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defining synthetic biology [#6814]
Dear colleagues

My name is Paul Freemont and I am co-founder and co-director of the Centre for Synthetic Biology and Innovation at Imperial College (http://www.imperial.ac.uk/syntheticbiology). I am also co-founder and co-director of the UK national Innovation and Knowledge Centre for Synthetic Biology SynbiCITE (ww.synbicite.com), which aims to translate academic synthetic biology technologies into industry. 

There has been much discussion on defining synthetic biology and the problem may result from the rebranding of existing research fields into a broader definition e.g. chemical biology, protein engineering, metabolic engineering.  A widely accepted definition is “Synthetic biology aims to design and engineer biologically based parts, novel devices and systems as well as redesigning existing, natural biological systems” (1,2). What really differentiates synthetic biology from molecular biology, genetic engineering or other areas of biotechnology is the concept of engineering design and systematic processes fused with human practise and societal considerations (3). These have never been applied to the repurposing of biological systems in any concerted way before. The main thrust of the field particularly in the United States and UK is in the development of foundational tools and work practices to enable the systematic design of biological systems at the genetic level. This is also evidenced by the fact that all the major academic research centres in the US are in engineering faculties.  Another widely held view is that synthetic biology can be considered as a new approach to biotechnology where engineering design at the genetic parts level with characterisation, modelling and testing (forming the engineering design cycle for synthetic biology) is at the centre of the process. One of the driving forces of this approach is in our ability to sequence (‘read’) and synthesise (‘write’) DNA. This has allowed synthetic biologists to establish design frameworks at the DNA level using modelling and Bio-CAD tools to enable this design process with synthesis and DNA assembly methodologies enabling testing of designs in the laboratory often with automation.

Another area of synthetic biology is genome engineering, which can be split into two areas namely genome synthesis and genome editing.  The most recent genome synthesis project involves researchers from the USA, UK, Singapore, Australia and China involved the refactoring and synthesis of the yeast genome (Sc2.0; http://syntheticyeast.org/sc2-0/). The synthetic yeast project if successful will represent the first synthetic eukaryotic genome operating in a natural yeast cell with all the information and reagent made freely available to academic communities worldwide.  A variety of tools have also been developed that allow large scale genome editing (e.g. CRISPR/Cas/ MAGE) and these are beginning to have significant impacts on academic and translation research particularly in healthcare applications.

Another important aspects of mainstream synthetic biology (as described above) is the communities desire to establish open source platforms and sharing of knowledge. For example the Biobricks foundation (http://biobricks.org/) aims to ensure that the engineering of biology is conducted in an open and ethical manner to benefit all people and is developing legal agreements to allow ‘parts’ to be freely available in an open innovation system. A number of standardised part databases are being developed the largest being the iGEM student project registry of parts (http://parts.igem.org/Main_Page) although other more professional registries have been established (JBEI; https://public-registry.jbei.org/login; BioFAB http://biofab.synberc.org/; SynBIS at Imperial College).

In terms of the other areas of synthetic biology e.g. protocells and xenobiology, these are existing fields that have emerged from more chemical biology based approaches to understanding biological systems. There are clear overlaps and these fields are historically aimed at developing a fundamental understanding of biological systems and may lead to potential future applications or be incorporated into main stream synthetic biology as described above.

Apologies for the long introduction but I wanted to describe the emerging field of synthetic biology from my perspective which i hope would allow more informative debate around synthetic biology and biological diversity.

In terms of the relationship between synthetic biology and biological diversity, one needs to consider the applications of the technology. Mainstream synthetic biology is an extension  of biotechnology (although potentially transformative) and many of the organisms currently being designed and constructed are for the  bio-manufacturing of chemical products (often designed to utilise sustainable carbon sources). Such organisms are derivatives of natural organisms and would fall under the definition of LMO’s. Such applications require contained use (bioreactors/bioprocessing manufacturing units) and are in the EU covered by existing GMO regulations and approval processes. However there are potential applications for synhetic biology (e.g. bioremediation) that could require deliberate release of LMO’s and thus there is much debate around the safety of highly engineered strains of natural organisms being released in terms of horizontal DNA transfer and unopredictable interactions with the natural world. The  synthetic biology research community is trying to address such issues (e.g. D. J. Mandell et al 2015 Nature 518, 55–60; O Wright et al 2014 ACS Synth. Biol. http://dx.doi.org/doi:10.1021/sb500234s). 

This is a potential application area that would clearly be relevant to biodiversity and more research is required to explore the safety contexts of such applications. These organisms would still be derivatives of existing organisms and would be LMO’s and their safety in terms of interfacing with natural organisms requires further research. The development of completely synthetic organisms that are not related to any existing LMO is a future possibility and as such would require similar safety assessments. The application of systematic engineering in synthetic biology would automatically provide a framework to explore safety and testing similar to how current engineering practise works.

(1) Royal Academy of Engineering Report: Synthetic Biology: scope, applications and implications 2008 (http://www.raeng.org.uk/publications/reports/synthetic-biology-report)
(2) Synthetic Biology A Primer ICL press (2012 -ISBN: 978-1-84816-862-6)
(3) A Synthetic Biology Roadmap for the UK http://www.rcuk.ac.uk/RCUK-prod/assets/documents/publications/SyntheticBiologyRoadmap.pdf
posted on 2015-04-28 10:57 UTC by Mr. Paul Freemont, Imperial College London