Team:Edinburgh OG/HP/Silver

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SILVER REQUIREMENT

How we have identified, investigated and addressed
the biosafety issue in the context of the ExpandED project.


The Edinburgh OG iGEM 2016 team has directly worked with non-model organisms and ultimately the goal of our project is to encourage future iGEM teams to use these microorganisms as well as domesticate additional, novel microorganisms. We therefore have an obligation to review and inform the current situation regarding the use of non-model organisms, the current regulatory framework and its biosafety and biosecurity status. As synthetic biology develops at a faster pace than the regulatory framework in which it exists the onus is placed upon practitioners to deliver the tools and safeguards required for adequate risk assessment and safe delivery of the technology (Purnick and Weiss, 2009).

As previously mentioned, the intended expansion of strains to be used within the context of synthetic biology (SynBio) through the domestication of uncommon microorganisms comes with biosafety and biosecurity issues that need to be addressed properly. For example, when analysing our microorganisms, we found out that filamentous fungi are able to produce a wide array of important secondary metabolites (e.g. naphto-γ-pyrones and ß-lactam antibiotics, such as penicillin) with diverse biological activities relevant for the food, pharmaceutical and cosmetic industries: antimicrobial, antioxidant, anti-cancer, anti-tubercular, anti-HIV and anti-hyperuricuric (Choque et al. 2014). Nonetheless, they may also produce mycotoxins that can cause unwanted health and environmental problems, such as human disease (myxotoxicoses) (Peraica et al. 1999) and food and silage spoilage (Filtenborg et al. 1996).

ENVIRONMENTAL IMPLICATIONS


The commercial applications of SynBio might entail the release of genetically modified organisms (GMOs) into the environment. For instance, the NTU-Taida 2012 iGEM project involved the direct interaction of genetically modified bacteria with humans as they engineered Escherichia coli as a vector to deliver peptide drugs to the human gut and thus sewage and water systems (NTU-Taida iGEM 2012). Other examples of iGEM projects that are associated with the release of GMOs to the environment are the Imperial College London 2011 team, which used genetically modified E. coli to secrete the auxin indoleacetic acid (IAA) to prevent erosion (Imperial College London iGEM 2011), and the Lethbridge 2011 team, which developed a toolkit based on genetically modified E. coli to be used for the cleanup of polluted lakes (University of Lethbridge iGEM 2011).

One has to consider that, once released, GMOs cannot be retrieved and this poses a major risk to the environment. For instance, the differences in the physiology of synthetic and natural microorganisms might alter the manner those interact with their surroundings. Furthermore, the GMOs may survive, evolve and adapt quickly, hence competing successfully with wild-type strains. Another important risk is their gene transfer ability, based on which GMOs could take up genetic material from the environment or exchange it with other microorganisms (Dana et al. 2012).

CURRENT REGULATIONS AND RISK ASSESSMENT PRACTICE


Since the events in the US of 9/11 and the anthrax attacks on that same year, security concerns have increased due to the increasing threat of biological or chemical terrorist attacks. These concerns have been compounded by recent developments in the SynBio toolkit through which it is now possible, for example, to synthesise entire microorganisms (Hamilton 2015). As a consequence, these incidents have extended the concerns about biosecurity among the entire research community. Therefore, new efforts have been made towards designing new ways to hinder malicious uses of these developed technologies (Garfinkel et al. 2007).

A proper and integral way to approach the biosafety and biosecurity aspects is through risk assessment methods that evaluate SynBio activities and techniques in order to determine whether they can be deemed as safe in terms of research or commercialization, or both (Schmidt 2009).

As the Convention on Biological Diversity (CBD) along with the Cartagena and Nagoya Protocols – its two supplementary agreements – address, SynBio activities and their risk assessment methods must comply with local regulatory frameworks and international legislation that oversee biosafety and biosecurity (Marles-Wright 2016). For instance, the European Union has regulations regarding the exposure chain of potential hazards of genetic engineering applications to human health and the environment (Scientific Committees 2015). Specifically, the European Directives 2009/41/EC, 2001/18/EC and (EU) 1829/412 relate to the contained use of GMOs, their deliberate release to the environment and their possible restriction by Member States. Of special importance is the Directive 2001/18/EC, which states that a way to assess the potential adverse effects of a GMO, they should be compared to the ones from non-modified organisms (European Commission 2016).

Furthermore, in the United Kingdom (UK), the Genetically Modified Organisms (Contained Use) Regulations 2014 document states that the risk assessment of the contained use of microorganisms and GMOs must identify the potential hazards of their activities and the level of severity (HSE 2014). Its complement, the Scientific Advisory Committee on Genetic Modification (SACGM) Compendium of Guidance, mentions the regulations of risks presented with the insertion of exogenous DNA sequences in host strains and the need to identify all probable hazards that stem from GMOs (HSE 2004). On the other hand, in the US the NIH Guidelines on the Use of Recombinant or Synthetic Nucleic Acid Molecules specify the practices regarding their construction and handling (NIH 2016). Moreover, the World Health Organisation (WHO) and the Advisory Committee on Dangerous Pathogens (ACDP) Approved List of Biological Agents have a globally accepted classification of microorganisms according to their risk levels called the Control of Substances Hazardous to Health (COSHH) Regulations, such as the one presented for the iGEM competition to label different microorganisms (HSE 2004).

However, the existing biosafety and biosecurity framework pertaining to molecular biology was created before the fast-paced developments in SynBio, such as DNA synthesis, sequencing and high-throughput assembly, took place. Moreover, risk assessment methods are usually limited to paperwork that is completed and signed off by senior members while other laboratory members do not contribute in a relevant manner to those assessments (Marles-Wright 2016).

PREVIOUS RISK ASSESSMENT PROPOSALS


Accordingly, numerous improvements to risk assessment methodologies can be made to ensure that biosafety and biosecurity are guaranteed while the benefits of SynBio developments are not compromised, such as having better communication and cooperation between the SynBio community and society in general (Schmidt 2009) in order to ensure that the biosafety and biosecurity components are integrated in molecular and synthetic biology research. On this matter, it has been proposed that, by fostering both social intelligence and public knowledge about science, the contribution of science to benefit society is assured (van Doren & Heyen 2014).

In fact, progressively, more initiatives are being presented for the above reasons. For example, the SYNBIOSAFE project and the SynBio Engineering Research Centre (SynBERC), funded by the European Commission’s Seventh Framework Programme and the US National Science Foundation (NSF) respectively, aim to ensure a successful scientific development while gathering information about the risks and achievable strategies to minimise them (Calvert & Martin 2009).