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Empirical economic analysis shows cost-effective continuous manufacturing of cultivated chicken using animal-free medium

Nature Food volume 5, pages 693–702 (2024)Cite this article

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Abstract

Cellular agriculture aims to meet the growing demand for animal products. However, current production technologies result in low yields, leading to economic projections that prohibit cultivated meat scalability. Here we use tangential flow filtration for continuous manufacturing of cultivated meat to produce biomass of up to 130 × 106 cells per ml, corresponding to yields of 43% w/v and multiple harvests for over 20 days. Continuous manufacturing was carried out in an animal-component-free culture medium for US$0.63 l−1 that supports the long-term, high density culture of chicken cells. Using this empirical data, we conducted a techno-economic analysis for a theoretical production facility of 50,000 l, showing that the cost of cultivated chicken can drop to within the range of organic chicken at US$6.2 lb−1 by using perfusion technology. Whereas other variables would also affect actual market prices, continuous manufacturing can offer cost reductions for scaling up cultivated meat production.

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Fig. 1: High flux, high density culture of chicken fibroblasts.
Fig. 2: Animal-component-free medium supports post-harvest recovery.
Fig. 3: Continuous manufacturing of cultivated chicken.
Fig. 4: Empirical economic analysis of 50,000 l continuous manufacturing facilities.

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Data availability

All data supporting the findings of this study are available within the paper, its Extended Data figures, its Source Data and Supplementary Information. Source data are provided with this paper.

References

  1. Pereira, P. M. & Vicente, A. F. Meat nutritional composition and nutritive role in the human diet. Meat Sci. 93, 586–592 (2013).

    Article  CAS  PubMed  Google Scholar 

  2. Babbitt, C. C., Warner, L. R., Fedrigo, O., Wall, C. E. & Wray, G. A. Genomic signatures of diet-related shifts during human origins. Proc. Biol. Sci. 278, 961–969 (2011).

    PubMed  Google Scholar 

  3. Shepherd, G. M. Smell images and the flavour system in the human brain. Nature 444, 316–321 (2006).

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Aiello, L. C. & Wheeler, P. The expensive-tissue hypothesis: the brain and the digestive system in human and primate evolution. Curr. Anthropol. 36, 199–221 (1995).

    Article  Google Scholar 

  5. Min, S., Bai, J.-f, Seale, J. & Wahl, T. Demographics, societal aging, and meat consumption in China. J. Integr. Agric. 14, 995–1007 (2015).

    Article  Google Scholar 

  6. Alexandratos, N. & Bruinsma, J. World Agriculture Towards 2030/2050: The 2012 Revision (FAO Agricultural Development Economics Division, 2012).

  7. Falcon, W. P., Naylor, R. L. & Shankar, N. D. Rethinking global food demand for 2050. Popul. Dev. Rev. 48, 921–957 (2022).

    Article  Google Scholar 

  8. Jiménez Cisneros, B. E. et al. in Climate Change 2014: Impacts, Adaptation, and Vulnerability (ed Kundzewicz, Z.) 229–269 (Cambridge Univ. Press, 2014).

  9. Tuomisto, H. L. & de Mattos, M. J. Environmental impacts of cultured meat production. Environ. Sci. Technol. 45, 6117–6123 (2011).

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Tuomisto, H. L., Ellis, M. J. & Haastrup, P. In Proc. of the 9th International Conference on Life Cycle Assessment in the Agri-Food Sector (eds Schenck, R. & Huizenga, D.) 1360–1366 (ACLCA, 2014).

  11. Tuomisto, H. L., Allan, S. J. & Ellis, M. J. Prospective life cycle assessment of a bioprocess design for cultured meat production in hollow fiber bioreactors. Sci. Total Environ. 851, 158051 (2022).

    Article  CAS  PubMed  Google Scholar 

  12. Risner, D. et al. Preliminary techno-economic assessment of animal cell-based meat. Foods https://doi.org/10.3390/foods10010003 (2020).

  13. Humbird, D. Scale-up economics for cultured meat. Biotechnol. Bioeng. 118, 3239–3250 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Negulescu, P. G. et al. Techno-economic modeling and assessment of cultivated meat: impact of production bioreactor scale. Biotechnol. Bioeng. 120, 1055–1067 (2023).

    Article  CAS  PubMed  Google Scholar 

  15. Garrison, G. L., Biermacher, J. T. & Brorsen, B. W. How much will large-scale production of cell-cultured meat cost?. J. Agric. Food Res. 10, 100358 (2022).

    Google Scholar 

  16. Vergeer, R, Sinke, P & Odegard, I. TEA of Cultivated Meat. Future Projections of Different Scenarios—Corrigendum Publication code 21.190254.020 (CE Delft, 2021).

  17. Li, X. et al. A conceptual air-lift reactor design for large scale animal cell cultivation in the context of in vitro meat production. Chem. Eng. Sci. 211, 115269 (2020).

    Article  CAS  Google Scholar 

  18. Meuwly, F. et al. Conversion of a CHO cell culture process from perfusion to fed-batch technology without altering product quality. J. Biotechnol. 123, 106–116 (2006).

    Article  CAS  PubMed  Google Scholar 

  19. Pasitka, L. et al. Spontaneous immortalization of chicken fibroblasts generates stable, high-yield cell lines for serum-free production of cultured meat. Nat. Food 4, 35–50 (2022).

    Article  PubMed  Google Scholar 

  20. National monthly pasture raised poultry report. USDA Livestock, Poultry, and Grain Market News (USDA, 2024).

  21. Pollock, J., Ho, S. V. & Farid, S. S. Fed-batch and perfusion culture processes: economic, environmental, and operational feasibility under uncertainty. Biotechnol. Bioeng. 110, 206–219 (2013).

    Article  CAS  PubMed  Google Scholar 

  22. Shiozuka, M. & Kimura, I. Improved serum-free defined medium for proliferation and differentiation of chick primary myogenic cells. Zool. Sci. 17, 201–207 (2000).

    Article  Google Scholar 

  23. Stout, A. J. et al. Simple and effective serum-free medium for sustained expansion of bovine satellite cells for cell cultured meat. Commun Biol 5, 466 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Francis, G. L. Albumin and mammalian cell culture: implications for biotechnology applications. Cytotechnology https://doi.org/10.1007/s10616-010-9263-3 (2010).

  25. Hammer, M. E. & Burch, T. G. Viscous corneal protection by sodium hyaluronate chondroitin sulfate and methylcellulose. Invest. Ophthalmol. Visual Sci. 25, 1329–1332 (1984).

    CAS  Google Scholar 

  26. Goldblum, S., Bae, Y.-K., Hink, W. F. & Chalmers, J. Protective effect of methylcellulose and other polymers on insect cells subjected to laminar shear stress. Biotechnol. Prog. 6, 383–390 (1990).

    Article  CAS  PubMed  Google Scholar 

  27. Shulman, M. et al. Enhancement of naringenin bioavailability by complexation with hydroxypropyl-beta-cyclodextrin. PLoS ONE 6, e18033 (2011).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cruz, H. J., Freitas, C. M., Alves, P. M., Moreira, J. L. & Carrondo, M. J. T. Effects of ammonia and lactate on growth, metabolism, and productivity of BHK cells. Enzyme Microb. Technol. 27, 43–52 (2000).

    Article  CAS  PubMed  Google Scholar 

  29. Freund, N. W. & Croughan, M. S. A simple method to reduce both lactic acid and ammonium production in industrial animal cell culture. Int. J. Mol. Sci. 19, 385 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Pavlova, N. N. et al. As extracellular glutamine levels decline, asparagine becomes an essential amino acid. Cell Metab. 27, 428–438 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Genovese, N. J., Domeier, T. L., Telugu, B. P. & Roberts, R. M. Enhanced development of skeletal myotubes from porcine induced pluripotent stem cells. Sci Rep. 7, 41833 (2017).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ding, S. et al. Maintaining bovine satellite cells stemness through p38 pathway. Sci Rep. 8, 10808 (2018).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  33. Ben-Arye, T. et al. Textured soy protein scaffolds enable the generation of three-dimensional bovine skeletal muscle tissue for cell-based meat. Nat. Food 1, 210–220 (2020).

    Article  CAS  Google Scholar 

  34. Abecasis, B. et al. Expansion of 3D human induced pluripotent stem cell aggregates in bioreactors: bioprocess intensification and scaling-up approaches. J. Biotechnol. 246, 81–93 (2017).

    Article  CAS  PubMed  Google Scholar 

  35. Clincke, M. F. et al. Very high density of CHO cells in perfusion by ATF or TFF in WAVE bioreactor. Part I. effect of the cell density on the process. Biotechnol. Prog. 29, 754–767 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Martin, C. S. et al. Novel small scale TFF cell retention device for perfusion cell culture systems. BMC Proc. 9, 1–2 (2015).

    Article  Google Scholar 

  37. Specht, L. An Analysis of Culture Medium Costs and Production Volumes for Cultivated Meat (The Good Food Institute, 2020).

  38. Huang, Y. M. et al. Maximizing productivity of CHO cell-based fed-batch culture using chemically defined media conditions and typical manufacturing equipment. Biotechnol. Prog. 26, 1400–1410 (2010).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the Sam and Rina Frankel Foundation (donation; Y.N.) and Believer Meats (Y.N.) for funding this work. Further, we thank H. Zukerman Narodizky, M. Gabay, M. Mendelovich, K. Pasternak, A. Bohadana, L. Shirony, A. Keter, A. Fallek and J. Amar for technical support.

Author information

Authors and Affiliations

  1. Grass Center for Bioengineering, The Hebrew University of Jerusalem, Jerusalem, Israel

    Laura Pasitka, Muneef Ayyash & Yaakov Nahmias

  2. Believer Meats, Rehovot, Israel

    Guy Wissotsky, Muneef Ayyash, Nir Yarza, Gal Rosoff, Revital Kaminker & Yaakov Nahmias

  3. Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel

    Yaakov Nahmias

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  1. Laura Pasitka
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Contributions

Conceptualization and funding by Y.N. Investigation by L.P., G.W., M.A., N.Y., G.R. and R.K. Methodology by Y.N., L.P., G.W., M.A., N.Y., G.R. and R.K. Writing by Y.N. and L.P.

Corresponding author

Correspondence to Yaakov Nahmias.

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Competing interests

Y.N. is a director and shareholder in Believer Meats. G.W., N.Y., G.R., M.A. and R.K. are employees of Believer Meats. The other author declares no competing interests.

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Nature Food thanks Xin Wu and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Extended data

Extended Data Fig. 1 Expansion of chicken fibroblasts in perfused bioreactor systems.

(a,b) Filtrate flux and Cell-specific perfusion rate (CSPR) in ATF and TFF experiments in lab-scale. (c) Comparison of cell densities obtained in hollow fibre (0.2 μm cut-off) experiments in ATF and TFF mode. (d) Filtrate flux in hollow fibres in ATF and TFF. (e) Glucose, lactate, glutamine and ammonium concentrations measured in hollow fibre experiments operated in ATF and TFF mode. (f) Shear rates through hollow fibres in ATF and TFF.

Source data

Extended Data Fig. 2 Development of animal-component-free culture medium for chicken fibroblasts.

(a) Schematic showing the selection of various culture medium compounds to replace albumin. (b) Cell density in ACF with various methylcellulose concentrations. Data are presented as means plus standard error of the mean (n=3). Error bars represent variation of biological repeats. (c) Cell density in ACF with various antioxidant solution concentrations. Data are presented as means plus standard error of the mean (n=3). Error bars represent variation of biological repeats. (d) Cell density in ACF with various 2-hydroxypropyl-β-cyclodextrin (HPBCD) concentrations. Data are presented as means plus standard error of the mean (n=3). Error bars represent variation of biological repeats. (e) Viable cell density, and glucose and lactate concentrations in finalized SFM and ACF compositions, respectively. Data are presented as means plus standard error of the mean of technical repeats (n=2). Panel a created with BioRender.com.

Source data

Extended Data Fig. 3 Development of a perfused chicken fibroblast culture with contiguous partial harvests.

(a) Multiple TFF experiments showing first ten days following inoculation in SFM and ACF, respectively. TFF circulation indicates the day on which the bioreactor suspension started circulating in the TFF loop. (b) TFF circulation rate is identical to the low-shear magnetic levitation pump output, describing the circulation speed in the TFF loop. (c) Shear rate as a result of TFF circulation rate does not exceed 2500 s−1 to prevent shear damage. (d) Contiguous harvest experiments in SFM. (e) Metabolite concentrations in contiguous harvest experiments in SFM. (f) Contiguous harvest experiments in ACF. (g) Metabolite concentrations in contiguous harvest experiments in ACF. (h) Summary of run parameters for contiguous harvest experiments in SFM and ACF. Average plus/minus standard error of the mean of two experiments in SFM, and three experiments in ACF, respectively. (i) Filtrate flux and Cell-specific perfusion rate (CSPR) in SFM and ACF experiments in lab-scale.

Source data

Extended Data Fig. 4 Characteristics of a chicken fibroblast culture with contiguous partial harvests.

(a) Relative daily uptake of amino acids measured in spent medium of samples taken daily from the TFF-bioreactor. (b) Cell diameter measured in samples taken from the TFF-bioreactor run daily for analysis on days 0 through 20. Data are presented as means plus/minus standard error of the mean of biological repeats (n=2).

Source data

Extended Data Fig. 5 Scalability of perfusion technologies.

(a,b) ATF and TFF system assembly in pilot-scale (300 l bioreactor vessel).

Source data

Supplementary information

Supplementary Information

Supplementary Tables 1–11.

Reporting Summary

Source data

Source Data Fig. 1

Statistical source data.

Source Data Fig. 2

Statistical source data.

Source Data Fig. 3

Statistical source data.

Source Data Fig. 4

Statistical source data.

Source Data Extended Data Figs. 1–5

Statistical source data.

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Pasitka, L., Wissotsky, G., Ayyash, M. et al. Empirical economic analysis shows cost-effective continuous manufacturing of cultivated chicken using animal-free medium. Nat Food 5, 693–702 (2024). https://doi.org/10.1038/s43016-024-01022-w

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