Reza Ovissipour wants to make meat. Earth’s population is projected to reach 10 billion people by 2050. To feed everyone, “we have to increase our food production by one hundred percent and our meat production by seventy percent,” says Ovissipour, a food scientist at Virginia Tech. “Our current agricultural practices are not sustainable enough to provide that much food for people, so we need to find other ways to produce food.”
In September 2021, as part of efforts to address this challenge, the United States Department of Agriculture (USDA) awarded a five-year, $10 million grant to a multi-institute team of researchers, including Ovissipour, for the creation of a National Institute of Cellular Agriculture—the first ever investment by the USDA in lab-based meat production. The project, led by David Kaplan of Tufts University, will focus on scaling up cultured meat, which has less of an environmental impact than traditional meat, to feed Earth’s growing population.
In addition to helping humanity cope with future food shortages, Ovissipour says, cellular agriculture—the generation of products from cells in a lab or industrial setting rather than from whole animals—could have other benefits, such as supplying alternative food for aquaculture (currently, large farmed fish eat other fish, either caught or farmed); reducing the risk of pathogens, such as Salmonella, found in livestock and farmed seafood; and improving the traceability of food products.
In 2020, financial investment in the area passed $350 million—double the investment of all previous years combined.
Lab meat’s potential has already attracted significant interest from the biotech industry. Already, more than 70 cultivated meat startups exist worldwide, according to a 2020 state of the industry report from the Good Food Institute, a nonprofit that awards grants to researchers working on so-called alternative proteins and tracks progress in the industry.
And although there are substantial challenges in scaling up the technology and getting products to the market, it’s a rapidly growing sector: in 2020, financial investment in the area passed $350 million—double the investment of all previous years combined. And in December of that year, the world saw its first regulatory approval of the public sale of cultured meat, from the Singapore Food Agency (SFA), for chicken made by Eat Just, Inc., a San Francisco–based food company.
“Hopefully, that is the first of many, and we’ll be starting to see more of it,” says Claire Bomkamp, a scientist specializing in cultivated seafood at the Good Food Institute, “not just one or two restaurants, but regular people being able to find this stuff.”
The right cells
At a small scale, the process of cultivating meat shares its basic premise with regular cell culture in the lab. Choosing the right cells is important: some labs grow muscle cells derived directly from animals, while others prefer to start with stem cells that can differentiate into muscle or fat cells in vitro. Lucy Lee, an expert in fish cell culture at the University of the Fraser Valley in Canada, explains that the selection step is critical. The choice of cell line will determine the taste of the cultured meat as well as the technical parameters—time, temperature, and nutrients, for instance—needed to grow the cells on scaffolds or other structures to produce a 3D product, says Lee, who advised the California-based company Finless Foods on the development of a tuna muscle cell line.
Researchers also have to look for cells that can grow continuously. To make any cultured meat sustainable, a cell line ought to grow and maintain particular features—including cells’ shape, size, and ability to differentiate into different types—forever, so that researchers don’t have to keep starting over. This works for some cell lines: Lee’s group has been growing the same line of muscle cells from killifish—a small fish that’s not very good to eat but is great for research due to its short lifespan—since at least 2014. But other organisms have proved trickier. “I haven’t been able to grow shellfish cell cultures continuously,” she says. “Although I can get them to grow a long time, they sort of die off after about nine, ten passages”—one passage being a culturing step where cell samples are harvested and transferred to a new culture dish with fresh media. “That’s one big struggle that people are still working on.”
To address this issue, UK-based cultured meat biotech HigherSteaks Ltd is focusing on induced pluripotent stem cells (iPSCs), which, like other stem cells, have no problem dividing indefinitely. These cells “have huge growth potential,” explains Ruth Faram, the company’s chief scientific officer.
Using iPSCs has other advantages for cell agriculture, too: it allows researchers to produce multiple tissue types from a single cell line. “When you think about what meat is, it’s not just muscle, it’s not just fat, it’s a concoction of cells,” Faram says, adding that a single iPSC can be nudged with growth factors and molecular signals to become either muscle or fat. At the moment, she says, her team is most excited about an iPSC line developed in-house by reprogramming a sample collected noninvasively from a pig. The work at HigherSteaks is still in the development phase, but Faram says that the group’s cell line differentiates well into muscle and fat.
It’s unclear how widespread the iPSC approach is more generally, as companies don’t typically share this information publicly. In a summary from the Good Food Institute curating 47 commercially available or in-development cell lines appropriate for use in cellular agriculture, however, only a handful are classified as stem cell–like, while the rest are proliferative cells committed to a cell fate such as muscle or fat.
Meating market demand
Making cultivated meat viable on a commercial scale carries challenges beyond those associated with regular cell culture. Typically, cells in culture grow affixed to flat dishes, but in order to get to the volume needed for eventual commercialization, the goal is to use bioreactors, vessels with a capacity of 200,000 liters or more in which the cells grow in liquid suspension containing nutrients and growth factors, and often small beads, or microcarriers, made of gelatin, glass, or plastic that the cells can adhere to.
Scaling up comes with an accompanying problem: cost. “In my lab, I can produce, in a test tube, maybe a gram of cells,” explains Lee, who is currently working with a rainbow trout muscle cell line. (She says that she has tasted it and “it does taste like fish.”) But “that’s a tiny, tiny little sample. . . . When you add up the culture ingredients, the time, the supplies, it’s about five hundred dollars a gram. So who’s going to buy rainbow trout for five hundred dollars a gram?”
One of the most expensive parts of culturing cells in the lab concerns the choice of growth media, which typically contain nutrients, vitamins, minerals, growth factors, and proteins. The source of many of these components in traditional cell culture media is fetal bovine serum. Lexi Duscher, a molecular biologist who works with Ovissipour at Virginia Tech, explains that this serum costs up to $800 per liter and also comes with other issues, including variability and ethical questions about how it’s sourced.
According to Bomkamp, there are some serum-free options out there that could avoid the variability and ethical issues. But “the serum-free formulations that exist are [mostly] coming from the pharma industry” for growing cell lines while controlling as many variables as possible, she adds. “They’re not produced with food-compatible cost structures in mind, so of course they’re expensive.”
Even with the best serum-free media, though, most cells won’t grow as quickly as those cultured with serum, because the level of nutrients, vitamins, and minerals is lower. This in itself can bump up costs: “For cultured meat . . . the longer it takes for the cells to divide, the longer the process will take, the more money it will cost, and then ultimately the end product will be much more expensive,” says Martina Miotto, chief scientific officer and cofounder of CellulaREvolution, a UK-based biotech working on improving cell culture for cultivated meat and biomedical applications. Finding cells that grow well in serum-free conditions is essential, Miotto explains, which reinforces the need to choose starting cells carefully.
The team at CellulaREvolution is working on a bioreactor that will allow simultaneous harvest of cells while proliferation continues, and can refresh media and remove waste constantly, Miotto says—a strategy that saves resources while boosting productivity. The company also coats its microcarriers with a peptide molecule from which cells can detach when they’ve matured, which saves space and also seems to help cells grow in serum-free media. The team has trialed the bioreactor at a small scale, Miotto says, and is currently developing larger prototypes to test. “There are challenges from beginning to end,” she tells The Scientist, so it’s important to carefully consider which aspects of traditional cell culture will work at commercial scale “to make cultured meat something viable.”
Regulatory and consumer approval
Whatever way the field gets to the larger volumes they’re aiming for, Bomkamp says, “we’re really at sort of what feels like an inflection point” in the cultivated meat industry. One of the most exciting developments, she explains, is the approval in Singapore of cultured chicken made by Eat Just, which creates and distributes plant-based eggs in the US. The company launched the chicken at the private members club 1880 in Singapore but recently discontinued the arrangement and switched instead to supplying the Cantonese restaurant Madame Fan and home delivery service foodpanda. Vítor Espírito Santo, director of cellular agriculture at Eat Just, says that about 700 customers have tried the meat since its approval in 2020, but that the demand is much greater. “Our main focus is being able to produce sufficient amounts to feed the markets in Singapore,” he says. “We wish we were producing more than where we are now.”
Public perception could also play a role in the success of these products.
He adds, though, that the green light in Singapore provides “a clear path” toward approval from other regulatory agencies, including the United States Food and Drug Administration. The regulatory process will vary from country to country depending on existing regulation. For instance, according to a summary from the Good Food Institute, in Japan, cultivated meat already complies with current rules, so the government is focusing on integrating those regulations with guidelines to foster consumer acceptance. Researchers in the UK and US, meanwhile, are working under the assumption that approval will require being transparent with regulators about how products were made, and thus are keeping careful track of “every single compound that these cells have ever interacted with any point in the life cycle,” says Faram.
Public perception could also play a role in the success of these products, notes Christopher Bryant, a social scientist who consults for alternative protein companies. “There’s a variety of views towards cultured meat,” he says, “ranging from people who are very excited about it and techno optimists who like to be innovators and the first amongst their friends to try new products and new technologies, right through to the people at the other end who maybe have a worldview whereby natural things are good and deviations from nature are somehow bad in themselves.” Bryant and his colleagues have shown that in focus groups, it’s common for people hearing about cultivated meat for the first time to be unsettled by the idea, but that this changes with more exposure to the idea. “Throughout the course of the conversation, basically, they have more time with the concept and learn about the benefits and are a bit more familiar with it, and by the end tend to be a bit more on the fence than then they were at the start.”
He recommends that cultivated meat companies highlight in their communications the full range of benefits, from what he calls the more obvious—needing to kill fewer animals—to the less obvious, such as avoidance of antibiotics during production and lowered risk of common foodborne diseases. “Those things are probably more important to consumers, but not quite so obvious.”
One thing that is clear is that the industry alone isn’t going to be able to fulfill worldwide food needs any time soon. “We need more food in general, so we’re not necessarily trying to take away from fisheries, aquaculture, or farmers,” says Duscher. “We just want to add something additional that’s just as healthy, safe, effective, tasty, to feed this growing population in a hopefully sustainable manner.”
Correction (February 14): The caption for the second image in this article has been updated to clarify that the pictured bioreactor was constructed in the US, not Singapore. Also, the story has been updated to indicate that Eat Just’s chicken is no longer available at 1880, but is available through other venues. The Scientist regrets the errors.
This article was featured in February 2022, Issue 2 of the digest