Clean meatball from Memphis Meats





To put the developments of the past few years into perspective, Mark Post’s first burger cost $330,000 to produce, and within a few years, Memphis Meats was producing meat for less than one-fiftieth of that price tag. By 2020, Post plans to sell Mosa Meats’ burgers for about $10 a patty , and within about five years after that, for about the cost of the least expensive meat on the market.





So how do we get there?





One way to understand clean meat’s scientific path to commercialization is to envision a system of intertwined gears inside a clock, all of which need to move in tandem to function effectively.





(I know, you use your phone to check the time, but bear with me.)





In this clock, there are four critical “gears” to pay attention to: cell lines, media (a.k.a. growth serum), scaffolding, and bioreactor scale-up.

















Cell Lines





At its most basic, clean meat production involves growing a small sample of cells into a full-fledged piece of meat. That initial sample is what is called a cell line, which you can think of as the “starter pack” of clean meat. These lines contain the different types of cells—muscle, fat, and more—that are then proliferated in cell culture.





The science behind this process is already well advanced thanks to extensive research on tissue-engineering in the medical field. Now, it’s up to motivated researchers to take the wealth of knowledge gained from this medical research and apply it to clean meat production by establishing animal cell lines.





(What exactly is their motivation, you ask? The answers you seek are here !)





At this point, you might be wondering why anyone needs to “establish” cell lines if we can simply take direct samples from an animal. There are two primary reasons for this. When cells are obtained directly from an animal, they only have the capacity to divide and grow a limited number of times (20–50 times, in case you’re curious), leaving companies and researchers in need of new samples frequently. This is not only impossibly inefficient for large-scale production, it’s also counter to the objective of entirely removing animals from the meat-production process.





One solution is to establish “immortal” cell lines that can be shared between clean meat producers and used as a consistent, indefinitely reproducing source of meat. While even differentiated cell lines can be immortalized through genetic tricks, pluripotent and multipotent stem cells—which can differentiate into all of the necessary cell types within the final product—are often naturally immortal, making these especially appealing for clean meat applications.





An exciting recent development in this area occurred when New Harvest research fellow and North Carolina State University graduate student Marie Gibbons, along with her adviser Dr. Paul Mozdziak, successfully grew a small turkey nugget from an immortal cell line they created. With access to this cell line, any scientist could produce the same results in just over two weeks.





Compare that to raising a turkey from birth to slaughter--which takes about 6 months and wastes more than 90 percent of the caloric inputs —and you’ll understand why advocates for sustainable food production are so excited about this technology!





Once cell lines are widely available, production moves to the next step: connecting these cells with the nutrients needed to replicate.









Cell Culture Media











These nutrients are commonly referred to as “media.” Media is a mixture of ingredients that works as a food source for cell lines, encouraging them to grow and divide.





As it stands, researchers often rely on animal-based serum to get their small sample of cells to grow. This is problematic not only because it relies on animals, but also because serum is notoriously inconsistent from batch to batch, is in limited supply and thus extremely costly, and carries a risk of pathogen contamination. GFI’s Senior Scientist Liz Specht presented on this topic at the Cultured Meat Conference and mapped out the way forward on animal-free media. Quite simply, there will be no animals used in media by the time clean meat is commercialized, for both ethical and practical reasons.





Conceptual presentation at the Cultured Meat Conference: “Pookie” the pig is said to be alive and well!

Fortunately, hundreds of animal-free media formulations have been developed for medically relevant cell types, including human stem cells. However, there has not yet been much impetus among commercial media suppliers to make formulas optimized for cell types like chicken myocytes (muscle cells) or cow adipocytes (fat cells), which come with a completely novel set of requirements for growth and replication.







Then there’s the fact that media developed for the biomedical industry isn’t subject to the same cost constraints that we have for food products (no one barters with a hospital over the cost of replacement knee cartilage). If clean meat is going to be competitive with the highly subsidized animal agriculture industry, a hamburger can’t cost as much as an expensive medical procedure. Further innovation is needed to develop lower-cost formulations and media recycling capabilities in order for clean meat to reach price parity with conventional meat.





There’s more to meat than just a price point, of course. Once lower-cost animal-free media are widely available, the corresponding cell lines must be made to grow in the correct ratio and shape so that clean meat perfectly matches the texture, taste, and look of conventionally produced meat.









Scaffolding









This is where scaffolding comes in.





Scaffolding is essential for producing meat that has the ideal ratio of cell types as well as the familiar shape of conventionally produced meat—whether the goal is to produce ground beef or a chicken breast.





Scaffolding directs the differentiation of various cell types to encourage an organized pattern rather than randomly interspersed co-cultures of muscle, fat, and connective tissue cells. Several materials that are already used in food products are being explored as edible clean meat scaffolds, and the Bay-area startup Geltor is looking at the possibility of creating scaffolding using animal-free collagen. In some cases, these scaffolds serve merely as temporary supports until the cells themselves can form their own support structure.





While the first clean meat burgers and meatballs were comprised entirely of muscle cells, a realistic clean meat product must contain different cell types not only in the right ratios but also in the proper arrangement and spatial orientation. Meat is not a uniform product, and the variation from bite to bite adds to the appeal for many consumers.





Conceptual presentation at the Cultured Meat Conference: Taste and texture are key for clean meat’s commercial success

While scientists work to perfect clean meat’s taste, texture, and shape, still more engineers are needed to develop the large-scale bioreactors required to produce enough clean meat to make it to grocery store shelves. As it happens, these bioreactors are the fourth gear in our clock.











Bioreactors









The bioreactors used for clean meat production function similarly to fermenters in a beer brewery (fermenters are bioreactors). Just like yeast feeds on sugars in a fermenter to produce beer, animal cells feed on media in bioreactors to produce muscle, fat, and connective tissue.





The problem? There’s never been a need to create bioreactors specifically designed to produce the amount of clean meat required to disrupt the food system. Luckily, clean meat pioneers have proposed several options for the large-scale production of clean meat, including stirred tank reactors, perfusion reactors, and packed-bed reactors (which, going back to the brewery analogy, is conveniently abbreviated as “PBR”). Developing and testing this equipment simply requires (you guessed it) additional funding and a coordinated engineering effort.





At the laboratory scale, biotech companies have designed and built bioreactors that could be applied to clean meat to help differentiate and stimulate cells for better tissue growth. One such unit, the Bose bioreactor by TA Instruments, applies tension to a very small scaffold seeded with cells to mimic the stress these cells would experience in an animal’s body during movement. This encourages the cells to grow, much like exercise helps us bulk up muscle.





Likewise, cell culturing company Xcell Biosciences has designed the Avatar, a bioreactor that mimics the oxygen levels, hydrostatic pressure, and more that cells would be exposed to in nature, which encourages natural growth.





Sounds like a homey environment, doesn’t it?





Avatar from Xcell Biosciences





If this technology were used to grow clean meat, the Avatar’s variable oxygen and pressure capabilities could allow a chef to change the type of cells being grown simply by changing the conditions inside the bioreactor. I could (and probably will) write about three more blogs just exploring the flavor possibilities!









Conclusion











All of the barriers facing clean meat on its path to commercialization can be overcome with continued work by biologists, engineers, entrepreneurs, and investors. In fact, this was a central theme at the inaugural New Harvest Cellular Agriculture Conference in July 2016 where the top scientists in the field, including Dr. Valeti, Dr. Post, and Dr. Mozdziak, agreed that support from both the public and private sectors will be necessary for the success of this revolutionary technology.





Of course, clean meat won’t commercialize itself. That five-year goal is ambitious and is probably only achievable with significant and concerted effort. It’s for this reason that GFI is focused on working with businesses, grant-making agencies, and governments—in addition to scientists and engineers—to encourage the greatest possible progress in the field.





To find out more about how you can get involved and what GFI is doing to accelerate clean meat technology, visit our website







