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From crops to cattle to dogs, humans have always sought to improve their living conditions by adapting plants and animals of their surroundings to their needs^[1]. However, these occur over a lengthy selection processes over hundreds, possibly thousands of years. New developments in the field of biology has enabled us to progress much faster, by interfering with an organism’s DNA directly. Synthetic biology is an emerging scientific and biotechnological field that uses these developments at its core. It combines biology and engineering principles, with the aim of designing and building new biological systems and functions. Synthetic biology has been gaining interest among ambitious science students who are seeking to bring their research outside the lab and be involved in more application-based solutions. The International Genetically Engineered Machine (iGEM) competition brings together thousands of students across the globe to develop synthetic biology solutions and collaborate with one another based on the common passions. Among hundreds of teams that participated in this year’s event, Team Toulouse-INSA-UPS, Team NUSGEM (Singapore Team-A), and Team ULaval came together to exchange ideas about relevant issues regarding synthetic biology. Before writing this report, we discussed different topics ranging from ethics, environmental impact, public engagement, repercussions on public life, and more. We chose three main subjects to discuss: bioethics in synthetic biology; economic aspects; and society’s perspective of synthetic biology. Bioethics in Synthetic Biology (Toulouse) A lot of factors have to be considered when evaluating the benefits and risks of using synthetic biology. To develop a new production method for example, one must first closely study the available techniques that do not employ synthetic biology. If something can be produced chemically, then a comparison has to be established between this process and the potential new synthetic biology based process. Once this comparison is made, and if synthetic biology can offer an advantage (less costly, quicker, more environmentally friendly, etc), then it is sound to develop a new method based on synthetic biology. The process of bringing a new product from the lab to the market will often result in the oversimplification of technical knowledge and the associated ethical considerations. People who are involved in this process, be it a businessman or a policymaker, should, in our opinion, be aware of issues that emcompasses the use of synthetic biology in their products. One area that is especially important to talk about is bioethics. A discussion about bioethics can help society define both possibilities that are welcomed and boundaries in which society should remain. The advantages brought by modifying living organisms are far from minor^[2]. Here, we will take the example of two industries central to this field: the pharmaceutical industry works in the medical sector and aims to improve the daily lives of suffering patients, while the agri-food industry seeks to feed the world, and the optimisation of its yields may seem secondary in comparison to pharmaceutics. However, the human population is ever growing, and feeding billions more mouths may become a more pressing problem than what we may first think. In these two major areas, the synthetic biology industry is making great leaps forward and enabling innovations that directly affect society. The first is the creation of new medicines and skincare techniques that could improve and enhance the quality of life for everyone. The second is to increase the profitability of certain foodstuffs, which could help reduce hunger in the world. Take the example of Taxol: it is a cancer chemotherapy agent, acting on spindle stabilisation. Its effects are proven on cancer but remain very inaccessible to many because of its price (about 6000 USD for a full cycle^[3]). The reason behind the high cost is the inefficient extraction process from the Pacific yew tree that produces not only low yields of Taxol, but also impure mixtures of compounds. By going through a synthetic biology process, we can simplify the production and purification process. The cost of this drug could then drop dramatically^[4] and therefore be much more readily available to those who need it. Similarly, allowing the creation of plants for continuous food production regardless of the season would result in a significant cost reduction of food which could reduce hunger in the world. This raises the issue of the spread of this technology in the environment, which remains a major problem. Through the spread of artificial products, some ecosystems could become seriously threatened, and maybe even face disappearance. Humans introducing foreign species into different environments has, historically, not gone well, as the Australians can tell you regarding rabbits^[5]. Introducing a species which is genetically engineered to be more resistant to harsh temperatures or produce more seeds could therefore lead to even greater problems. The question to ask ourselves here is no longer “can we achieve this?”, but rather “should we achieve this?”. We have ventured into the technology necessary to modify living beings to our design, creating new subspecies in our free time. We must now study with intense scrutiny the impact of our actions and the moral justifications behind them. The prospect of developing more efficient antibiotic formulations might seem attractive, yet the reckless and unregulated use of antibiotics will soon spawn new strains of resistant bacteria, harbinging a storm of more drug-resistant infectious diseases. Unfortunately. the current state of matters leads to the very distasteful and unpalatable consequence of breeding drug-resistant pathogens. Effects of these drug-resistant pathogens places undue pressure on the pharmaceutical industry, for the Sisyphean task of developing newer antibiotics to keep up with the development of stronger drug-resistance. As the saying goes, prevention is better than cure - we strongly believe that judicious usage of the available classes of antibiotics, coupled with vigilant antibiotic stewardship programmes in healthcare settings, should become more commonplace. The fearsome tragedy of having no available antibiotics for treatment, such as in the case of carbapenemase-resistant Enterobacteriaceae, harkens back to the Dark Ages before the discovery of antibiotics, and must not be allowed to catch us off guard. Once we have our priorities settled, even more important questions need to be asked. Is modifying the human genetic code different to modifying that of the plants and animals around us? Again, the risks and benefits require heavy evaluation. Fixing a deleterious mutation causing diabetes or multiple sclerosis could change someone’s life, but deciding what your child’s eye colour will be is probably going too far. To conclude, it is safe to say that these new developments are not much more different than others before it. Humanity has caused a great deal of damage to the environment through greenhouse gases and deforestation, all for the sake of ease of life and financial profit, to cite only one example. While synthetic biology affects a more profound basis of life, the leaders of any scientific revolution must always reflect on the impact that it will leave on the world before declaring that we are living in a brave new world. Economic Aspects towards Synthetic Biology (NUS) For some, genetic engineering is akin to playing God. However, to many synthetic biologists and life science researchers, genetic engineering is a key pathway to exploring a plethora of new applications and technologies. Unfortunately, few of such technologies have been successfully commercialised. Yet, for these select few, they are largely disruptive in their own fields. To illustrate this point is the development of the antimalarial drug, artemisinin. Artemisinin was first extracted from Artemisia annua, or sweet wormwood, in the 1970s^[6]. Since then, global demand for artemisinin has only increased, especially after 2001, when the World Health Organisation identified artemisinin-combination therapies as the recommended first-line treatment for malaria^[7]. Yet, the supply of artemisinin remained variable due to the limited cultivation of sweet wormwood, which in turn translated to fluctuating and volatile costs of artemisinin-combination therapies. The vagaries of the artemisinin supply inspired several companies and researchers to set about developing novel alternative methods for the synthetic production of artemisinin to complement plant-derived sources. Sanofi, a Paris-based pharmaceutical company, for example, employed the use of a genetically-engineered yeast that used glucose as a feedstock, to produce artemisinic acid, a precursor of artemisinin^[8]. This genetically-engineered yeast was also simultaneously “engineered” by Jay Keasling, a researcher at the University of California (Berkeley), who also developed the chemical pathways necessary for the successful bioproduction of artemisinic acid^[9]. The advantage a synthetic biology-approach of artemisinin production provides, such as cheaper and more stable source of artemisinin, is clear. However, the concerns arising over synthetically-produced artemisinin (which manifests as market resistance), such as the monopolistic behaviour of pharmaceutical companies, and the loss of livelihood of the Artemisia farmers, must not be ignored. The balance between novel technologies, and its social and ethical implications must be carefully considered - is synthetic artemisinin really cheaper? How can synthetic biology help the farmers whose livelihoods have been disrupted by a decrease in demand for sweet wormwood? How can synthetic artemisinin be responsibly produced and consumed? Without giving due thought and consideration to the existing methods of artemisinin production, it would be a travesty and tragedy to brashly impose synthetic artemisinin on all its consumers. Drugs aside, there are currently exciting ongoing research involving the food industry. Biotransformation is a multidisciplinary platform within A*STAR focused on developing microbial fermentation processes to produce high value ingredients more sustainably^[10]. By using microbial and synthetic biology methods of producing ingredients, food production becomes less land and weather dependent and in higher quantity. A similar case in chemical manufacturing is the story of truffle oil. Truffle oil was previously available only through foraging of truffles, which are also seasonal. However, with artificial truffle oil in production since 1980s, constraints on quantity and seasonality have been greatly removed or eliminated^[11]. Synthetic biology is also actively applied to other fields, leading to the development of potentially transformative applications, such as in therapeutics and biomaterial production. For example, in California, at the startup Bolt Threads, spider silk is produced using genetically engineered yeast^[12]. A major obstacle preventing widespread adoption of these novel synthetic biology-based technologies is economic feasibility. Yield is a common problem affecting many new bioreactor fermentation and bio-manufacturing processes. As engineered cells are not naturally inclined to produce the intended products, doing so induce metabolic burden. increasing yield must therefore be achieved by balancing against cell metabolic stress due to production. Furthermore, semi-biologically produced drugs and compounds are larger than chemically produced ones, presenting production challenges and keeping costs high. In large-scale bioreactors, due to the time taken for the diffusion of substrates, heterogeneous conditions between different parts of the bioreactor can create different kinds of reaction conditions and different stresses for different cells. This variability makes bio-manufacturing more expensive and unpredictable. Lastly, for drug production and quality control, the conditions for protein 3D-folding also makes it susceptible for viral contamination^[13]. Nonetheless, the global bio-based market remains a growing market with high potential, driven by synthetic biology^[14]. It is anticipated to reach US$38.7 billion by 2020, based on predictions by market research company Allied Market Research^[15]. Governments all around the world, from the United States to China, are increasingly acknowledging the immense potential of biotechnology, and are increasing investments in an effort to develop biotechnology and its related fields. China, for example, has identified synthetic biology as one of the priority research areas of the country, and its Ministry of Sciences and Technology has invested heavily in funding schemes and initiatives concerning synthetic biology. Perhaps more convincingly the importance the Chinese government places on synthetic biology development, synthetic biology was recently identified as a key industry for China’s Five-Year Plan (which was recently published in 2016)^[16]. Singapore (a notably different country from China) has similarly invested $25 million (about USD 18.2 million) in its recently-launched “Synthetic Biology Research and Development Programme”, which includes groundbreaking projects ranging from exploring uncharted biosynthetic pathways for the production of medical cannabinoids, to engineering microorganisms that are able to convert readily available and renewable substrates into valuable organic compounds. In 2015, Singapore set-up its first research centre dedicated to synthetic biology, SynCTI, at the National University of Singapore with the aim of anchoring Singapore as a leading Synthetic Biology Hub in the world. In 2016, the Singapore Consortium for Synthetic Biology, SINERGY, was launched in order to create a vibrant and globally connected bio-based economy in Singapore ^[17]. Likewise in Australia, where the Australian Council of Learned Academies recently published a outlook report on the prospects, opportunities, and issues associated with synthetic biology ^[18]. Synthetic biology was identified as critical to Australian economic development - from complementing and supporting the continuous growth of industries in which Australia has been traditionally strong in, i.e. agriculture, to providing new opportunities for further research and development, in the fields of health and medicine, and the environment. The focus on synthetic biology has been welcomed by the Australian government, whose Research Infrastructure Investment Plan supports research initiatives and studies into synthetic biology. Compared to chemically synthesized products, bio-manufacturing offers a competitive advantage for producing products that are both economically viable and ecologically sustainable. An appealing option nowadays, as both consumers and governments are changing consumption patterns and policy regulations to take into account the negative externality that is environmental pollution. An example of the competitive advantage in environmental sustainability that synthetic biology can offer is optogenetic regulation. This new tool in synthetic biology provides the potential to eliminate chemical-dependent control, removing the carbon footprint from chemical production and waste treatment and further enhancing its environmental sustainability. Synthetic biology is an emerging market with many techniques and tools that have yet to mature^[19]. Strong governmental support is required to aid in the development of this market, but current signs for its development are promising. Recent start ups such as Zymergen and Ginkgo Bioworks have experienced explosive growth and are making big waves in the synthetic biology industry. Synthetic biology itself has shown potential for high applicability in various different fields. Nonetheless, the development of new technologies, as always, requires acceptance and support from society. Society’s perspective of synthetic biology (ULaval) Genetic engineering impacts society in many different ways, such as in health and nutrition to name a few. However, most people are unaware that their food or medicine has been produced by mean of synthetic biology. Perhaps, provided with such knowledge, they would reject such products because many people are afraid of what they do not understand. In this section, we attempt to explore and elucidate the following: Is the society knowledgeable enough about biological synthesis? How can they be better informed? How accepting is the general public towards GMOs? Who are the opponents to this technology? Fear is closely linked to ignorance^[20]. Currently, synthetic biology remains an embryonic technology. It is common to think of those novel and unfamiliar technologies as bold science fiction, given the common movie trope of man-made disasters arising from that so very arrogant scientist who tried to “play God”. One of the best known is Jurassic Park, in which scientists succeed in bringing dinosaurs back to life from amber-preserved DNA. While scientists are easily able to identify science fiction not grounded in actual science, science fiction can appear convincingly real to the uninitiated, even to the point of believing such science fiction is actually achievable in reality. Because of sheer ignorance, synthetic biology is often stereotyped to be “bad”, and hence, “dangerous” to health and the environment despite approvals by regulators and scientists, and their benefits recognized to date, like biofuels^[21] and increased yields and agricultural growth^[22]. To prevent these misconceptions, the scientific community has to invest more time to popularize synthetic biology to educate and inform the public and allow them to better understand how GMOs are designed. Public scepticism towards new technology is not unfounded. Indeed, scandals in the recent history of the scientific community have put a damper on the credibility that science is supposed to demonstrate^[23]. For example, disasters in healthcare like the prescription of tobacco as an anti-stress medicine^[24] and the tragedy over the prescription of thalidomide to pregnant women^[25]. Other tragedies also happened in the food industry, like the mad cow disease^[26]. However, while healthy scepticism is good, anti-intellectualism is developing in some parts of the world, hampering the development of science. In the US, there is an increasing group who mistrust experts^[27]. Despite the urgency of global warming and the general unequivocal consensus by the scientific community that global warming is man-made, public scepticism is one of the factors delaying the much needed development of more environmentally sustainable technologies^[28]. To counter this slowdown, education of the general public is necessary. In order to communicate with them and debate sensitive topics, scientists need to popularize their work. Popular science is closely linked to the scientific process, and is part of researchers’ missions^[29]. It represents a bridge between scientific literature and popular knowledge. Meaningful citizen participation in deliberations regarding synthetic biology requires familiarity with general concepts in the science of this particular developing field. In other words, scientists should taken it upon their personal mission to increase the public’s “scientific literacy”. A recent study examined perspectives of Millennials regarding GMOs, specifically GM foods^[30]. Being a very large generational group, their perspectives are expected to have a major impact on acceptance of GMOs. Overall, Millennials have somewhat unfavorable views toward GM foods. In an attempt to understand that attitude toward synthetic biology, we made our own survey, which we distributed to a large public. It was answered by 381 persons, whom were mostly Millennials studying at university, from Canada and Europe. We asked respondents how they feel about GMOs and most of them seemed to feel safe about them, depending of the use that is made of them.

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We’re using synthetic biology to change the way the world thinks and functions.

We’re a little disruptive, dangerous and maybe a tad too bold. But the world needs some shaking up every now and then, and we think we’re just the right people for that.

Together we’re going to engineer biology and create something awesome.

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