The day is coming when there will be a more efficient supply chain for the production of meat and meat by-products. A new field of science known as Cellular Agriculture is using bioengineering technology to produce meat, poultry, eggs, dairy, and leather, in a laboratory instead of on a farm. You could drink cow’s milk, and eat eggs, meat, and poultry without the unwanted saturated fats, cholesterol, hormones, and antibiotics. Tissue engineering is even being employed in biofabrication of leather and fur, negating moral issues of raising animals for clothing and luxury. All of this without the use or slaughter of  animals.

What is Cellular Agriculture? 

Cellular agriculture is a new way to cultivate foods normally produced through traditional agriculture. Instead of raising livestock for meat, dairy, and other meat by-products, these items are produced in a lab, without the slaughter and continuous use of animals. Foods like eggs, milk, and beef can be bioengineered ex-vivo – using cell culture methods. Cellular agriculture can produce both cellular and acellular products. Cellular products, like beef, chicken, and turkey, are made by culturing cells derived from the original animal. Acellular products on the other hand do not contain any mammalian cells, and are derived from bioengineered microbes.

Cell Culture

Cell culture is a method of growing animal or plant cells outside of the organism they were derived from. Cells are isolated from tissue samples from living organisms and grown in treated plastic flasks or dishes, in special growth medium. The medium contains a host of nutrients and other substances necessary to promote the growth and survival of cells. Cell culture medium is often supplemented with Fetal Bovine Serum, but serum-free solutions that are not animal sourced, have been developed.

Benefits of Bioengineered Food

With the world’s population growing, there is a constant and increaasing demand for food. globally traditional agriculture consumes massive amounts of land, water, and energy. Globally, traditional agriculture consumes massive amounts of land, water, and energy. Additionally, in developing countries forests are cleared to create the land necessary to produce food, which disturbs, and  threaten previously pristine ecosystems. Cellular agriculture can help preserve the environment by producing food in vitro. 

Bioengineered foods would be more environmentally friendly and efficient than traditonal farming. Far less time, land, water, and energy are needed to produce meat and dairy in a lab than is required to raise livestock. As a result, fewer green house gases and other waste products are produced. Additionally, producing foods via cellular agriculture eliminates the need for pesticides and antibiotics.

Other benefits of Cellular Agriculture pertain to cost, quality, and public health. Due to crowded conditions, livestock are often plagued with outbreaks of diseases, like bird flu, swine flu, and Mad Cow disease, that can spread to humans, and destroy supply. Outbreaks of diseases on farms cause shortages, which then cause prices to go up. Sick animals must be culled, and sometimes whole herds and flocks are terminated. This not only  impacts the quantity, but also the quality of supply. Even when animals are healthy, bacteria like, Salmonella and E.coli commonly contaminate poultry, meat, and eggs. Sterile techniques necessary for cell culture would eliminate these  public health hazards, and because cells are proliferated in vast quantities during the process,  bioengineered foods would provide a stable and consistent source of meat, poultry, and dairy.

History of Cellular Agriculture

Acellular Products

Cellular Agriculture is not a 21st century phenomenon. The very first genetically engineered product for food production was actually approved by the United States FDA in 1990. Rennin or Chymosin, is an enzyme used to coagulate milk for making cheese. Rennin, is the major enzyme component of Rennet, and is responsible for clotting the milk protein casein, to produce curds. Traditionally, rennet is obtained by scraping the dried fourth stomach of  10 to 30 day old calves, and the rennin is extracted. However, bioengineered rennin is produced by genetically modified microorganisms. The cow gene responsible for producing rennin is cloned and inserted into E. Coli or yeast. The recombinant microbes are then grown in fermentation tanks to increase yield. Bioengineered rennin is indistinguishable from natural rennin, and produces the same results.

Cellular Products

The idea of growing meat in vitro is not new either. In fact, Winston Churchill, was quoted in 1931, as saying; “we shall escape the absurdity of growing a whole chicken in order to eat the breast or wing, by growing these parts separately under suitable medium”. The first government-funded research on cultured meat was conducted in the Netherlands from 2005 to 2009, but a patent for the idea had been  filled by Willem Van Eelen since 1997.

Bioengineered Beef

Recently, n August 2013, the first cell-cultured hamburger was cooked and tasted live on television. The beef cells that would become that burger were created by professor Mark Post at the University of Maasstricht in England. The burger was composed of approximately 20,000 cell cultured strands of muscle, combined with egg powder, bread crumbs, and other materials. Though novel, it did not represent a completely animal-free system for generating cell cultured meat, as the cells were grown in media containing Fetal Bovine Serum (FBS). Fetal Bovine Serum or Fetal Calf Serum (FCS) is a costly growth supplement obtained from slaughtered cows or calves. The idea of bioengineered meat is to reduce the need for killing animals to produce food, so using FBS/FCS is not ideal.

The cells used to produce cultured meat could be derived from a single animal and grown continuously in a lab. The process involves growing small strands of beef from muscle stem cells called myosatellite cells. Myosatellite cells are cultured on a substrate that the cells can adhere to and contract around. Van Eelen used a collagen mesh as  a scaffold. Myosatellite cells have also been grown around porous microbeads suspensions in large bioreactors. Adhering to a substrate allows the stem cells  to proliferate and differentiate into mature muscle cells. By enabling them to contract, the cells can build bulk, like they would in the body. The resulting strands of beef  are then used to produce mince-like meat products.

Many researchers have investigated culturing meat in vitro. Aside from replacing FBS/FCS with serum substitutes, there are several other complications that have to be overcome. For one, growing mammalian cells in flasks on flat scaffolds, or on porous beads in a bioreactor only produces monolayer cells and two-dimensional tissue. To have a truly comparable meat substitute, synthetic meat or poultry need to be three-dimensional.

Tissue Engineering

Tissue engineering developed to create human tissue to be used in research and development, for drug testing. It is now normally used to generate organs and tissues for grafts and transplants, but tissue engineering can be harnessed to produce meat in a lab. However, in a petri dish or cell culture flask, cells don’t ordinarily grow the way they would inside of an organism. While it is easy to supply oxygen to a single layer of cells , diffusing this essential gas through tissues composed of many layers of cells requires special vasculature systems. In the body we have the cardiovascular system, a network of veins and capillaries, that deliver and transport nutrients and oxygen into tissues and organs, while carrying away carbon dioxide via arteries. Oxygen is necessary for the cells to survive and grow properly. One idea being used to solve this problem, is to grow mammalian cells on a prevascularized three-dimensional scaffold – decellularized plant tissue.

Decellularized Apples

Decellarization is a process of removing cells, nucleic acids, lipids, and proteins of a donor tissue from its extracellular matrix. The remaining extracellular matrix of a plant is essentially purified cellulose. Cellulose is structurally strong, inert, and resists degradation, making it a good scaffold for three-dimensional (3D) cell culturing and tissue engineering. Cellulose is also edible.

Plants, fruit, and vegetables have vasculature similar to animals. By removing the cells from plants through the process of decellularization, the extracellular matrix, can be used to grow mammalian tissue. The difference between these scaffolds and ones that are made synthetically, is they have pre-existing vascular networks, capable of delivering nutrients throughout a mass of cells. Their 3D structures make it possible to grow synthetic meat that is more anatomically similar to conventional meat.  Once, decellularized, the plant scaffolds are repopulated with mammalian cells. The cells then grow in and around the plant matrix in a manner more reflective of their natural development.

Researchers have demonstrated that cells can attach and proliferate on decellularized plants. Spinach leaves and even apples have been decellularized and used as plant derived 3D scaffolds. The decellularized matrix of an apple maintains a cell wall with pores and air pockets, that serve the same function as vasculature, to permit the transfusion of nutrients, air, and water. Plant derived scaffolds are effective and environmentally friendly, as they can easily be produced from a renewable source. They are also abundant in supply, and cost efficient.

Plant based 3D scaffolds solves the problem of diffusion limitations in the delivery of oxygen and water within complex tissue, and of  maturation and structural development. However, there are other complication researchers need to surmount before the ideal meat or poultry product can be introduced to the market. In the meantime, others have sought to use biotechnology to produce less complex foods in the lab, such as milk and eggs.

New Harvest

New Harvest is a non-profit research agency based in New York. It was launched in 2004 to promote and encourage the field of cellular agriculture by providing funding for research. New Harvest has helped to fund and conduct research leading to the developing of two start-up companies, Perfect day (originally Muufri), and Clara Foods.

Acellular Products

Perfect Day and Clara Foods uses cellular agriculture to produce acellular products. Acellular products do not contain any cellular or living material, but are made of organic molecules. The milk and egg whites produced respectively by these two companies, are made by yeasts.

Perfect Day

 

With the global demand for milk increasing, California-based company, Perfect Day, is working on bringing cow’s milk, made without cows, to the market. Perfect Day, will make milk, yogurt, and cheese from yeast and plants that have been bioengineered to produce milk proteins.  Several genes encoding for the main milk proteins found in cow’s milk, have been inserted into genetically modified yeast cells. The non-dairy milk, cheese, and yogurt produced using these proteins would not contain the cholesterol, hormones, or lactose which are negatively associated with traditional dairy products.

 

Clara Foods

Clara Foods is a start-up located in San Francisco California; launched by New Harvest’s Egg Project in 2014. The project was designed to find a way to make egg whites in the lab, using cell culture. Instead of getting egg whites from hen-laid eggs, these egg whites are made by yeast. The process is  Similar to the system used by Perfect Day to make milk. The genes necessary for the production of several proteins found in egg whites were inserted into yeast cells. The yeast then produce these proteins, which are later isolated and combined with other ingredients – yeast not included – to produce egg whites.
These eggs can be designed to enhance the useful properties of egg whites. By selecting which proteins are produced, egg whites with better binding capabilities, that whip up fluffier can be created.

Cellular By-products

Modern Meadow

After working with his father’s business, which provided bioprinting devices for tissue engineering, CEO Andras Forgacs, was inspired to apply the same technology outside the field of medicine.

Brooklyn based, startup, Modern Meadow, is using biotechnology to develop real leather from cells cultured in a lab. The process works by manipulating DNA that is then inserted into bovine cells to optimized collagen production. Collagen is one of the major proteins found in mammalian skin, and is responsible for structure and elasticity. The collagen fibers grown by the cells are assembled along with other essential proteins, and fashioned into leather. Biofabricated leather is the same as real leather, but can be customized to be more durable and malleable. Since the tissue engineered skin does not develop a tough epidermis, it is easier to process, and less chemicals required for tanning are needed. Biofabricated leather can be used for making wallets, clothing, and anything else leather is used for. The company is not looking to replace the leather industry, but to add to it, by offering an alternative, and providing an improved product.

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Bioengineered Fur

It is even possible to bioengineer hair. The adult hair follicle maintains the ability to regenerate itself, and epithelial and dermal cells found in the bulge of the hair follicle or in the surrounding skin have stem cell -like characteristics. In studying thricogenesis for the treatment of male-pattern balding (androgenic alopecia), researchers have been able to use these cells to induce new hair follicle formation in rats and mice. The process involves isolating hair follicle stem cells from donor tissue  and expanding them via cell culture, then implanting them into epithelium where more hair will grow. This same technique could be used to produce animal fur in a lab,  as an alternative to killing mammals for their pelt.  

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Cellular Agriculture: Limitations and Concerns

All foods derived through the use of modern technology are regulated by the U.S. Food and Drug Administration (FDA). They must demonstrate to be as safe as their non-bioengineered counterparts. In order to be approved, Bioengineered or in vitro meat, has to have a nutritional value equal to or surpassing that of conventional meat. Meat and dairy produced using cellular agriculture would have higher protein content, less fat, and be free of pesticides, antibiotics, hormones, and disease. Nutrition aside, the issue of texture and taste similarity may limit the publics acceptance of these products as true alternatives.

Cell cultured meat has not yet been developed on an industrial scale, which would be necessary for commercial use ( Perfect Days milk is forecasted to be available by 2018). However, once they arrive on the market, they are likely to face the same public scrutiny as genetically modified foods. Although cellular agriculture produces food with the help of genetically modified organisms (GMO), they are not, themselves, genetically modified.

Summary

The concept of cellular agriculture is not new. By re-imagining current technology, and harnessing advancements in cell biology, Cellular Agriculture may be a  practical, environmentally sound, solution for the demands of today’s society. Cells derived from as little as one animal can be stored and propagated continuosly to sustainably produce food. Without confining or slaughtering livestock, animal tissue can be grown in vitro under sterile cell culturing conditions to provide not only meat and dairy, but other by-products of animals such as  leather and fur.

References

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Modulevsky, Daniel J; Lefebvre, Cory; Haase, Kristina; Al-Rekabi, Zeinab; Pelling, Andrew, 2014. Apple Derived Cellulose Scaffolds for 3D Mammalian Cell Culture.
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Paula Frank, 2001. ‘Moo’ving Toward Biotechnology. Dairy Field; Northbrook Vol 184.7 p 65.

Malcolm Gladwell, 1990. Genetically Engineered Enzyme OK’d by FDA for Making Cheese. Austin American Statesman; Austin Texas Vol 24 p A2

Roush W., 2014. Xconomy: Modern Meadow Grazes on $10M to Grow Leather Without Cows. Newstex Trade & Industry Blogs, Chatam. June 18.

K. Stenn K., Parimoo S., Zheng Y., Barrows T., Boucher M., Washenik K., 2007. Bioengineering the Hair Follicle. Organogenesis Vol 3(1) p 6-13.