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2015 | OriginalPaper | Buchkapitel

Hazards, Risks, and Low Hazard Development Paths of Synthetic Biology

verfasst von : Bernd Giese, Arnim von Gleich

Erschienen in: Synthetic Biology

Verlag: Springer International Publishing

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Abstract

In early stages of research and innovation a precise investigation of technological risks, as well as the analysis of particular beneficial features, is confronted with a lack of knowledge about exact process or product qualities, application contexts and intentions of users. Therefore, an appropriate identification of anticipated risks, accompanied by the achievements of synthetic biology, should rather focus on basic properties and functionalities of the objects of synthetic biology which will be exploited in future products and processes. Accordingly, the aim of this chapter is to determine major risk factors of synthetic biology creations with a focus on the technology itself. In consideration of the demand to cover these risks by appropriate counter measures, the question is raised, whether there are suitable strategies to achieve a high level of safety. In this regard, the discussion will be extended to feasible alternatives, e.g. by introducing trophic and semantic isolation strategies for synthetic organisms as an approach to overcome major drawbacks of classical biosafety mechanisms. Finally, functional reduction, a concept which is already aspiring to achieve efficient biosynthesis, is suggested as a measure for the reduction of risk-related functionalities. This strategy is worth further investigation if the full potential of synthetic biology is to be obtained in a safe and sustainable way.

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Vorheriges Kapitel The Cellular Chassis as the Basis for New Functionalities: Shortcomings and Requirements

Nächstes Kapitel Synthetic Biology and Genetic Engineering: Parallels in Risk Assessment

Unlimited consequences are defined as ramifications of causes and effects with a high range in space and time, ultimately global and irreversible.

The concept of risk has different definitions. In the well-known current understanding risk originates from an adverse incident and its occurrence probability. This chapter refers to a definition of risk in an (eco)toxicological sense. Here, risk is defined as a function of hazard on the one side, and exposure on the other. Therefore, a hazard, caused by specific qualities and functionalities, is defined as the potential of an agent (entity or noxa) to cause an adverse effect on a receptor (e.g. organisms, systems, (sub)populations) (IPCS 2004). Exposure is defined as the concentration or amount of a particular agent that reaches a target organism, a system, or a (sub)population in a specific frequency for a defined duration (IPCS 2004). Special functionalities and qualities of an agent, as the ability for self-replication, persistence in organisms and the environment (including bio-accumulation), mobility in environmental media and within organisms and—as an external driver—mass production, are therefore leading to a high probability of exposure. The notion of sensitivity (and bioavailability of an agent) of the exposed receptor is additionally important, because one and the same agent may lead to quite different effects in systems depending on the systems’ states (developmental phase, trajectory, intensity, energy content etc.).

Cf. Commission Decision, Annex Nr. 3.2.5 of Directive 90/219/EEC.

The societal position regarding genetic engineering (GE) obviously reflects this policy, when more research into microorganisms and into medicines/vaccines is massively supported by the European population but applications concerning farm animals, food and plants have the weakest support (cf. Eurobarometer 1993).

Cf. OpenWetWare, an information platform managed by the BioBricks Foundation: “All in all, biologically speaking, these sets of problems boil up to two things: horizontal gene transfer and excessive proliferation, although emergent properties of synthetic systems could make these problems worse.” And: “Other bacteria that seem harmless could cause harm too if released in the environment because of a potential negative consequence of horizontal gene transfer or excessive proliferation which could disrupt the ecosystem.” http://openwetware.org/wiki/How_safe_is_safe_enough:_towards_best_pratices_of_synthetic_biology#iv._Physical_harms, accessed: July, 03 2013.

In this context an additional functionality which cannot be further discussed due to restrictions of space is mobility which increases inner and outer exposure, realized either passively by transport or actively by an entities own capacity to change its location.

Cf.: Guidance notes on the objective, elements, general principles and methodology of the environmental risk assessment referred to in annex II to directive 2001/18/EC Commission Decision, 24 July 2002, (2002/623/EC).

Self-replication of living organisms depends on genetic information. But for less complex entities other forms of molecular self-organization are possible, as for example revealed by self-replicating peptides (Lee et al. 1996).

E.g. the impact of prions (Norrby 2011), though they are also proliferative in a broader sense.

E.g. tipping point characteristics of large-scale components of the Earth System, cf. Lenton et al. (2008).

Cf. Wright et al. (2013, 1223): “Biology can achieve a lot in a contained environment; however, physical containment alone offers no guarantees. For example, no matter how ingenious a protective device or material may be for a GMM field application, an inventive way will eventually be found by an operator to compromise it. Failure in this case is a matter of when, not if. Although some form of physical containment is obviously prudent, inbuilt biological mechanisms remain crucial to biosafety.”

These “classic” auxotroph-strategies are based on a deletion or at least a deactivation of a gene whose gene product is essential for survival of the GMO (Wright et al. 2013).

Cf. Marlière (2009).

Trophic containment basically resembles the auxotrophic approaches of current safety strategies.

Cf. Marlière (2009).

The term xeno-nucleic acid (XNA) was first proposed by Herdewijn and Marlière for synthetic genetic polymers (Herdewijn and Marlière 2009).

E.g. unnatural nucleobases in quadruplet codons.

As already known for persistent chemicals (e.g. CFC’s) or more visually apparent as plastic waste in the oceans.

See also Heinemann and Panke (2006, 2791): “Finally, there are strong ongoing efforts towards minimal (bacterial) systems and it can be expected that such systems—owing to their reduced complexity—have a much smaller number of cross-reactions, so that implementation of novel elements stands a much better chance of remaining functionally isolated.”

Cf. Jewett and Forster (2010).

Ibid, (698): “Thus, if additional nutrients were supplied in the extracellular medium (and perhaps their uptake aided by encoding extra transmembrane transporters) it may be feasible to delete many more genes. This could take us down to a truly minimal, protein-coding cell: one sufficient for replication but not for metabolism of most small molecules.”

Cf. Forster and Church (2006, 1): “Safety concerns for synthetic life will be alleviated by extreme dependence on elaborate laboratory reagents and conditions for viability.”

Cf. e.g. Zawada et al. (2011).

Cf. Xu and Anchordoquy (2011, 1): “While viruses offer greater efficiency of gene delivery, it is generally agreed that synthetic vectors would be preferable due to safety concerns, and viral vectors may be more suited for ex vivo applications.”

A dehydrogenase to regenerate the required cofactor NADH from glucose or formic acid (Robins et al. 2013).

Cf. the NEST-Report of the European Commission (2005, 5): “In essence, synthetic biology will enable the design of ‘biological systems’ in a rational and systematic way.”

Cf. Forster and Church (2007, 5): “And engineering flexibility is much greater in vitro, unshackled from cellular viability, complexity, and walls.”

Interfering background reactions as a cause for perturbed functions or diminished product recovery rates can occur in cellular extracts as well. However, extracts can be improved by mutation and selection of the required strains (Knapp et al. 2007).

Hockenberry and Jewett (2012, 257) also mention the benefits for standardized elements in synthetic biology: “While the search for biological ‘parts’ has proven fruitful for in vivo synthetic biologists, many of these parts are still highly context dependent. In cell-free systems, these parts exist in a context outside of cellular adaptation and evolution and the results are therefore expected to be more tunable and reproducible.”

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Titel: Hazards, Risks, and Low Hazard Development Paths of Synthetic Biology
verfasst von: Bernd Giese
Arnim von Gleich
Verlag: Springer International Publishing
Buch: Synthetic Biology
Print ISBN: 978-3-319-02782-1

Electronic ISBN: 978-3-319-02783-8

Copyright-Jahr: 2015
DOI: https://doi.org/10.1007/978-3-319-02783-8_9

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