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Ann. N.Y. Acad. Sci.

ISSN 0077-8923

A N N A L S O F T H E N E W Y O R K A C A D E M Y O F SC I E N C E S
Issue: Frontiers in Agricultural Sustainability

An alternative animal protein source: cultured beef


Mark J. Post
Department of Physiology, Maastricht University, Maastricht, the Netherlands

Address for correspondence: Mark J. Post, M.D., Ph.D., Department of Physiology, Maastricht University, Universiteitssingel
50, 6229 ER Maastricht, the Netherlands. m.post@maastrichtuniversity.nl

Alternative sources of animal proteins are needed that can be produced efficiently, thereby providing food security with
diminished ecological burden. It is feasible to culture beef from bovine skeletal muscle stem cells, but the technology
is still under development. The aim is to create a beef mimic with equivalent taste, texture, and appearance and
with the same nutritional value as livestock-produced beef. More specifically, there is a need for optimization of
protein content and fat content. In addition, scalability of production requires modification of current small-scale
bioreactors to the largest possible scale. The necessary steps and current progress suggest that this aim is achievable,
but formal evidence is still required. Similarly, we can be optimistic about consumer acceptance based on initial
data, but detailed studies are needed to gain more insight into potential psychological obstacles that could lead to
rejection. These challenges are formidable but likely surmountable. The severity of upcoming food-security threats
warrants serious research and development efforts to address the challenges that come with bringing cultured beef
to the market.

Keywords: cultured beef; food security; stem cell; skeletal muscle

rigorous restraint in meat consumption, but success


Introduction
is unlikely given the steady small size of the vegetar-
As a result of projected population growth and in- ian population in industrialized meat-eating coun-
creases in welfare, meat demand is expected to in- tries. Also, meat analogues from vegetable protein
crease by 73% by 2050, while production of meat sources, thus far, fail to capture a substantial mar-
through livestock may remain stagnant.1 Livestock ket share beyond the traditional vegetarian target
production of beef is particularly inefficient, as cat- population.
tle reach a conversion rate of feed to animal proteins The development of cultured beef from
of approximately 15%. Pigs may reach a conversion bovine skeletal muscle stem cells through tissue-
rate of 30% and chickens reach even higher rates. engineering techniques is potentially a resource-
Livestock consume a large part of our natural food efficient way to grow meat. Proof of concept was
resources that we could use to directly feed humans provided in 2013 by our lab, yet it is fair to say that
and which could potentially eliminate food short- the technology is still in its infancy and that some
ages at a global scale. In addition, livestock con- obstacles need to be cleared before it can reach its
tribute appreciably to greenhouse gas (GHG) emis- full potential.
sion, in particular methane emitted by ruminants. For cultured beef to become a viable alternative
It is estimated that livestock farming contributes to livestock beef, its production needs to be resource
up to 15% of total GHG emission. The numbers efficient, sustainable, scalable, and lead to a product
are alarming, but also provide the opportunity to that is indistinguishable from current beef. In ad-
improve the current production system and revert dition, consumers need to accept cultured beef as a
some of the negative outcomes of beef production.2 worthy and ultimately preferable equivalent of the
Alternatively, we could strive for a global reduc- traditional product. These challenges are formidable
tion in meat demand by promoting vegetarianism or but likely surmountable. The severity of upcoming

doi: 10.1111/nyas.12569
Ann. N.Y. Acad. Sci. 1328 (2014) 29–33 
C 2014 New York Academy of Sciences. 29
Cultured beef Post

food security threats warrants serious research and medium. The proliferation phase requires the largest
development efforts to address the challenges that amount of medium: 80% of the total medium used
come with bringing cultured beef to the market. for culturing beef. This technology would still pro-
duce a sixfold higher efficiency (225 g instead of
Efficiency of cultured beef
1.33 kg for 200 g beef protein). Some of that gain in
The stem cell technology to produce cultured beef efficiency will be lost again with the production of
requires four steps (Fig. 1): (1) harvesting of stem purified amino acids that are palatable for cells in
cells, (2) expansion of stem cell numbers, (3) differ- culture. Although the resources needed to produce
entiation of stem cells into skeletal muscle cells and beef could be reduced, this does not automatically
fibers, and (4) assembly into the final meat product. mean that the cost of production will be lower as
Skeletal muscle–specific stem cells, so-called well. For instance, cells require single amino acids
satellite cells, are harvested from a small piece of as feed, and they need to be synthesized or retrieved
bovine muscle tissue (e.g., taken through a biopsy from proteins through digestion, adding costs to the
needle). A needle biopsy is a harmless and small production process.
procedure that requires little resources, other than The production of the final meat product is equiv-
some labor. The subsequent mechanical and en- alent for beef produced through livestock or cell
zymatic digestion steps to isolate the satellite cells culture and will therefore not result in differences
also mainly cost labor and very little material or in efficiency.
energy.
Sustainability of cultured beef
Expansion of cells, on the other hand, requires
feed in the form of cell culture medium, a fluid that For this discussion, sustainability will be used in a
contains glucose, amino acids, minerals, vitamins, very strict sense, meaning that no natural resource
and buffers. The amino acids are typically produced will be depleted to threaten long-term production
by bacterial fermentation, and a large percentage of of beef at a scale that is sufficient to satisfy the pro-
amino acid production is already used to supple- jected future demand. Sustainability issues should
ment feed for livestock. Energy sources such as glu- be largely related to resource efficiency or produc-
cose are typically of plant origin and easy to extract tion. However, current particulars of cultured beef
and purify. Vitamins are synthetized or extracted are inherently unsustainable. Traditional cell cul-
from plants. During differentiation and tissue gen- ture requires the addition of serum to the culture
eration, the cell density is higher and, consequently, medium for the cells to survive and grow. Serum
less cell culture medium is used. is a blood-derived product that is harvested from
The economic outcome for cell expansion in bovine fetuses. Apart from the animal welfare issues
terms of spent material resources heavily depends arising from the harvesting of fetal blood and the
on the specific methods used to scale the produc- regulatory issues surrounding an ill-defined biolog-
tion process. Estimates at this stage are tentative ical product, the natural-source fetal bovine serum
at best, as no particular process has been designed will be depleted very quickly when cultured beef
and tested yet. The current outlook, however, is that obviates the need to keep large herds of cattle. As
cells will be grown on microcarriers in large (e.g., a result, breeding programs and, with them, fetal
25,000 L) fermentation incubators at a maximum bovine serum will be decimated.
cell density of 5 × 107 cells/mL. With an estimated Fortunately, for many cell types, serum-free cul-
5 × 1010 cells per kg of meat and 15 medium changes ture medium and corresponding cell culture meth-
during the expansion cycle, 45 L of medium is ods have been developed. Most of these products
needed to produce 1 kg of meat or roughly 200 g are animal free and contain recombinant proteins
of protein. Nutrient (amino acids, glucose) content such as growth factors that substitute for serum
of medium is 5 g/L, so 225 g of nutrients are used proteins.3 For satellite cells, which are dependent
to produce 200 g of beef protein. In contrast, for on unusually high concentrations of serum, such a
livestock beef with a feed conversion ratio of 7, one serum-free medium is not yet available and there-
needs 1.33 kg of protein (7 kg of grain with 19% fore needs to be developed building on the existent
protein) to produce the same 200 g of protein. The expertise with other cell types. Once such a serum-
differentiation phase would require another 20 L of free medium has been developed, it will need to be

30 Ann. N.Y. Acad. Sci. 1328 (2014) 29–33 


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Post Cultured beef

Figure 1. Process of culturing beef. Culturing beef requires taking a muscle biopsy from a cow and retrieving the satellite cells.
Satellite cells can be expanded to large numbers. Suspending satellite cells in a gel and providing anchor points while supplying
differentiation medium allow them to differentiate in cross-striated muscle fibers over 3 weeks. Fibers can be harvested and
assembled into a patty together with separately grown fat tissue (not shown).

tested in a large-scale microcarrier-based bioreac- self-assembles and forms a hydrogel induces


tor setup. Time and additional resource efforts will hemostasis in much the same way as natural col-
be needed to accomplish these goals, but they seem lagen does.4,5 Other complex matrix proteins have
attainable. been mimicked and formulated into a gel to create
A similar problem exists for other animal-derived a coating that allows cells to grow and that directs
materials that are required for the production of cul- differentiation of stem cells.6 We have been able to
tured beef. The most prominent of these is the hy- grow satellite cells on this synthetic matrix in a sim-
drogel that enables differentiation of satellite cells. ilar fashion as on MatrigelTM (unpublished results).
Currently, differentiation is initiated by reduction Application as a self-assembling support for bovine
of serum in the medium and by placing the cells in muscle fibers has not been tested yet.
a specific hydrogel consisting of denatured bovine
collagen, which allows the cells to self-organize into Scalability
muscle fibers. This is a crucial event in muscle differ- Satellite cells, like all cells of mesodermal origin,
entiation, as this induces the cells to build up tension are anchor dependent and thus grow only when
and contractile proteins. Tension can only be gen- adhered to surfaces or in a 3D environment and
erated if the muscle fibers are firmly anchored. In not in suspension. For the production of the pro-
previous designs, we provided fixed anchors for the totype hamburger, we used traditional 10-layer cell
cell–gel combination to adhere to, but cells adhere factories, but it is evident that, for the production
to each other when laid down in a ring shape around of large quantities of cells, fermenter-type setups,
a central elastic material, for instance, an agarose gel such as the 25,000 L tank described earlier, are the
column. only realistic alternatives to date.7 In order to grow
Synthetic variants of matrix proteins have adherent cells in those tanks, either a floating sur-
been produced successfully. Synthetic collagen that face needs to be offered or cells need to grow in

Ann. N.Y. Acad. Sci. 1328 (2014) 29–33 


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Cultured beef Post

aggregates suspended in the culture medium (for Collective emotions associated with cultured beef
review see Ref. 8). In our hands, satellite cells can be (or any other unfamiliar foods such as insects)
grown on commercially available microcarriers as are referred to as the “yuck factor.”10 At a rational
well as in aggregates, but both approaches still need level, however, consumers appear to be receptive
further optimization (unpublished data). Published to the need for a meat alternative and a majority
data on stem cell production in a microcarrier sys- looks favorably at the cultured beef development.
tem are currently limited to tank sizes of 5 L or less,9 For instance, in a cross-sectional study in the
so there is considerable work ahead to bring this Netherlands among 15,000 people (7700 respon-
production to scale. dents), 63% supported the development of cultured
beef.11 When questioned if they would buy cultured
Biomimicry beef when available in the supermarket, 23%
We have been working with the assumption that answered “certainly,” 29% “probably,” 23% “not
cultured beef should mimic the livestock-derived sure,” 13% “probably not,” and 12% “certainly not”
product as close as possible with respect to taste, ap- (Fig. 2). These results are still preliminary and
pearance, texture, and nutritional value. Since cul- limited to specific cultures, but they indicate that
tured beef originates from the same cells that pro- future acceptance of cultured beef is conceivable.
duce the livestock product, it is, in theory, possible To better understand the various cognitive and
to create a phenocopy that faithfully replicates all emotional determinants of this yuck factor, they
of meat’s features. On the basis of our experiences need to be identified and specifically addressed in
with the first prototype, we are currently focusing future research. This will facilitate the development
on complementing the muscle tissue with fat tissue of targeted information and narratives to increase
and enhancing protein production, notably myo- acceptance of novel foods that have rational benefits.
globin (heme–Fe, color, taste) and the contractile
proteins myosin and actin. We believe these three Conclusion
optimizations are attainable and will lead to a sig- In summary, cultured beef is an alternative animal
nificantly improved cultured beef quality compared protein source that could relieve some of the envi-
to the first prototype. ronmental, sustainability, and ethical issues associ-
ated with livestock beef production. The technology
Consumer acceptance
has the potential to create a product that is nearly
It is not immediately obvious that consumers will identical to current beef, unlike meat substitutes that
accept cultured beef, as it is an unknown product, are based on vegetable or insect proteins. However,
produced with a hitherto unexploited technology. the technology is still in its infancy, and well-defined

Figure 2. Result from a public survey among 15,000 participants forming a representative cross-section of the Dutch population
age 18 years or older.11 The survey was conducted in the spring of 2013. Figure reproduced (translated from Dutch by author) with
permission of Flycatcher.

32 Ann. N.Y. Acad. Sci. 1328 (2014) 29–33 


C 2014 New York Academy of Sciences.
Post Cultured beef

research goals have been identified to establish qual- 5. Kumar, V.A., N.L. Taylor, A.A. Jalan, et al. 2014. A nanostruc-
ity improvement, sustainability, scaling of produc- tured synthetic collagen mimic for hemostasis. Biomacro-
molecules 15: 1484–1490.
tion, and consumer acceptance.
6. Jin, S., H. Yao, J.L. Weber, et al. 2012. A synthetic, xeno-free
Conflicts of interest peptide surface for expansion and directed differentiation of
human induced pluripotent stem cells. PloS One 7: e50880.
The author declares no conflicts of interest. 7. Rowley, J., E. Abraham, A. Campbell, et al. 2012. Meeting lot-
size challenges of manufacturing adherent cells for therapy.
BioProcess Int. 5: 6.
References
8. Moritz, M.S.M., S.E.L. Verbruggen & M.J. Post. 2014. Alter-
1. FAO. World livestock. 2011. Livestock in Food Security. FAO natives for large-scale production of cultured beef. J. Integr.
publications. Agric. In press.
2. Wu, G., J. Fanzo, D.D. Miller, et al. 2014. Production and 9. Rafiq, Q.A., K.M. Brosnan, K. Coopman, et al. 2013. Culture
supply of high-quality food protein for human consump- of human mesenchymal stem cells on microcarriers in a 5 l
tion: sustainability, challenges, and innovations. Ann. N. Y. stirred-tank bioreactor. Biotechnol. Lett. 35: 1233–1245.
Acad. Sci. 1321: 19. 10. Post, M.J. & C. van der Weele. 2014. “Principles of tissue
3. Bjare, U. 1992. Serum-free cell culture. Pharmacol. Ther. 53: engineering for food.” In Principles of Tissue Engineering. R.
355–374. Lanza, R. Langer & J.P. Vacanti, Eds.: 1647–1658 Amsterdam:
4. O’Leary, L.E., J.A. Fallas, E.L. Bakota, et al. 2011. Multi- Elsevier.
hierarchical self-assembly of a collagen mimetic peptide 11. Flycatcher. Kweekvlees 2013. Cited February 6, 2014. http://
from triple helix to nanofibre and hydrogel. Nat. Chem. 3: www.flycatcherpanel.nl/news/item/nwsA1697/media/
821–828. images/Resultaten_onderzoek_kweekvlees.pdf.

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