Inside the effort to cut the cost of cultivated meat

In early 2018, the California-based start-up Memphis Meats, now called Upside Foods, was celebrating progress in its quest to make meat from animal cells grown in a bioreactor—a product that many firms call cultivated meat.

Cultivated meat companies hope to do away with slaughterhouses and to sustainably feed the world’s growing population by slashing the amounts of fossil fuel, water, and land required to produce meat. Traditional food companies trying to lower their own environmental footprints are very interested.

Over the previous year, Memphis Meats had served lab-grown chicken to a group of taste testers and raised over $17 million in funding from Cargill, Tyson Foods, and other investors.

But at the time, Memphis Meats’ chicken was highly expensive to produce. One of the biggest issues was the cost of growth media: the mix of sugar, proteins, and other nutrients that feed the cells in a bioreactor.

So that summer, the company hired Kevin Kayser, a veteran of the life sciences industry. He had previously led a division of MilliporeSigma that sells growth media to pharmaceutical companies, which use animal cells to produce drugs.

“One of the reasons I was hired was raw material inputs,” says Kayser, who was recently promoted to chief scientific officer at Upside. “When I first started, it was top of the list.”

Over the past 5 years, Upside and other cultivated meat companies have significantly lowered the cost of growth media, but they will need to lower it even further if they hope to compete with conventional meat producers.

The cost-cutting process begins with firms reducing their use of proteins, the most expensive component of most growth media; the price of those proteins will also have to come down. Another critical step will be moving away from media made with a mix of individually produced amino acids and instead providing those nutrients all together through processed crops.

Today, cultivated meat companies’ production is minuscule. Kayser predicts that cultivated meat companies won’t demand large quantities of low-cost growth media for years. But he says it’s important to build the supply chain before that happens. “You have to work on it now in order to be ready.”

Steak without cows

For decades, scientists dreamed of growing animal cells in labs as a way to avoid the many downsides of livestock farming. But the concept was confined to science fiction until 2013, when the Dutch scientist Mark Post produced a hamburger from lab-grown beef cells—at a cost of over $300,000.

Soon after, a handful of start-ups launched to commercialize the technology. California-based Good Meat secured permission to sell cultivated chicken in Singapore in 2020. And this year, Good Meat and Upside started selling cultivated chicken in the US.

At Bar Crenn in San Francisco, a six-course meal that includes Upside’s chicken—fried in a recado negro–infused tempura batter and accompanied with burnt chili aioli—costs $150. A tasting menu featuring Good Meat’s chicken marinated with anticucho sauce and served with potatoes and ají amarillo chimichurri at China Chilcano in Washington, DC, will set you back $70. Meanwhile, the tab for grabbing a Good Meat chicken lunch at Huber’s Bistro in Singapore is under $15.

In all, more than a dozen companies are operating pilot-scale facilities, the largest of which are capable of producing dozens of metric tons of cultivated meat per year, according to a recent report from the Good Food Institute, a nonprofit that advocates for the cultivated meat industry.

In contrast, the Food and Agriculture Organization (FAO) of the United Nations estimates that conventional slaughterhouses produced 328 million metric tons (t) of meat in 2020.

But producing meat at that scale takes an enormous toll on the planet. Animal agriculture accounted for 17% of humanity’s greenhouse gas emissions in 2018, according to the FAO. The meat industry also pollutes the oceans, fouls the air, and reduces the efficacy of life-saving antibiotics.

Cultivated meat companies claim their process will reduce meat’s environmental impact, and they’re eager to scale up. Upside recently announced plans for a facility near Chicago that it hopes will make 13,000 t of meat per year, and Good Meat is planning a similar-sized facility in the US.

But even with large facilities, cultivated meat isn’t likely to be able to compete with conventional meat at the grocery store unless the cost of growth media falls significantly, according to an economic analysis published by a team at the University of California, Davis (Biotechnol. Bioeng. 2022, DOI: 10.1002/bit/28324) .

Growth media for medical research or drug manufacturing can cost hundreds of dollars per liter, according to David Block, a UC Davis cultivated meat researcher who contributed to the analysis. “To make cultivated meat commercially viable, that number is probably going to have to be $1 per liter or less—so orders of magnitude lower,” he said at a conference in September.

Less is more

In addition to basic nutrients like amino acids, many animal cells require specialized proteins to help them proliferate. Those proteins can be extremely costly, so cultivated meat researchers are trying to minimize the amount required or find cheaper alternatives.

Pharmaceutical researchers often supply all the proteins that cells need through fetal bovine serum (FBS), an expensive product made from cow’s blood. Cultivated meat companies want to avoid using FBS because it is both costly and an animal-derived product, says Kate Krueger, president of the biotechnology research firm Helikon Consulting.

“Transitioning any kind of product from a research scale to a production scale is going to have to account for the high-value proteins in fetal bovine serum,” Krueger says.

FBS works well because it’s loaded with dozens of helpful proteins. Albumin is a Swiss Army knife of a protein, with functions such as binding to beneficial molecules and making them available for cells. Transferrin helps cells take in iron. Signaling molecules like insulin and growth factors like basic fibroblast growth factor (FGF2) regulate growth and other cell functions.

Many companies are replacing proteins in FBS with recombinant versions made using fermentation. But recombinant proteins are also expensive, so using fewer of them is critical to reducing costs.

In 2020, the Northwestern University stem cell researcher Paul Burridge began making an FBS-free medium using only a few recombinant proteins. Researchers in David Kaplan’s cultivated meat lab at Tufts University adapted the medium to grow cow cells. But the Tufts medium still contained recombinant albumin, which rendered it too expensive for large-scale production of cultivated meat.

Some researchers say that plant versions of albumin or transferrin would be cheaper to use than recombinant proteins, For example, last year, Kaplan’s team improved on its medium by replacing recombinant albumin with a substitute from rapeseed, which is grown to make cooking oil. Andrew Stout, then a Tufts graduate student who led the project, produced the protein from agricultural waste using basic extraction methods. “He wanted to take the simplest approach,” Kaplan says. “Keep it low cost. Use available sources.”

While this low-cost replacement doesn’t work for all cells, Kaplan says he’s optimistic about switching to plant proteins. “We’ve made so much progress,” he says.

BlueNalu, a cultivated seafood company based in San Diego, is already using plant-based proteins to eliminate the use of albumin, insulin, and transferrin to grow its tuna cells, according to Lauran Madden, the firm’s chief technology officer.

The switch has helped reduce the cost of BlueNalu’s growth media by an order of magnitude over the past 5 years. Madden says the firm will likely have to bring costs down by another order of magnitude to make its tuna cost competitive.

In addition to reducing the cost of materials used to grow their cells, BlueNalu and Upside are trying to develop cells that will thrive in leaner growth media.

When Upside scientists select a cell line for cultivated meat, Kayser says, they look for cells that reproduce rapidly or grow at high density. But they also try to pick cells that grow in media with fewer proteins.

“Let’s build a process and then select for a cell line that does what we want it to do,” Kayser says. “It’s going to be a lot more up-front work, but in the end it’s going to translate to better cost.”

Upside still uses albumin sourced from cows to grow the whole-cut chicken breasts it began selling at a restaurant in San Francisco this year. But Kayser says the cell lines Upside uses to make ground chicken, the product for the planned large-scale facility, don’t need any albumin, transferrin, or insulin. The company is also hoping to eliminate the need for albumin in the whole-cut production process.

Growing growth factors

Growth factors, such as FGF2, are the most expensive proteins—and some of the most challenging to remove from growth media. While a bench scientist today might pay a few hundred dollars for a gram of insulin or transferrin, some growth factors can cost millions of dollars per gram, according to a 2020 analysis from the Good Food Institute.

Though growth factors are typically used in quantities of just nanograms per liter of medium, they still need to be cheaper, Kreuger says. These proteins are currently made in small volumes via fermentation for the drug industry, and simply scaling up may be enough to make them affordable for cultivated meat. “That technology is very well known,” she says. “The main issue is how to do it at scale.”

Laurus Bio, an India-based supplier of growth factors to the drug industry, already plans to boost production for cultivated meat. The company says economies of scale alone will reduce costs by 35%, and it hopes to cut them further by simplifying postfermentation processing steps.

But CEO Rajesh Krishnamurthy says Laurus Bio won’t start using bigger bioreactors to make growth factors until customers are ready to place large orders. “Most of the cultivated meat companies have not reached a scale that may require hundreds of kilograms of these materials,” he says. “Unless we have visibility into that demand, we cannot invest.”

Other companies think new technologies are a more effective way to reduce costs. The Spanish start-up Cocoon Bioscience hopes to produce growth factors using cabbage moths: while they are in their cocoons, they are injected with a modified virus that induces them to produce a target protein.

Unlike fermentation processes, using moths to produce growth factors doesn’t require big investments in bioreactors, CEO Joshua Robinson says. “We don’t have that, because our bioreactors are the insects.” Cocoon Bioscience hopes to open a facility next year that will be able to make 10–15 kg of growth factors per year.

BioBetter, which spun out of Oded Shoseyov’s protein engineering lab at the Hebrew University of Jerusalem, aims to make growth factors in genetically modified tobacco plants.

Using tobacco avoids the need for expensive bioreactors and simplifies extraction and purification of proteins, BioBetter says. The firm is already growing tobacco plants that express FGF2. In September, it opened a pilot facility that can produce a few hundred grams of growth factors per year.

“Tobacco in particular is an amazing plant,” Shoseyov says. “It can make really complex proteins in a cost-effective manner.”

Given the progress, says Elliot Swartz, the principal scientist working on cultivated meat for the Good Food Institute, it’s only a matter of time before growth factors and other key proteins are affordable enough for cultivated meat producers.

He is more concerned about the cost of basic nutrients. “Amino acids are next on the chopping block,” he says.

The new feedlot

While it’s possible to eliminate certain proteins from growth media, cells can’t live without basic nutrients, including salt, sugars, and amino acids. These are much cheaper than recombinant proteins but are needed in large quantities. The costs add up, particularly for amino acids.

Each amino acid in a typical growth medium is produced separately. Some amino acids, such as lysine, are already produced cheaply via fermentation for the animal feed industry. Others, such as arginine, aren’t used as widely.

Scaling them up could lower costs, but not by enough, Swartz says. That’s in line with an influential analysis published in 2020 by the chemical engineer David Humbird that concluded individual production of all the amino acids needed for growth media is not likely to ever be cheap enough for cultivated meat companies.

“That means you can’t rely on the existing industry,” Swartz says. “You have to start up a whole new supply chain.”

Moreover, producing purified, pharmaceutical-grade versions of every ingredient in growth media separately could make cultivated meat’s carbon emissions higher than those of conventional meat, according to a report from UC Davis that hasn’t been peer-reviewed.

Swartz expects cultivated meat companies to eventually get amino acids from the same place they are starting to get replacements for albumin: plants. Specifically, he points to hydrolysates, which are made by treating plant proteins with heat and acid to break them down into a soup of multiple amino acids.

Providing all the amino acids that cells need in one fell swoop with a hydrolysate would be much more efficient than producing each one individually. But Swartz says researchers are still investigating how to ensure that the amino acids from hydrolysates match up with the ones that cells need. In addition, companies have to make sure that unwanted molecules in a hydrolysate don’t slow cell growth.

“It’s a hard research and development challenge,” Swartz says. “It’s not just simply swapping in the amino acids.”

Feeding animal cells with hydrolysates made from rapeseed, soy, cottonseed, and other crops would move the cultivated meat industry one step closer to the feedlots it is trying to replace, where animals mostly eat grains supplemented with amino acids and vitamins.

Indeed, cultivated meat companies can learn a lot from farmers, says Susanne Wiegel, head of the alternative protein program at the Dutch animal feed company Nutreco. “Feeding cells isn’t that different from feeding animals,” Wiegel says.

Nutreco has invested in BlueNalu and Mosa Meat, the start-up founded by Mark Post after he introduced his $300,000 burger. Nutreco helped both firms transition from pharmaceutical- to food-grade amino acids. Mosa Meat estimated that the change would make its production process 100 times cheaper without affecting yield.

Wiegel says amino acids from crop-derived hydrosylates are the next step. “We need to look at how animal feed is done,” Wiegel said at an event hosted by the Good Food Institute. “The majority of nutrients are provided through agricultural crops.”

While developing cheaper growth media is still one of the cultivated meat industry’s priorities, the progress so far means it’s no longer the top concern. A bigger issue now is securing financing for huge bioreactors and transferring pilot-scale processes into those larger plants.

Some companies are already encountering problems as they scale up. The engineering firm building bioreactors for Good Meat has stopped working on the project and is now suing Good Meat for unpaid bills, according to court documents.

Upside also has a huge challenge ahead. Its current cultivation happens in vessels ranging from 1 L bottles to 2,000 L tanks. At its recently announced plant, the company hopes to eventually use 100,000 L bioreactors, bigger than any ever used to grow animal cells.

Kayser says that Upside is ready to move to commercial scale but that it’s unclear if the firm will have to adjust its growth media to work in a bioreactor of that size.

“When you start talking about 100,000 L or greater, I don’t know if that’s going to take any change in the media,” Kayser says. “We haven’t gotten to that level.”