Subscribe
Share
Share
Embed
Sounds of Science is a monthly podcast about beginnings: how a molecule becomes a drug, how a rodent elucidates a disease pathway, how a horseshoe crab morphs into an infection fighter. The podcast is produced by Eureka, the scientific blog of Charles River, a contract research organization for drug discovery and development. Tune in and begin the journey.
Mary Parker:
I'm Mary Parker, and welcome to this episode of Eureka's Sounds of Science. Since the beginning of civilization, meat cultivation has been a staple of human society, but with a growing world population and increasing pressures from climate change, it's time to start looking into alternatives and bring food science into the 21st century. One solution might be cellular agriculture or the lab production of meat and other animal products. I'm joined today by two experts to discuss this topic. Steven Miklasz, a director from our Biologics Testing Solutions Team. And Ramsey Foty, Scientific Director for Fork & Good, a cultivated meat company. Welcome Steven and Ramsey.
Ramsey Foty:
Thanks, Mary. Nice to be here.
Steven Miklasz:
It's my pleasure to join you, Mary.
Mary Parker:
I'm glad to have both of you. But let's start off with introductions so that the listeners can get to know you. Ramsey, can you tell us a bit about your background and how you came to be in this industry?
Ramsey Foty:
Sure. So as you mentioned, I'm a science director at Fork & Good, a cultured meat company in Jersey City, New Jersey. I'm actually a dyed in the wool academic. I've been in academic science for roughly 30 years. Started off my career as a scientist at the Robert Wood Johnson Medical School, where I led the basic research program in the Department of Surgery. I'm a cell biologist, a developmental biologist by training, and roughly five years ago I was contacted by an ex-colleague of mine, who I'll discuss with you guys a little bit later, Dr. Gabor Forgacs, who has started three companies. This is his third company and he discussed with me the possibility of joining Fork & Good in 2019, and I've been there ever since.
Mary Parker:
Just out of curiosity, what has been the transition like for you career-wise going from an academic setting to more applied sciences?
Ramsey Foty:
Right. So the science is the science, biology is biology. Whether you're studying it in an academic setting or in a more applied setting, that hasn't changed. What was really different for me was the whole application business. I really needed to start thinking in a totally different way. In a startup, we really don't have the luxury of time that typically one would have in academia. You have to hit the ground running, you have to be very efficient in how you think about science, and always in the back of your head, we always have to think about the techno economics.
Mary Parker:
Yeah, that makes perfect sense. All right, Steven, how about you? What's your background? How did you get into science?
Steven Miklasz:
So without getting too sentimental, my early career path was highly influenced by a revolutionary immunologist by the name of Paul Ehrlich. In the early 1900s, he described this concept of the magic bullet. This is where some compound can selectively target and kill disease causing organisms. As it happened to be in the time of my undergraduate education, I was made aware of George Kohler and Cesar Millstein in the mid-80s winning the Nobel Prize in medicine for the development of monoclonal hybridoma technology. So with these cell lines, you can clone them so that you guarantee that they're clean. You can freeze them so that they're immortalized, so that you can thaw them out and regrow the same stocks of materials so that they're identical year over year from place to place. And they can be scaled up.
And scaling up in bio manufacturer is a big aspect of my career as well, where I started making these antibodies at the University of Illinois Urbana-Champaign in the early years of the hybridoma field. And I spent 25 years developing antibodies with fine specificity to many hundreds of targets, and up through in delivering these the targets of disease. So I live that challenge of bio-manufacturing scale that is moving a target cell line from microgram to milligram scale to many kilogram scales. And this forms the basis of our current manufacturing scale for antibody drugs. So one of my interests from this previous experience is the challenge of scale that is facing the cell cultured meat industry. There are several regulatory hurdles facing that industry, and as you know, the antibody drug industry has great experience facing these regulatory challenges for bringing highly complicated bio-molecules or biologics to patients.
Mary Parker:
Yeah. We'll get into that a little bit later how Charles River fits into this puzzle, and I just wanted to mention that I think it's very cool that you were inspired by this voice from the past, basically. I just had a similar epiphany when I was in college of being inspired by an old scientist. In my case it was Francis Bacon, and one of the things that he talked about was how science can be done by anybody. It doesn't have to be super geniuses like Aristotle passing things down to just be revered by generations. It can be technicians up. He didn't know what that was at the time, but that was basically what he was saying, was that people contribute to science in every way, including the so-called drudgery of just producing good data.
Steven Miklasz:
Exactly. And the creativity of our fore bearers in these fields, the concept of a magic bullet, it drove my whole career.
Mary Parker:
Yeah, that's very cool. Well, getting back to the topic at hand, for any cellular agriculture novices out there, Ramsey, can you give a broad definition of what it is?
Ramsey Foty:
Yeah, sure. It's basically growing meat without using an animal to do it. That's about the simplest definition I can give you. I can get definitely more technical if you like, but that's basically what we're doing, is growing meat without using the animal.
Mary Parker:
Steven, could you expand on that a little? Because I know that there's different ways of growing the meat. Can you give maybe two different versions of how to do it?
Steven Miklasz:
Yeah. I guess the meat industry is mixing muscle cell and fat cell, and so there's actually multiple ways that they can produce product that bears flavor similar to that which we expect from hamburger or pork. And so mixing those together, growing separate cultures and then mixing the ratios to create the flavor attribute, would be one way that people are doing that. Another way is to take those cells and actually try to embed them into some biologic matrix, like a scaffolding, and to grow the cells in those ratios in the scaffolding. And then when they come to confluency, then that product can be harvested and sliced and prepared similarly to cold cuts or some type of standard meat that we would be used to.
Mary Parker:
Ramsey, can you tell us about Fork & Good and their method for lab grown meat?
Ramsey Foty:
Yeah, sure. So Fork & Good started in 2018 by Gabor Forgacs, who's currently our CSO, and Niya Gupta, who's our current CEO. Dr. Forgacs, in 2011, was actually the very first person to ever taste cultured meat. That was his first company. It was called Modern Meadow. They have since moved on to basically brewing bio-materials, one of them being leather. And part of Modern Meadow at the time was a cultured meat company. Gabor was able to generate things that they called meat chips. It was beef chips. They were able to do it successfully in 2011. The problem was each chip they produced cost $100. So what I mentioned earlier on about the techno economics being very important, that jumped up and bit them in 2011.
In 2018, they rethought how they planned on relaunching the cultured meat project that they had in mind, and what they did to launch Fork & Good was to start from a totally different direction. Rather than starting to think about the science, they started to think about the techno economics. How could they make the science fit the techno economics? That's basically what Fork & Good is all about these days. What we do is we design the science to make it as efficient and as cost-effective as possible. That way at the end of the day, not only do we have the science working, but we also have the techno economics working.
Mary Parker:
I love that. I love a pragmatic approach to these sorts of issues because I think that, on the one hand, the pie in the sky dreamer scientist who comes up with all these new crazy things is so important, but then you have to bring that stuff down to earth to a point where it's affordable, it's sustainable, it's good for the environment. You need to get all those pragmatic things into the equation for it to actually have a huge impact on society. So Steven, you attended a conference a while ago where this topic of cellular agriculture was discussed at length. Can you tell us some of the topics that came up in that conference? What's the industry getting excited about?
Steven Miklasz:
Yes, I did. Actually, both Ramsey and I attended the Industrializing Cultivated Meats and Seafood Summit in Boston last July. The focus of that meeting covered a broad range of topics spanning both R&D process and scale to regulatory guidance, investment landscapes, consumer acceptance and market adoption, hybrid products where they mix plant-based proteins with cell cultured meat and actual meat-based products augmented with cell cultured meats, and as I said earlier, the mixing of different muscle cells with fat cells to achieve flavor and other attributes. So it was stimulating to listen to many of these talks, and what impressed me the most about the meeting was how collegial people were, their overwhelming enthusiasm for the prospects of delivering these sustainable products that will achieve scale and check the box for flavor, nutritional content, and safety for our consumers.
Mary Parker:
Yeah, absolutely. And I don't think we're going to get into consumer adoption just because I feel like that's a whole separate podcast in and of itself, but it is obviously an important consideration with any extremely new technology in any field, not just food science, obviously. That is an interesting one, but we'll get into that another time. But besides that, for both of you, what are some potential roadblocks for this emerging industry? Steven, you want to start?
Steven Miklasz:
I can imagine several different roadblocks. Perhaps the economy that we're in right now is probably the most immediate challenge, but in the long haul, cost considerations will be a resounding theme that drives this industry. And by cost I simply mean things like the cost of the raw materials to make the product, the cost of production to scale, the costs associated with lost or spoiled product, costs associated with regulatory testing, and also costs for bringing these products to adoption. So ultimately the market will either bear these costs or they won't, and we need to find a clear path for cultivated meats at large scale. Somehow it seems antithetical to me that a product bearing higher associated front end cost will be selected as our solution to feed the masses. So we'll have to be focused on ways to creatively control the costs without sacrificing quality or safety.
Mary Parker:
What about you, Ramsey? What are some of the challenges facing Fork & Good?
Ramsey Foty:
Cost.
Mary Parker:
Yeah.
Ramsey Foty:
It's all about cost, and we've been working very hard to think about how one can mitigate the cost of actually making the product. So there are basically three pillars that we have to control. The first pillar are the cells, the second pillar is the medium that you need to feed the cells, and the third is, how do you actually manufacture your product? Costs are associated with each part. Less so with the cells. Very much so with the culture medium that you use to feed those cells. There will be economy at scale, but what I can tell you, I can share this with you, is that, at Fork & Good, one of the major cost reductions that we were able to make was by actually using non-pharma grade water. Yeah, pharma grade water is probably one of the biggest cost drivers of the medium, that and growth factors. We actually found that we could reduce the cost of that water tremendously just by using good old-fashioned New Jersey tap water rather than pharma grade water.
Of course, we have to clean it up a little bit and polish it a little bit, but we were able to reduce a lot of the cost of the tissue culture medium by going that route. As far as the manufacturing of the cultured meat product itself, we also don't use pharma grade bioreactors. They tend to be incredibly expensive. So we've gone to using smaller bioreactors that are non-pharma grade, and the reason why we've been able to do that really has to do with the cells that we've generated and the medium that we used to feed them. So we're able to generate very, very high cell densities in a very inexpensive medium using non-pharma grade bioreactors. And that collectively has allowed us to really reduce the cost on the upfront end.
Mary Parker:
That makes perfect sense and I think the crux of the whole industry in terms of its viability going forward is, it basically came from a sort of pharma perspective, but it needs to get into the realm of food regulations, which they're different from pharma regulations because of how our bodies process drugs and food differently. There's scientific reasons. It's not just because food is more lax. So this next one's for Ramsey, are there ways for traditional and cultivated meat production to work together to improve sustainability and reduce prices?
Ramsey Foty:
Oh, most absolutely. We cannot afford to be in competition with big meat. That would be the Bambi meets Godzilla scenario. There is no way that we would be able, the cultured meat industry could directly compete with big meat manufacturers. So what we've done at Fork & Good is we really want to bring big meat to our side. And how are we doing that? Well, typically when we make our cultured meat product, it comes out of the bioreactor basically as a paste. We have to mix it with other substances in order to give it better texture, better color, better taste. We can either go the plant route, so we can mix ourselves with plant products, but we've also now decided to start mixing our cells with meat products.
So we can have, for example, 20% to 30% cultured cells and 70% to 80%, let's say, ground pork. That solves a tremendous amount of issues. Now we have the color, we have the texture, we have the bite, we have the taste. But what we've been able to do with the meat industry is to give them an opportunity to reduce the amount of meat product in whatever they're manufacturing by 20% or 30%.
Mary Parker:
That makes a big difference, not just from their production level, but, most importantly, I think from an environmental perspective. It's like if you could make the cell grown meat in a more environmentally friendly way than using that as just even some of the portion of the traditionally grown meat, I think that would make a big difference.
Ramsey Foty:
Yeah. And we've had a lot of interest from the meat industry in that regard.
Mary Parker:
Yeah, I'll bet. So from each of your perspectives, I think we've already answered this, but how likely do you think it is for cultivated meat to replace traditional meat entirely?
Steven Miklasz:
Do you mind if I start with this one?
Mary Parker:
Absolutely. Go ahead.
Steven Miklasz:
Yeah. I think in some markets, maybe Asia Pacific and more specifically in Singapore, the adoption of the cell cultured meat product is fast. As a matter of fact, they already have marketed and approved a product for chicken bites. Singapore also has led the way in establishing regulatory guidance for manufacturing and product safety. As you can imagine, allergens as well as other introduced variables could really affect the safety of such products. But other markets, let's take away the Asia Pacific. Let's go to the EU. They have very strong ethical pulls to reduce the use of livestock in commercial foods. However, they also have a resistance to GMO products. GMO can impact cost of goods. They also would rather than embrace the manufacturing benefit of GMO, lean more heavily towards where Ramsey was just referencing the idea of blending cultivated meat product, cell cultured meat, with plant-based meats, and supplementing real meats in an effort to reduce the slaughterhouse products.
So this strategy, as you can imagine, is incremental and it will take time, but then you've got these groups of people who are going to be resistant, clusters of adopters. So I actually don't really see with all these different head winds replacement as being complete, and I think 50% replacement as a global target goal over many decades would be fairly optimistic.
Mary Parker:
Okay. Yeah, that makes sense. To follow up with that, Steven, if you can share, can you tell us a bit about some inquiries that Charles River has had? Have any companies reached out to us asking about services we can provide to help validate their cellular agriculture processes?
Steven Miklasz:
On the European side, we've had a few inquiries, mainly from the Middle East and also in Europe for generating cell banks. These are the starting materials that are going to be necessary for the manufacturing path. We've also, as you know Fork & Good joins us, we've engaged with them also in similar areas. But yeah, there's a slow but steady trickle of clients that are beginning to develop the interest in our services for cell line testing and cell line banking. And again, as I tried to say earlier, cell line banking is the immortalization of these products, providing consistency over generations, potentially securing the initial work that was put into generating these products. We offer that under GNP, so we have some areas of overlap for this industry that biologics testing can definitely contribute to.
Mary Parker:
Excellent. Ramsey, is there anything else you would like to tell us about Fork & Good or about your own research that people would think is interesting?
Ramsey Foty:
We're always trying to invent the better mousetrap as far as cells are concerned, so we've opted to start with muscle cells. A lot of our colleagues have opted to use stem cells where they have to differentiate, re-differentiate, maintain the differentiation state, et cetera. So they're essentially turning an embryonic type cell into a muscle cell. We chose to sort of start with the muscle cell to make more of them. Of course, that comes with certain challenges. Primary cells that you can take from a small biopsy from the animal typically don't like to grow for very long or very quickly. Certainly, they would not be the cell line to start making tons of cultured cells with. So we have to do a little bit of genetic modification to them. We take a very precise approach and a very minimal approach to genetically modify the cells so that they actually perform as we need them to perform.
And then, of course, we tweak the tissue culture medium for each of the cell lines that we make commercially available. Tissue culture medium tends to have a lot of components to them. Quite often cells don't use all the components that are in the commercially available media so we've had to find a way to determine exactly what our cells need in order to grow optimally. So we formulate our media ourselves. We don't use pharma grade components. We try to use either feed grade or food grade components that we could buy at scale and relatively cheaply. We've eliminated the use of fetal bovine serum. We're currently testing a very promising serum free medium for our cells. They grow very well in it, and we've been able to reduce the costs, again, 63-fold from when we first started.
Mary Parker:
Wow.
Ramsey Foty:
So yeah, we've taken a pragmatic approach to link the cells with the median that they grow with. We've been able to leverage biochemical and molecular technologies that actually can track exactly what nutrients our cells use in the bioreactors that we grow them in to further optimize the growth rate and minimize the cost of the medium that we're feeding them.
Mary Parker:
Wow. It just occurred to me, and this is getting probably way off track, but do you think there's any chance of cellular agricultural technology being reverse engineered back into pharmaceutical grade for doing things like, I don't know, growing skin grafts for patients or even the ultimate ideal of somehow printing organs for organ transplants?
Ramsey Foty:
Yeah, I think so. We've had to be pretty creative with how we do things, and some of that creativity, I think could be reverse engineered back into the bio-pharmaceutical industry. Ultimately, as far as bio-pharmaceuticals are concerned, the safety issue is paramount. It's very important for cellular agriculture as well, but maybe not quite as important as it would be in pharmaceuticals. After all, we're just eating the product that we're making.
Mary Parker:
Exactly, yep. It is a lot. That's the thing that I think can trip consumers up sometimes is the difference between a drug that might go into your bloodstream or might be used surgically or something versus eating something and having it go through your digestive system. There's different standards for a reason. It interacts with your body in completely different ways.
Ramsey Foty:
Sure, sure. We spoke a little about roadblocks. The other one I might be able to just throw out there right now, part of the issue with cultured meat these days is this whole concept that we're putting something into our body that somehow might sense they're cells. Sometimes they're genetically modified cells. So people maybe are a little bit worried that somehow these live cells can find their way into the body. But what I can tell you is, I mean, we eat foreign material all the time. We genetically modified foods all the time. Nothing happens. These cells have to go through the digestive tracts. They're essentially broken down into their constituent elements. It's never an issue. We eat cows and pigs and whatever else and we don't sprout horns or tails. So I really don't think it's as big of an issue as people make it out to be.
Mary Parker:
No, not at all.
Steven Miklasz:
I would agree with that, Ramsey, that the whole concept of digestive systems and meat and protein and nutrition should put a lever against, this going to become tumorigenic, for example. But I think from a viral safety perspective, there are many known organisms and contaminants that can project themselves through the digestive system and into the host. So there is still room for safety. I think GMO is probably one of the least concerning. I think viral safety is probably paramount.
Ramsey Foty:
Of course, that's where the FDA comes in and Charles River comes in. So I think it's wonderful that the FDA is involved. It's very important for us to make sure that whatever product we're making is completely safe.
Mary Parker:
So, finally, what manufacturing processes or new technology could help improve the scale and distribution of cultivated meat?
Steven Miklasz:
I think, off the top of my head, we look to disruptive technologies that will help drive down the cost while improving quality attributes of the cell cultured meat manufacturing process. In my mind, I can imagine us evolving fully automated continuous culture manufacturing plants that wed themselves with this inline testing so you can test and grow in parallel. And these features, along with things like artificial intelligence, can help us predict production schedules and to help automate a process where it can support a 24-hour seven-day production line with fewer hands, less labor force, where quality testing being a phase appropriately integrated process will speed that production to grocery shelves.
Mary Parker:
Anything to add to that, Ramsey?
Ramsey Foty:
Well, I think distribution is key. What we envision at Fork & Good is, rather than having a central plant with humongous reactors, we're thinking more along the lines of a scale out where you have smaller reactors, but maybe a battery of them in something that might resemble a micro-brewery, and having these micro-breweries distributed strategically across the country to help mitigate distance traveled to market, and that could significantly impact environmental concerns.
Mary Parker:
That would be so cool. I mean, people do love locally sourced produce and meat, and so this would be locally sourced cellular agriculture. That'd be pretty rad.
Steven Miklasz:
It's a great model.
Mary Parker:
Yeah, absolutely. Thank you both so much. This has been a fascinating conversation. I'm so glad you were both here and sharing your expertise with me.
Ramsey Foty:
Quite welcome. Really enjoyed it.
Steven Miklasz:
Anytime, Mary. Thank you for having me.
Mary Parker:
Thank you for coming.