Cellular agriculture

Cellular agriculture is an interdisciplinary branch of science at the intersection of medicine and farming. Cellular agriculture capitalizes on breakthroughs in tissue-engineering, material sciences, bioengineering, and synthetic biology to design new ways of producing existing agricultural products like milk, meat, fragrances, and rhino horn from cells and microorganisms.^[1]

The most famous example of a cellular agriculture product is Professor Mark Post's cultured burger from 2013, which demonstrated proof of concept for cultured meat.^[2]

History

Although cellular agriculture is a nascent scientific discipline, cellular agriculture products were first commercialized in the early 20th century with insulin and rennet.^[3]

In 1922, Frederick Banting, Charles Best, and James Collip treated the first diabetic patient with an insulin injection, which was originally collected from the ground-up pancreases of pigs or cattle.^[4] In 1978, Arthur Riggs, Keiichi Itakura, and Herbert Boyer inserted the gene carrying the blueprints for human insulin into an E. coli bacteria, prompting the bacteria to make insulin identical to the insulin made by humans.^[5] The vast majority of insulin currently used worldwide is now biosynthetic recombinant "human" insulin engineered by yeast or bacteria.^[6]

On March 24, 1990, the FDA approved a bacteria that had been genetically engineered to produce rennet, making it the first genetically engineered product for food.^[7] Rennet is a mixture of enzymes that turns milk into curds and whey in cheesemaking. Traditionally, rennet is extracted from the inner lining of the fourth stomach of calves. Today, the majority of cheesemaking uses rennet enzymes from genetically engineered bacteria, fungi, or yeasts because it is more pure pure and consistent and less expensive than animal-derived rennet.^[8]

Winston Churchill also predicted the advent of a mainstream cellular agriculture paradigm of meat production in his 1931 essay, Fifty Years Hence.

"Fifty years hence...we shall escape the absurdity of growing a whole chicken in order to eat the breast or wing, by growing these parts separately under a suitable medium."^[9]

In 2004, Jason Matheny founded New Harvest which was first a cultured meat advocacy organization but whose mission is now to "accelerate breakthroughs in cellular agriculture."^[10] New Harvest is the only organization focused exclusively on advancing the field of cellular agriculture, and are funding the first cellular agriculture PhD at Tufts University^[11] as well as opening a wet lab in the Netherlands, New Harvest Labs, for the purpose of creating cellular agriculture research tools open source.^[12]

Since 2014, IndieBio, a synthetic biology accelerator in San Francisco, has incubated several cellular agriculture startups, hosting Muufri (making milk from cell culture), Clara Foods (making egg whites from cell culture), Gelzen (making gelatin from bacteria and yeast), Afineur (making cultured coffee beans) and Pembient (biofabricating rhino horn). Muufri and Clara Foods were both launched by New Harvest.

In 2015, Mercy for Animals created a sister organization called Good Food Institute, which promotes cellular agriculture meat and dairy alternatives in addition to plant-based options.^[13]

In July 13, 2016, New Harvest hosted the world's first international conference on cellular agriculture in San Francisco, California.^[14] The day after the conference, New Harvest hosted the first closed-door workshop for industry, academic and government stakeholders in cellular agriculture.^[15]

Research tools

Several key research tools are at the foundation of research in cellular agriculture.

Cell lines

A fundamental missing piece in the advancement of cultured meat is the availability of the appropriate cellular materials. While some methods and protocols from human and mouse cell culture may apply to agricultural cellular materials, it has become clear that most do not. This is evidenced by the fact that established protocols for creating human and mouse embryonic stem cells have not succeeded in establishing ungulate embryonic stem cell lines.^[16][17][18]

The ideal criteria for cell lines for the purpose of cultured meat production include: immortality, high proliferative ability, surface independence, serum independence, and tissue-forming ability. The specific cell types most suitable for cellular agriculture are likely to differ from species to species.^[19][20]

Growth media

Today the status quo for growing animal tissue in culture involves the use of fetal bovine serum (FBS). FBS is a blood product extracted from fetal calves. This product supplies cells with nutrients and stimulating growth factors, but is unsustainable and resource-heavy to produce, with large batch-to-batch variation.^[21]

After the creation of the cell lines, efforts to remove serum from the growth media are key to the advancement of cellular agriculture as fetal bovine serum has been the target of most criticisms of cellular agriculture and cultured meat production. It is likely that two different media formulations will be required for each cell type: a proliferation media, for growth, and a differentiation media, for maturation.^[22]

Scaling technologies

As biotechnological processes are scaled, experiments start to become increasingly expensive, as bioreactors of increasing volume will have to be created. Each increase in size will require a re-optimization of various parameters such as unit operations, fluid dynamics, mass transfer and reaction kinetics.

Scaffold materials

For cells to form tissue, it is helpful for a material scaffold to be added to provide structure. Scaffolds are crucial for cells to form tissues larger than 100 µm across. An ideal scaffold must be non-toxic for the cells, edible, and allow for the flow of nutrients and oxygen. It must also be cheap and easy to produce on a large scale without the need for animals.

3D tissue systems

The final phase for creating cultured meat involves bringing together all the previous pieces of research to create large (>100 µm in diameter) pieces of tissue that can be made of mass-produced cells without the need of serum, where the scaffold is suitable for cells and humans.

Applications

Cellular agriculture is a scientific field that designs new mechanisms to produce existing agriculture products. While the majority of discussion has been around food applications, particular cultured meat, cellular agriculture can be used to create any kind of agricultural product, including those that never involved animals to begin with, like Gingko Biowork's fragrances.

Over the last three years, several cellular agriculture start-ups have been created applying cellular agriculture to make a number of agricultural products and consumables.

Meat

Impossible Foods

In the Impossible Burger produced by Impossible Foods, the heme that gives the burger its bloody look and taste is produced by taking the soybean gene that encodes the heme protein and transferring it to yeast.^[23]

SuperMeat

SuperMeat is an Israeli startup that launched an Indiegogo campaign in 2016 to create cultured chicken meat.^[24][25]

Memphis Meats

Memphis Meats is a United States startup that made a prototype of a cultured meatball in 2016.^[26][27]

Mosa Meats

Mosa Meats is a Dutch startup that is an outgrowth of Mark Post's cultured burger, which was tasted in London in 2013.^[28]

Milk

Muufri

Muufri is a San Francisco-based startup that started as the New Harvest Dairy Project and was incubated by IndieBio in 2014. Muufri is making milk from yeast instead of cows.^[30][31]

Eggs

Clara Foods

Clara Foods is a San Francisco-based startup that started as the New Harvest Egg Project and was incubated by IndieBio in 2015. Clara Foods is making egg whites from yeast instead of eggs.^[32]

Gelatin

Gelzen

Gelzen is a San Francisco-based startup that was incubated by IndieBio in 2015. Gelzen is developing a proprietary protein production platform that uses bacteria and yeast to produce gelatin.^[33][34]

Coffee

Afineur

Afineur is a Brooklyn-based startup fermenting coffee beans to improve the taste and digestibility of craft coffee.^[35]

Horseshoe Crab Blood

Sothic Bioscience

Sothic Bioscience is a Cork-based startup incubated by IndieBio in 2015. Sothic Bioscience is building a platform for biosynthetic horseshoe crab blood production. Horseshoe crab blood contains limulus amebocyte lysate (LAL), which is the gold standard in validating any medical equipment and medication.^[36][37]

Fragrances

Gingko Bioworks

Gingko Bioworks is a Boston-based organism design company culturing fragrances and designing custom microbes.^[38]

Silk

Spiber

Spiber is a Japanese-based company decoding the gene responsible for the production of fibroin in spiders and then bioengineering bacteria with recombinant DNA to produce the protein, which they then spin into their artificial silk.^[39][40]

Bolt Threads

Bolt Thread is a California-based company creating engineered silk fibers based on proteins found in spider silk that can be produced at commercial scale. Bolt examines the DNA of spiders and then replicates those genetic sequences in other ingredients to create a similar silk fiber. Bolt’s silk is made primarily of sugar, water, salts, and yeast, which combined forms a liquid silk protein. Through a process called wet spinning, this liquid is spun into fiber, similar to the way fibers like acrylic and rayon are made.^[41][42]

Leather

Modern Meadow

Modern Meadow is a Brooklyn-based startup growing collagen, a protein you find in animal skin, to make biofabricated leather.^[43]

Academic Programs

New Harvest Cultured Tissue Fellowship at Tufts University

A joint program between New Harvest and the Tissue Engineering Research Center (TERC), an NIH-supported initiative established in 2004 to advance tissue engineering. The fellowship program offers funding for Masters and PhD students at Tufts university who are interested in bioengineering tunable structures, mechanics, and biology into 3D tissue systems related to their utility as foods.^[46]

References