"

From 2014.igem.org

Envisioning mösbi’s as a piece of synthetic biology’s doorstop

Since 2009, public awareness of Synthetic Biology has broadly stagnated (Hart Research Associates, 2013 (1)). Yet in about the same period of time the number of teams in iGEM has increased by 80% (igem.org), DIYbio.org was founded and its discussion forum has “grown to over 3,500 members” (The Biologist, 20143); the world’s first community lab opened (TechHive.com, 20114) and has since been joined by at least 11 others around the world; and worldwide synthetic biology research has flourished (The Wilson Centre, 20135). Something doesn’t quite stack up, and it had us thinking, “Where does this gulf between the poles of growth and general public perception come from? What can we do to open this incredible technology up to a wider audience?” The Economist (2014)6 suggests one barrier to amateur bio-hacking: “Building a biological device is a lot more complicated than putting together a robot or designing a new circuit board.”

We think that building a biological device could be as simple as a Mendelian cross. This is the whole concept behind mösbi: a modular, open-source biosensing platform that you can custom-build from the comfort of your own home, simply by crossing pre-transformed plant lines that contain the modules you want. A process made simpler still by the physiology of Marchantia polymorpha, with gametophores that grow right up towards you in a far-red-light inducible sexual phase. So, all you’d need for your custom multi-cellular biosensor is a place to grow some small hardy plants, a red light, and a coffee stirrer.

We believe that mösbi could be a game-changer in giving more people a gateway into synthetic biology without the need for expert knowledge or any high-tech tools. Here we’ll present the research that took us beyond the bench and had us convinced, and the historical basis of cautious but successful modifications to plant husbandry practices.

The field of Synthetic Biology is set to boom. Current estimates predict the global market for synthetic biology to “grow to $16 billion by 2018” (The Atlantic, 20147). Launching mösbi in such a promising landscape for industry growth gives great prospects for its ongoing evolution and improvement. Within and proximal to the biohacker community there is already an interest in using biotech to improve plant aesthetics: 49% of respondents to a survey by revolutionbio.org would “purchase garden plants with new colours & scents developed by biotechnology."8 - a demand that fits perfectly with our use of chromoproteins (colours) and raspberry ketones (scents) as circuit outputs.

Having such a promising potential user-base for mösbi is integral to why we think it could become so instrumental in introducing new people to synthetic biology. For example, as hobbyists and enthusiasts tinker with and refine mӧsbi, they’ll make new modules that broaden the combinatorial options available through crossing. We believe that our chassis could rapidly embody one of the easiest hands-on introductions to principles of synbio design.

Mösbi could also significantly improve how people engage with synthetic biology by way of the innate simplicity and familiarity of how it works: mankind has been using cross-pollination to produce plants with desired traits for hundreds years (ISAAA, 20069). Plus, performing cross-pollination is still common in amateur horticulture, and is one of the top three techniques recommended by a British gardening company that is currently running a competition to “find or create a new plant”10. Hence our project uniquely capitalises on already popular concepts with which the wider public is already comfortable. By promoting crossing as the principle means of ‘transformation’ with our chassis, we could really help to demystify synthetic biology and dispel the apprehension often experienced by people coming across the technology for the first time (The Wilson Centre, 2013)5.

One difficulty that remains is that recombining genes between related organisms already existing in the natural world is quite different to directly inserting new genes or even complete genetic circuits into living organisms – and that is a difference that is not without controversy. Many express concerns such as the potential unknown effects of new genes being released into the environment by “hybridisation with wild relatives”11. As a team, we have deliberated issues of biocontainment both in our lab practice and in our ideas around mösbi. Engineering auxotrophy into our chassis repeatedly came to the fore as one of the key ways in which we could achieve biosecurity with our concept, and we have also considered genetic counters that limit successive generations. For a full analysis of our thoughts, please refer to our wiki page on Biosafety.

The controversy implicit in this is an important idea to consider. Without clear ideas of what makes a new technology controversial, and how originally controversial ideas can become commonplace and common practice, the synthetic biology community is in a weaker place to put forward its products and goals to the general public who will one day potentially be using them.

History has been full of controversial new technologies, and very topical at the moment is the standoff surrounding cultivating and eating genetically modified crops. Although GM soya now makes up more than 94% of soya grown in the US (12), and has been consumed by humans for years with no documented ill effect, there is still a sense of unease in many people about the technology.

This stems from two main feelings. The primary is a general neophobia that prevents us from eating foods that we are not familiar with. This shows itself universally: Westerners will generally go hungry rather than eat chicken heart, fried tarantulas or fish eyes, even though these dishes are clearly safe and apparently delicious to the palates of people who enjoy them. Perhaps this reflects how we see putting something inside our bodies as the ultimate sign of trust in it. The second most important reason is that people are less likely to trust a system that they do not fully understand, until it has been shown to benefit them enough to make them overlook their lack of understanding.

Mösbi will help on both counts. If people were to want to use it in their homes, especially for unimportant, unintrusive tasks such as monitoring phosphate levels in their windowboxes, the idea that genetically modified organisms are novel, and hence one should be wary of them, will gradually become untrue as GM technology becomes first normal, and gradually mundane. This mirrors technologies like electricity. People, due to a general neophobia as well as more reasoned fear of electrocution, were slow to take up what became one of the most useful technologies ever to be invented. Originally electricity was a phenomenon worked on in labs, but after the first practical outputs came along, it was taken up on a personal level by people like Henry Villard (a friend of Thomas Edison, and later founder of the predecessor to General Electric) who understood that the dangers can be well-managed, and lit one of his boats electrically. Once the technology is being used by normal people, publically and safely, the path to general acceptance is a short one.

The same gradual normalisation has been seen with public reaction to tomatoes and potatoes, both of which were feared poisonous when they were introduced to Europe (to the extent that during a famine in 1774 potatoes sent to peasants for free by Frederick the Great were left uneaten), and were not accepted into the staple fare of Northern Europe for many years (13). This was the case even when tomatoes were known to be eaten with no ill effect in Spain and Italy, such is the neophobia surrounding food. Eventually of course these foods were accepted as it became clear that their ease of growing and nutritional content made this fear gradually less important until it disappeared. Even to this day some of this writer’s friends’ grandparents distrust tomatoes...

What is interesting is that this process of normalisation can occur for something as useful as electricity even when there are obvious dangers associated with the technology like electrocution and accidental fires. The key to this acceptance was an accumulating history of safe use, and a usefulness that makes the technology worth the risk. Both of these factors are becoming true for synthetic biology, and from now it may only take practical outputs (mirroring lightbulbs and washing machines for electricity) which will make normal peoples’ lives easier and more convenient, for example more nutritious food where the reduced cost of farming GM compared to a wild type crop is passed not onto the farmer (as is the case with glyphosate tolerant crops) or the biotech company that created the line, but to the consumer. So by offering a plant that could easily be grown at home, but without pushing the question of it being eaten, mösbi is helping normalise synthetic biology for the really important matter of food security.

Mösbi is also helping in addressing the lack of understanding that can lead to fear. With its clear, open, workings and the try-it-yourself nature of creating a new combination of modules, it is both a useful tool and an educational exercise. If people are happy to use a plant to assess water contamination, soil nutrients, toxins or any useful property or particle someone can invent an input module for, it will be easier to bring about what happened with cars: Although few people truly understand what is going on under the bonnet, or how it is made, and most people know that cars are incredible dangerous, the huge majority of people are happy to use them because they make life so much easier.

As the risks of synthetic biology are so much lower than those of driving (on a death rate basis the comparison is of course ludicrous), and the benefits potentially as great, it is an exciting time to be working in synthetic biology.

Over the past 11 years, the iGEM competition has trail-blazed the path in expanding synthetic biology away from the preserve of academia and research and into a field for enthusiasts and hobbyists all over the world. We believe that mösbi will play a key role in continuing this legacy. As a small multicellular chassis, with simple transformation protocols built on common plant knowledge and modularity, mösbi is primed to boost synthetic biology further into public consciousness. The door to acceptance of this new technology has been slightly ajar for a number of years, and we hope that mösbi will form a small part of the doorstop that will help it to open fully.

References 1. Hart Research Associates, 2013. Awareness & Impressions Of Synthetic Biology – A Report of Findings. Washington: Hart Research Associates. http://www.synbioproject.org/site/assets/files/1289/synbiosurvey2013.pdf [Accessed: 05/10/2014]
2. Previous competition team lists. Source: The iGEM Foundation (2014), https://igem.org/ [Accessed 08/10/2014]
3. Ireland T, 2014. Do it Yourself. The Biologist 61(3): p12-15. https://thebiologist.societyofbiology.org/biologist-features/158-biologist/features/893-the-unlikely-labs [Accessed: 07/10/2014]
4. Mulroy J, 2011. Genspace: The World's First Community Laboratory. PCWorld. http://www.techhive.com/article/220747/Genspace_Worlds_First_Community_Laboratory.html [Accessed: 07/10/2014]
5. The Wilson Center, 2013. Tracking the Growth of Synthetic Biology: Findings for 2013. [online]. https://www.cbd.int/doc/emerging-issues/emergingissues-2013-07-WilsonCenter-Synbio_Maps_Findings-en.pdf [Accessed: 08/10/2014]
6. The Economist Monitor, 2014. Biohackers of the world, unite. London: The Economist Newspaper Limited [print]. Online: http://www.economist.com/news/technology-quarterly/21615064-following-example-maker-communities-worldwide-hobbyists-keen-biology-have [ Accessed: 01/10/2014]
7. Garthwaite J, 2014. Beyond GMOs: The Rise of Synthetic Biology. The Atlantic [online]. http://www.theatlantic.com/technology/archive/2014/09/beyond-gmos-the-rise-of-synthetic-biology/380770/ [Accessed: 08/10/14]
8. RevBio, 2014. Survey Says. Revolution Bio blog. http://revolutionbio.co/blog-2/ [Accessed: 07/10/2014]
9. International Service for the Acquisition of Agri-Biotech Applications, 2006. Pocket K No. 13: Conventional Plant Breeding. [online] http://isaaa.org/resources/publications/pocketk/13/default.asp [ Accessed: 08/10/2014]
10. Thompson & Morgan, 2014. £500 Reward - or more - when you find or create a new plant! http://www.thompson-morgan.com/discover-new-plants [Accessed: 09/10/2014]
11. "Science for Environment policy": European Commission DG Environment News Alert Service, edited by BIO Intelligence Service. 2007. [online] http://ec.europa.eu/environment/integration/research/newsalert/pdf/64na3_en.pdf [Accessed: 16/10/2014].
12. http://phys.org/news/2013-06-gmo-corn-soybeans-dominate.html [Accessed: 16/10/2014].
13. http://www.history.com/news/hungry-history/once-forbidden-foods [Accessed: 16/10/2014].