Is in vitro meat the future of food production?
The concept of growing meat separately from a living animal was documented as far back as 1932 when Winston Churchill wrote that “fifty years hence, we shall escape the absurdity of growing a whole chicken in order to eat the breast or wing by growing these parts separately under a suitable medium” (1). It’s 30 years later than predicted but the idea of in vitro meat now appears to be much closer to realisation.
Since 2004 research groups in the Netherlands have been working on the development of “kweekvlees” (cultured meat). The project was initiated by Willem van Eelen, who patented the theory in 1999. The research has captured the attention of the media and certain sectors of society, such as animal rights groups and environmentalists and expectations are high for the imminent arrival of the first in vitro burger.
What’s the attraction?
There’s no doubt that the introduction of cultured meat would have a positive impact on the world, both in terms of society and the environment. By 2030 the World Health Organisation predicts a rise of up to 44% of livestock products with a meat deficit of 5.9 million tonnes per year. Increased demand for livestock will result in a negative impact on the environment, such as increased greenhouse gas production and yet more destruction of natural habitats. There would also be more risk to public health due to closer proximity of farms to urban areas.Even before examining the ethics of breeding animals for slaughter, which is a more subjective and controversial topic, it’s obvious that an alternative to livestock farming is urgently needed. This can come from the government, by more effective regulation of livestock farming, or from scientists, who can develop farming methods to increase productivity or methods to generate alternative sources of meat through tissue culture.
To those of us who have little knowledge of the subject it may seem like there has been little progress in the area since the dedicated research project was established in 2004. However, there are many difficulties which need to be overcome that are not immediately apparent to those who have no experience in the area. To give some idea of the work that goes into this area, four of the most fundamental problems are outlined below.
Which cells should be used?
The choice of which stem cells to use is very important. The essential attributes for the stem cells are that their capacity for replication should be extremely high and also that they can then be directed to differentiate specifically into muscle cells (myoblasts).
A high capacity for replication will enable a large amount of tissue to be grown from a small number of cells, a process which is termed proliferation. Once the cells have proliferated into a large enough number, they must then be able to differentiate into myoblasts.
Several types of stem cell would be appropriate for this purpose. For example, embryonic stem cells have a high proliferation capacity and can differentiate into many different tissues. However, there are many ethical issues to consider in the use of embryonic stem cells, making them less attractive to the consumer who will, in the end, dictate the commercial success or failure of the technology.
Another option would be to use adult stem cells. Although these can differentiate into only a few types of tissue, this would not be an issue as they should be able to form muscle tissue. Adult progenitor cells have also already been derived from some animal sources, including pigs and cattle. The main disadvantage to the use of adult stem cells is that their capacity for proliferation is not well established and they may not be able to form a large enough culture.
Other possible options would include iPS cells (2, 3), which are cells that have already differentiated but which have been reprogrammed to an embryonic-like state. However, this technology needs some more work in order to be made safe for human consumption. Mesenchymal or satellite cells could also be used.
Formation of authentic meat
Differentiation of cells
Muscle fibres have a high nuclear domain – i.e. several nucleii throughout each cell are required to allow control of the large, elongated cells that are characteristic of muscle fibres – and a highly ordered structure. In vitro culturing of muscle fibres results in cells that have a high nuclear density, meaning the nucleii are not scattered throughout the cell, and that often lack the proper structure. This indicates the tissue is composed of immature primary myotubes rather than the desired secondary myotubes.
To form secondary myotubes, myoblasts must differentiate into primary myotubes, and then again into secondary myotubes. This gives mature muscle tissue. These fibres must then form an organised structure of sufficient mass to resemble meat.
Promotion of the final differentiation could presumable be best achieved by mimicking the in vivo situation. One way to do this would be through co-culturing. This is a process in which other cell types that are present in developing muscle fibres in vivo, such as fibroblasts, would be included in the medium.
Formation of a 3-dimensional structure
Another problem is that cultured meat tends to form two-dimensional structures that must be harvested and processed to form the three-dimensional structure for consumption. This is due to limited dispersion of essential nutrients throughout the culture which only allows the culture to form in sheets of a few layers, rather than building into the desired form.
To overcome this issue, the preferable culture would be a suspension culture as opposed to a solid support culture. Suspension culture could be achieved by including edible micro-carrier beads which would provide a solid support but would allow stirring of nutrients through the mixture, enabling them to access the cells and promote three-dimensional growth. For this an appropriate bioreactor must be developed in which the appropriate culture method can be scaled up to allow industrial production of the meat. Use of suspension culture would allow previously gained knowledge to be put to use in this respect.
As well as this, exercise of the muscle fibres could be stimulated mechanically, using a vacuum to apply pressure and stretch the tissue down, and electrically to simulate muscle contraction.
These factors greatly influence the natural muscle appearance of the meat and successful application of these techniques should result in a much more authentic product.
Production of a variety of meats
Stem cells from the desired farm animal must be extracted and grown. So far, the stem cells of these types of animals have not been grown with unlimited replication potential. This has only been achieved from the embryonic stem cells of mouse, rhesus monkey, human and rat, all of which would most likely be met with public resistance. Use of adult stem cells of the desired animal seems to be the way forward in this respect but again there are several problems with the proliferation and successful culturing of these cells (4, 5).
Consumer demand and funding
Consumer requirements will be a major issue for this project. The product will not appeal to the majority of consumers if it doesn’t resemble what we recognise as meat. The product must also be safe for consumption and, for those who can’t eat meat products, the culture should not require the use of any animal derived substances such as fetal calf serum, other than the stem cells. These are just a few issues to consider when it comes to consumer demand.
Finally, this is a project which will require a lot of funding in order to move on at the required pace. Given that the estimated cost for a burger made in vitro is US$345000 (6) the project would seem to be unattractive for an investor. However, when the technique is sufficiently refined and factors such as energy, land and water use are taken into account, it is projected that only poultry farming would be cheaper (7, 8, 9).
At this time there is a very small research group dedicated to this work. The main barrier in obtaining funding would appear to be that large companies and investors will not want to invest in the research until there is tangible evidence that industrial and profitable production of cultured meat is possible. This is something of a “catch 22” situation as funding is needed in order to produce this evidence.
These are just a few of the more immediately obvious problems faced in this area, even before the issue of taste is considered. It’s now more apparent why, despite expectations that the first in vitro burger would be released by the end of 2012, there is no sign as yet of this burger. The progress that has been made is, in fact, very impressive. There has been some meat tissue generated, which, although aesthetically unappealing shows that the concept is possible. If in vivo type conditions can be successfully applied to the process we will hopefully eventually see something on our supermarket shelves which closely resembles what we know as meat.
Perhaps not everyone will be comfortable eating meat that has been developed in this way, but it is the urgent need for meat alternatives and the ethics of raising animals for slaughter which will hopefully drive this project forward in terms of consumer demand and funding.
For some more in-depth reviews of this project please see the following references (10, 11, 12).
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3. Esteban MA et al (2009) Generation of induced pluripotent stem cell lines from tibetan miniature pig. J Biol Chem 284: 17634-17640
4. Talbot NC, Blomberg LA (2008) The pursuit of ES cell lines of domesticated ungulates. Stem Cell Reviews and Reports 4 (3): 235–254
5. Bhat ZF, Fayaz H (2011). Prospectus of cultured meat—advancing meat alternatives. J Food Sci Technol. 48(2): 125-140.
6. Kate Kelland. (2011) Petri dish to dinner plate, in-vitro meat coming soon. Available: http://link.springer.com/content/pdf/10.1007%2Fs13197-010-0198-7. Last accessed 15th April 2013.
7. Akiyama M, Tsuge T, Doi Y (2003) Environmental life cycle comparison of polyhydroxyalkanoates produced from renewable carbon resources by bacterial fermentation. Polymer Degradation and Stability 80: 183-194
8. Chisti Y (2008) Response to Reijnders: Do biofuels from microalgae beat biofuels from terrestrial plants? Trends in Biotechnology 26: 351-352
9. FAO (2006) Livestock’s long shadow – environmental issues and options. Food and Agricultural Organization of the United Nations, Rome. P. 390.
10. Langelaan MLP, Boonen KJM, Polak RB, Baaijens FPT, Post MJ, van der Schaft DWJ (2010) Meet the new meat: tissue engineered skeletal muscle. Trends in Food Science & Technology. 21(2): 59 – 66
11. Post MJ (2012) Cultured meat from stem cells: Challenges and prospects. Meat Science. 92 (3):, 297-301
12. Haagsman HP, Hellingwerf KJ, Roelen BAJ (2009) Production of Animal Proteins by Cell Systems. Available: http://new-harvest.org/wp-content/uploads/2013/03/production_of_animal_proteins_1207.pdf. Last accessed 15th April 2013.
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