Where’s the Beef? A First-Hand Assessment of Cultivated Meat Progress
As pioneers and industry leaders, we believe it is important to acknowledge and address some of the reasonable skepticisms being voiced about the commercial viability of cultivated meat. Critical review is an essential part of the scientific process. Mosa Meat in particular invites this conversation because we know it will ultimately help test our assumptions, optimize our processes and reach commercialization of our beef in a more efficient manner.
Many critiques do not come from a place of malice for the potential of cellular agriculture, but from a lack of access to information that individual companies are not incentivized to share. To advance a constructive dialogue we’d like to share an “under the hood” perspective, based on our extensive research and experience. Specifically, we will address points articulated in recent articles such as The Counter, Mother Jones, and The Guardian. To streamline the discussion, we have clustered those points into five categories:
growth media
life cycle and techno-economic analyses
hardware and production scalability
open source vs. private research
the role of investors
In short, the underlying argument about this technology is true: cultivated meat at commercial scale is not inevitable. A number of the companies around the world attempting it now may not exist in five years. However, something being difficult and something being impossible are light years apart. We have been and will continue to be successful in this endeavor with resources, expertise, and time. Investors evaluating opportunities in cellular agriculture should expect a transformation of the meat industry over decades and continue to employ intensive due diligence before entering this arena.
To our peers in the industry, we say that the process of writing this paper was a helpful exercise to illuminate possible internal blindspots and an excellent opportunity to provide additional information for those who have an open mind. We encourage all members of our industry to do the same, even if they do not share the results.There is a natural tension between needing to generate excitement in order to raise funding and not overpromising on important milestones. As our industry navigates that balance, we believe that it is critical that we hold ourselves to the highest standard of integrity about progress reports and timelines. The importance of maintaining and growing trust with stakeholders (investors, regulators, consumers, storytellers) cannot be overstated.
Introduction
The theory of cultivating meat lived in the minds of futurists like Frederick Edwin Smith, Winston Churchill, and Margaret Atwood up to 100 years before the technology and scientific knowledge existed to make it a reality. In 2005 it was a Dutchman, Willem van Eelen, that set into motion a government funded research collaborative and our founders ensuing partnership that would finally move the needle of progress. It was a hard row to hoe. In the eight years leading up to the 2013 proof-of-concept burger, there were more failures than successes and resources were almost always scarce. Our final product was far from perfect, but it changed the conversation from ‘can it be done’ to ‘when can it be done at scale’.
Fast forward eight more years and there are 80+ companies around the world using the technology we advanced in the Netherlands to grow meat and animal products at various scales. Now with 115+ talented employees from 24 countries, Mosa Meat has a long list of scientific breakthroughs under our belt. We, and others, are now in the phase of seeking regulatory approval for our meat and building a pilot production facility. There has even been a regulatory approval for cultivated chicken in Singapore. This industry wide progress has invited praise and skepticism. Both have merit when based on data.
A recent article by The Counter relies heavily on a techno-economic analysis (TEA) conducted by Dr. David Humbird on behalf of Open Philanthropy, an organization funded by Facebook co-founder Dustin Moskovitz. The Open Philanthropy TEA is based on public data and assumptions from a biopharmaceutical context. It is more pessimistic in its outlook than a 2021 TEA by CE Delft using data from cultivated meat companies. Humbird is quoted in The Counter as saying it was “hard to find an angle that wasn’t a ludicrous dead end” and “it seems like a lot of hooey to me.” In some instances the feedback reads as personal rather than rigorous hypothesis testing. The piece also prompted a number of thoughtful responses from the Good Food Institute, and individuals like George Peppou, Isha Datar and a blog by Dr. Elliot Swartz titled “Rational optimism for cultivated meat.”
One researcher quoted in Mother Jones states that the challenges associated with cultured meat are “nearly on par with the engineering challenges with taking a man to the moon.” We do not believe that to be true, but if we did, that still means it’s eminently doable. For context, the United States spent $280 billion from 1960-1973 (adjusted for inflation) on the Apollo program and concluded 6 manned Moon missions. Approximately $1 billion has been spent thus far on cultivated meat with significant progress; from a proof of concept to a regulated product on the market in less than 8 years. And, considering the $1.4 trillion that consumers spend on meat each year, there is ample motivation to succeed by companies around the globe.
Recent articles have missed a number of opportunities to include available information about scaling costs, growth media, cells and scaffolding in their reporting about progress and long term prospects. This is unfortunate as we, and others, have been researching and addressing these topics for years in public formats and in peer-reviewed journals including in this 2020 paper in Nature Food titled “Scientific, sustainability and regulatory challenges of cultured meat.” Below we have aggregated some of that research and included new information not previously released.
1. Growth Media
A common concern mentioned by both supporters and skeptics of cellular agriculture is around the use of fetal bovine serum (FBS) as a source of micronutrients for cell proliferation. FBS is derived from blood collected from the calves of pregnant cows at slaughter. A small amount of FBS was used in our 2013 burger and every cultivated meat company that we know of has used it in the research and development process. Mosa Meat decided early on that if an alternative to FBS could not be developed that we would discontinue our work and not bring any products to market. This decision was based on both moral and economic grounds.
Much of the focus on FBS as a barrier has been based on research from 2012 by Dr. Christina Agapakis, which precedes substantive scientific progress on this issue. First, it is important to note that there have been animal cell cultures performed for years that are serum-free. There is nothing fundamental to animal cell culture that requires the use of animal serum. Second, specific progress toward serum-free cultured meat has been demonstrated publicly including in this February 2020 paper by Drs. Anna Kolkmann and Mark Post showing that serum-free media “have the potential to become as effective as the current serum-containing medium when it comes to cell proliferation.” Additionally, this May 2021 journal article titled “Simple and effective serum-free medium for sustained expansion of bovine satellite cells for cell cultured meat” demonstrates success with a serum-free media (B8) when mixed with recombinant albumin.
Developing an alternative to FBS was a difficult task that took Mosa Meat years of research, but our scientists have been able to completely remove it from our media. This is true for both muscle and fat culture, demonstrating the possibility of broad application across species and cell types. And our animal-free media now performs on par or better than FBS-based media at increasingly lower cost. We announced this milestone publicly in 2019 and we have submitted a patent for the formula. In addition, our team is awaiting the publication of peer reviewed research that lifts the veil on this remarkable achievement soon. Mosa Meat will not request regulatory approval for or commercialize a product that includes FBS. It is antithetical to our mission of reducing the number of animals (and the associated externalities) required to feed a growing planet. Whether for moral or economic reasons, we have reason to believe that other cellular agriculture companies will arrive at the same conclusion.
There have been additional questions about how the cost of nutrients in the growth media can be lowered. The comparative analyses we have seen thus far focus on the cost of pharmaceutical grade ingredients, which are expensive. Humbird states that “the cost of growth factor production may never come down significantly. It’s a non-starter.” While his sentiment is more definitive than most, it is in line with a common concern that a supply chain does not exist to deliver the ingredients and hardware needed to reach economies of scale and bring costs down. This is a legitimate concern, but it is by no means insurmountable. Our industry is actively moving away from pharmaceutical grade ingredients and identifying suitable food or feed grade alternatives that are exponentially less expensive. This kind of research and development is not envisioned in Humbird’s assumption that we are constrained to pharmaceutical grade materials.
Using amino acids as an example, food grade protein hydrolysates have been commercially available for a long time at prices that are orders of magnitude lower than their pharmaceutical equivalent. The same holds for feed-grade glucose. Mosa Meat has already demonstrated their effectiveness, even without any additional optimization, for our basal media. Furthermore, until now there has not been a high volume demand for specific micronutrients that can be recombinantly produced (similar to how insulin is made) at lower costs. However, more producers are now stepping into the market after doing due diligence on the potential for our industry. It is plausible to expect that nutrient suppliers motivated by a new revenue stream will fill our demand.
2. Life Cycle & Techno-economic Analyses
Relying heavily on Humbird’s research as a comparison, The Counter article offered a critique of the most recent TEA on cultivated meat conducted by CE Delft, an independent think tank in the Netherlands that specializes in environmental sustainability research. The TEA was sponsored by the Good Food Institute (GFI), an NGO that advocates for alternative proteins and does not have a financial interest in cultivated meat.
In conducting the analysis, CE Delft incorporated data provided by cultivated meat companies on the condition that it be anonymized to maintain confidentiality. Previous studies, including Dr. Humbird’s, have been based on publicly available data and insights from parallel fields like biopharma. Although it is realized that these studies are anticipatory because production processes have not been consolidated yet, Mosa Meat enthusiastically contributed to this important research with our current data to get an objective view of the progress of our industry beyond such parallel comparisons. This has provided focus to our production steps, as anticipated now, that could be a challenge or liability.
That is the value of such analyses. A TEA is a method of modeling the economic performance of an industrial process based on available data. Ideally, it produces a model that represents the best current understanding of the proposed production process and identifies research priorities that improve profitability while de-risking the industry. The data input into building the model is essential to the quality of the performance indicators that will be produced as outputs. These data should accurately reflect the business model of the industry.
Dr. Humbird rightly acknowledges key differences between the current biopharma industry and cultivated meat in that “…conventional animal cell-culture processes are carried out on a vastly smaller scale than food production. In addition, they have not necessarily been optimized for the same economic levers as industrial fermentation, e.g., yield of cell mass or even media cost. Instead, they have individually been optimized for something else which is process- and product-specific. The scale-up laws and economics of animal cell mass production thus remain uncertain.” We agree with that assessment. The value of this kind of research and development is to clarify and resolve those uncertainties, rather than broadly extrapolating pharma practices to this nascent food industry.
There is no evidence to indicate that the current production capacity of the biopharma industry is capped by a technological ceiling. Rather, it is intentionally designed to deliver vaccines and pharmaceuticals in the quantities that the market demands. In those cell culturing processes, cells are used to secrete their products and then the cells and growth media are usually discarded as a waste by-product. More than 50 years of research has gone into optimizing cell lines to maximize secretion while minimizing cell biomass. And, given the profit margins of the pharmaceutical industry, the recycling of growth medium has gotten less attention. Our industry is optimizing to do the opposite. We optimize to create large healthy cells that proliferate by orders of magnitude while secreting as little waste as possible. The profit margins of the meat industry and our dedication to sustainability also motivate us to reduce water waste and recycle media where possible.
While the base technologies of our two industries are similar, the production processes have divergent motivations and any modeling drawing comparisons need to take that into account. Even diligent projections like that by CE Delft will have to incorporate some assumptions based on the best available data at the time. This sector is taking shape in real time and the use of TEAs and LCAs will continue to play an important role in understanding how we can explore uncertainties, maximize profitability and our positive impact on the planet. We encourage skeptics and supporters alike to continue to use these tools to assess our progress and we are willing to assist with data collection for the best possible inputs.
3. Hardware & Production Scalability
The Counter article, in particular, hones in on the scalability of cultivated meat with some valid points based on the information underpinning its assumptions. The conclusions boil down to the technological challenges of preventing contamination, costs of production facilities being beyond financing limits, and growth media being too expensive for the economics of cultured meat to make sense.
The absolutist language used in the article to lay out these arguments is notable. Terms like “always” and “never” are used in place of an assessment of probabilities based on the current information available. In an October 20th Q&A session hosted by New Harvest on Reddit, Mr. Humbird stated that the TEA was “a thorough and well-reasoned analysis of an absolutely banana-pants idea. The technical issues highlighted within (and brought to light by The Counter) are the products of a well-honed bullshit detector.” While the tone feels rather personal, Mr. Humbird also pointed out in the same Q&A session that the emotion behind cultivated meat may be what makes the difference. “Yes, biofuels offer the most direct lesson on the challenges incurred upon scale-up of biotech/fermentation. Cultured meat scale-up may yet fail for the same or similar reasons. The opportunity, as I see it, is mostly emotional. We tend to care a lot more about what goes in the mouth vs what goes in the car. This could bring a new shade of innovation to the field that biofuels couldn’t muster.”
The risk of contamination in the culturing of animal cells, or any food production, is a very real concern. Which is why creating facilities and a production process that minimizes those risks is a top priority for our company. Similar to the opportunities discussed above around moving growth medium ingredients from pharma- to food-grade quality, there are significant opportunities to do the same in cultivated meat facilities as well.
It is correct that we will need ISO Class 8 and Class 6 clean rooms. Where we will differ is in the size of the clean rooms that will be necessary. We are producing what is, in pharma terminology, a low bioburden product. In other words, our beef will meet or exceed all international food safety standards, which are different from the requirements for intravenous drugs. Hence we can design our facility such that the largest part is in a CNC (clean non classified) area and limit the process steps we need to execute in a classified clean room environment.
For example: the seed stage of the bioreactors will be in an ISO Class 6 area, as it is one of the most critical steps with regards to possible microbial contamination. However, this is a small section compared to the footprint of the rest of the upstream process. We believe that the bioreactors can be set up in a CNC area, as these are completely closed processes. The meat harvesting process and the transfer between proliferation and differentiation stages would likely be in an ISO Class 8 area, but not the entirety of the production plant.
This type of closed system for production would reduce complexity of facility layout and save costs by orders of magnitude without compromising the product quality. The pharmaceutical production model isn’t always taking advantage of these opportunities because, as this report in the Journal of Pharmaceutical Science and Technology puts it: “Improvements in equipment design and operation, especially the use of closed systems, allow certain process steps to take place in controlled environment areas rather than in classified cleanrooms. However, the design of facilities has not developed to reflect these technological advancements. The result is that facility designs are more complex with multiple environmental classifications, resulting in far higher capital and operational costs than necessary given current technology and understanding..”
Our closed system will start with sterile inputs, and remain sterile until harvest, not only reducing the need for clean room specs, but also the need for antibiotics use. Even today large (>1000L) systems with mammalian cells run successfully without antibiotics in the pharmaceutical industry. As we are designing these facilities from the ground up, we have the opportunity to leverage the most recent knowledge in equipment and operations to design a suitable production environment around them.
As to the overall volume of potential production capacity, it’s mentioned that the biopharmaceutical industry capacity is roughly 6,300 cubic meters in bioreactor volume, and that for significant volumes of meat production, a multitude of that would be needed. That is true and as discussed above, there is no reason to believe biopharma capacity is capped by technological limitations. Rather it appears to be a self imposed limit that fits that business model.
It is more useful to compare our industry’s scaling ambitions with the production capacity of other large scale food products like lysine, quorn, baker’s yeast, potable ethanol, citric acid, and the wine industry. Even assuming a 100% market share scenario using our current expectations for output of meat per production batch (cell density, amount of batches per year, etc.), roughly 30 billion liters of bioreactor volume would be needed to satisfy the global yearly meat consumption of ~300 million tons. Using the wine industry as an example, yearly wine consumption is ~15 billion liters, so with an average residing time of 2 years in the vessels, that compares quite well to a 30 billion liter capacity for meat.
In another example, a conceptual evaluation of a 300 cubic meter air lift reactor [X. Li et al, Chemical Engineering Science 211 (2020) 115269] demonstrate that it is in principle possible to meet the hydrodynamic requirements (mixing time, shear stress constraints, mass transfer) in a reactor of such scale. The authors point out that there is an inverse relationship between the bioreactor size, volume of product to produce and the product's selling price. The pharmaceutical industry produces high value products at relatively low volume and hence employ small(er) bioreactors. Cultured meat would be competing in a market comparable to the scale of operations of the present day industrial microbial fermentation plants. Therefore, rather than previous proposals to consider multiple factories, scaled out with a bioreactor of 20 cubic meter [van der Weele, C., Tramper, J., 2014. Cultured meat: every village its own factory?. Trends Biotechnol. 32, 294–296.], it is suggested to consider a 300 cubic meter reactor as the base unit for a factory. With the proposed design, an output of 750 000 kg per year could be possible, which places the required investment cost in a realistic range, for a food commodity.
In short, there are credible reasons to believe that this can be done within our business model using optimized production processes and a fully developed value chain. The more important question is how long it will take for our industry to scale to that point and the accurate answer continues to be a decade or more.
4. Open Source vs. Private Research
The founders of Mosa Meat first came together because of a government grant to explore opportunities to advance the field. It was their hope that the 2013 burger would trigger a ‘moonshot’ level of public investment in research to make the technology ready to scale for the benefit of the world. When that did not happen, they formed Mosa Meat. Private funding was then essential to further develop research and development. However the values of sharing knowledge and promoting the technology have remained at the core of our company. Few companies have done as much to contribute to the open advancement of the cellular agriculture industry as a whole.
In addition to members of our team authoring peer-reviewed articles on our research, Dr. Mark Post co-organizes the yearly International Scientific Conference on Cultured Meat with Maastricht University and we regularly share scientific insights on our blog. At the 2020 conference, we shared and then published what components of the growth medium are most important to grow full tissue, and what techniques we used to get those insights. When we patented a system for scalable differentiation, we supported the community in open analyses of what these patents mean and what our approach is with them.
We encourage all companies in this space to make similar contributions. We understand the tension that can exist between protecting your investors’ ROI and sharing the details behind your scientific milestones. There will be a day when we compete for market share in the food service and retail arena, but it is in our collective interest to build a thriving innovation ecosystem that includes both private and public contributions toward the advancement of the industry.
Now with more than 80 companies, dozens of academic institutions and NGOs worldwide working on cellular agriculture, incredible progress has been made since we unveiled the 2013 burger. There are also significant and growing public investments in the field. During COP26, the United Kingdom announced funding in this space because they “believe developing cultivated meat is one of the most significant advances that we can make, as a country and as a planet, to tackle the scourge of food shortages and climate change.” This comes on the heels of the United States Department of Agriculture (USDA) granting $10 million in public funding for the establishment of the National Institute for Cellular Agriculture at Tufts University and similar investments in Iceland, Norway, Korea, Japan, the European Union, Singapore, and Australia.
5. Role of Investors
Several articles have taken aim at the investor community backing cellular agriculture startups. Some of the rhetoric is unnecessarily pointed and misinformed by portraying our industry to simply be a creature of Silicon Valley. “It’s a bunch of men with a lot of money in tech, who got bored with apps and are now excited to put their money towards this so-called solution to factory farming,” said one person in The Guardian.
The reality of the funding landscape for cellular agriculture tells a different story. Yes, a handful of investors and venture capital firms based in California have been strong supporters of the industry. At the same time, dozens of investors, VCs and established corporations from around the world are betting on cultivated meat to be transformative and profitable in the long-term. At least three companies, including Mosa Meat, Aleph Farms and Upside Foods, have closed ‘Series B’ rounds of investment. The risk tolerance for investors in this round is considerably lower and involves rigorous due diligence by the investor’s in-house teams and third party experts under the scope of non-disclosure agreement.
The size and caliber of the companies that have now begun investing in cultivated meat gives a clear signal about the perceived viability of cellular agriculture. Many of these investors are also potential value chain partners that bring to the table expertise and strategic partnerships to help the industry commercialize more efficiently. It would be unfair and inaccurate to characterize them as uninformed or naive.
GFI’s 2020 report on the investor landscape points out that “life science companies like Merck KGaA, large-scale cell culture experts like Esco Aster, and multinational food/feed material suppliers like Nutreco, Griffith Foods, DSM, and Mitsubishi Corporation have made major strategic business decisions to orient themselves toward opportunities in the cultivated meat field. These companies understand the ins and outs of large-scale cell culture and the procurement of massively scaled inputs. They have seen “under the hood” at cultivated meat companies and often have hired industry experts from all over the world to help them assess the risks and opportunities, to a sufficient degree to justify significant business decisions and potential reputational risk among their existing clients”.
Conclusion
The hallmark of successful innovation and entrepreneurship is to learn from failure and to leverage it to work around the next barrier. We have faced and conquered many scientific and technological barriers in our journey so far. As a mission-driven company, we are committed to sharing as many of those lessons learned as possible for the greatest impact on the food system.
Constructive criticism is important and is a sign of a healthy scientific and innovation ecosystem. Based on our first-hand experience, we believe the questions being posed by the publications discussed above are the right ones. However, some of the fundamental conclusions they have drawn are based on incomplete and outdated data. Mosa Meat has successfully addressed many of these challenges already. And, yes, there are still barriers to be overcome with time and resources. The progress made on FBS from 2012-2019 is illustrative of our ability to identify solutions that may have previously seemed insurmountable. In summary, there is strong evidence to indicate that full scale commercial production of cultivated meat is not only possible but probable.
Proving out the technical feasibility of cultivating meat at scale is important and will happen in due time. In the interim, it is critical that our nascent industry fosters a culture of transparency and integrity to build trust with stakeholders and consumers as well. As the Texas born and Dutch raised Margaret Heffernan famously said, “[f]or good ideas and true innovation, you need human interaction, conflict, argument, debate”.
In that spirit, we welcome a robust and open dialogue about the development of our beef. Toward that effort, Dr. Mark Post (our co-founder) and Maastricht University have invited Dr. David Humbird, and he has graciously accepted, to participate in a discussion later this month at the 7th edition of the International Scientific Conference on Cultured Meat on the feasibility of cultivated meat.
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