Paul Freemont & Richard Kitney
Co-Directors of the Centre for Synthetic Biology and Innovation and the UK Innovation and
Knowledge Centre for Synthetic Biology (SynbiCITE)
Imperial College London
South Kensington Campus
London SW7 2AZ UK
Synthetic biology is an emerging interdisciplinary field that aims to design and engineer biologically based parts, novel devices and systems as well as redesigning existing, natural biological systems. This definition, which is widely accepted around the world, was first described in the UK's Royal Academy of Engineering Report on synthetic biology published in 2009. In simple terms, synthetic biology strives to make the engineering of biology easier and more predictable. Governments, internationally, have become very excited about the economic promise of synthetic biology. A recent assessment by BCC Research (a Boston-based market analysis company, concluded that the value of the global synthetic biology market will grow from US$1.6billion in 2011 to $10.8bn by 2016, a CAGR of 46.5%. BCC claim that the largest market segment, enabled end-products, is estimated at $1.4 billion in 2011 and growing at a CAGR of 46.5% to reach nearly $9.5 billion in 2016. Whilst such estimates may be somewhat inaccurate, and their timing optimistic, they have, however, driven a rapid international R&D investment strategy involving academic institutions, not-for-profit charities and governments. The UK government is among the international leaders in investment having already committed over US$150 million to synthetic biology research and training.
Synthetic chemistry developed during the second half of the 19th century through into the 20th century. Many of the great industries of the 20th century resulted from synthetic chemistry based processes which use oil based feedstocks. Due to the ever increasing demand for oil, there is now a need to develop an alternative industrial pathway. Many observers feel that this can be achieved through bio-based feedstocks being processed using synthetic biology methods to achieve new industrial processes and products. (see Figure 1)
The origins of synthetic biology can be traced back to the early 1960's when developments in our understanding of the genetic code, in the form of DNA, led to the 'central dogma' of molecular biology where DNA encodes RNA, which encodes protein macromolecules. This powerful dogma — combined with techniques first developed in the 1970s that allowed the manipulation, transfer and cloning of DNA — has underpinned much of the new understanding of molecular and cell biology that led to the genome revolution which we are currently experiencing. This rapid growth in molecular and genomic understanding was enabled by the parallel developments of new technologies and capabilities — including increasing computing power and the establishment of sophisticated information systems, and the ability to rapidly sequence DNA. Together, these components culminated in 2001 to a landmark moment in human scientific understanding namely the complete genetic sequence of a human being.
In 2014, we now have complete genome sequences for nearly every major class of organism on the planet. For the first time we have complete lists of the basic components (open reading frames that encode proteins) that constitute living systems, accessible from any web-browser in the world, including on a mobile phone. This rapid accumulation of biological information is correlated with the increasing interdisciplinary nature of biological research — with physicists, chemists and computing scientists attracted to answering fundamental questions related to living processes. The new discipline of synthetic biology now extends this interdisciplinary landscape to include engineers, who in the past were often engaged in technology developments underpinning biological research, but, rarely, in addressing biological questions or biotechnology applications at the molecular design level. This new interdisciplinary landscape has led to the emergence of synthetic biology — with a driving force to make biological design and implementation easier and more predictable in biotechnology applications like bioenergy, therapeutics and bio-manufacturing. The conceptual engineering framework that underpins synthetic biology translates the techniques used in engineering design — standardization, modularity, abstraction, mathematical modelling and characterization — to the design of biological systems at the genetic level. The field of synthetic biology has also, in part, been driven by an influential student competition (the Internationally Genetically Engineered Machine (iGEM) competition) which has been used to illustrate the power of synthetic biology as an innovative research and training science. Interestingly, UK undergraduate teams, as exemplified by our own Imperial College team, have been among the most successful iGEM teams, in terms of winning prizes. Another unique aspect of synthetic biology is the integration into the field of ethical, legal and societal issues surrounding the applications of synthetic biology research at a very early stage in the development of the field. The main driver is to provide a framework for stakeholders in synthetic biology — from researchers, public, professional policy makers — to allow the development of synthetic biology applications in a responsible and broadly acceptable way. In the UK this framework has been named the Responsible Innovation Framework, and represents a key part of the UK synthetic biology scene.
Why Is Synthetic Biology Different?
Synthetic biology is concerned with applying the engineering principles of systems design and control to biological systems in order to produce predictable and robust systems with novel functionalities that do not necessarily exist in nature. Although overlapping with (and becoming) an increasingly large part of the Industrial Biotechnology market, synthetic biology seeks to use and expand the mechanisms that control biological organisms using engineering approaches. Traditional biotechnology generally tackles technological challenges by manipulating existing bio-molecules cells or organisms, which is, to some extent, similar to synthetic biology. However, whereas industrial biotechnology tends to proceed in an ad hoc or empirical manner, synthetic biology uses a more rational approach to the design and redesign of living systems. This is done through the application of a systematic design cycle to allow more complex systems to be achievable — for example, synthetic gene regulatory networks, redesigned operons and synthetic chromosomes, complex sensor systems, logic circuits etc. These activities are also leading to the development of professional registries of biological parts and devices1,2 and bio-CAD tools3,4 for computational design.
Current UK Government Investment
The UK government has responded to the future potential of synthetic biology. The current government Minister for Universities and Science, the Rt. Hon. David Willetts MP, has identified synthetic biology as second in the UK Government's list of "eight great new technologies". As a result, there is strong support for the development of synthetic biology research in the UK — through investment. The Minister has also established a Synthetic Biology Leadership Council (SBLC) to provide strategic oversight and coordination of the UK synthetic biology sector. The SBLC works in close partnership with companies, academia, research organizations, funding agencies and government. In consultation with industrial, academic and societal stakeholders, it has developed a UK roadmap for synthetic biology (published in 2012) which provides a framework for a coordinated investment strategy in the UK, with a focus on industrial translation. The UK Government is currently investing over US$150million through the UK Research Councils and Technology Strategy Board in a variety of ground-breaking initiatives. These include:
- $10 million to establish the, internationally leading, Centre for Synthetic Biology Research and Innovation at Imperial College London, the first centre in the UK which aims to develop new platform technologies for synthetic biology applications (www.imperial.ac.uk/syntheticbiology)
- $42 million in a new national 'Innovation and Knowledge Centre' (SynbiCITE) led by Imperial College London, with collaboration from 17 universities and 13 industrial partners. The mission of SynbiCITE is to facilitate and accelerate the uptake of emerging synthetic biology tools, processes and applications from academia into industry (https://www.synbicite.com/).
- $8 million to establish the Flowers Consortium that comprises five UK universities with internationally recognized expertise in synthetic biology research (led by Imperial College London, and including Cambridge, Edinburgh, King's College London and Newcastle). The consortium provides the critical mass and synergies required to make synthetic biology a well-characterized and usable tool for developing commercial applications and products (www.synbiuk.org).
- $60 million to launch three new multidisciplinary Synthetic Biology Research Centers at the University of Bristol; University of Cambridge and the John Innes Centre in Norwich; University of Nottingham. These new Centers will complement the existing research network in the UK and will work closely with SynbiCITE.
- $15 million investment fund established by the UK Government in the Rainbow Seed Fund for synthetic biology spinouts and start-ups. The fund is also open to co-investment from overseas investors (midven.co.uk/funds/ rainbow-seed-fund).
Examples of Innovative UK-Based Synthetic Biology Companies
The UK investment strategy and development of the academic base in synthetic biology has also lead to several companies focusing their business strategies on utilizing and developing synthetic biology technologies. A group of nine SME's have recently formed a synthetic biology grouping within the Bioindustry Association (www.bioindustry.org) and include:
The UK synthetic biology scene, and that of synthetic biology more generally, can be summarised succinctly in Figure 2.
- Algenuity builds foundational technologies to support the emerging algal biotechnology sector (www.algenuity.com).
- BioSyntha Technology is an industrial biotechnology company that specializes in developing proprietary routes to key commodity platform chemicals and biofuels from renewable raw materials (www.biosyntha.com).
- Genabler provides innovative synthetic biology solutions to companies in the pharmaceutical and chemicals sectors (www.genabler.com).
- Green Biologics is a global industrial biotechnology company that produces low-cost renewable n-butanol and carboxylic acids from a variety of renewable biomass sources (www.greenbiologics.com).
- Oxitec is pioneering a more effective approach to tackling dengue fever and agricultural pests (www.oxitec.com).
- Prokarium is developing an innovative platform for the oral delivery of protein vaccines (www.prokarium.com) .
- Synpromics is developing a series of synthetic promoters that can be used to control genes under a variety of settings (www.synpromics.com).
- Synthace produces high value bio-based chemical and biological products through the application of synthetic biology (www.synthace.com) .
- Ingenza (www.ingenza.com) is a worldwide leader in the application of industrial biotechnology and synthetic biology, providing efficient scalable bioprocesses to manufacture chemicals, biologics, pharmaceuticals and biofuels from sustainable sources. In addition there is significant growth in the establishment of micro-SME's specialising in computational tool development e.g. https://www.labgeni.us/welcome/
The underpinning academic displines are industrially translated through a hierarchy comprising DNA and its assembly — leading to biologically-based devices. By the implementation of biologic, pathways and networks can be modified and constructed according to human design. In addtion, the application of genome engineering will result in new and modified biological systems and industrial synthesis processes. Within the field of synthetic biology all of this comes under the heading of the development of foundational technology which can be applied across a range of industrial and market sectors. The advent of fast and reliable DNA sequencing and chemical synthesis, at economically viable cost, has opened the application of engineering science and processes to biology. This is the field of synthetic biology-which the World Economic Forum considers to have major economic potential.
About the Authors
Professor Paul Freemont is co-director and co-founder of the EPSRC Centre for Synthetic Biology and Innovation (since 2009) and the National UK Innovation and Knowledge Centre for Synthetic Biology (SynbiCITE; since 2013) at Imperial College London. He was previously the Head of the Division of Molecular Biosciences (2005-2012), Head of the Imperial College Centre for Structural Biology (2000-2005) having joined Imperial from Cancer Research UK London Research Institute. His research interests span from understanding the molecular mechanisms of human diseases to the development of synthetic biology platform technologies and biosensors and is the author of over 170 scientific publications. Along with Prof. Kitney, he has appeared regularly on radio and television broadcasts on the subject of synthetic biology and has successfully co-supervised Imperial undergraduate iGEM teams since 2006.
Professor Richard Kitney is Professor of Biomedical Systems Engineering; Chairman of the Institute of Systems and Synthetic Biology; and Co-Director of the EPSRC National Centre for Synthetic Biology and Innovation. He was Head of the Department of Bioengineering, Dean of the Faculty of Engineering and Senior Dean of Imperial College. He Chaired The Royal Academy of Engineering Inquiry into Synthetic Biology and is a member of the Ministerial Leadership Council for Synthetic Biology. Kitney is recognised as a leading research worker in the field of synthetic biology and, with Professor Paul Freemont, has been responsible for developing the UK National Centre for Synthetic Biology - which is now recognised as one of the leading international centres in the field. This summer they were successful in winning the competition to establish the UK national industrial translation centre for synthetic biology. Kitney has worked extensively in and with industry.
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