Cultured meat

Cultured meats are animal flesh products made from extracted animal cells that are grown in bioreactors and harvested for consumption. Cells are taken from animals such as a chickens, cows, or tuna, and grown using scaffolding and/or self-organizing constructs in bioreactors.

The first known experiment investigating the potential of culturing meat in bioreactors was in 1912 at the Rockefeller Institute in New York City. The French surgeon and biologist Dr. Alexis Carrel began experimenting with embryonic heart muscle cells taken from a baby chick. Carrel was able to make the cells live thirty-four years (1946) until a scientist working in his lab forgot to feed the cultured cells. The cells were able to survive outside of the chick because Carrel was able to constantly supply the cells with growth medium (energy and nutrients) and constantly remove waste products.

Figure 2 of Carrels study. A hand drawn sketch of plate 76 after fifty days of culturing connective tissue.

Fig 3 of Carrels study. A peripheral sketch of plate 76 after fifty days of cultured connective tissue growth.

Carrel's success culturing cells made him hopeful for creating immortal in-vitro cell lines and wrote "These facts show that experiments made with these or with more perfect techniques and followed over long periods of time may lead to the solution of the problem of permanent life of tissues in-vitro, and give important information on the characters acquired by tissues liberated from the control of the organism from which they were derived." Carrel dreamed of becoming famous for creating the world's first immortal cell strain, and his research played an important role in the development of theories regarding cellular aging.

Later experiments confirmed that cells in culture do have a limited lifespan, and embryonic chick fibroblasts can undergo around 30 doublings (4 months) before dying. This in stark contrast to Carrells culturing experiments with embryonic chick heart muscle cells that survived for thirty-four years. This is in direct conflict with the Hayflick limit. There are three unconfirmed theories regarding the "immortal cells" cultured by Alexis Carrel at the Rockefeller Institute during this time. (1) The cultured chick cells underwent an infinite growth transformation allowing them to grow indefinitely. (2) Carrell accidentally replenished his cultured cells with new cells coming from the chick embryo extract he was including in his growth medium. (3) Deliberate addition of fresh tissues.

On December 5, 2002 NASA published a research paper titled "In Vitro Edible Muscle Protein Production system (MPPS): Stage 1, Fish". The goal of this study was to build a culturing meat system that would give astronauts a viable and sustainable source of protein for long-term space travel. In this study, NASA cultured the adult dorsal abdominal skeletal muscle of Gold Fish (Carassius auratus). NASA chose to culture mature skeletal muscle explants because the explants taken from the gold fish had all the tissue types present that are commonly recognized as food.

Graphical representation of explant behaviour in NASA's muscle protein production system

Standard pattern of fibers and cells in NASA's muscle protein production system after 3 weeks (150X)

Before this experiment, tissues were typically cultured from embryonic myoblast cells. Embryonic myoblast cells are difficult to successfully culture into meat products, due to the highly differentiated nature of skeletal muscle tissues. NASA found success culturing muscle explants in this study because their muscle protein production system (MPPS) was better at mimicking in-vivo conditions—conditions muscle tissues experience in the animal organism—leading to healthy cell proliferation and differentiation/un-differentiation and ultimately a cultured fish fillet.

Layer of differentiated bone tissue after 4 months of culturing a pig's bone marrow mesenchymal stem cells.

Oron Catts began the Tissue Culture & Art project in 1996 in hopes of exploring technologies and questions originating from creating tissues, semi-living objects, and sculptures using cellular agricultural techniques. The Tissue Culture & Art Project focused on the artistic manipulation of biological and chemical tools of modern science for the creation of cultured art projects. Catts began manipulating the growth and three-dimensional formation of tissues on tissue scaffolds in hopes of creating a system for artists to explore what is possible with tissue culturing technologies.

Semi-living worry doll.

The Tissue Culture Arts Project was the first attempt to expand cellular agriculture and tissue engineering beyond medical applications. Catts and his team were able to make tissue engineered sculptures by obtaining cell lines or primary cells, seeding them on scaffolds, and culturing them.

The most famous sculpture to come out of the Tissue Culture Arts Project was the semi living worry dolls. The project was made to bring attention to anxieties people feel about corporate biotechnology and eugenics. The worry dolls were cultured inside of an "artificial womb" bioreactor designed by Oran Catts and Ionat Zurr. The artificial womb provided micro-gravitational conditions and acted as a surrogate body for tissues growth. The artificial womb had hand-crafted bio-degradable polymers that degraded as the tissues grew. Throughout the growing process, tissues were sewn together using surgical sutures to assist the worry dolls growing into their final form.

Visual diagram published by Oran Catts and Ionat Zurr on how they made the semi-living worry doll.

SEMI-LIVING WORRY DOLLS_TISSUE CULTURE AND ART PROJECT

Photo of William Frederick van Eelen with a cow in the Netherlands.

Willem Frederick van Eelen is often referred to as the "Godfather" of cultured meat. He pioneered many new processes and technologies for growing cultured meat, including being granted the first cultured meat patent in 1999, titled "Industrial production of meat from in vitro cell cultures".

The co-founder of Google, Sergey Brin, funded the development of the worlds first commercial cultured meat product. The product was a cultured beef burger made by Dr. Mark Post and his team at Maastricht University. The cultured beef burger sold for $330,000 and was cooked by Richard McGeown on August 5, 2013. The cultured beef burger was tasted by two food critics, Hanni Ruetzler and Josh Schonwald. Ruetzler said the following about the cultured beef burger "I was expecting the texture to be more soft... there is quite some intense taste; it's close to meat, but it's not that juicy. The consistency is perfect". Studies show people are very willing to pay a premium for lab-grown meat.

Cultured beef burger tasting London Aug 2013

Culturing meat involves taking muscle cells from an animal and growing them independent of that animal in a bioreactor. There are two categories of bioreactor manufacturing techniques for cultured meat products: scaffold-based techniques and self-organizing techniques.

Scaffold manufacturing methods rely on the proliferation of extracted muscle satellite cells, or embryonic myoblast cells, on material scaffolds that can be perfused with a culture medium in a bioreactor. The resulting cellular network grown on the scaffold can be harvested and cooked like normal meat after being differentiated by environmental cues into connected myofibers.

Scaffold techniques for growing cultured meat were developed by a cohort of Dutch scientists in the Netherlands in the late 1990s and early 2000s. Scaffold culturing techniques make cultured meats with simple structures like ground and boneless meats for hamburgers and sausages, but not for meat products with more complicated structures such as steak.

More complex structures in cultured meat products, such as steak, require the proliferation of self-organizing cellular constructs in-vitro. Self-organizing constructs are used to create 3-dimensional tissues, typically using animal tissue explants. Many of the techniques used in self-organizing constructs for cultured meat products were developed in 2002 by scientists looking for ways to produce in-vitro protein production systems (MPPS) for long-term space voyages.

In an article published on June 2, 2018, the Institute for Electrical and Electronic Engineers (IEEE) weighed the benefits and challenges of using cells (as opposed to plant products) to develop animal-free meat. They noted that using cellular components can allow developers to control proportions and types of fats in the final products, allowing them to control the flavor and nutritional content. Also, since the final product would actually be meat, it could be more palatable and convenient to consumers. However, a major hurdle for scientists looking to generate meat from cells is what to put into the nutrient mixture which coaxes the cells toward muscle fibers. Currently fetal bovine serum is used, a product derived from fetal calves in a costly and unsustainable process. These are problems that have been considered by several cell-based meat companies including Memphis Meats, Just, Inc., and SuperMeat, and others.

The FDA cooperates with the United States Department of Agriculture’s Food Safety and Inspection Service (USDA-FSIS) to ensure compliance with regulation in order for food developers to introduce safe and appropriately labeled products to the market. In 2019, the FDA and USDA-FSIS formed an agreement on how the organizations would use their regulatory capacity to help ensure that foods comprising or containing cultured animal cells entering the U.S. market are safe and appropriately labeled.

This agreement delineated which parts of the process were to be overseen by each agency and was the first step toward developing the framework to support safe production of cultured foods and providing clarity on the requirements for producing, distributing, and selling these products in the U.S. The FDA's role is to oversee cell banks and the collection, growth, and differentiation of cells. The USDA takes over regulatory oversight from the harvesting stage of the cell-culturing process onwards, overseeing the production and labeling processes. The FDA and USDA-FSIS have held public meetings to achieve a better understanding of animal cell culture technology, potential hazards, labeling considerations, and to gain insight into the concerns of consumers.

According to the FDA, regulatory oversight of human foods comprised of or containing cultured animal cells depends on the animal species used as the source of cultured cells and is based on the supervising agencies’ existing jurisdiction over products. The responsibilities divided among the FDA and USDA-FSIS are the following:

• The FDA is responsible for regulating all live animals to be utilized as products for consumption up until the processing stage.

• In the case of animals intended for human consumption and regulated under the Federal Meat Inspection Act (FMIA) (i.e., cattle, sheep, swine, goats, and fish of the Siluriformes group) or the Poultry Products Inspection Act (PPIA) (i.e. chicken, turkeys, duck, geese, guineas, ratites, and squab), USDA-FSIS is responsible for regulation during processing.

• For foods made from the cultured cells of animals not regulated under the FMIA or PPIA or foods intended for animal consumption, the FDA is responsible for regulation during processing. The FDA has issued applicable requirements under both the Federal Food, Drug, and Cosmetic Act (FFDCA) and Public Health Service Act.

The FDA's approach to cultured meat regulation is to carry out a pre-market consultation process and inspections of records and facilities. The pre-market consultation process includes evaluating the production process and produced biological material, including tissue collection, cell lines and cell banks, manufacturing controls, and all components and inputs. Following a successful pre-market safety consultation, the FDA intends to conduct routine inspections as well as other oversight activities at cell banks and facilities where cells are cultured, differentiated, and harvested.

The goal of these inspections is to help ensure that potential risks are being addressed and that biological material exiting the culture process is safe and not adulterated as per the FFDCA's definition. In conducting inspections and other oversight activities, the FDA aims to be able to refer to the results of the pre-market consultation and an assessment of production records maintained by the facility being evaluated. In the event that the inspections detect instances of noncompliance, the agency will take appropriate action.

According to the FDA, during the cell harvesting stage the agency will cooperate with USDA-FSIS to coordinate the transfer of regulatory oversight to USDA-FSIS. USDA-FSIS will conduct inspections at facilities where cells derived from livestock and poultry are harvested. These facilities will be required to have USDA grants of inspection and meet the USDA-FSIS regulatory requirements, including those pertaining to sanitation as well as the development and implementation of Hazard Analysis and Critical Control Points systems. USDA-FSIS inspectors will be tasked with the examination of batch records produced during cell culturing and the verification of compliance with applicable USDA-FSIS regulatory requirements during product processing, packaging, and labeling to verify that the products featuring cultured meat are safe, wholesome, unadulterated, and truthfully labeled. If cells are shipped to other establishments for further processing into food products intended for human consumption, these establishments will also be subject to USDA-FSIS inspection.

USDA-FSIS inspection of cell harvest and processing will occur at a frequency of at least once per shift, the inspection frequency also required for processing traditional meat and poultry products. This level of verification is necessary for products to receive the USDA mark of inspection. Finally, the USDA-FSIS will ensure that cell-based products are labeled truthfully and consistent with coordinated FDA and USDA-FSIS principles for product labeling and claims. Under the requirements of the FMIA and PPIA, all labeling of human food products made from the cultured cells of livestock or poultry must by pre-approved by FSIS.

• FDA Seeks Input on Labeling of Food Made with Cultured Seafood Cells (October 6, 2020).

• USDA/FDA Launches Joint Webinar on Roles and Responsibilities for Cultured Animal Cell Human and Animal Food Products (July 31, 2020).

• USDA and FDA Announce a Formal Agreement to Regulate Cell-Cultured Food Products from Cell Lines of Livestock and Poultry (March 07, 2019).

• Statement from USDA Secretary Perdue and FDA Commissioner Gottlieb on the regulation of cell-cultured food products from cell lines of livestock and poultry (November 16, 2018).

• USDA and FDA announce joint public meeting on use of animal cell culture technology to develop products derived from livestock and poultry (September 10, 2018).

Australia and New Zealand share a joint food regulatory framework and a joint food regulatory agency, called Food Standards Australia New Zealand (FSANZ). FSANZ is responsible for developing food standards governing the composition, production, handling, promotion, sale, and transport of food. Under FSANZ’s "novel food" regulation, cultured meat and seafood manufacturers must apply to have their products approved as novel foods if they intend to sell them in either country. This requires a safety assessment of the production process carried out by FSANZ that is likely to last for at least fourteen months.

In Canada, cultured meat and seafood are characterized as “novel foods” that require the submission of detailed information in an application for premarket approval. This information includes evidence that the food is safe for consumption, including molecular characterization, nutritional composition, toxicology and allergenicity, and types and levels of chemical contaminants. The approval process has three distinct requirements:

• A letter of no objection for human food use through the novel food assessment process
• A premarket assessment for new animal feed
• An environmental assessment under the New Substances Notification regulations

Companies are not allowed to sell their products in Canada until they satisfy these conditions.

In the EU, the Novel Foods Regulation (Regulation (EU) No 2015/2283) governs pre-market authorization for foods produced from animal cell or tissue culture. However, if genetic engineering is used in the production, the Regulation on genetically modified food and feed (Regulation (EC) 1829/2003) may apply instead. Applications under the Novel Foods Regulation must be addressed to the European Commission and its Directorate-General for Health and Food Safety. The European Food Safety Authority (EFSA) normally carries out a risk assessment and provides a scientific opinion on the safety and nutritional aspects of the product. If that opinion is positive, final approval rests with the European Commission and representatives from all EU member states.

After exiting the EU, the UK ceased to participate in the EU’s common food authorization procedures. As of May 2021, any cultured meat companies intending to market their products in the UK are required to apply for authorization to the UK Food Standards Agency (FSA). The UK retained relevant EU law and the substance of the risk assessment of both novel foods and genetically modified food authorization remains the same as in the EU. There is a significant difference between the UK and EU final approval decision process. In the UK, the government ministers are responsible for final approval, and in the EU final approval rests with the European Commission and representatives from all twenty-seven EU member states.

Depending on the production method, some cultured meat may fall within the existing regulatory regime in Japan and be exempt from requiring a premarket assessment or approval. The Japanese government is also developing a specific regulatory framework to control the market while improving food safety and consumer acceptance. Industry groups are being formed to create industry standards and cooperate with the regulator to create a process to promote consumer confidence.

The Singapore Food Agency (SFA) approved the 'chicken bites' product by company Eat Just in 2020, following two years of testing and review, making Singapore the first country in the world to approve the use of cultured chicken in a commercial product.