Team:Uppsala/Description
A world in crisis
Figure 1. Global pandemic
Figure 2. Antibiotic resistance
Our world is currently facing a number of existential crises. We are at the tail-end of the COVID19 pandemic, one of many zoonotic diseases that has hit us in the past decade [1], [2] and surely not the last to plague mankind. Another serious threat to global health is also the increasing rate of antibiotic resistance around the world and the danger to society it presents [3].
In addition to health crises, this summer also saw the release of the sixth IPCC report on climate change, stating that human influence is responsible for the warming of our atmosphere, oceans and land and that rapid changes in these systems have already occurred [4]. Due to climate change, extreme weather events are increasing in frequency in many places, with northern Europe and North America reaching heat records in 2021 while western Europe was hit with unprecedented floods [5]. Another more subtle crisis we are currently facing is a rapid decrease in global biodiversity with up to 1 million species threatened with extinction, many within decades [6].
Figure 3. Climate change
Figure 4. Extreme weather
Figure 5. Biodiversity loss
The impact of animal agriculture on these crises
One substantial culprit in all these crises is animal husbandry. With 14.5% of all greenhouse gas emissions due to animal husbandry [7], it is one of the single largest contributors to climate change. The global food system is also responsible for 86% of biodiversity loss [8] with 77% of agricultural land, directly or indirectly used for animal husbandry [9]. As for the previously mentioned health crises, many of the zoonotic diseases that plague us, as well as increasing antibiotic resistance have their roots in animal husbandry [10], [11]. Any one of these facts should cause us to reconsider our meat consumption, however meat consumption is increasing worldwide [12]. This is due to meat becoming economically available to a growing number of consumers and the fact that meat consumption has important cultural value all over the world. So how do we square the significant drawbacks of animal agriculture with the fact that meat consumption is increasing globally and is predicted to rise for the foreseeable future?
Figure 6. Animal husbandry
A feasible solution: Cellular Agriculture and Cultivated Meat
A solution to the problems associated with animal husbandry, that does not require dietary change, is cellular agriculture. This is the practice of growing animal cells in bioreactors to create products traditionally made using animal husbandry like meat and leather. The subfield of cellular agriculture concerned with growing meat cells for consumption is called cultivated meat and it is this area we decided to focus on for our 2021 iGEM project.
Cultivated meat helps solve many of the problems associated with animal husbandry. Cultivated beef, for example, requires 95% less land and emits 74-87% less greenhouse gasses than conventionally produced beef [13]. This helps stop both biodiversity loss and also climate change. It also removes the dangers of zoonotic diseases and antibiotic resistance due to animal husbandry. However, if cultivated meat is as good for the world as we claim, why is it not available at your local grocery store?
Figure 7. Cultivated meat
Factors holding cultivated meat back
There are still a number of hurdles in cultivated meat production, the main ones being legislative holdbacks and high production costs. However, the legislative hurdles have already been addressed in some regions of the world. At the end of 2020, Singapore became the first country in the world to approve the sale of a cultivated meat product, cultivated chicken nuggets [14]. However, the cost of cultivated meat is still orders of magnitude larger than conventionally produced meat and to make cultivated meat products competitive on the market, we need to drastically reduce its production costs. Through our literature research we found that 55-95% of the marginal cost of cultivated meat is due to the cost of the growth medium used to grow the cells [15] and that the largest single price driver of the cell culture media is a single growth factor, called FGF2, which makes up 53% of the cost of the medium [15]. This means that up to HALF of the marginal cost of cultivated meat can be attributed to the price of this single growth factor . We decided the aim of our 2021 iGEM project would be to explore how synthetic biology could be used to bring down the price of this growth factor through producing it more cheaply and making it more efficient.
Figure 8. Cost
Figure 9. FGF2
Our project
To make FGF2 more efficient, we decided to focus on improving its binding affinity to its receptors, improving its thermal stability and reducing trypsin degradation. To improve the binding affinity of FGF2 to its receptors, we did extensive protein modelling, which you can read about here, followed by mutagenesis of the wildtype protein to induce the most promising mutations. We also found literature on mutations that could improve thermal stability and a chimeric fusion of FGF2 and FGF1 that could improve thermal stability and reduce trypsin degradation. We created BioBricks here of all of these variants, transformed them into E. coli and managed to show protein overexpression of all variants. We also managed to purify these variants that can be used to test on cell culture.
Another way to reduce the cost of FGF2 in cell culture media is to scale-up production of the protein. Upscaling of the production is the second pillar of our project and also makes up our proof-of-concept that you can read more about here. We also put a lot of time and effort into mapping out how the advent of cellular agriculture could impact small-scale farmers and how the transition to cellular agriculture could be favourable to this community. You can read more about our human practices here. We hope the work we did this year can serve as groundwork for future iGEM teams on how synthetic biology can be used in conjunction with cellular agriculture. We believe this union of synthetic biology and cellular agriculture can help bring about a more sustainable food system and eliminate the crises that threaten our world today and in the future.
References
[1] nhs.uk. 2021. Swine flu (H1N1). [online] Available at: https://www.nhs.uk/conditions/swine-flu/ [Accessed 13 October 2021].
[2] NHS choices. [Online]. Available: https://www.nhs.uk/conditions/bird-flu/ [Accessed: 13-Oct-2021].
[3] “Antibiotic resistance,” World Health Organization. [Online]. Available: https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance [Accessed: 13-Oct-2021].
[4] “Ar6 climate change 2021:The Physical Science Basis,” Sixth Assessment Report. [Online]. Available: https://www.ipcc.ch/report/ar6/wg1/ [Accessed: 13-Oct-2021].
[5] “Summer of extremes: Floods, Heat and fire,” World Meteorological Organization, 16-Jul-2021. [Online]. Available: https://public.wmo.int/en/media/news/summer-of-extremes-floods-heat-and-fire [Accessed: 13-Oct-2021].
[6] “UN report: Nature's dangerous decline 'unprecedented'; species extinction rates 'accelerating' – united nations sustainable development,” United Nations. [Online]. Available: https://www.un.org/sustainabledevelopment/blog/2019/05/nature-decline-unprecedented-report/ [Accessed: 13-Oct-2021].
[7] “Key facts and findings,” FAO. [Online]. Available: http://www.fao.org/news/story/en/item/197623/icode/ [Accessed: 13-Oct-2021].
[8] “Our Global Food System is the primary driver of ...” [Online]. Available: https://www.unep.org/news-and-stories/press-release/our-global-food-system-primary-driver-biodiversity-loss [Accessed: 13-Oct-2021].
[9] H. Ritchie, “Half of the world's habitable land is used for Agriculture,” Our World in Data. [Online]. Available: https://ourworldindata.org/global-land-for-agriculture [Accessed: 13-Oct-2021].
[10] T. Levitt, G. Blight, B. van der Zee, E. Hilaire, and J. McDonald, “Covid and farm animals: Nine pandemics that changed the world,” The Guardian. [Online]. Available: https://www.theguardian.com/environment/ng-interactive/2020/sep/15/covid-farm-animals-and-pandemics-diseases-that-changed-the-world [Accessed: 13-Oct-2021].
[11] M. J. Martin, S. E. Thottathil, and T. B. Newman, “Antibiotics overuse in animal agriculture: A call to action for health care providers,” American journal of public health, Dec-2015. [Online]. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638249/ [Accessed: 13-Oct-2021].
[12] “Meat consumption,” Meat consumption - Department of Agriculture. [Online]. Available: https://www.agriculture.gov.au/abares/research-topics/agricultural-outlook/meat-consumption [Accessed: 13-Oct-2021].
[13] “Growing meat sustainably: The cultivated meat revolution - GFI.” [Online]. Available: https://gfi.org/wp-content/uploads/2021/01/sustainability_cultivated_meat.pdf [Accessed: 13-Oct-2021].
[14] K. Gilchrist, “This multibillion-dollar company is selling lab-grown chicken in a world-first,” CNBC, 01-Mar-2021. [Online]. Available: https://www.cnbc.com/2021/03/01/eat-just-good-meat-sells-lab-grown-cultured-chicken-in-world-first.html
[15] “An analysis of culture medium costs and production ... - GFI.” [Online]. Available: https://gfi.org/wp-content/uploads/2021/01/clean-meat-production-volume-and-medium-cost.pdf [Accessed: 13-Oct-2021].
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