Cellular food

Foods made from lab grown cells promise to be far less environmentally damaging. And meat is not the only produce that scientists are striving to manufacture this way. Anthony King reports

The term cellular agriculture was coined in 2015 and is often synonymous with cultured meat. In 2013, Mark Post at Maastricht University grabbed news headlines by making a hamburger patty grown directly from cells. Fast-forward to December 2020, and diners in Singapore tucked into a dish of lab-grown chicken made by a US start-up, Just Eat, after the country’s food agency approved the sale of cultured meat.

But cultured meat is not the only produce that scientists and start-up companies are striving to manufacture using cellular agriculture. Cells can be grown to generate cheese, milk, foie gras, leather, coffee, cocoa and even palm oil, although these efforts are not yet commercial. The objective is to make such foodstuffs using far less resources than traditional production methods.

‘What is now at the stage of commercialisation is the microbial systems,’ says Rischer Heiko at the Technical Research Centre of Finland, which can be genetically altered by inserting, for example, a gene to make the important milk protein casein. ‘You can get, more or less, the same proteins you would otherwise get from animal sources.’

Nourish Ingredients in Canberra, Australia, relies on yeast fermentation to brew animal-free fats for the food industry, while Geltor in California, US, creates animal-free gelatin by using yeast to generate the protein collagen. In Finland, Solar Foods is producing a protein-rich powder as a food ingredient using sunlight, CO₂ and nutrients.

Such ‘acellular’ products comprise ‘organic molecules like proteins and fats and contain no cellular or living material in the final product,’ whereas cellular products are made of living or once-living cells, notes US-based New Harvest, a nonprofit research institute dedicated to advancing cellular agriculture. Since the 1990s, the essential enzyme rennet in cheese making has been made by genetically engineering microbes such as bacteria and yeast, with 80% of rennet now produced by fermentation. Previously, this had to be extracted from the stomach lining of calves.

But proponents of cellular agriculture look beyond microbes, to animal and plant cells. ‘The idea is to cultivate in a vat or lab those tissues of either a plant or an animal that are desirable for human consumption.’ says Johannes le Coutre at the University of New South Wales, Australia. He is researching, among other topics, the use of fermented Australian plant material as a feedstock for animal cells used to culture meat products. A food scientist with decades of experience in Nestlé, le Coutre frames cellular agriculture as ‘something of historical significance’ – like the invention of fire to cook meat.

[Cellular agriculture] used to be used synonymously for cultured meat, whereas now people are really understanding, at least in industry, the breadth of products even beyond foods.
Bianca Le director and founder of Cellular Agriculture Australia

‘When I learnt about cellular agriculture in 2018, I realised there was a really effective way to use my expertise to solve so many of the world’s most pressing challenges,’ says Bianca Le, Director and Founder of Cellular Agriculture Australia. She sees ‘cell ag’ as a way cell to help mitigate against climate change, reduce animal suffering and boost sustainability. The term cellular agriculture ‘used to be used synonymously for cultured meat, whereas now people are really understanding, at least in industry, the breadth of products even beyond foods,’ she adds.

Ironically, while cultured meat garners headlines and startups attract funding, growing meat in a dish is more complicated than culturing microbes or plant cells. This is the view of Heiko in Finland, who notes that animal cells usually prefer to grow attached to a surface rather than in a suspension and require complex media. ‘Plant cells are actually a little bit behind in development [in cell ag],’ says Heiko. His lab recently grew cells from coffee plants, starting with clumps of cells that plants typically produced when injured. This wound tissue was sterilised and then incubated on growth media at 23-27°C.

Heiko placed his coffee cells into a liquid broth of salts, nutrients and micronutrients as well as sucrose as a source of energy for the cells. The coffee cells did not photosynthesise, but grew as ‘heterotrophs’ in a bioreactor, absorbing nutrients from the liquid medium. ‘We wanted to showcase the technology from the start to the end with a product that was very tangible,’ explains Heiko. The smoothie-like reactor output was dried and roasted in an oven before being added to boiling water to produce a hot beverage. ‘In chemical analyses of this brew and of conventional coffee, there was significant overlap of flavour compounds,’ says Heiko, adding that a sensory panel was amazed when comparing its aroma and taste to conventional coffee.

Coffee made this way would reduce the amount of water, fertiliser inputs and run-off and pesticide used, explains Heiko. It might also allow for coffee production using cells in northern Europe, meaning that the commodity would not have to be shipped long distances. Asked about concerns about coffee farmers being ousted by cell ag coffee, Heiko says climate change will threaten coffee growing in many areas and naturally grown coffee could end up attracting a premium price, above that of cell-based produce.

In another example, Regine Eibl and Tilo Hühn at Zurich University of Applied Sciences in Switzerland made chocolate in a bioreactor. Eibl recently reviewed cellular agriculture and noted that microorganisms grown in bioreactors already produce egg and milk proteins, sweeteners, and flavours for human nutrition, as well as leather and fibres for shoes, bags and textiles (Annu. Rev. Food. Sci. Technol., 2021, 12, 51). She made her lab chocolate by first slicing cocoa beans and then growing them in complete darkness on a culture medium, where a rough callus grew on the cut surfaces after about three weeks. This material was placed into a liquid medium that was then placed into a shaking flask in the lab. The slush from the bioreactor was dried to produce a powdery compact material that was roasted to give a more chocolate-like colour and aroma. This material was mixed with cocoa butter, sugar and lecithin, to then make 70% dark chocolate bars. It tasted less bitter and more fruity than regular dark chocolate, according to a sensory panel.

Plant cultures are already used in the pharma industry to make compounds at scale. Phyton Biotech headquartered in Canada manufactures almost 1000kg of pharmaceutical-grade paclitaxel at a plant cell fermentation facility near Hamburg, Germany, that is sold as chemotherapy drug Taxol by Bristol-Myers Squibb. The fermentation involves a cell line developed from the Chinese yew, Taxus chinensis v. marei, and does not involve genetic engineering.

The challenge for cellular agriculture, however, is cost. High prices are fine for pharmaceutical ingredients, but agricultural commodities are often incredibly cheap. The Swiss scientists estimate that their chocolate would cost five to ten times more than traditional organic chocolate, though large-scale production would be expected to bring the price down. ‘With plants, the whole game really boils down to economic feasibility and numbers,’ says le Coutre, while he notes that for cellular agriculture, the biggest improvements necessary will be scaling up and making costs affordable.

The cost challenge is also a hurdle for cellular meat. ‘I think consumers will always go for the most affordable meat, which at this point is still obtained through factory farming,’ says le Coutre, especially since ‘the current price of conventional animal-based meat is too low’ and doesn’t include the true costs to the environment.

In the UK, chemical engineer Chris Chuck at the University of Bath has switched his focus from biofuels to sustainable oils for the food industry, especially sustainable palm oil. In 2018, 71m t of palm oil was produced, with two-thirds of the oil going into foods. But palm oil is a major driver of deforestation, leading to the loss of biodiverse rainforests in countries such as Indonesia and Malaysia. Around 70% of palm oil is used as a cooking oil or as a food ingredient, but it is also used in the manufacture of oleochemicals and surfactants for cleaning and personal care products. Creating cellular systems for palm oil is a big challenge. First, palm oil is solid at room temperature and contains more palmitic acid than other oils, which adds mouthfeel. It is also one of the cheapest oils. ‘The price fluctuates dramatically between [approximately] $500 and $1000/t, whereas rapeseed oil is $1200 to $1500/t,’ says Chuck. He estimates cell-based systems for palm oil would cost $3000 to $5000/t.

Even at its theoretical optimum best, ‘you cannot compete with the simplistic growing of a palm plantation,’ says Chuck (Biotechnol. Biofuels, 2021, doi: 10.1186/s13068-021-01911-3). To reduce costs and boost sustainability, he has converted woody biomass into valuable chemical products using low temp microwave heating with fermentation of the ubiquitous yeast species Metschnikowia pulcherrima (J. Cleaner Production, 2018, 198, 776). This robust species of yeast, under certain conditions, produces 40% of its own weight in oil in a semi-continuous process, says Chuck. His previous research showed how this yeast could be used to generate fuel oils and valuable hydrocarbons for the polymer industry (ACS Sustainable Chem. Eng., 2015, 3, 1526-35).

But generating palm oil alone at high yields is unlikely to achieve commercial viability. ‘We are looking to develop this technology by moving beyond the idea of separating out a pure oil to compete directly with palm oil, but rather producing other products in a biorefinery, such as fragrances,’ Chuck explains. ‘As soon as you produce more than one product, you can spread the costs of production across multiple products.’ This involves a UK-registered company called the Clean Food Group that is now at pilot scale and perhaps three to five years away from commercialising the process.

Meanwhile, there has been a rising tide of consumer and investor interest. ‘There is a lot of investor money around in the cell ag space currently,’ confirms Heiko, ‘with dedicated investors for cell ag. This is amazing.’ Mostly they are funding startup companies, while the big food groups keep a watching brief.

However, Le Coutre cautions: ‘It’s important to attract interest and inject funding, but when it comes to overselling, we have to be cautious. Such as when people said in 2015, we would have products on the shelves in two years, and its 2021 and still there’s nothing on the shelves, then you have to be careful to maintain credibility.’