Insect Cell Culture

June 1, 2020

We are excited to partner with the Cultured Meat and Future Food podcast for a multi-part series highlighting the research being conducted by New Harvest research fellows. In the inaugural episode, Alex Shirazi interviews New Harvest Fellow Natalie Rubio about lab-grown meat, insect cell culture (which she has coined entomoculture), and how the Kaplan Lab became a hub for cultured meat research. Transcript is below. 

Transcript

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Alex (01:09):

Natalie, I’m excited to welcome you to the Cultured Meat and Future Food show.

Natalie (01:13):

Thanks, Alex, I’m excited to be here!

Alex (01:14):

Natalie, tell us a little bit about yourself, your background, and what projects you’re working on.

Natalie (01:20):

Yeah, of course. So I am currently a graduate student at Tufts University, which is in Boston, Massachusetts. And I work in the Department of Biomedical Engineering under Dr. David Kaplan who runs a tissue engineering and regenerative medicine lab. And I work on cultured meat research funded by a New Harvest Cultured Meat Fellowship. For my background, I received my Bachelor’s degree in Chemical and Biological Engineering from the University of Colorado back in 2015 and before I started graduate school I had opportunity to work a little bit for New Harvest and I also worked for Perfect Day Foods and then a software company called Quartzy, which is like a platform for science supplies and reagents. And then I started my graduate school in 2016.

Alex (02:09):

So we’ll go into New Harvest a little bit more later on during this conversation. But how did you first hear about New Harvest?

Natalie (02:17):

Yeah, I believe it was in 2013 so I was going to school in Colorado and I think I found out about the concept of cultured meat actually through Modern Meadows’ website when they were working on meat before they pivoted to leather. And I was just blown away by the concept. It was the most exciting thing I had ever heard about. So I was like, I need to get involved. So I remember just scouring the internet and trying to collect email addresses of anyone who was involved, which was maybe a handful of people at that time. And eventually someone connected me with Isha. So I messaged them a bit because they were advertising an internship opportunity on their website at the time. Maybe like six months later I started communicating with Isha and then I just kind of jumped right in and started volunteering with the nonprofit tasks. And everything took off from there.

Alex (03:16):

In the field of cellular agriculture, we see a lot of people have different types of personal motivations, whether it’s changing the food system or just interests in the technology. What would you say your personal motivation is for working in the field?

Natalie (03:32):

My personal motivation has definitely evolved a little bit. It a hundred percent started out as animal welfare concerns. I became a vegetarian when I was in high school and I kind of immediately, upon kind of having that epiphany of why going vegetarian was a good thing to do that came really interested in animal advocacy, animal rights advocacy. This was before, this was way before I found out about cellular agriculture and I just remember kind of trying to convince everyone around me to just stop eating meat.

I thought it would be really simple and I really disheartened to see that by just kind of talking to people about the issues that didn’t persuade anyone to change their habits. And then so I kind of gave up on that passion even though I remained a vegetarian and then years down the road when I discovered cultured meat, it just instantly seemed like such a great solution. So when I reached out to New Harvest, I was really only aware of the animal welfare impacts of meat production and I didn’t really know anything about all the other impact areas. So it was really while working for New Harvest, you know, creating content for their platforms that I started to learn about all the statistics for the environmental and health impact areas. And same with, during my PhD, just doing background research. And most recently I’ve really become motivated by biodiversity loss. Just, you know, when I’m, when I’m writing papers I create like an introduction section where I’m looking at the impacts and instead of just listing off kind of the same environmental, animal, health impacts, I’ve tried to kind of dig into the more nuanced areas. So lately I’ve been reading a lot about extinction rates of plant, animal, insect species and just kind of finding out more about that has kind of led that to be what currently is my primary motivation.

Alex (4:17):

You did touch on it, but on this show we like to kind of, answer the “explain it like I’m five” questions. So when it comes to biodiversity loss, what are the impacts of biodiversity loss over time?

Natalie (05:26):

Yeah. So usually I kind of think about it in terms of the Amazon rainforest. I think that’s the most straightforward example. So deforestation is a big result of animal agriculture because people need to clear land either to graze livestock or to make room to grow crops to feed. So the Amazon rainforest is being kind of just torn down at an alarming rate. And with that comes just crazy rates of habitat destruction for all the animals and plants and insects that live there. And there are species in certain habitats that don’t exist anywhere else. So when we destroyed their habitat we’re wiping out entire species, and this is just kind of bad, obviously, for the species themselves that took millions of years to evolve and then humans are just destroying them. But also, you know, there’s a lot of interesting things that humans can learn from, from different species. There’s a lot of interesting research on medicinal compounds that are found in the Amazon. And so besides just the facts of biodiversity loss on the animals themselves, there are all these interesting pieces of knowledge and research that are also being eliminated.

Alex (06:49):

And I guess all for having that burger or having that steak. So to shift gears back to David Kaplan’s lab at Tufts University, can you tell us a little bit about his lab?

Natalie (06:60):

Yeah, so his lab is in the Department of Biomedical Engineering, and the focus of the lab is tissue engineering and regenerative medicine. Specifically, the lab focuses on developing novel biomaterials, so scaffold systems, to support three-dimensional cell culture for kind of endless applications. So it’s a really big lab at any given time, there’s between 50 and 70 people working in the labs. So this is undergraduates, post-docs, PhD lab techs, visiting scholars. And the lab has kind of segmented into smaller groups, kind of segmented by what organ you’re working on. So there’s a cardiovascular or neuroscience, lung, kidney, skin, fat groups. And then the newest group is the group that that me and my fellow graduate students are working in is the cellular agriculture group. So this is the first time the lab has focused tissue engineering for food applications and this started back in 2015. So now we have, let’s see, four graduate students working full time on cellular agriculture projects, which is really exciting. When I first started it was, it was just me. So it feels really awesome to have a team and kind of be moving the academic effort forward and yeah. Oh, and then the other fun fact that I don’t think a lot of people know is Ryan Pandya the CEO of Perfect Day Foods was actually an undergraduate and David’s lab. So there’s that interesting connection to the field as well.

Alex (07:26):

Wow. Interesting. Okay, I have this question later down on the list. I see that you also worked for Perfect Day Foods and at the time it was Muufri and those were the early days. Can you tell us about that experience and did it have anything to do with Ryan Pandya at David Kaplan’s lab?

Natalie (08:52):

Yeah, that’s, it’s an interesting convoluted web, but I’ll start about talking about my experience at Perfect Day. This was through my internship at New Harvest, so I started working for New Harvest remotely. Isha was working out of Toronto and I was still in Colorado, so I would just do remote work for Isha. And one day she messaged me and she was like, “Hey, we’re starting a company and we’re going to go do this incubator program and in Ireland if you want to come along”. So I just remember telling my parents that I had met some people online and I was going to go fly to Ireland to watch them start a company, which was because I hadn’t met anyone in person before. So my parents actually flew with me because they thought it was so sketchy what was describing to them. So I went to Ireland with my parents so they could monitor the situation and then just started participating in the accelerator program with Isha and Ryan and Perumal. And obviously we soon realized that they were really good people and this was a legitimate situation. So I basically just shadowed them for a couple months. It was really not that much lab work at the time. It was kind of difficult to get all the reagents we needed on a timely basis, but it was a lot of just brainstorming about how to come up with the message that we wanted to communicate with people, which was a really exciting thing to be involved with them. And I definitely learned so much from them. I had never really thought that anybody could just start a company because they wanted to, that thought had really never crossed my mind. So being able to watch people just kind of like dive in and figure it out as they go along was definitely a pivotal experience for my own career.

Alex (10:40):

That is definitely a good story. So back to your PhD research, tell us about, back to that conversation about David Kaplan’s lab and how in 2015 they started working on cellular agriculture projects, which brought the first kind of food work to their lab. How did you bring up the topic of insect?

Natalie (10:62):

So there was a graduate student before me, Amanda, and she was working on growing insect muscle cells for bioactuators. So bioactuators are basically, it’s the concept of growing robots from skeletal muscle. So mini biological robots and the advantages of this would be that they might be more sustainable, they can self assemble, self-heal. So that was her project and she was actually the first student who started thinking about cell culture in the lab for food applications. So she started to do really early experiments with trying to isolate and grow cow cells and she was Ryan Pandya’s graduate student mentor. So he was working for her. So he got involved in some of the early experiments going on at Tufts before I ever joined. So that was kind of where it initiated, but there wasn’t any official funding to work on those projects so they were really small side projects. So when I came in to the lab, I had funding from New Harvest. So I had a lot of freedom to work on whatever cultured meat project inspired me at the moment. And the first year I was working on maybe 10 different projects. I just felt like there was so much to explore and start working on. So I was very unfocused for my first year, but I was kind of taking up where Amanda left off too with the insect muscle culture. Basically this idea derived from the fact that if we go back and think about the key challenges with commercializing cultured meat, the technical hurdles are that it’s really expensive to grow right now and we don’t really know how to scale it to large volumes. And this is mainly because mammalian cells are expensive to grow and difficult to scale.

Natalie (12:53):

And then when we think of maybe other cell types like insect cells, well these have been used in other industries like the recombinant protein production industry for many, many years. And they are often preferred over mammalian cells as a recombinant protein production host because they are so robust, which makes them easier to scale up to larger volumes. And they are cheaper to grow because they kind of sustain themselves on a more simple media formulation. So while we were growing insect muscle for the soft robotics application and working on cultured meat at the same time, we kind of had this epiphany that “Hey, maybe we could apply this to foods and, say, have these interesting innate benefits that kind of address some of the key challenges for cultured meat as a whole”. So the first research experiment that I worked on was kind of just seeing if the properties that make insect cells easy to grow, apply to insect muscle specific cells.

Natalie (13:53):

So can we get them to grow without fetal bovine serum? How much media do they need, what are their proliferation rates look like? And we really found that they do have a lot of interesting properties that could make them a more cost effective and scalable platform for cultured meat production. So now I’m working on applying tissue engineering principles so that we’re actually getting something that looks like a palatable meat product. Tissue engineering has really only been applied to mammalian cell types, obviously, because that’s what’s relevant to the clinic for human and medical applications. So there is really nothing done with tissue engineering for invertebrate cells. And because they behave differently, we kind of in some regards need to start from scratch and design new systems for tissue fabrication from these different cell types.

Alex (14:55):

So these insect cells, the overall goal is to turn it into a palatable meat-like product. Is that correct?

Natalie (14:53):

Yes. So I think sometime there is a miscommunication on my part that we’re trying to kind of grow edible insects and this isn’t really kind of how I see the technology progressing. I see, you know, trying to create the same products that other people are working on, you know, conventional meat products and then just using a different cell type. And because we can select which cells we want to grow, we could end up with something that tastes way more like meat than it would like an edible insect. That said, I kind of theorized that insect cells would be able to create something that tastes more like seafood products. Because when people eat edible insects that have a lot of muscle and fat, kind of think of like a caterpillar or grub rather than something like a cricket, they kind of report the taste and texture to

being really similar to crab or lobster or other seafood species. So we haven’t really developed constructs large enough to get a good sense of whether that’s true, but that’s my current theory.

Alex (15:57):

For your research, what specific types of insects are you working with?

Natalie (15:61):

So I’m working with two different cell types. The first one is fruit fly muscle cells, which sounds kind of weird, but fruit flies, Drosophila, are really well characterized organisms or model organism for a lot of different branches of research. And so there’s a lot of research tools available to characterize these cells. And then secondly, I’m working with caterpillar muscle cells and this is because we have access to caterpillar colony through my co-advisor lab, Dr. Barry Trimmer in biology. So we have access to these caterpillars, we obtain cells from the caterpillar eggs and then differentiate those into muscle specific cells. And I think those are more relevant from a food perspective in terms of kind of muscle size and also just being able to market the idea. I think people would kind of scratch their heads at the idea of fruit fly meat.

Alex (16:59):

Are you aware of anyone else in the field of cellular agriculture that might also be working on insects?

Natalie (16:66):

A short answer? No. I have been approached by a few different groups who are intrigued by the idea and we’re kind of probing for how I saw like the commercialization potential of the concept. There are some students who are kind of interested in the idea and I think if they can get away in the lab, they might want to pick up on that idea. But currently, I don’t know of anyone else working on insect cell types for cultured meat applications.

Alex (17:38):

When it comes to cellular agriculture products and cultured meat, consumer perception is something that is often discussed. When it comes to consumer perception of the type of work that you’re doing, what do you think people will think about? Do you think they’ll think it’s more or less strange? I guess it’s hard to phrase the question because I don’t want to phrase the question by saying that people think cultured meat is weird, right? So I guess when it comes to consumer perception, do you think that people will be pushed towards insects or maybe away from insects or will they look at cellular agriculture as a whole? What are your, just some general thoughts on it?

Natalie (18:19):

Yeah. So I have a lot of different responses to this question. I think it really depends on how the message is communicated and it is not a simple message to communicate. I think after I gave a conference talk at the last New Harvest conference, I think people were still a little confused about why and what it was that I was proposing. So I think I need to work on how I relay the concept to people. I think one thing I always wanna make clear is that, and I don’t even know if this is important or not, but it’s not, this isn’t research I’m pursuing for the novelty aspect just because it’s something crazy. I really do think there are interesting benefits, you know, not just in terms of production efficiency and cost, but insects have really beneficial nutrient profiles. And if this is something that translates into, you know, developing cultured meat from insect species, I think that could be really interesting. And so, yeah, my initial

thoughts are that people will be grossed out by it. There aren’t really good, nice ways of talking about it. Like lab grown insect meat doesn’t have a nice ring to it. So I’ve tried to come up with a few different terms to use when talking about it. But from the conversations I’ve actually had with people, I haven’t come across anyone who was like, I would eat cultured meat, but I would never eat cultured insect meat. To me, it seems like just, anecdotally, when people are on board with cultured meat, they’d also be interested in trying something even a little bit more novel. But I also obviously run in a really scientific circles, so I haven’t done kind of a general public probe into the general opinions.

Alex (20:15):

It’s definitely an interesting thing to think about and totally one that you do have to kind of wrap your head around if you’re first hearing about it. So what would you say is the most exciting part about doing your PhD in cellular agriculture?

Natalie (20.31):

The opportunities that I have come across since starting my PhD have just been more than than I ever anticipated. I didn’t really know what I was getting into when I started graduate school. It wasn’t something I had considered previously in my life, so I didn’t really know what it was like to go to graduate school or do research full time. But it’s been, you know, just the best experience of my life. I really love working with David. He is an amazing advisor. The team at Tufts, you know, Andrew and John and Kyle are my fellow PhD students working on this. It’s a really awesome team and we just, because what we’re working on is so interesting to a lot of people, we just get a lot of different opportunities, whether that’s speaking engagements, a lot of student outreach. We had the opportunity this last semester that just wrapped up to design and teach our own course. So Andrew, John, and I designed a cellular agriculture course. It was lab based and taught a bunch of undergraduate students, kind of the fundamentals of cellular agriculture. And then we got to bring them into the lab to do a bunch of initial experiments to kind of introduce them to the idea. So that’s probably the most exciting part of it is just the extra curriculars outside of the research itself.

Alex (21:56):

Earlier you had mentioned that when you had the funding from New Harvest, you pretty much had free reign to work on whichever cellular agriculture topics you were interested in. Is that when you’re doing PhD research, do you usually have so much freedom or is that something that’s a little bit more unique would you say?

Natalie (22:18):

Yeah, so this is definitely something I learned once I started and I had no idea how graduate research operated before, but it’s very tied to funding, which makes sense. You know, someone is paying for the experiments you run. So everything is tied to grants. So if you have a grant from the National Science Foundation or National Institutes of Health to work on kidney tissue engineering, then you know, a certain number of graduate students can be funded to work on something that is relevant to what the grant application was written for.

Natalie (22:52):

So before the New Harvest funding, their primary projects had to be focused on something that there was funding for. And so there wasn’t freedom to work on anything. And even, I think now New Harvest has graduate student applicants apply with a proposal. So they will outline what research project they’re going to work on before they start. Because I was kind of one of the first Fellows to get on board, that structure hadn’t been put in place yet, so I didn’t have a specific proposal written when I got in. So I kind of had even more freedom, which was hard because I didn’t have a good idea of where to start, but kind of just had me exploring everything for the first year.

Alex (22:27):

What would you say is the most challenging part about doing your PhD in cellular agriculture?

Natalie (23:36):

That is a great question. I think I have two answers. The first would be just a lack of clarity, whether I’m on the right track. I think in other fields there are so many experts, so kind of the foundation for what approaches you take to certain things are a little laid out for you, so you kind of know whether you’re doing something that’s worthwhile or not. There’s pros and cons to that. I think it gives us more freedom to be creative without, you know, those historic constraints. But it just makes it difficult to know whether what we’re doing is actually going to translate into something beneficial for society. And then secondly, I would say the probably the most difficult part for me personally right now is kind of what I said was the most exciting part. Just the amount of opportunities is almost too much at times. I have a really hard time saying no. So I find myself over committed to just multiple different projects. So I struggled with focus, but that’s really not the worst problem to have.

Alex (24:49):

Because there are so many startups in this space, but there are also a lot of researchers doing research, do you see that the cellular agriculture community will be sharing research more openly, or is it hard to get information about what others are doing?

Natalie (25:07):

Yeah, so personally I have found that obviously at New Harvest, the Good Food Institute, the new nonprofits are really excited to share everything they’re working on, which has been just incredibly helpful from a lot of perspectives. And then academia itself, I think, you know, I’ve kind of heard about other fields being competitive or not wanting to share with each other. I have found the academic space for cellular agriculture is extremely excited to collaborate and share. That’s never really been an issue for any of the situations I’ve been in. The companies themselves, I haven’t had that much experience with openly sharing what they’re working on unless kind of I have an inside connection or if I’m consulting for them, which makes sense that they have IP they want to protect. And I think it’s, I think it’s an okay system. I think the research, the fundamental research being shared by nonprofits and the academic sphere have been really helpful and sufficient to move the field forward. And I think, you know, down the road once products start coming out and companies are a little more established, maybe they can share some of what they’re working on when it’s the right time for them.

Alex (25:18):

Before we start wrapping things up, I have to ask the question, can you imagine that, you know, your research will end up going into a food product where we might be eating, and I don’t want to say burgers or hotdogs, but that is the most simple example. For example, a burger that we would purchase at the grocery store, similar to Impossible Burger or Beyond Beef. Can you imagine what that might look like? Have you thought about that or is it just so far removed?

Natalie (26:27):

Yeah, no, I do think about it. The more I work and progress my research, the more feasible I think it is. Obviously the more questions come up, but you know, sometimes I’ll just have days where I’m like, wow, this makes so much sense and I can really see it moving forward. Lately I’ve been thinking about sushi. I think it would be really cool to have insect muscle and fat based sushi products. So that’s kind of what I think of when I think of commercializing what I’m working on specifically. But I can definitely see the path there and definitely watching all the companies in the space make progress is really inspiring and I still keep that optimism. I think working in academia definitely has made me more skeptical of a person in general, but I’m still extremely optimistic about the field as a whole and that we’ll get there sooner or later.

Alex (26:43):

You can learn more about Natalie on LinkedIn and learn more about new harvest at www.new- harvest.org. Natalie, do you have any last insights for our listeners today?

Natalie (27:52):

Yeah, I would just want to give a shout out to all the students who are interested in getting involved but don’t know how. There are many opportunities once you kind of just show initiative and if you can be persistent with reaching out to people. There’s a lot of people in the field who are excited to help students get involved so we can grow this field in the longterm.

Alex (28:27):

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

Natalie (28:42):

Thanks Alex.

Alex (28:33):

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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