Feed the World

C&I Issue 1, 2017

Cellular agriculture involves making foodstuffs from cell cultures in bioreactors. The products are chemically identical to meat and dairy products, and it’s claimed they have the same taste and texture. The technology is an attractive option not least because it would reduce the world’s reliance on livestock, which is unsustainable, but would also have potential knock-on benefits of lower greenhouse gas emissions, and reduced water, land and energy usage than traditional farming. Safety too would be improved since existing livestock practices have been linked to antibiotic resistance, viral outbreaks and cases of bacterial food contamination. Moreover, products could be tailored for specific markets, such as meat with fewer saturated fats, milk without lactose, or eggs without cholesterol.

IndieBio is in the business of helping biotechnology startups. Since 2014, it has funded several US-based startups in cellular agriculture: Perfect Day, formerly Muufri, makes milk from cell culture; Clara Foods is developing a way to make egg whites from cell culture; Memphis Meats is focusing on animal-free meat using tissue engineering; Gelzen is trying to make gelatin from bacteria and yeast; and Afineur is working on cultured coffee beans where fermentation using specific microbes eliminates unwanted bitter notes. According to IndieBio, start-up companies developing this technology attracted over $20m investment funding in 2016.

Growth is driven by the clear benefits this technology offer, says Ron Sigeta, IndieBio’s chief scientific officer. ‘It takes 144 gallons of water to make a gallon of milk or 53 gallons of water to make an egg. Cellular agriculture products don’t require such large water supplies, or large tracts of land, or produce the same level of greenhouse gas emissions.’ He continues: ‘Ultimately, cellular agricultural companies are producing the same food on a molecular level and when this is seen and tasted, it will be clear how useful this approach is. There really is nothing else promising to help us all eat affordably in a world of 10bn people and live in equilibrium with the planet.’

Food safety is a big issue. ‘Cellular agriculture makes products in an entirely controlled environment so it’s a source of food we can understand with a transparency that is simply not possible now,’ says Sigeta. ‘For example, Memphis Meats is producing meats with no bacteria, which is not possible for slaughtered meat. Perfect Day will produce milk which has a bacterial content not possible from dairy milk.’ Raw unpasteurised milk can carry bacteria like salmonella etc which is not a problem for Perfect Day’s milk as no bacteria-carrying animals are involved. The company says it will be ‘free of the food safety and bacterial contamination risks that come with dairy products’. However, it also says that it will probably pasteurise its milk just to be on the safe side.

Significantly, Sigeta adds that the time to market for these technologies is shorter than one might think. ‘Start-up economics don’t allow 10-year runways to get a product to market. It’s three to five years typically, and these small companies can show that they have a good chance of making those milestones.’


So how does it work?

Cellular agriculture products can be acellular, ie made of organic molecules like proteins and fats, or cellular ie made of living or once-living cells.

Acellular products are made without animals by using microbes like yeast or certain bacteria. Scientists alter the yeast by inserting the gene responsible for making the desired protein, for example casein if making milk. Since all cells read the same genetic code, the yeast, now carrying recombinant DNA, makes casein molecularly identical to the casein cows make.

Animal insulin was possibly the first acellular agriculture product. In 1978, Arthur Riggs, Keiichi Itakura and Herbert Boyer inserted the gene for making human insulin into a bacteria, allowing the bacteria to make insulin identical to human insulin. Today, the vast majority of insulin is made this way. Another example is rennet, a mixture of enzymes that turns milk into cheese. Traditionally, rennet was extracted from the inner lining of the fourth stomach of calves. Today, the majority of cheese-making uses rennet enzymes from genetically-engineered bacteria, fungi, or yeasts. 

There are several acellular animal products getting close to market. For example, Perfect Day plans to start selling its dairy-free milk in late 2017. The company is genetically engineering a standard yeast to ferment sugar to create the milk proteins casein and whey. These proteins will then be combined with plant-based, ie lactose-free, sugar, plant fats such as sunflower oil, vitamins and minerals. None of the yeast appears in the final product. The company claims the product has the same taste and texture as cow’s milk.

Other products like meat and leather are produced by a cellular approach. Using tissue engineering techniques, muscle, fat or skin cells can be assembled on a scaffold together with nutrients. The cells can be grown in large quantities and then combined to make the product.

Mark Post at Maastricht University in The Netherlands made the world’s first cultured beef hamburger in 2013 using established tissue engineering methods to grow cow muscle cells. The process, however, was expensive and time-consuming, but his team has been working on improvements.

In his process, muscle-specific stem cells are taken from a cow in a harmless procedure, then isolated and allowed to proliferate so that trillions of cells arise from the sample. These cells self-assemble into groups of 1.5m to form small muscle tissues (2.5 x 0.1cm) similar to muscle fibres. The team uses 10,000 fibres to make a hamburger patty by adding salt, breadcrumbs and some binder.

In the near future, Post says they plan to grow fat tissue separately and combine it with muscle tissue in the patty. Fat cells are cultured from the same stem cells but follow a different path towards specialisation. Fat adds taste and texture to meat, and Post says they can control the amount of fat present. The team is also working on improving the protein content, most notably myoglobin, which gives the meat its red colour and heme-iron content.

Another focus of Post’s work is eliminating foetal bovine serum from the culture medium, the standard for culturing tissue. This is important, Post explains, because obtaining serum from unborn calves is incompatible with animal welfare standards and its use is inherently unsustainable, plus there is a disease risk. They’ve been ‘reasonably successful’ in developing alternatives he says, but are keeping them under wraps for the present.

Post with his colleague Peter Verstrate set up Mosa Meat in 2015 to commercialise cultured minced meat. They hope to introduce their first products in three to four years, probably to restaurants and speciality stores, and say it will be another two to three years before they reach supermarket shelves. ‘We are focusing on hamburgers because our process results in small tissues that are large enough for minced meat applications, which accounts for half of the meat market. To make a steak, one would need to impose a larger 3D structure to the cells to grow in. It is very important that such a structure contains a channel system to perfuse the nutrients and oxygen through to the developing tissue and to remove waste as a result of metabolic activity. This technology is being developed, but is not yet ready for large scale production.’

Since production is not yet at industrial scales, it is difficult to judge costs, but Post expects the price of a hamburger to be about $10. However, he foresees improvements in the technology will bring costs down and eventually cultured beef may even become cheaper than traditional beef as fewer resources are required to culture it.

Memphis Meats, founded in 2015 and based in California, is also growing meat using cells from pigs as well as cows. Set up by Uma Valeti, a cardiologist and associate professor of medicine at the University of Minnesota, with Nicholas Genovese, a stem cell biologist, and Will Clem, a biomedical engineer and restaurant owner, the company launched its first product – a meatball – in February 2016. The company expects shops to be selling its products within five years; it is also developing hot-dogs, hamburgers and sausages.

‘This is absolutely the future of meat,’ enthuses ceo Valeti. ‘We plan to do to animal agriculture what the car did to the horse and buggy. Cultured meat will completely replace the status quo and make raising animals to eat them simply unthinkable.’

Like any innovation-based company, Valeti says they have several patents under development to protect their process. Without disclosing any detail, he explains, ‘We start with real meat cells that have the ability to self-renew. We then feed these cells rich nutrients including vitamins, minerals and plants – the same way you’d feed grass to a cow – and let them grow into protein-packed meat. Once the meat has achieved the desired tenderness, we harvest it, and it is ready to be cooked. The whole process takes about two to three weeks; in contrast, it takes about 23 weeks to raise a cow for slaughter.’

Valeti faces the same challenges as Post. First, foetal bovine serum is used to initiate the process, although, like Post, they are developing a serum-free media. ‘We will be phasing out the use of serum in the R&D phase as soon as possible, and will never sell a product that requires serum,’ Valeti states. Secondly, cost is a major issue. ‘While our products are still too expensive for market,’ Valeti says, ‘we have seen significant reductions in the cost of production over the past few months, and are confident they’ll ultimately be more affordable than conventionally-produced meat.’

Meanwhile, Israeli startup SuperMeat says it is the first company to work on cultured chicken meat products for mass production and hopes to have a product on the market in around five years.  Co-founder Yaakov Nahmias at the Hebrew University of Jerusalem has developed a ‘unique technology’, which does not use any animal-derived ingredients besides the original cells.

Future outlook

A recent crowdfunding campaign shows the global massive support for the idea of clean meat, says Koby Barak, SuperMeat’s chief operating officer and co-founder. ‘While 99% of crowdfunding campaigns fail to reach $100,000 even though they already have a working prototype, we managed to raise more than $200,000 – from 5000 backers – of pre-ordered clean meat products from all around the world by giving vouchers for future purchase of SuperMeat’s products.’ In addition, the company aims to persuade meat companies to use its meat as their raw material instead of conventional meat. Barak says an Israeli meat company is in the process of joining the seed-round of investments at SuperMeat. ‘This cooperation is something that will pave the road for clean meat products to the global market,’ he adds.

However, New Harvest, a US non-profit research institute that funds cellular agriculture, points out the major challenges to commercialisation remain finding a cost-effective medium for cell nutrition; and developing the optimal bioreactor for industrial scale production.

Public perception may be another challenge. Will people buy synthetically engineered food? In early November, New Harvest and the Environmental Law Institute (ELI) in Washington DC launched a project to explore attitudes towards these products with the longer term aim of enabling more strategic investments in research. David Rejeski, who directs ELI’s project on technology, innovation and the environment, says: ‘Given the complex social and cultural forces that shape food consumption, understanding public perceptions will be critical to shaping research investments and commercialisation strategies.’

However, Barak believes these challenges will be overcome, and once they are, it will be a short time before companies see ‘massive funding’ in this field and the creation of clean meat factories all around the world. 


Seeking new hides
It’s not all about food. New York biotech company Modern Meadow is working on leather hides. It has genetically engineered a cell-line to produce collagen, a protein found in animal skin. The collagen cells group together to form triple helix collagen molecules, which then form into bundles of nanofibres. The company engineers the nanofibers to have properties such as suppleness and breathability, as well as new properties not possible from animal hide, such as improved strength-to-weight ratio.

Andras Forgacs, co-founder and ceo of Modern Meadow, says their biofabricated product reduces waste by up to 80% compared to traditional leather, since, unlike animal hide, it can be produced according to the size and shape required.

Having raised $53.5m in June 2016, Forgacs is now moving the company from R&D into commercialisation.‘We are going to be manufacturing our products at pilot scale and ultimately bringing them to market sometime in 2018.’


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