Synthetic biology is an emerging discipline within the life sciences that raises a number of difficult security issues, primarily whether the technology will enable the re-creation of extinct viruses or the modification of existing pathogens to increase their virulence. The United States has pioneered this research, and the country has led a debate on these security aspects of synthetic biology and the potential for its deliberate misuse, particularly by terrorists. European countries and the European Union (EU), however, have recognized the strategic potential of synthetic biology and are also beginning to invest in the field. This article focuses mainly on European perspectives towards the security implications of synthetic biology, which appear to differ somewhat from U.S. views.

What is Synthetic Biology?
Synthetic biology is a new interdisciplinary field that includes biologists, engineers, chemists, and computer modelers in three converging scientific and technological areas: molecular biology, electronics and information technology, and nanotechnology. According to an online community of synthetic biologists, the field involves “the design and construction of new biological parts, devices, and systems” alongside “the re-design of existing, natural biological systems for useful purposes.” [1] A U.S. working paper submitted to the August 2008 Meeting of Experts under the Biological Weapons Convention (BWC) described synthetic biology as poised to become “the next significant transforming technology for the life sciences and beyond.” [2] A report on synthetic biology by the UK Health and Safety Executive said that it has “the potential to drive industry, research and employment in the life sciences in a way that could rival the development of the computer industry from the 1970s to the 1990s.” [3] Similarly, a European Commission paper in 2005 described synthetic biology as an area of “enormous strategic and economic significance”. [4]

The potential applications of synthetic biology include new therapeutics, environmental biosensors and novel methods to produce food, drugs, chemicals, or energy. One potential application of synthetic biology, for example, is the production of artemisinin, an anti-malarial drug, which is traditionally obtained from plant extraction at a high cost and with low efficiency. [5] If successful, synthetic biology should make the drug cheaper, of consistent quality, and more widely available.

Synthetic biology is also related to the process of DNA sequencing, the global market for which totaled approximately $7 billion in 2006 and is expected to grow at 10-15 percent annually through 2007-2009. In comparison, the market for synthesis is smaller, but it is growing even more quickly, and total sales of synthetic reagents could exceed $3 billion by 2015. One estimate puts the current global market for commercial DNA synthesis at US$40-50 million, growing at 30 to 50 percent annually. [6]

As with many advances in technology, however, synthetic biology brings not only benefits but also risks. It is therefore “a quintessential ‘dual-use’ technology—a technology with broad and varied beneficial applications, but one that could also be turned to nefarious, destructive use.” [7] An independent review commissioned by the UK Biotechnology and Biological Sciences Research Council (BBSRC) identifies a broad set of ethical and social challenges raised by synthetic biology: uncontrolled release; patenting and the creation of monopolies; trade and global justice; creating artificial life; and bioterrorism. [8] Certain experiments carried out in recent years have heightened concerns: the 2002 synthesis of an infectious poliovirus [9], the 2005 re-creation of the highly virulent 1918 ‘Spanish Flu’ virus [10], and in early 2008 the synthesis of the first bacterial genome. [11] Just recently scientists have also reconstructed the bat variant of the corona virus that caused the SARS epidemic of 2003. [12] Opponents of such experiments argue that they present unnecessary risks to public health and the environment and that publication of the genomes of such viruses could aid bioterrorists. [13] One U.S. report summarizes the challenge: “over the next five years constructing an infectious virus will remain more difficult than obtaining it from nature or from laboratory stocks, with a few important exceptions. In ten years, however, the situation might be reversed. For someone hoping to inflict harm, constructing a pathogenic virus might actually be easier than going to the trouble of isolating it from nature or stealing it from a secure laboratory.” [14]

The Biosecurity Debate in the United States
Given that the United States is the pioneer of synthetic biology research, U.S. government
officials, scientists, and other organizations have considered the wide range of implications of this new technology for some time. The debate should be seen in the context of 9/11 and the subsequent anthrax letters, which significantly heightened concerns about the threat of bioterrorism. It also fits into the broader context of U.S. attempts to understand and oversee developments in the life sciences more generally, particularly reports by the National Academies of Science [15] and the establishment of the National Science Advisory Board for Biosecurity (NSABB) in 2004. [16] In November 2005, the NSABB launched a working group on synthetic genomics tasked with examining the potential biosecurity concerns raised by synthesis of select agents [17] and identifying, assessing, and recommending strategies to address potential dual-use concerns arising from synthetic biology in general. This group reported back to the NSABB in December 2006 with a number of recommendations, including that the government publish guidance and clarification on the select agents and synthetically-derived DNA, that synthetic DNA providers improve the screening of orders, and that the government foster an international dialogue on these issues. [18] Within the White House, the Homeland Security Council has created a Policy Coordinating Committee to address biosecurity as it relates to synthetic biology. [19]

Alongside this discussion within federal agencies, synthetic biologists themselves have devoted significant time to considering the security implications of their work. Some are very aware of the potential risks involved, and many are keen to avoid the imposition of federal regulation. They have, therefore, been proactive in proposing various self-regulatory measures. Early examples include George Church’s “synthetic biohazard non-proliferation proposal” which involves the licensing of equipment and agents and screening of orders for select agents. [20] At the Synthetic Biology 2.0 conference at the University of California Berkeley in May 2006, participants devoted time to discussing biosafety and biosecurity issues, building on discussions held during various prior meetings. [21] A document produced for the conference stated that “[S]ynthetic biologists have an obligation to make sure that their work does not amplify earlier risks or create new ones. … Today, synthetic biologists share a deep understanding of the biosafety/biosecurity problem and – in some cases – emerging consensus about what can and should be done to manage it.” [22] The document went on to argue that “community self-governance provides a realistic and potentially powerful complement or alternative to regulation, legislation, treaties, and other interventions by outside entities.” [23] This approach was strongly opposed, however, by a coalition of 35 civil society groups that argued that “scientific self-governance doesn’t work and is anti-democratic” and that broader society must fully engage in dialogue on research and products. [24] Others, though, think that self-governance is one of the most effective ways in which to address synthetic biology’s global reach and diffusion: “At least potentially, it also means that community and commercial initiatives can have a worldwide impact.” [25]

In October 2007, the J. Craig Venter Institute and the Massachusetts Institute of Technology – two synthetic biology pioneers – and the Center for Strategic and International Studies published a report based on 20 months of research and consultation within the synthetic biology community. The report makes no recommendations but presents a range of policy options for governing synthetic biology targeted at three intervention points: commercial firms that sell synthetic DNA; owners of laboratory “bench-top” DNA synthesizers; and users of synthetic DNA and the institutions that support and oversee their work. [26] In response to this report, the NSABB report, and others, the U.S. government has stated that “the development of any oversight must balance the need to minimize the risk of misuse with the need to ensure that science, innovation, and trade are encouraged. The process for identifying options for any oversight mechanism must involve engaging the synthetic nucleic acid industry, the scientific community, and other stakeholders.” [27]

European Perspectives on Synthetic Biology and Security
The United States dominates the international synthetic biology community. U.S. scientific publications on synthetic biology, for example, constitute 63 percent of the relevant papers produced in English, compared with 19 percent for the EU and 15 percent for Japan, Israel, Switzerland, Canada, and South Korea combined. [28] In 2006, a Dutch report found that “a European Synbio community – in the sense of researchers branding themselves as ‘synthetic biologists’ and feeling connected to this field – is still very small.” [29] The community has since developed, helped by the 2007 Synthetic Biology 3.0 conference in Zurich, EU-funded projects, and subsequent conferences such as BioSysBio and the European Conference on Synthetic Biology. It is hard to find information on communities outside Europe and the United States, however. (Synthetic Biology 4.0 held in October 2008 was hosted in Hong Kong and almost half of the event’s 600 participants hailed from Asia. This event might serve to stimulate the more formal organization of new communities of interest in the region.)

In contrast to their U.S. counterparts, European synthetic biologists are less aware of the security implications of their field. A survey carried out in 2007 found “a low to medium level of awareness in quantitative terms on [the] part of European synthetic biology practitioners in relation to key developments and reports in the biosecurity area.” [30] European synthetic biologists seem more concerned about biosafety, practical applications, and public engagement, while their U.S. counterparts emphasize biosecurity factors. [31]

The European Union
The European Commission declared of synthetic biology that “Europe must invest in this development in order to build up the necessary intellectual and physical structures to capture a share of the valuable intellectual property that is at stake.” [32] In 2003 the Commission issued a call under its New and Emerging Science and Technology (NEST) pathfinder initiative for proposals to stimulate forward-looking cross-disciplinary research to demonstrate key principles and generate tools and parts for synthetic biology. [33] Under this initiative, 18 projects have been funded, most of which support laboratory research, but some that examine ethical and safety issues specifically. One such effort is the SYNBIOSAFE project [34] which recently conducted an e-conference on the societal aspects of synthetic biology. [35] In 2005, the NEST program convened a high-level expert group on synthetic biology. In its report, this group stated that, “we will not be able to eliminate the possibility of abuses of synthetic biology, any more than we can do so for other technologies. However, there are steps that can be taken to minimize risks.” [36] Among the steps mentioned are mandatory screening by DNA synthesis companies and the establishment of an international committee to develop new guidelines aimed at preventing the misuse of synthetic biology which would then be reflected in new laws at the national level.

The United Kingdom
Attention to synthetic biology in the United Kingdom has been growing, prompted in part by concerns raised in the media about the ease of obtaining synthetic DNA sequences. A New Scientist investigation, for example, found that of twelve gene synthesis companies, only five screened every sequence received. [37] A subsequent Guardian investigation was able to obtain a short sequence of smallpox DNA from a UK-based gene synthesis company. [38] Following these reports, in August 2006 the government convened a cross-departmental meeting to consider the feasibility and potential risks of the synthesis of viruses. This meeting concluded that, “current legislation is adequate to address the current risk. Additional regulation would be inappropriate at the present time, although the situation will be kept under review; and any risk should be considered within the wider agenda to prevent the misuse or dual use of biotechnologies.” [39] The government also asked the Royal Society, the Biosciences Federation, the Biotechnology and Biological Sciences Research Council, the Medical Research Council, the Nuffield Trust, and the Wellcome Trust to alert the Science Minister if they become aware of “any step change in technologies which could make it much easier to construct or modify pathogenic organisms.” [40]

Other parts of the UK government are also involved in monitoring advances in synthetic biology. In its Defence Technology Strategy published in October 2006, the Ministry of Defence identified synthetic biology as a new technology that “could impact significantly upon future defence capability” and said that it would review its current methods for identifying and exploiting emerging technologies. [41] In December 2006, the MOD held a workshop on synthetic biological engineering which concluded that synthetic biology was not an immediate threat or opportunity for the UK, but which did identify longer term threats and opportunities. The MOD is maintaining a watching brief on the issue and has requested a more detailed review of synthetic biology [42] while the Defence Science Advisory Council has agreed to examine the military opportunities and threats that synthetic biology may present. [43] In addition, the Health and Safety Executive (HSE) is actively monitoring advances in synthetic biology and its Horizon Scanning Intelligence Group issued a short report in March 2007. [44] The report stated that synthetic biology is currently covered by HSE’s genetic modification regulations but that, given the potential for its rapid expansion over the next ten years, synthetic biology needed to be monitored, the complex risks associated with synthetic biology should be considered, and suitable guidance for its use and control needed to be in place.

In June 2007, the Royal Society (the UK’s equivalent of the U.S. National Academies of Science) launched a call for views on synthetic biology to inform its future policy work in the area and encourage a wider debate on the social, ethical, and legal issues. [45] The Royal Society subsequently established a Synthetic Biology Policy Coordination Group with participation from organizations with a role in the funding and regulation of synthetic biology, involved in undertaking research in synthetic biology, or with a stake or interest in the direction and development of the technology. The Group is intended to “track and stimulate policy activities and processes to encourage the responsible and responsive development of synthetic biology.” [46] In June 2008, the Royal Society hosted a discussion meeting on synthetic biology attended by 120 leading academics, policy makers, and other stakeholders from the United States, the UK, and Europe. The Royal Academy of Engineering and the BBSRC have both established working groups on synthetic biology, with the former due to publish its report very soon. The BBSRC has also funded seven university-based research networks which, while primarily scientific, all have to address the ethical, legal, and social issues of synthetic biology as an integral part of their research. [47]

The Netherlands
Since 2006, synthetic biology has also been gaining prominence on the Dutch political agenda. [48] The debate has focused mainly on the safety and ethical aspects of synthetic biology, but it has also addressed biosecurity issues. In February 2006, the Netherlands Commission on Genetic Modification (COGEM) issued a report intended to inform the Dutch authorities about the technology and implications of synthetic biology which called for a comprehensive risk assessment of the technology. [49] Later in the same year, the Rathenau Institute, the parliamentary technology assessment organization in the Netherlands, published a report focusing on the social and political aspects of synthetic biology. The report identified a number of aspects requiring attention: monitoring scientific and technological developments; studying scientific and social effects; evaluating risks; considering social and ethical aspects; involving social organizations, politicians, and ecologists; public communication; regulation; discussing how to protect intellectual property; international networking; and bringing knowledge and people together. The Royal Netherlands Academy of Arts and Sciences produced a biosecurity code of conduct in August 2007 in an attempt to raise awareness in the Netherlands about the potential for misuse of the life sciences. [50] In September 2007, the Rathenau Institute submitted a technology assessment of synthetic biology to Parliament which called both for national and international harmonization between safety experts, universities, and firms and for action to increase scientists’ safety awareness. [51]

In September 2008, Dutch government agencies published two reports addressing different aspects of synthetic biology. The Health Council of the Netherlands, the Advisory Council on Health Research, and the Royal Netherlands Academy of Arts and Sciences published a report on technological developments in synthetic biology and the opportunities these developments presented for the Netherlands. [52] The report recommended that a substantial focus be given to research into, and communication about, the societal aspects of synthetic biology. Simultaneously, COGEM published a monitoring report that focused on risk assessment, regulation, and ethical and societal aspects. Similar to the UK government, it found no current need for new regulations in the areas of security and risk management for synthetic biology, stating that the current legal and regulatory regimes were adequate, as were the current security measures for working with genetically modified organisms. Both reports stress the need to keep developments in synthetic biology under review given the speed with which the field is advancing.

Future Governance Options
While some differences of emphasis appear to exist between the United States and Europe, particularly concerning whether to focus on biosecurity or biosafety aspects of synthetic biology, these have yet to manifest themselves as serious divergences. While the U.S. synthetic biology community appears to be more concerned with the security aspects of synthetic biology, this might be partly because the field first developed there, providing the country with a longer time to assess all of the implications of the technology and partly because Europe lacks such a clearly defined “community.” It also undoubtedly relates to the prominence of biosecurity issues in the United States following 9/11, the anthrax letters, and federal attention to the oversight of dual-use research.

Most actors, whether governments, scientists, or NGOs, seem to acknowledge the importance of raising awareness and the need for an informed and detailed public debate of the full range of ethical and societal issues associated with synthetic biology. For example, a UK working paper to the 2008 BWC Meeting of Experts stated that: “A key issue is the early consideration of a wide range of policy, social and ethical issues in the development of strategies for the control, oversight and governance of emerging technologies and their applications. This enables an appropriate balance between the benefits and risks to be struck. An interdisciplinary approach, involving experts from across government, academia, industry, civil society, social science and ethics is essential to this process.” [53] An important related issue is when such a public debate should be started. A recent survey in the United States found that 89 percent of Americans had heard nothing at all or just a little about synthetic biology. [54]

Actors on both sides of the Atlantic who have considered the security aspects of synthetic biology are the commercial DNA firms, driven partly by the existence of export control regimes. In 2006 a number of international synthetic biology companies established the International Consortium for Polynucleotide Synthesis (ICPS). [55] Similarly, in 2007 European companies established the Industry Association Synthetic Biology (IASB). [56] Both groups are committed to improving biosecurity and working with governments. In April 2008 the IASB convened a workshop on biosecurity in synthetic biology, the report of which was published in September 2008 reflecting “a clear consensus around several strategies that can and should be part of a unified strategy towards increased biosecurity in synthetic biology.” [57] The participating companies agreed to harmonize their screening strategies and establish a technical biosecurity group. IASB companies also agreed to launch an “IASB Biosecurity Seal” demonstrating their commitment to biosecurity screening. The IASB made a presentation to the December 2008 BWC Meeting of States Parties and circulated a draft code of conduct for DNA firms. [58]

Perhaps the biggest question in both the United States and Europe with regard to the security aspects of synthetic biology is the contentious issue of regulation. The IASB workshop report stated that “ultimately, the definition of standards and the enforcement of compliance with these is a government task” and a subsequent Nature editorial said “the IASB has taken laudable first steps in providing government regulators with guidelines they can build from. Now, the regulators need to act.” [59] Others argue against strong government regulation, however, and in favor of self-regulation by the synthetic biology community. One argument against regulation is that dramatic increases in productivity, exponential reductions in cost, and the global diffusion of cutting-edge research into developing countries mean that “imprudent regulation of biological technologies could create more problems than it solves.” [60] Arguments in favor of self-regulation focus on its speed of decision-making, the fact that measures are agreed by consensus rather than imposition, and its inherently international character. [61] Ultimately, however, an “either/or” outcome is unlikely; instead, the best solution would be “a smart combination of self-regulation and government regulation.” [62] A discernable transatlantic divergence on this issue does not seem to exist, with proponents of both views in both the United States and Europe.

Conclusion
As mentioned above, an absence of information marks the views of countries around the world on the security implications of synthetic biology other than the United States or Europe. It is not clear why this is or what it might mean. Possible answers could include a lack of awareness on the part of scientists in other regions of the globe; a determination that the security implications are not of concern; or a singular emphasis on the contributions of synthetic biology to future economic development. This absence of a consideration of the security implications of synthetic biology may be important because any attempt at regulation – whether from the government or from within the community itself – is only likely to succeed if it is done on an international basis. This will require support from the rest of the world. The United States and Europe cannot effectively govern this new technology by themselves. The fact that these issues have not surfaced in other parts of the world – where significant investment in biotechnology is underway – could therefore be of concern.

Daniel Feakes - University of Sussex