Lab-Grown Meat: Strategies for Lowering Production Costs

Maurizio Ferri

Livestock farming and conventional meat production pose significant environmental, health, and animal welfare challenges. In seeking sustainable protein alternatives, in the last decade, cultivated meat technology has made considerable advancements to offer the opportunity, together with plant-based foods, seafood developed from animal cells, and protein produced through fermentation, to make animal protein production more sustainable, and with reduced environmental footprints. Several peer-reviewed life cycle assessment (LCA) studies have demonstrated that using cellular agriculture, cultured meat reduces nitrogen emissions, land use, and animal welfare concerns, offering a sustainable solution to meet global protein demand.

The cell-cultured protein industry is still very much in development, and one of its biggest challenges is how to feed protein cells cost-efficiently, sustainably, and at scale. Today’s production of cultured meat borrows heavily from the pharmaceutical industry's know-how, infrastructure, and bioprocesses, with appropriate adaptations. This implies the high cost of culture media containing pharmaceutical-grade ingredients, growth factors, and recombinant proteins. To be a viable and sustainable alternative to conventional meat production and to scale up, cellular agriculture requires cost-effectiveness analysis of materials, lowered cost, and optimization of culture media, with environmentally friendly nutrients, developing cheaper plant-based growth factors that are non-GMO, new media formulations to maximize production, reduction in energy and consolidation of related supply chains.

Traditional cultured meat production techniques rely on chemically undefined media using fetal bovine serum (FBS), which has economic and ethical limitations, and chemically defined culture media using specific growth factors. Among the cost drivers, culture media,?which contain nutrients and growth factors, account for 50% to 99% of the material costs of producing cultured meat. Start-ups and research centres are making significant strides to reduce costs or quantities (g/kg) and to support the scaling up of the sector. Today, there is a range of solutions to reduce costs, which include:

• selection of lower-cost ingredients
• use of smaller amounts of culture media
• new culture media formulations that allow efficient cell growth through the modeling of metabolic pathways
• replacement of pharmaceutical components of high-cost media with food or feed-grade components
• alternative protein sources (e.g. new proteins obtainable with the use of light for photo molecular platform)
• alternative growth factors and/or their recycling
• engineering of cell lines to reduce feed conversion ratios and waste (lactate and ammonia)
• use of immortalized cells (e.g. chicken fibroblasts) that adapt to low serum or serum-free culture media.
• recycling of culture media

Microalgae as a source of glucose

Most of the glucose in traditional culture media for lab-grown meat comes from growing grains such as corn and wheat, which impact the environment through water consumption, fertilizers, and pesticides. Recent research points to microalgae as a key player in the future of cultured meat, making it less dependent on grain and animal inputs, and with many other benefits.

A study carried out in Japan showed that two strains of microalgae (Chlorococcum littorale, and Chlorella vulgaris) can provide cell cultures with glucose, amino acids, and other nutrients. The cultivation of microalgae, which does not require fertilizers and pesticides, and has low water consumption, can also take place on land not suitable for agriculture, including urban areas. Moreover, microalgae-based systems can feed a circular system of cell culture in which, at the end of the cycle, the residual culture media that contain ammonia and lactates can feed the microalgae capable of removing up to 80% of the ammonia and 16% of phosphorus. The immediate goal is to have a closed system of 30 m2 capable of producing one kilogram of cultured meat per day by 2030.

This circular system, which works without the addition of grain-derived nutrients and animal sera, could help reduce environmental impact and resource/energy consumption in future cultured meat production. An important waste compound in cultured animal cells is L-lactate, which is naturally used by most algae. To remove lactate from waste culture media and develop a sustainable animal cell culture system, Japanese researchers introduced a gene from Escherichia coli into Synechococcus, a unicellular cyanobacterium widespread in the marine environment, that encodes L-lactate dehydrogenase, which converts lactate into pyruvate, a metabolite that can, in turn, be converted into glucose by cells. Research laboratories and companies in Asia, Europe, and the United States are pursuing similar concepts. The company Mewery is even co-cultivating animal cells with microalgae, that consume ammonia, provide oxygen, express recombinant growth factors, and become part of the final product. This strategy could provide a less energy- and land-intensive solution for large-scale culture media production. Future studies should scientifically compare the costs and environmental impact of cultured meat production supplemented with microalgae versus more conventional means of producing inputs for the land.

The hydrolysates

Two new LCA studies of cell culture media for cultured meat published by Tufts University Center for Cellular Agriculture (TUCCA) and the University of Helsinki, while confirming the environmental impact of the culture media, demonstrated that plant proteins, such as rapeseed protein isolates or agricultural hydrolysates of animal products (e.g. egg whites) can replace high-impact recombinant proteins or animal serum, thus significantly reducing the environmental impact. The Tufts LCA study showed that reducing the level of FBS in the media from 10 to 2% (v/v) allowed for reductions in all the environmental impact items studied. Further reductions were achieved when FBS was completely replaced by basal media, such as DMEM/F12, Essential 8?, protein hydrolysates, and recombinant growth factors. Soil used was the least reduced input, as the reduction was conditioned by the starch extraction to produce the glucose required for the DMEM/F12 medium. The culture medium with protein hydrolysates from egg white achieved higher impact reductions than the FBS-containing medium.

An Australian study showed that, under certain conditions, hydrolysates from Kikuyu grass, alfalfa grass, and cattle-rearing pellets promoted the growth of C2C12 myoblast cells in culture media containing just 0.1% or even 0% serum. Cell proliferation was most pronounced when hydrolysates were combined with growth promoters, such as insulin, transferrin, and selenium.

A similar study from Texas A&M University demonstrated the potential of alfalfa protein isolate as a promising component of serum-free culture media for the proliferation of bovine satellite cells (BSC). These results confirm that existing, low-cost feedstocks can provide a suitable nutrient source for cultured cells, and highlight the need for continued research into alternative protein sources and new media formulations to support the sustainable and ethical production of cell growth media.

The Good Food Institute (GFI), a non-profit organization that supports needed research, policy, and investment in alternative proteins, stated it will fund several projects on hydrolysate optimization through the end of 2024. Future studies should focus on modeling the food manufacturing processes of current large-scale suppliers of amino acids, recombinant proteins, and other inputs that serve the industry. Moreover, study is needed into processes for preparing and shipping finished powder formulas, such as those being pursued in new facilities. Nutreco, which has previously partnered with several startups to provide low-cost culture media, announced that it has completed construction on the world’s first dedicated food-grade powder production facility for cell feed in Boxmeer, The Netherlands, and brought it up to commercial operation. This facility is now producing the first cell feed product developed specifically for the cell-cultured meat industry.

Growth factors and recombinant proteins

Growth factors (also contained in FSB) and other recombinant proteins, essential for helping muscle cells grow and differentiate via a carefully orchestrated set of biochemical signals, are another important cost item for the production of cultured meat, with over 95% of this cost driven by albumin and transferrin, which are typically sourced from animal serum, such as FSB. Manufacturers are currently oriented towards scaling growth factor production using microbes, fungi, or plants as expression systems, or replacing growth factors and recombinant protein with plant-based alternatives, especially for proteins used at high concentrations in the culture media, such as albumin and transferrin. Recombinant production of these proteins in transgenic plants and microorganisms is a powerful and scalable approach, but it still poses limitations in terms of cost, scale, and infrastructure requirements. Identifying and validating native plant sources of proteins with suitable functionality to mimic the roles of serum albumin and transferrin would reduce the need for extra research and development in recombinant production and allow for greater scalability via direct extraction from crops. Japanese researchers have cultivated animal cells without using FBS, by incubating the cell culture medium with cells from farm animal organs, such as livers or placentas, which secrete growth factors. In this way, it will no longer be necessary to resort to the expensive purification process of growth factors derived from other sources.