Cultured meat
Cultured meat, also known as cultivated meat among other names, is a form of cellular agriculture where meat is produced by culturing animal cells in vitro.[1][2][3] Cultured meat is produced using tissue engineering techniques pioneered in regenerative medicine.[4] Jason Matheny popularized the concept in the early 2000s after he co-authored a paper[5] on cultured meat production and created New Harvest, the world's first non-profit organization dedicated to in-vitro meat research.[6] Cultured meat has the potential to address the environmental impact of meat production, animal welfare, food security and human health,[7][8][9][10][11][12][13] in addition to its potential mitigation of climate change.[3]
In 2013, Mark Post created a hamburger patty made from tissue grown outside of an animal. Since then, other cultured meat prototypes have gained media attention: SuperMeat opened a farm-to-fork restaurant, called "The Chicken",[14] in Tel Aviv to test consumer reaction to its "Chicken" burger,[15] while the "world's first commercial sale of cell-cultured meat" occurred in December 2020 at Singapore restaurant 1880, where cultured meat manufactured by United States firm Eat Just was sold.[16]
While most efforts focus on common meats such as pork, beef, and chicken which constitute the bulk of consumption in developed countries,[17] companies such as Orbillion Bio focused on high-end or unusual meats including elk, lamb, bison, and Wagyu beef.[18] Avant Meats brought cultured grouper to market in 2021,[19] while other companies have pursued different species of fish and other seafood.[20]
The production process is constantly evolving, driven by companies and research institutions.[21] The applications for cultured meat led to ethical,[22] health, environmental, cultural, and economic discussions.[23] Data published by the non-governmental organization Good Food Institute found that in 2021 cultivated meat companies attracted $140 million in Europe.[3] Cultured meat is mass-produced in Israel.[24] The first restaurant to serve cultured meat opened in Singapore in 2021.[25] However, cultured meat is not yet widely available.
Nomenclature[edit]
Besides cultured meat, the terms healthy meat,[26] slaughter-free meat,[27] in vitro meat, vat-grown meat,[28] lab-grown meat,[29] cell-based meat,[30] clean meat,[31] cultivated meat[32][33] and synthetic meat[34] have been used to describe the product.[35] Although it has multiple definitions, artificial meat is occasionally used.[36]
Between 2016 and 2019, clean meat gained traction. The Good Food Institute (GFI) coined the term in 2016,[37] and in late 2018, the institute published research claiming that use of clean better reflected the production process and benefits.[38][39] By 2018 it had surpassed cultured and "in vitro" in media mentions and Google searches.[40] Some industry stakeholders felt that the term unnecessarily tarnished conventional meat producers, continuing to prefer cell-based meat as a neutral alternative.[41][42]
In September 2019, GFI announced new research which found that the term cultivated meat is sufficiently descriptive and differentiating, possesses a high degree of neutrality, and ranks highly for consumer appeal.[32][43] A September 2021 poll indicated that the majority of industry CEOs have a preference for cultivated meat, with 75 percent of 44 companies preferring it.[44]
History[edit]
Initial research[edit]
The theoretical possibility of growing meat in an industrial setting has long been of interest. In a 1931 essay published by various periodicals and later included in his work Thoughts and Adventures, British statesman Winston Churchill wrote: "We shall escape the absurdity of growing a whole chicken to eat the breast or wing, by growing these parts separately under a suitable medium."[45]
In the 1950s, Dutch researcher Willem van Eelen independently came up with the idea for cultured meat. As a prisoner of war during the Second World War, Van Eelen suffered from starvation, leaving him passionate about food production and food security.[46] He attended a university lecture discussing the prospects of preserved meat.[47] The earlier discovery of cell lines provided the basis for the idea. In vitro cultivation of muscle fibers was first performed successfully in 1971 when pathologist Russel Ross cultured guinea-pig aorta. In 1991, Jon F. Vein secured patent US 6835390 for the production of tissue-engineered meat for human consumption, wherein muscle and fat would be grown in an integrated fashion to create food products.[48]
In 2001, dermatologist Wiete Westerhof along with van Eelen and businessperson Willem van Kooten announced that they had filed for a worldwide patent on a process to produce cultured meat.[49] The process employed a matrix of collagen seeded with muscle cells bathed in a nutritious solution and induced to divide.[50] That same year, NASA began conducting cultured meat experiments, with the intent of allowing astronauts to grow meat instead of transporting it. In partnership with Morris Benjaminson, they cultivated goldfish and turkey.[51] In 2003, Oron Catts and Ionat Zurr exhibited a few centimeters of "steak", grown from frog stem cells, which they cooked and ate. The goal was to start a conversation surrounding the ethics of cultured meat—"was it ever alive?", "was it ever killed?", "is it in any way disrespectful to an animal to throw it away?"[52]
In the early 2000s, American public health student Jason Matheny traveled to India and visited a factory chicken farm. He was appalled by the implications of this system. Matheny later teamed up with three scientists involved in NASA's efforts. In 2004, Matheny founded New Harvest to encourage development by funding research. In 2005, the four published the first peer-reviewed literature on the subject.[53]
In May 2008, PETA offered a $1 million prize to the first company to bring cultured chicken meat to consumers by 2012.[54] The contestant was required to complete two tasks to earn the prize, namely to produce a cultured chicken meat product that was indistinguishable from real chicken and produce the product in large enough quantities to be competitively sold in at least 10 states. The contest was later extended until 4 March 2014. The deadline eventually expired without a winner.[55]
The Dutch government has invested $4 million into experiments regarding cultured meat.[56] The In Vitro Meat Consortium, a group formed by international researchers, held the first international conference hosted by the Norwegian Food Research Institute in April 2008.[57] Time magazine declared cultured meat production to be one of the 50 breakthrough ideas of 2009.[58] In November 2009, scientists from the Netherlands announced they had managed to grow meat using cells from a live pig.[59]
First public trial[edit]
The first cultured beef burger patty was created by Mark Post at Maastricht University in 2013.[60] It was made from over 20,000 thin strands of muscle tissue, cost over $325,000 and needed 2 years to produce.[61] The burger was tested on live television in London on 5 August 2013. It was cooked by chef Richard McGeown of Couch's Great House Restaurant, Polperro, Cornwall, and tasted by critics Hanni Rützler, a food researcher from the Future Food Studio, and Josh Schonwald. Rützler stated, "There is really a bite to it, there is quite some flavour with the browning. I know there is no fat in it so I didn't really know how juicy it would be, but there is quite some intense taste; it's close to meat, it's not that juicy, but the consistency is perfect. This is meat to me... It's really something to bite on and I think the look is quite similar." Rützler added that even in a blind trial she would have taken the product for meat rather than a soya copy.[62]
Process[edit]
Cell lines[edit]
Cellular agriculture requires cell lines, generally stem cells. Stem cells are undifferentiated cells which have the potential to become many or all of the required kinds of specialized cell types. Totipotent stem cells have the capacity to differentiate into all the different cell types found within the body. Pluripotent stem cells can mature into all cell types save those in the placenta, and multipotent stem cells can differentiate into several specialized cell types within one lineage. Unipotent stem cells can differentiate into one specific cell fate.[200]
Challenges[edit]
Growth factors[edit]
The culture media is an essential component of in vitro cultivation. It is responsible for providing the macromolecules, nutrients and growth factors necessary for cell proliferation. Sourcing growth factors is one of the most challenging tasks of cellular agriculture. Traditionally, it involves the use of fetal bovine serum (FBS) which is a blood product extracted from fetal cows. Besides the argument that its production is unethical, it also violates the notion that the cultured meat is produced independent of the use of animals. It is also the most costly constituent of cultured meat, priced at around $1000 per litre. Furthermore, chemical composition varies greatly depending on the animal, so it cannot be uniformly quantified chemically.[214] FBS is employed because it conveniently mimics the process of muscle development in vivo. The growth factors needed for tissue development are predominantly provided through an animal's bloodstream, and no other known fluid can single-handedly deliver all these components.[2]
The current alternative is to generate each growth factor individually using recombinant protein production. In this process, the genes coding for the specific factor are integrated into bacteria which are then fermented. Due to the added complexity of this process, it is particularly expensive.[2] Future Fields, a Canadian company focused on overcoming the economic and environmental costs of traditional growth media, is developing serum-free growth factors from fruit flies.[215]
The ideal medium would be chemically quantifiable and accessible to ensure simplicity in production, cheap and not dependent on animals.[50] It will most likely be derived from plants and while this may reduce the possibility of transmitting infectious agents, it may induce allergic reactions in some consumers.[216] Such culture sera may also require modifications specific to the cell line to which it is applied. Companies currently invested in developing effective plant based culture includes Multus Media and Biftek.[217][218]
The Good Food Institute (GFI) put out a report in 2019 in support of the concept that cell-based meat could be produced at the same cost as ground beef and in 2021 they commissioned a report from CE Delft on the Techno-Economic Analysis of cultivated meat.[219] Another approach is to subject the cell lines to a magnetic field, which stimulates the release of molecules that have regenerative, metabolic, anti-inflammatory and immunity-boosting properties, eliminating the need for serum.[220]
Surface area[edit]
A common challenge to bioreactors and scaffolds is developing system configurations that enable all cells to gain exposure to culture media while simultaneously optimizing spatial requirements. In the cell proliferation phase, prior to the introduction of the scaffold, many cell types need to be attached to a surface to support growth. As such, cells must be grown in confluent monolayers only one cell thick which necessitates a lot of surface area. This poses practical challenges on large scales. As such, systems may incorporate microcarriers—small spherical beads of glass or other compatible material that are suspended in the culture medium. Cells adhere to these microcarriers as they would to the sides of the bioreactor, which increases the amount of surface area.[221]
In the cell differentiation phase, the cells may be seeded to a scaffold and so do not require the use of microcarriers. However, in these instances, the density of the cells on the scaffold means that not all cells have an interface with culture media, leading to cell death and necrotic centers within the meat. When muscle is cultivated in vivo, this issue is circumvented as the extracellular matrix delivers nutrients into the muscle through blood vessels. As such, many emerging scaffolds aim to replicate such networks.[221]
Similarly, scaffolds must simulate many of the other characteristics of the extracellular matrix, most notably porosity, crystallinity, degradation, biocompatibility and functionality. Few materials that emulate all these characteristics have been identified, leading to the possibility of blending different materials with complementary properties.[202]
Research support[edit]
Cellular agriculture research does not have a significant basis of academic interest or funding streams.[23] Consequently, the majority of research has been undertaken and funded by independent institutions. This is incrementally changing as not for profits drive support and interest. Notably, New Harvest has a fellowship program to support graduate students and groups at various academic institutions.[222] Additionally, a growing number of governments are funding research in cellular agriculture. In August 2020, the Grant Management Services of the European Commission awarded a €2.5 million grant to ORF Genetics.[223] That same month, the Japanese Ministry of Economy, Trade and Industry granted Integriculture $2.2 million through their New Energy and Industrial Technology Development Organization.[224]
The European Union's Horizon 2020 R&D funding framework awarded a €2.7 million grant to a consortium led by BioTech Foods.[225] In 2021, the Spanish government granted €3.7 million for Biotech Foods to investigate the potential health benefits of cellular agriculture.[226] The National Science Foundation awarded a $3.55 million grant to a team of researchers at UC Davis for open-access cultured meat research.[227] Non-profits also drive support and interest in the field. Notably, New Harvest has a fellowship program to support the research of specific graduate students and groups at various academic institutions and the Good Food Institute funds open-access research through its Research Grant Program.
Consumer acceptance[edit]
Consumer acceptance of the product is critical.[228][229] A study looking at acceptance of cultured meat in China, India, and the US "found high levels of acceptance of clean meat in the three most populous countries worldwide."[230] Several potential factors of consumer acceptance of cultured meat have been identified. Healthiness, safety, nutritional characteristics, sustainability, taste, and lower price, are all contributing factors.[231] One study found that the use of highly technical language to explain cultured meat led to significantly more negative public attitude towards the concept.[232] Transparently communicating the science is important, but oversharing the wrong aspects of the product could draw unfavourable attention to safety concerns.[233] Thus one of the challenges in how cultivated meat is marketed is striking the balance between transparency of the science behind it, but communicating it in a way that it does not evoke resistance.[234] One study suggested that describing cultured meat in a way that emphasizes the final product rather than the production method was an effective way to improve acceptance.[235] The role of nomenclature is also crucial. Although the 'lab-grown meat' portrayal of cultivated meat is favoured by media, it has been opposed by industry leaders as it seeds an innately unnatural image of cultivated meat in consumer's perceptions.[236]
The use of standardized descriptions would improve future research about consumer acceptance of cultured meat. Current studies have often reported drastically different rates of acceptance, despite similar survey populations.[237] Lou Cooperhouse, CEO of BlueNalu, shared on the Red to Green Podcast that "cell-based" and "cell-cultured" were suitable terms to differentiate it from conventional meat whilst being clear about the process by which it was made.[238] There also exists a challenge in how to use these descriptions in labelling. For example, in the United States there is no overarching federal legislation that regulates how cultured meat should be labeled for the consumer. While traditional meat producers are attempting to prevent cultured meat companies from using the term "meat," cultured meat producers argue that the word is necessary for consumer acceptance.[239]
Global market acceptance has not been assessed. Studies are attempting to determine the current levels of consumer acceptance and identify methods to improve this value. Clear answers are not available, although one recent study reported that consumers were willing to pay a premium for cultured meat.[231][232][235][240][241][242][243] Low percentages of older adult populations have been reported to show acceptance for cultured meat. Green eating behavior, educational status, and food business, were cited as most important factors for this population.[242] There is also a lack of studies relating the methods of producing cultured meat with its taste for the consuming public.
Regulations[edit]
In 2020, Singapore became the first country in the world to approve cultured meat for sale. The Singapore Food Agency has published guidance on its requirements for the safety assessment of novel foods, including specific requirements on the information to be submitted for approval of cultivated meat products.[244]
In March 2023, Italy's Meloni government approved a draft bill banning the production and commercialization of cultivated meat for human and animal consumption;[245][246][247] this move, which the government said was intended to protect food heritage,[248] was criticized, including by scientists, for being at odds with global trends of openness and legalization,[249] as misguided,[250] and for possibily worsening climate change in Italy.[251] By October 2023, it was reported the Italian government had retired the draft bill,[252][253][254] and withdrew the Technical Regulation Information System notification, a procedure aimed at preventing the creation of barriers within the European Union's internal market, for the bill.[255] Francesco Lollobrigida, Italy's minister of agriculture, said that the withdrawal of the proposed anti-cultured meat bill Italy submitted to the European Union "is not a step back", which many speculated was because the government wanted to avoid a likely rejection by the European Commission. He added that the bill was not going to be retired and would move forward.[256] Italy became the first country to ban cultured meat in November 2023, when the government approved the bill.[257][258]
Regulatory matters must also be sorted out. Prior to being available for sale, the European Union, Australia, New Zealand, the United Kingdom, and Canada require approved novel food applications. Additionally, the European Union requires that cultured animal products and production must prove safety, by an approved company application, as of 1 January 2018.[259] In September 2020, the Food and Drug Administration (FDA) and the United States Department of Agriculture (USDA) have agreed to jointly regulate cultured meat. Under the agreement, the FDA oversees cell collection, cell banks, and cell growth and differentiation, while the USDA oversees the production and labeling of food products derived from the cells that are meant for human consumption.[260] Several U.S. states, such as Missouri, South Carolina, Texas, and Washington, have passed legislation limiting the use of the term meat on cultured meat packaging.[261][239] Lawmakers in Florida have also proposed a full ban of cultured meat, making it a criminal offense to sell.[262]
Differences from conventional meat[edit]
Health[edit]
Large-scale production of cultured meat may or may not require artificial growth hormones to be added to the culture for meat production.[263][264] As cultured meat is grown in a sterile environment, there is no need for antibiotics.[265] Today, the widespread use of antibiotics in conventional agriculture is the main driver of antibiotic resistance in humans.[266] According to the World Health Organization, antimicrobial resistance represents "an increasingly serious threat to global public health that requires action across all government sectors and society"[267] – predicting up to 10 million deaths annually by 2050.[268] Cultured meat could provide an effective solution to help mitigate this major risk to human health.
Researchers have suggested that omega-3 fatty acids could be added to cultured meat as a health bonus.[56] In a similar way, the omega-3 fatty acid content of conventional meat can be increased by altering what the animals are fed.[269] Research is currently underway in Spain to develop cultivated meat with healthier fats, which could reduce cholesterol and the risk of colon cancer typically associated with red meat consumption.[270] An issue of Time magazine suggested that the cell-cultured process may also decrease exposure of the meat to bacteria and disease.[57]
Due to the strictly controlled and predictable environment, cultured meat production has been compared to vertical farming. Some of its proponents have predicted that it will have similar benefits in terms of reducing exposure to dangerous chemicals like pesticides and fungicides, severe injuries, and wildlife.[271] There is also a lack of research on the comparison on the health effects of production cultured meat with the industrial meat or the biologic organic meat ways of production.
Artificiality[edit]
Although cultured meat consists of animal muscle cells, fat and support cells, as well as blood vessels,[272] that are the same as in traditional meat, some consumers may find the high-tech production process unacceptable. Cultured meat has been described as fake or "Frankenmeat".[273] On the other hand, cultured meat can be produced without the artificial hormones, antibiotics, steroids, medicine, and GMOs commonly used in factory farmed meat and seafood, though not used on organic biologic production. If a cultured meat product is different in appearance, taste, smell, texture, or other factors, it may not be commercially competitive with conventionally produced meat. The lack of bone and cardiovascular system is a disadvantage for dishes where these parts make appreciable culinary contributions. The lack of bones and/or blood may make many traditional meat preparations, such as buffalo wings, more palatable to some people. Furthermore, blood and bones could potentially be cultured in the future.[274][275][276]
Continuing development[edit]
Education[edit]
In 2015, Maastricht University hosted the first International Conference on Cultured Meat.[315] New Harvest[316]—a 501(c)(3) research institute—as well as The Good Food Institute[317] host annual conferences to convene industry leaders, scientists, investors, and potential collaborators. The two organizations also fund public research and produce educational content. Organizations such as the Cellular Agriculture Society, Cellular Agriculture Canada, Cellular Agriculture France, Cellular Agriculture Australia and Cellular Agriculture New Zealand were founded to advocate for cultured meat in their respective countries. Publications such as Cell Agri and the Protein Report have also emerged in order to provide updates concerning the technology and business within the field.
Research[edit]
Research continues on many fronts, including entomoculture, interactome maps of cardiac tissue,[318] substrate design,[318] scaffold design,[318] nutritional profile,[318] reaction kinetics, transport phenomena, mass transfer limitations and metabolic stoichiometric requirements,[318] and bioprinting process.[318]
Accelerators and incubators[edit]
Multiple venture capital firms and accelerator/incubator programs focus on assisting cultured technology startups, or plant-based protein companies in general. The Big Idea Ventures (BIV) Venture Capital firm launched their New Protein Fund to invest in emerging cell and plant-based food companies in New York and Singapore. They invested in MeliBio, Actual Veggies, Biftek.co, Orbillion Bio, Yoconut, Evo, WildFor and Novel Farms.[319] Indie Bio is a biology oriented accelerator program that has invested in Memphis Meats, Geltor, New Age Meats and Finless Foods.[320]
Related processes[edit]
Fermentation[edit]
Acellular agriculture is producing animal products synthesized from non-living material. Such products include milk, honey, eggs, cheese, and gelatin which are made of various proteins rather than cells. These proteins must be fermented much like in recombinant protein production, alcohol brewing and the generation of many plant-based products like tofu, tempeh and sauerkraut.[331]
Proteins are coded for by specific genes, the genes coding for the protein of interest are synthesized into a plasmid—a closed loop of double helical genetic information. This plasmid, called recombinant DNA, is then inserted into a bacterial specimen. For this to happen, the bacteria needs to be competent (i.e. able to accept foreign, extracellular DNA) and able to horizontally transfer genes (i.e. integrate the foreign genes into its own DNA). Horizontal gene transfer is significantly more challenging in eukaryotic organisms than prokaryotic organisms because the former have both a cell membrane and a nuclear membrane which the plasmid needs to penetrate whereas prokaryotic organisms only have a cell membrane. For this reason, prokaryotic bacteria are often favoured. In order to make such a bacteria temporarily competent, it can be exposed to a salt such as calcium chloride, which neutralizes the negative charges on the cell membrane's phosphate heads as well as the negative charges on the plasmid to prevent the two from repelling. The bacteria can incubate in warm water, opening large pores on the cell surface through which the plasmid can enter.[332]
Next, the bacteria is fermented in sugar, which encourages it to grow and duplicate. In the process it expresses its DNA as well as the transferred plasmid resulting in protein. Finally, the solution is purified to separate out the residual protein. This can be done by introducing an antibody raised against the protein of interest that will kill bacteria cells that do not contain the protein. Through centrifugation, the solution can be spun around an axis with sufficient force to separate solids from liquids. Alternatively it could be soaked in a buffered ionic solution that employs osmosis to leach the water from bacteria and kill them.[333]