Is Cultivated Meat for Real? [Archives]

Cultivated meat faces a wall of scientific skepticism, but investors haven’t been deterred. A decade in, how close are we to seeing it on our plates?

By Robert Yaman - originally published March 2023 in the Food Issue.

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A decade ago, the optimism around cultivated meat (also known as “cultured meat,” or less appetizingly, “lab-grown meat”) was infectious. Mark Post, a professor at Maastricht University, unveiled the first cultivated burger in 2013. It cost $325,000, was financed by Sergey Brin, and received a breathless profile in The New York Times. Excitement grew and investment poured in for new organizations trying to develop their own products. Commentators envisioned a world where meat would remain exactly the same, but the way it was made would change behind the scenes.

For those who care about animal welfare, cultivated meat holds tremendous promise. Instead of convincing people to stop eating meat entirely, we can give them what they want but remove animals from the equation. In 2013, it almost seemed like a cheat code to skip to a world where animals were treated with compassion, without the messiness of slow, painstaking social change.

Instead, timelines for initial market entry were repeatedly pushed back, and some experts began to voice skepticism. Year after year, cultivated meat failed to appear on grocery store shelves. The gossip was that the technology might just be vaporware.

In 2022, cultivated meat was back in the news. Believer Meats broke ground on a 200,000-square-foot commercial plant, and GOOD Meat announced massive facilities in Asia and the U.S. Another company, UPSIDE Foods, received a green light with the Food and Drug Administration’s approval in December — a sign that cultivated meat might soon be available in the U.S. 

But while the industry releases increasingly optimistic projections, well-informed commentators remain skeptical. It’s still unclear if cultivated meat can be made affordable or at large-enough scale to compete with conventional animal products. As we approach the decade anniversary of Mark Post’s first burger, many are confused as to when, if ever, cultivated meat will be on their plates.

After spending a few years inside the industry, I’ve come to believe that the true prognosis for cultivated meat is somewhere in the middle, between that exuberant initial hopefulness and more recent cynicism. I agree with the pessimistic commentators that “The Dream” of cultivated meat — full bio-replicas, cost competitive, at scale — is not feasible in the short term. However, comparison to other technologies like solar energy suggests that cultivated meat may take decades and hundreds of billions of dollars in investment — but is ultimately possible. If we accept longer time scales, many of the seemingly intractable problems become tractable. In the meantime, companies can justify large venture capital investments by pursuing cheaper products that combine cultivated and plant-based components.

Cultivated meat is by no means inevitable. But it’s still a bet worth making.

The Challenges of Cultivated Meat Are Real

In 2020, David Humbird published a techno-economic model that took a critical eye to the technology. There were, he noted, some massive technical challenges. His critique was popularized in a 2021 piece in The Counter. The challenges he identified — which include fundamental cost barriers for input materials, challenges in scaling production processes, difficulty maintaining sterility at large scales, and constraints set by investors — make a convincing case against The Dream of cultivated meat being feasible within the next 5 to 10 years. 

The Prices of Input Materials 

The manufacturing of cultivated meat requires three inputs:

1. Starter cells, often stem cells of some type. 

2. Nutrients that the cells need to duplicate and turn into the relevant tissue types. These include sugars, fats, minerals, and amino acids.

3. Signaling molecules that tell the cells how to behave, called “growth factors.” Unlike many types of microbes, animal cells don’t multiply by default. GFs’ presence in animal cells’ environment gives them the cue to multiply or turn into different tissue types.

Early economic analyses pointed to GFs as the costliest input to cultivated meat,¹ but Humbird deemphasizes this as a long-term bottleneck, and I agree. GFs are expensive now, but GF production via precision fermentation is easily scalable. Bulk purchases often yield massive drops in unit price. The supporting industries that produce the relevant GFs at massive scales don’t exist yet, but they should be able to grow at least as quickly as cultivated meat itself. Companies can also modify the starter cells to require lower concentrations of GFs or to forgo them entirely.

Put another way, GFs carry information, which is fundamentally easier to manipulate than mass. There are unlikely to be long-term thermodynamic or biochemical limits on getting information to cells.

This same is not true for amino acids. Amino acids are the fundamental building block of the proteins in meat; cells can’t be engineered to need less. In Humbird’s model, amino acids alone may constitute $7 to $8 per pound of cultivated meat (although there is by no means a consensus about this). They also have to be pure enough to avoid negatively affecting the cell culture, which adds to the price. Absent new breakthroughs, it’s possible that price floors on bulk amino acids could be a fundamental bottleneck on the price of cultivated meat.

Scaling Up the Manufacturing Process

Manufacturing cultivated meat happens in two stages: proliferation and differentiation. During proliferation, the starter cells continually divide to create more cells until there’s a sufficient quantity of “cell slurry” — a mass of cells mixed in a liquid. During differentiation, cells in the slurry transform into the desired tissue type, like muscle or fat.

There are various types of suitable manufacturing processes for both stages. For the proliferation stage, the most common is a “stirred tank” process, where materials are mixed in a container of liquid, which is stirred to ensure a homogeneous distribution of cells, nutrients, and GFs. This type of process has a long history of use in other industries, like biopharmaceutical manufacturing. While cultivated meat would likely require substantially larger tanks in the long term, the basic procedure is well understood.

The differentiation stage is more complicated. Since large-scale cell differentiation isn’t a challenge other industries face, cultivated meat companies have to design new processes. UPSIDE Foods distributes cell slurry onto a “sheet” where cells adhere to some substrate and turn into tissue. Alternatively, Mosa Meat has developed a novel culture vessel where muscle cells grow in a ring around a central pole and are then sliced off when fully formed.

Even with proven technology, scaling up to successively larger sizes of bioreactor is costly and challenging. Each process characteristic needs to be reevaluated for each level of scale. For example, going from a 1,000-liter to a 10,000-liter stirred tank reactor involves more vigorous stirring to keep cells and nutrients homogeneously distributed. Cells might not thrive in this more tumultuous environment and could stop growing or break open entirely. Operationalizing these larger bioreactors might involve reworking fundamental characteristics of the input cells, and even then they may not be able to achieve the same cell densities. The number of possible problems increases with bioreactor size, as does the cost of running each experiment. Reaching the bioreactor size needed to make a substantial dent in meat demand will be a massive engineering challenge.

Sarah Mazzetti

Maintaining Sterility at Scale

A bioreactor creates a closed environment designed to be perfect for biological growth. Unfortunately, cells aren’t the only things that want to grow here: External microbes carried in by humans or present in the input materials can also thrive. Since bacteria tend to duplicate much faster than mammalian cells, a single microbe can contaminate an entire batch of product. This makes cleaning a critical aspect of the manufacturing process.

This problem gets worse as scales increase. A bigger batch means a longer, more complex process with more materials — and a higher risk of contamination. To make matters worse, a larger contamination means more material goes to waste, leading to a larger financial impact. There are well-established procedures for maintaining a sterile environment for large-scale cell culture, but they require expensive and complex facility upgrades and cleaning procedures. They’ve also never been tested at the relevant scales. Wasted materials from contamination will need to be priced in to the total cost of the final product, meaning that maintaining sterility will be a major engineering focus of the industry as it matures.

Massive Capital Investments

Scaling and maintaining sterility are engineering problems, meaning that they can — at least theoretically — be solved with enough persistence and innovation (although not necessarily in a cost-effective manner). However, the only way companies will truly be able to tackle these challenges is with access to massive amounts of money.

Technological development in the physical world requires substantial capital, capital flows to things that investors think will succeed, and firms demonstrate potential for success through technological development. This is what I’ll call the “virtuous cycle of capital deployment.” Technology firms solicit funding from investors and promise certain milestones. Whether or not the investors invest is a function of how well firms have performed in the past, the financial situation of the investors, and the vibes of the investment environment.

The virtuous cycle can break if one of its parts slows down. If technology firms don’t hit their promised milestones, investors may start to lose faith. On the other hand, if there’s an economic downturn that causes investors to tighten their belts, money for speculative research and development or large capital projects can dry up. But a major technological breakthrough or a new funder (say, a government with sustainability goals) can catalyze a new flurry of investments.

Different investors are more suitable for different stages in a technology’s lifecycle. Right now, venture capitalists are the primary funders of cultivated meat, since their risk tolerance is high and the technology is unproven. As the technology matures and investments become less risky, investors with lower risk tolerance but much larger checkbooks — such as governments, public equity markets, and debt markets — may enter the scene.

Many milestones exist between now and The Dream of cultivated meat becoming a reality. First, companies have to develop scalable processes and demonstrate them in pilot plants. Regulatory agencies then need to certify that these processes yield products that are safe to eat. Then the long road of scaling and cost reduction begins. Companies will need to build and operationalize larger and larger facilities to increase production capacity, and invest in further R&D to lower costs, all the while demonstrating that there is consumer demand.

As each new milestone is hit, cultivated meat will seem more concrete and more possible, unlocking additional capital. However, the capital required to reach subsequent milestones will also increase. At some point, the low-hanging fruit of R&D will be plucked, and capital will begin to flow toward investing in scale to further decrease production costs.

Believer Meats’ recently announced $123 million facility in North Carolina is projected to be able to produce thousands of metric tons of product. This investment is an impressive and important step for the fledgling industry, but the projected capacity would still be a sliver of conventional meat production. Plants like this one generally take two to four years to finance, design, build, and operationalize. In order for cultivated meat to compete with conventional meat, thousands of much larger facilities will be needed in the U.S. alone, and the global supply chain will need to shift to meet the demands of this new product.

As the technology progresses there may come a milestone that’s too costly for investors to stomach, either because it’s too hard, or because investors have lost patience with the rate of progress. The feasibility of cultivated meat therefore comes down to whether the virtuous cycle can be sustained long enough and with sufficient resources to hit the relevant milestones.

The Goals Were Overly Ambitious

Back in 2021, the Counter article brought attention to a number of real challenges that cultivated meat will face. It then posited that they need to be solved in the next 10 years — but that isn’t true.

Cultivated meat is a capital-intensive industrial manufacturing technology that aims to produce high-volume, low-margin products. Industrial animal farming, the incumbent technology, is fully commoditized and has had decades to lower costs through scaling, optimization, consolidation, vertical integration, and R&D. However, these structural challenges are not unique. Other technologies have faced similarly daunting prospects, and some have even succeeded, albeit over many decades of slow, steady progress. Looking at how their stories played out can help us understand the path forward for cultivated meat.

Solar energy, now heralded as one of the most notable success stories of clean tech, is a particularly useful comparison. It also involves a completely novel industrial process and is capital intensive, low margin, high volume, and in a commoditized market.

The technology of photovoltaics was demonstrated at lab scales as early as the 1970s. Over the last 60 years, the virtuous cycle of capital deployment has gone through booms and busts, with periods of heavy investment from venture capitalists, oil companies, and governments. Many decades and hundreds of billions of dollars later, solar is now the cheapest source of new energy. However, it’s still a small part of global energy production, suggesting that even more time and money are needed to transition to a world run on renewable energy.

Looking back, there were periods of pessimism and missed milestones where many proclaimed the “death of clean tech.” In 2011, BP exited solar, saying it couldn’t “make any money,” despite being one of the technology’s champions in the previous decade. Around the same period, the International Energy Agency used the best data at the time to forecast future solar capacity and was consistently overly pessimistic.

How did solar and other technologies like it (e.g., electric vehicles and nuclear energy) succeed, given that investors generally look for profit within a few years? One answer is by finding intermediate business models that generate income on faster timelines, providing profits to reinvest in R&D and boosting investor confidence. For solar panels, this was getting energy to satellites and other remote locations not connected to the broader energy grid. For cultivated meat, it’s creating “hybrid products” that mix plant-based and cultivated components. By using a small amount of cultivated meat as an ingredient, hybrids will have a meatier taste than purely plant-based products, but with massively lower costs than fully cultivated meat.

Hybrid products could be seen as the next evolution of those made by companies like Impossible Foods, which uses biotechnology to produce heme, a critical component of meat taste. Adding a new tool to the alternative protein toolkit may be just what the plant-based sector needs to stimulate growth after its recent slump.

Many startups like Mission Barns, New Age Eats, and SCiFi Foods are explicitly adopting a hybrid approach for their initial market entries, and other industry leaders like Believer Meats and UPSIDE Foods haven’t ruled it out. While these products won’t be able to boast full biosimilarity to traditional meat, they’ll likely taste amazing and be reasonably priced. If they’re successful with consumers, they’ll validate the massive venture capital investments these companies have taken on and further stimulate the virtuous cycle of capital investment to keep advancing the core cell culture technology.

With less than a decade of R&D and only a few billion in funding, cultivated meat is still in its infancy. Companies have primarily been focused on setting up basic pilot-scale operations and acquiring regulatory approval. To my mind, only three demonstrable milestones have yet been hit: GOOD Meat’s regulatory approval in Singapore, its subsequent regular sale of product at pilot scale, and UPSIDE Foods’ FDA approval in the U.S. There hasn’t yet been a real opportunity to truly tackle the core technical challenges discussed above. Trying to predict the future of cultivated meat now is like trying to predict the future of solar in 1990 — it’s too soon to tell.

The Limits of Techno-economic Modeling

After the Humbird model was published, I argued that TEMs can show that something is possible but have a harder time showing that it isn’t. I used the analogy of trying to find your way through a mountain range. You try your hardest to find walkable paths, but you’ll never know if you’ve done a truly exhaustive search. You’ll also never know if there are creative options that didn’t occur to you, like building a helicopter and flying over.

TEMs try to project the economics of a technology once fully implemented at scale. They take inputs like the price of various feedstocks, bioreactor size, and the metabolic rates and doubling times of cells, and use them to calculate output metrics like cost per pound of product and volume of product produced. The pessimistic TEMs in cultivated meat argued that, even under idealized conditions, cultivated meat couldn’t get anywhere close to the price of conventional meat.

However, each of these assumptions can be creatively loosened, especially with a healthy dose of uncertainty appropriate when thinking on longer time scales.

In the next section, I’ll suggest some ways that companies might work around the identified bottlenecks. The following list is not exhaustive — given the intellectual property sensitivities in the space, the most creative and innovative work is most likely being done confidentially.

Cell Density and Alternative Processes

Since stirred tank bioreactors are the only ones with a track record of use for large-scale mammalian cell culture, Humbird understandably limits his analysis to this type of system. Indeed, stirred tank systems are likely to be common in the near future, while the industry is far away from the idealized conditions that Humbird assumes. However, other bioreactor systems may offer better trade-offs for cultivated meat in the longer term.

In “adherent” proliferation processes, cells are secured onto a substrate so they remain stationary, and liquid is circulated through the substrate to deliver nutrients and remove waste — similar to how blood flows in an animal’s body. Adherent processes can achieve massively higher cell densities than stirred tank systems, one of the core bottlenecks in Humbird’s analysis. It’s easy to see why: A liquid containing cells and nutrients becomes harder to mix effectively as it gets thicker and less viscous. However, if cells are kept stationary, they can be packed very tightly, as they are in natural tissue.

One reason these systems could be underexplored is that cultured meat is ultimately solving a different problem than the industries that precede it. In biopharmaceutical production, cells produce the end product, but for cultivated meat, cells are the end product. If a producer needs to extract a drug from the cell culture, it may be easier with everything loosely floating in a liquid, rather than trapped in a dense matrix of cells.

The problem with adherent systems is that it’s difficult to find comparable examples. Operationalizing and scaling up a new bioreactor system is massively more challenging when nothing is known about how cells might behave in the new environment.

Cell Size

One avenue to scalability that’s unique to cultivated meat is increasing the size of each cell. Even after the number of cells in a batch is set in the proliferation phase, more mass can be added during the differentiation phase. Fat cells in particular vary by orders of magnitude in volume and could likely be grown much larger than seen in nature. Fat will likely be critical to hybrid products, since fat carries many of the important flavor compounds we associate with meat.

Humbird’s TEM underweights the potential impact of cell size, since it only considers the proliferation phase. His rationale is likely that if cell slurry can’t be produced at comparable costs to meat, then neither can fully differentiated tissue. However, if significant mass is gained during the differentiation phase, this could be a critical aspect of the total cost competitiveness of the product. Since differentiation processes differ across companies, the possibility is difficult to model.

Genetic Engineering 

Until recently, one might have thought that any sort of explicit genetic tinkering would have been a regulatory non-starter. This would make it much more difficult to achieve the metabolic efficiencies and other desirable cell traits that Humbird views as necessary (but insufficient) for cost-competitive cultivated meat. Fortunately, UPSIDE Foods’ recent FDA approval included the use of genetic engineering to make cells overexpress a particularly helpful protein. This is a positive sign for the industry. It frees up companies to pursue a host of research directions to make cells more efficient and more suitable for large-scale cell culture.

Amino Acids

As I’ve discussed, amino acids could be a long-term cost bottleneck. Currently, cell culture media is made by combining each individual amino acid one by one. But this isn’t how animals get amino acids in nature. Rather, animals eat food, and then break down proteins into the constituent amino acids via digestion.

Technologies that mimic this process could help lower the cost of cultivated meat in the long term. Humbird explicitly mentions soy hydrolysates as a potentially promising solution. With this technology, soy (the main source of protein for livestock) is broken down in a chemical reaction with water and added to media as a single composite ingredient. This is a novel technology with its own host of challenges, but with a longer time horizon for cultivated meat, it isn’t out of the picture (just as our highly optimized system of growing corn and soy for animal feed developed alongside industrial animal agriculture).

Another avenue to decrease the cost of amino acids is to decrease the percentage of them in the final product by focusing on fat. Since fat cells have more lipids and fewer amino acids than muscle cells, they could be cheaper to produce at large scales. This could be an important factor in the cost competitiveness of hybrid products, which can primarily get amino acids from plant-based components.

A Bet Worth Making

When the Good Food Institute said that government support would be necessary for the success of cultivated meat, The Counter treated it as a “concession” from the industry. However, looking at the critical role world governments played in the development of solar, I see it differently. The Biden administration recently allocated $550 billion to clean energy and climate programs, much of which will be added to the $1.3 trillion already invested in solar energy last decade. These expenditures signal society’s belief that the future of the planet is worth enormous investment.

Cultivated meat can follow a similar path, if we as a society decide that it’s similarly worthwhile. This will take longer and cost more than originally thought, and in the meantime, companies will likely compromise with hybrid products. It will require buy-in from top institutions, entrepreneurs, and most importantly governments. But once one accepts longer time scales for The Dream of cultivated meat, it might seem less unreasonable to bank on massive engineering accomplishments, the concurrent development of multiple supporting industries, and a restructuring of the global agricultural supply chain. When you’re talking decades, paradigm-shifting advances are possible.

A longer time scale will come as a disappointment to those who bought into the early, more optimistic projections for cultured meat. But in the fight for animal welfare, there is no silver bullet. Plant-based meat has shown tremendous promise and has the potential to undercut conventional meat on price in the longer term, but it’s unclear whether consumer demand will be there. Traditional advocacy has had some major wins (a third of egg-laying hens in the U.S. are now cage-free), but social change is hard to steer and even more difficult to predict. Given how little we can truly know about how the future will play out, I believe we need to maintain a diversified portfolio of bets across cultivated, plant-based, and traditional advocacy and social change.

The eventual success of solar wasn’t augured by carefully constructed models of possible future outcomes. Rather, the decision to double down during one of solar’s pessimistic periods would have been an expression of determination that the future isn’t set in stone, but is shaped by idealists who take bold action in the face of uncertainty. When the stakes are as high as they are with cultivated meat, I think it’s worth making that bet.

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Robert Yaman previously led operations at the cultivated meat company Mission Barns, and now leads Innovate Animal Ag, a nonprofit that supports the development and adoption of new technologies that improve animal health and welfare. He blogs at robertyaman.com and can be followed on Twitter.