Abstract
Introduction
Synthetic biology has attracted the attention of the OECD for various reasons. Above all, the OECD is an organization involved with economics, and in its societal applications synthetic biology is currently contributing very little but it has the potential to grow enormously. In such cases, the OECD can become involved to see if there are barriers to growth that can be removed at governmental level, or if there are societal risks involved that need further regulation. Very often both removal of barriers and further regulation are relevant.
The OECD book Emerging Policy Issues in Synthetic Biology, published in June 2014, looks at both the promise of synthetic biology and the potential pitfalls. Hence it examines the current and potential future applications, with a significant emphasis on the growth of a new bioeconomy, and then looks at policy-related issues in some detail: research infrastructure; investment patterns; intellectual property issues; and governance and regulation. It then investigates governmental policies, those in existence in various countries, and how policy might develop in the future. The current work on synthetic biology underway at the OECD is more firmly focused on the bioeconomy, and specifically biobased production. This work will be published toward the end of 2014.
The Potential of Synthetic Biology
As a platform technology, synthetic biology addresses a wide range of industry sectors and types of applications. It has the potential to offer significant economic benefits and bring greater efficiency to manufacturing (e.g., low production volume, high-value chemicals and medicines, and high volume, relatively low-cost transportation fuels). It may also help meet bioeconomy objectives: reduction of greenhouse gas (GHG) emissions, and food and energy security. In the OECD countries, it is also seen as a platform technology that could be used to keep the chemicals sector competitive with Asia and the Middle East.
Meeting the Technical Difficulties
The immediate future of synthetic biology depends on reliable, accurate, and inexpensive DNA synthesis. Since 2003, the cost of DNA sequencing has dropped a million-fold and is now essentially negligible—with the cost to sequence a human genome having declined to about $1,000. For DNA synthesis—that is, writing the genetic code and creating genes and fragments of DNA—costs need to tumble by similar orders of magnitude to enable a roll-out from centers of excellence to the broader scientific community. This challenge is gradually being addressed, although the latest figures on synthesis costs show that the price may be starting to plateau at a level that is higher than desired. The technical difficulties involved are considerable and they create high financial risks for the typically small technology companies working to develop synthetic biology. These companies are always vulnerable in their formative years.
Governments can support these entities, typically either directly through grant and prize/award schemes, or indirectly through research and development (R&D) tax credits, advanced manufacturing tax credits, and public procurement. Innovative tools for decreasing private investment risk could reap rewards, and public-private partnerships may help reduce risk for vulnerable small companies. Eventually, synthetic biology applications can be expected to reduce innovation cycle times, thus making it more attractive to the venture capital community. However, governments have not backed DNA synthesis in the concerted way that they backed DNA sequencing technologies.
The technology bottleneck is rapidly becoming bioinformatics and software infrastructure as more and more sequence is being generated and stored. It is likely that sequencing centers will begin to serve principally as bioinformatics resources that lend computational resources and expertise to the research community. This presents several problems: the need to store and process large-scale genomic data; to provide easy access to data analysis tools; to enable efficient data sharing and retrieval; and to support cross-institutional collaboration.
Targeting Areas for Improvement
The Research Infrastructure
Some countries are now actively developing infrastructure and creating roadmaps to advance these goals, with the United States, China and the United Kingdom in the lead. Europe has a growing number of research groups, and some countries have strategies for developing synthetic biology (e.g., the UK Synthetic Biology Roadmap). Some governments are already developing centers of excellence based around key researchers and creating dedicated calls for research proposals. In the US, the National Institute of Standards and Technology (NIST) created a new center at Stanford University and has been working with the BioBricks Foundation (BBF) to develop novel approaches for the field. The US government's Defense Advanced Research Projects Agency's (DARPA) 1,000 Molecules component seeks to build a scale, integrated, rapid design, and prototyping infrastructure for engineering biology and enabling synthetic biology with numerous applications. The government is also creating a new budgetary program under DARPA called Advanced Capabilities in Engineering Biology (ACE), which will focus primarily on synthetic biology as a high growth area. In addition, the National Institutes of Health (NIH) formed two National Centers for Systems and Synthetic Biology at University of California San Francisco (UCSF) and Massachusetts Institute of Technology (MIT). It is also planning new support for synthetic biology and biodiversity and for natural products development using synthetic biology.
The US Department of Energy (DOE) is supporting a broad range of new initiatives and tools for the development of synthetic biology as part of its mission to explore the frontiers of genome-enabled biology and to undertake multi-scale explorations for systems understanding of biology. Those involving synthetic biology include the following: DOE Bioenergy Research Centers; work on biosystems design for biofuels production; the DOE Systems Biology Knowledgebase (KBase) for enabling predictive biology in synthetic biology; the development of new methods and technologies for Biosystems Design essential for synthetic biology; and new computational tools and bioinformatics for synthetic biology.
In the UK, the Engineering and Physical Sciences Research Council (EPSRC) invested £4.7 million (USD3.4 million) in 2009 to form the Centre for Synthetic Biology Research and Innovation (CSynBI) at Imperial College, London. A £10 million (USD16.9 million) investment in a national Innovation and Knowledge Centre (known as SynbiCITE) has leveraged a further £18 million (USD 30.4 million) from collaborating universities and companies. The center, located at Imperial College, involves 17 universities and 13 industrial partners including Microsoft, Shell, and GlaxoSmithKline. In January 2014 the UK Research Councils announced the first £10 million (USD16.9 million) phase of a total £20 million (USD33.8 million) investment to fund synthetic biology multidisciplinary research centers, with an additional 30 million (USD50.7 million) added subsequently. The BBSRC has invested £20 million (USD33.8 million) in six large research projects in synthetic biology, which will apply the technology to investigate major global challenges, such as producing low-carbon fuel and reducing the cost of industrial raw materials.
In addition to these examples, governments can also implement simple measures such as funding mechanisms for physical and virtual networking. These could include knowledge transfer networks or international exchanges. During the research for this book there was universal agreement on the need for the rapid “internationalizing” of synthetic biology for the benefit of all society.
Education and Skills
Education in synthetic biology is particularly challenging owing to the multidisciplinary nature of the field and the need for business and entrepreneurial skills, such as change management. The educational dilemma focuses on how to deliver depth as well as breadth. The route from the laboratory to the market is complex, and any country engaging in synthetic biology beyond the research phase will need a strong cadre of suitably trained individuals other than researchers—a new breed of technicians and apprentices. Synthetic biology companies engaged in the manufacture of advanced biofuels are finding the transition to full-scale production very difficult. There has long been a shortage of biochemical engineers, and the role of the chemical engineer could be enhanced. Yet to be addressed is how to create experimentalists who can design experiments in the face of huge amounts of data. Education and training policy will have to evolve to meet these challenges.
Intellectual Property
Much has been learned over the last 30 years about patenting life science inventions. The challenges specifically raised by synthetic biology should be recognized but should not be viewed as insurmountable and are generally manageable within the current intellectual property system. One of the more difficult questions is how to create freedom-to-operate (FTO) while controlling transaction costs. Potential solutions include open innovation and patent clearinghouses. However, open innovation may create a tension between the desire for openness in the academic world and the need for industry to protect IP in order to commercialize innovations. The biotechnology industry has always had technically complex patents, and intellectual property is a big draw for investors. Nevertheless, broad prophetic patents may actually inhibit or delay innovation.
Regulation
Many of the practitioners believe that regulation applicable to genetically modified organisms (GMOs) is sufficient for synthetic biology, but DNA synthesis may create unique issues, especially regarding biosecurity. Although synthesized DNA does not present a security risk as such, its translation into products may. Risk-based assessment could be used to deal with this, and direct communication between DNA synthesis companies and security agencies such as the US Federal Bureau of Investigation (FBI) is already occurring. On the other hand, if regulation is too heavy, countries/regions that undertake synthetic biology R&D may lose out, as commercial deployment and capacity building may take place elsewhere.
Public Opinion and Engagement
Use of synthetic biology to develop the bioeconomy can help address the grand challenges of our times. However, public resistance to genetic engineering technology can hinder the application of synthetic biology and inhibit bioeconomy capacity building. Continuing discussion among scientists, policy makers, and the public at large can help clarify misunderstandings. Governments can also support competitions (such as the International Genetically Engineered Machine, or iGEM, competition) to interest young people. They can encourage knowledge transfer networks, and social media open to the public as well as the scientific community may facilitate an exchange of ideas to build a common understanding.
Key Messages
The main question to be addressed is: “Is synthetic biology a radical departure, or just ‘business as usual’?” The answer is, of course, somewhere between the extremes. For some, synthetic biology means a new manufacturing paradigm that takes biotechnology to mass manufacturing after decades of research and development. For others, it is a logical extension of genetic engineering. Bringing engineering principles and rational design to biotechnology certainly opens up applications on a scale not previously seen. Nevertheless, other issues are more like “business as usual.” For example, intellectual property and regulatory demands create new issues but none are radically threatening to the current regimes. They require attention to detail and a watching brief for future developments.
If the field develops into a respected new industry, many policy gaps and hurdles will be encountered and will have to be navigated, but most of these are common to any new technology. The required effort will need to be long-term. It will require policy flexibility and recognition both of the potential societal benefits and the need for public acceptance for it to achieve its full industrial and economic potential. A high level of international exchange and cooperation will be needed. The OECD can play a pivotal role in providing appropriate mechanisms for discussion and assisting countries to address the policy issues of synthetic biology in a constructive and democratic manner. The OECD outreach goes beyond its current member states to several of the key developing economies that have much to gain from the realization of the potential of synthetic biology.