exploited decreases, then you’ll see increased reliance on aquaculture and that will have a cascading effect and all those problems will kind of balloon. So I think that the problem will only continue to get worse if we don’t address it. The decrease in diversity in terms of these aquatic ecosystems, I think could also manifest as a decrease in diversity of the kind of options you have on your plate, if you want to eat seafood. So if there’s just massive depletion of a wild fishery of a certain species say cod, for example, then the price of cod is going to go up and the availability of cod fish will go down and then there’ll be fewer options for people to eat. And that’s, what’s really beautiful about cellular agriculture is that you can establish cell lines for many species you’re interested in hypothetically and you can meet consumer demands exactly as it exists because you can produce tissue meat products using these cell lines from any species that consumers have a demand for.

Alex (08:09):

Tell us a little bit about your program and what kind of research you’re focused on right now

Cameron (08:15):

In a lab that focuses on protein, biochemistry and structural biology. And what I do is I take the methodology that we use in our lab, which has traditionally been used to study proteins involved in bacterial pathogenesis and antibiotic resistance. And I apply that methodology to studying growth factors derive from fish species. So these growth factors are really important because they tell cells to divide. So the way that these growth factors are typically supplied to cell culture is either through very expensive recombinantly produced growth factors or through a supplement called fetal bovine serum. So fetal bovine serum is something that the industry recognizes that they really want to get rid of because it’s a blood product derived from baby cows. So it’s not really compatible with the goal of reducing animal suffering and that sort of angle to cellular agriculture. And it also suffers batch to batch variation. It’s quite expensive. What I’ve done is I’ve looked at, okay, what are the key growth factors that are provided by this bovine serum? And can we produce the fish version of those? So just to take a quick step back is that if you take a look at the academic literature on fish cell culture, you’ll notice this really curious trend, which is in many cases, these fish cells are growing in culture, medium supplemented with fetal bovine serum. So that just seemed highly counterintuitive to me. Why are you using cow serum to grow fish cells? So I looked at the amino acid sequence diversity between the fish growth factors and the cow growth factors. And I saw that there was actually quite a bit of diversity there. So what that tells me is that you’re using cows serum is likely suboptimal for culturing fish cells. So there’s two angles to my project. One is can I use microbes to produce these growth factors at a lower cost and more efficiently than what’s currently available? And two, by studying these fish specific growth factors, can I improve the performance of fish cell culture and the proliferative rate of these fish cell lines that people might be using for cellular agriculture? And I was fortunate enough to have the project supported by New Harvest and that’s how I became involved as a researcher in cellular agriculture.

Alex (10:15):

It is definitely crazy how we are using fetal bovine serum to culture, fish cells. Coming from a non-science background. It just seems like you’re mixing oil and water there. And so I do have a question, so in a very simplistic way or very simplified answer, can you tell us what microbes are?

Cameron (10:34):

Yeah. So-so microbes typically be unicellular organisms. That would be the way that I’m classifying them as so there’s bacteria would be an example of a microbe, but then you also have you eukaryotic microbes as well. So this could be things like yeast or some fungal species, or even some protozoan species. So just very small, typically single cellular organisms is how I would define microbes in this context.

Alex (10:57):

Your research would essentially be creating new types of growth factors and that would be the cell culture medium, or would that be added to a media?

Cameron (11:06):

Okay. So the growth factors are key component of a cell culture, medium, but they’re certainly not the only components. Why we study them as they’re actually, I think it’s still correct to say that they are by far the most expensive component of cell culture media. So the commercially available growth factors, the ones that you can buy off the shelf right now, they’re very expensive and they’re typically only derive from mammalian species with few exceptions. So you can buy mouse growth factors. You can buy human growth factors. Do you want to purchase fish grow factors? You’d be hard pressed to do that kind of off the shelf. So you’d need to produce them on your own. And there’s not really much literature out there in terms of people trying to produce fish growth factors through this approach that I’m taking, which is using in my case, bacterial species to produce them. And then what we do is we produce them using these microbes. Then we purify and then we add them to the growth medium, which has other components. And then we will culture the fish cells in that growth medium supplemented with these recombinantly produced fish growth factors. And then hopefully the fish cells will be much happier responding to their own growth factors rather than cow growth factors. And then hopefully we can get improved performance or reduce doubling time accumulate a higher quantity of cells in a shorter amount of time. And that would obviously be very attractive to a cellular agriculture application because you want to be able to produce as much tissue for as low costs in as little time as possible.

Alex (12:27):

Would this application that’s optimized for fish cell culture potentially be very beneficial for other types of cells such as before pork or chicken?

Cameron (12:39):

Yeah, absolutely. So the methodology that we’ve been developing is working quite well. We’re getting close to writing up our first publication on the methodology. And we think that these kind of advances that we’ve uncovered in using microbes to produce these growth factors will be applicable to grow factors derived from pretty much any species. The caveat there being that sometimes proteins that are very similar can behave very differently. It might not work for every single version of a particular growth factor, but I’ve tested fish ones obviously. And the approach that I’ve developed, we’ve also used to produce growth factors from a number of other species. So mammals things like frogs and birds, and so all kinds of different species, their growth factors have been successfully produced using the methodology that we developed for the fish approach that I’m taking.

Alex (13:26):

That’s very exciting. And so when you are doing research on fish, are you using a specific type of fish?

Cameron (13:33):

We’re currently using a cell line derived from a rainbow trout. So that’s the current cell line that we’re working with, but we’re also planning to test our growth factors and test our culture media that we’re going to be developing on other species as well. We are very shortly going to be acquiring a bluegill cell line, and we are hoping to acquire a sea bass cell line as well. We’ll be working with multiple fish species when all is said and done, hopefully. And then we can show hopefully that the results of our research and that these growth factors are applicable to just not just one cell line, but multiple cell lines and the different cell lines we work on, or that we will be working on are different cell types as well. So it won’t just be one cell type. It will be different cell types. So hopefully we’ll be able to show and convince the peer reviewers, once we submit the paper, that’s a broadly applicable system.

Alex (14:17):

When it comes to media, some companies have pretty much said that they’ve quote unquote, figured it out. Is this something that can be figured out or is it something that’s just always continuously optimized?

Cameron (14:29):

I mean, I don’t want to speak for any specific company, but if I were to speculate, I would say that if a company is saying that they figured it out, they’re probably meaning that they’ve eliminated fetal bovine serum from their media formulation. That’s seen as a really important benchmark and milestones for cellular agriculture. So I think that if that’s the case, then they might be compelled to say that they figured it out. But I think that’s going to be an iterative approach to media developments. I think that these companies are always going to be looking for ways to produce costs and improve performance. And I think if you look at the staffing of a lot of these cellular agriculture companies, you’ll find that a lot of them are hiring many media development specialists. “Figured it out” I think is a relative term. I think that definitely some companies have likely made significant improvements, eliminated the needs for using fetal bovine serum. But I think that there’s still a lot of potential for cost reduction. And I think that it’s a major avenue for making cell cultured meat more economically viable

Alex (15:23):

Other than media development or growth factor development, what are some other areas that need focus when it comes to cell cultured fish?

Cameron (15:32):

Yeah. So one of the biggest issues right now is actually just a lack of well-characterized cell lines. So in general, the amount of research and literature available on fish, cell culture kind of pales in comparison to what’s out there for mammalian cell culture. So not only are you building on maybe a less stable foundation, but you also don’t have as many tools for building. So yeah, one of the big issues is cell line availability, cell line access. Obviously some of these early stage cellular agriculture companies have done some great things with cell line development, but those are proprietary at this point. You know, they’re benefiting those companies, but maybe not the industry as a whole or the research community as a whole. So I think that there’s a really desperate need for fish cell line development and just general tools in terms of not only just getting fish cell lines, but getting fish cell lines of the right cell type, you know, you want muscle cells so that you can generate the muscle tissue that’s found in the flesh that people consume when they eat fish products. Yeah. I think cell line development is really lagging behind and I know that there are some efforts out there to rectify and address the issue, but it’s still a work in progress. And as somebody who’s researching in this area, I can just say that cell line acquisition has been, I think saying it’s been a headache or a nightmare might be putting it mildly. That’s been very difficult to acquire some of these fish cell lines. So yeah, that’s definitely something that I want to see improve. And I think that the whole industry and the cell ag seafood side of things will really benefit from kind of a collective effort to improve cell line access for researchers as well as other people that they want to start new companies.

Alex (17:01):

I guess a personal question of mine is that, is there a central database for cell lines and not necessarily just for cellular agriculture, but for all types of research?

Cameron (17:11):

I mean, there was not one central database, but there are a number of centralized resources through which you can acquire cell lines. So ATCC is one common kind in North America, although they do supply worldwide. And there are a number of other companies and other sort of NGO organizations that acquire cell lines for researchers and then offer them for distribution for other researchers. So there are resources available, but they’re not well populated with cell lines derived from fish species, and the most easily accessible fish cell line would be one from zebra fish, which is a model organism used to study developmental biology, but they’re very, very tiny fish. So they’re not consumed by humans as a food product. At least not to my knowledge. Now there’s some people who say that maybe zebra fish tastes amazing. And if you can grow it in a cell culture system, then you eliminate that size restriction. That’s present based on the size of the actual organism, and maybe zebrafish is a viable option for cell cell-based seafood. But I think that if you’re investing this type of resources in starting a company, you probably want to start with a more well established product that already is going to have a degree of consumer acceptance, convincing someone to eat cell-based salmon. They’ve already tried salmon. They know what to expect, convincing them to eat cell-based zebrafish might be a bit of a tall order. That’s one of the issues is that the cell lines that are available and fairly well-characterized from fish species are not necessarily from species that would maybe be obviously relevant to cellular agriculture

Alex (18:34):

I’m imagining a huge zebrafish filet right now. And maybe that is the food of the future. If we can get it to that scale, that’s very interesting. So what resources do you rely on for your research? It could be coming from the New Harvest community, work of other researchers. What are some of the most valuable resources to you?

Cameron (18:56):

I can’t really say enough good things about the New Harvest community, the other Fellows, so the other researchers who are funded through New Harvest have been really wonderful in terms of providing their expertise and helping troubleshooting and letting them kind of bounce ideas off of them. So that’s been a phenomenal resource. This made maybe a bit of a surprising answer, but cellular agriculture Twitter is a pretty active community and I’ve actually found some pretty interesting links and some pretty interesting bits of information through there. I’m not super active on Twitter as a poster. I don’t write a lot of messages on there, but yeah, just to follow along and get a sense of what other people are working on in the field. That’s been super helpful. Going on pub med and searching academic literature, that’s never going to go away. I don’t think. That’s been huge in terms of helping with the project, other individuals as well. There’s a dedicated team at GFI who works on seafood and some of those individuals have been really helpful as well. So the community as a whole collectively, and then using those kinds of specific avenues for interacting with the community has been what I’ve relied on.

Alex (19:56):

That’s great. And from like a non-research or external standpoint, some of those reports specifically on seafood from GFI have been very helpful. So it’s very cool that they’re doing that. I love what’s going on in Canada. The Canadian ecosystem for cellular agriculture is quite large. Have you seen a sense of community there and why do you think Canada is a pretty big driving force when it comes to cellular agriculture?

Cameron (20:22):

Yeah, I mean, it’s definitely great to see the field taking off in Canada. We have a number of researchers working in the field. There’s multiple PIs at universities who are starting to focus more and more on cellular agriculture. And there’s just a great network that’s developing organically. People in Canada were either working in the field or interested in the field and this is really cross-disciplinary. So obviously you life science researchers such as myself, but I’ve been in contact with a number of people with business backgrounds and even marketing or policy backgrounds who really seem to want to engage this other agriculture in Canada. So that’s great. I give a lot of credit to Isha because she’s Canadian and she’s really a trailblazer in cellular agriculture and she really is proud of Canada’s potential and Canada’s role to date. So that’s been a big reason why.

Cameron (21:13):

Another reason why I think is Canada’s got a lot of really good research universities, right? There’s a lot of universities, you know, every single province. And there’s a lot of people working in research fields that are relevant to cellular agriculture, doing really cool stuff that even if they’re not already applying it to cellular agriculture could be applied to cellular agriculture. So I think it’s just a case of we have the talent and we have the resources and hopefully we’ll start to see an uptick in funding support from the federal government and the provincial governments. And then I think Canada is really gonna be primed to have a position of leadership as cellular agriculture progresses.

Alex (21:47):

It is cool to see that around each of the universities in Canada, you also get pretty big, I guess, tech hubs that kind of emerged from that. And the last time I was there, I did kind of a university tour and definitely notice that in some of the events that we were hosting, that’s definitely a great answer. And I’m excited to see what else will come and in terms of cellular agriculture from Canada, because it’s really becoming a powerhouse and I love it. What are your plans after your program is concluded? Are you interested in starting your own cell ag company or perhaps joining one of the startups in this space?

Cameron (22:24):

Yeah, that’s a tough question to answer. I don’t know that I have a definitive plan at this point. You know, I love research. I like academia, although it isn’t necessarily the most forgiving environment at all times. I’m open to any options. Maybe that’s pursuing a research career in academia. I do have ideas for startups, but taking that plunge, that kind of leap of faith to really start it. That’s a tall order. I have two young kids. I want to make sure that they’re cared for. So what I can say for sure is that no matter what direction I go, whether that be a career in academia or starting my own company or joining a startup company, I will continue to be involved in cellular agriculture I think for probably the rest of my career or at least a good chunk of it.

Alex (23:04):

That’s cool. And that’s great to hear. So the next question is kind of a fun question. If we were to walk into your lab space, what would we see at your bench and kind of in your area?

Cameron (23:18):

In a pretty hectic week so you’d see a colossal mass and a collection of used Eppendorf tubes and test tubes that need to be cleaned by me before I go home today. But what you’ll see is kind of a standard molecular biology toolkits. So I have pipettes and I have a whole bunch of solutions and regions, and I have my computer nearby because I’m always looking up protocols and taking lab notes. I’m a big advocate of keeping a digital notebook. I used to keep a physical, but I got too tired of flipping through pages when I need to reference something that I’d done previously. I’m fully on board with the digital lab notebook now. So now I can just control f and find what I’m looking for.

Alex (23:55):

Which ELN are you using?

Cameron (23:56):

You know, I just use OneNote actually.

Alex (23:58):

Oh, nice. Okay.

Cameron (24:00):

I like it because it seems to my phone on the cloud. So if I’m not at my bench or my computer, I can just pull my phone and look it up there. And it’s also good sometimes in the middle of the nights, I wake up thinking I forgot to do something. I can reference that. And so, yeah, that works for me, but there’s yeah, there’s obviously a lot of great options out there. Within a few feet of my lab bench. Our lab is a really cool equipment. We have a liquid handling crystallography robot, which we use for our structural biology studies and we have a gene synthesizer machines so we can create some DNA sequences from scratch. So we’ve got a lot of really cool equipment and I’ve used a lot of it in pursuit of my New Harvest research projects.

Alex (24:36):

Cool. Very cool. You can get in touch with Cameron on LinkedIn and learn more about New Harvest Cameron, do you have any last insights for our audience today?
Cameron (24:48):
I guess two things. One is that I would encourage anybody who’s interested in life sciences who was maybe in a similar position to I was where you think, Oh, this is a cool industry. And I’m just going to watch it develop while I work on my other project, I would encourage people like that to think maybe there’s a way that you can get involved and maybe there’s a way you can apply your expertise or your methodology that you’re familiar with to cellular agriculture. I would just say everybody that they enjoy the ride as cellular agriculture develops. And I really look forward to seeing these products available in the grocery store and at restaurants and trying them out. And we’re excited to see what other people’s reactions to them are. And yeah it’s going to be a cool next five to 10 years.

Alex (25:27):

Cameron, thank you so much for being with us today and sharing your insight on the Cultured Meat and Future Food show.

Cameron (25:33):

Thanks so much for having me.

Alex (25:34):

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


Transcribed by New Harvest volunteer Bianca Le. 

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