Researchers transplanted the genomes of Mycoplasma capricolum bacterium into Mycoplasma mycoides bacterium in 2007. They later accomplished the same feat with a synthetic genome in 2010. Photo: J. Craig Venter Institute.
Scientists have succeeded in developing the first living cell that is controlled entirely by synthetic DNA. The team, led by Dr. Craig Venter of the J. Craig Venter Institute (JCVI)—with offices in Rockville, Maryland and San Diego, California—published their work in the influential journal Science, on May 20, 2010.1 The advance has been hailed as a scientific landmark, but it has also led to an intense debate at the highest levels of U.S. government. The Committee on Health and Commerce of the U.S. House of Representatives held a hearing on May 27, 2010, to examine the impact of developments in the field.2
Additionally, President Obama rapidly directed his Presidential Commission for the Study of Bioethical Issues to undertake a six-month review of the implications of this scientific milestone and other advances that may lie ahead in the emerging field of bioscience research known as synthetic biology. The first meeting of the Presidential Commission was held on July 8 and 9, 2010, in Washington, DC.3 This leads us to wonder: what policy challenges have led to this unusually high degree of scrutiny, and how can we address them?
What is synthetic biology?
Synthetic biology is an interdisciplinary field of research at the intersection between life sciences and engineering. Several key enabling technologies have been critical to the emergence of the field over the past decade. Most notably, improvements to technologies for reading and writing DNA (sequencing and synthesis) have created the potential for cost-effective, large-scale genome engineering. Synthesis technology (the ability to write DNA) is now catching up with sequencing technology (the ability to read DNA); the latter of which enabled the successful completion of the Human Genome Project in the early 2000s.
The various types of scientific research captured under the broad heading of synthetic biology can be divided into three main objectives:
- Construct DNA-based devices to develop biological components that are functionally discrete and capable of being combined in a modular fashion easily, which draws on the engineering principles of standardization, decoupling, and abstraction. The resulting biological parts—called BioBricks—are available online in an open access library called the Registry of Standard Biological Parts. BioBricks can be used to create genetic circuits using, for example, logic gates, and oscillators (showing the explicit analogies drawn with electronic engineering);
- Engineer genome-driven cells to focus on whole genomes, which involves either the removal of excess DNA from existing genomes to make a more efficient chassis (framework) that could form a basis for new synthetic organisms, or de novo [Latin for “from the beginning”] synthesis of microbial genomes—for example the polio virus4;
- Create protocells to attempt to recreate living cells—for example, by inserting molecular components into lipid vesicles5 using existing genes and enzymes6 or novel synthetic components.
There are also more revolutionary research approaches, with no clear applications currently—including attempts to create an alternative genetic alphabet with new nucleotides beyond the four found in natural DNA.7
Many of the short-term, evolutionary applications of synthetic biology build on existing techniques of genetic engineering, and use more rapid development methodologies that are accessible to a wider range of people. Long-term, revolutionary visions involve highly innovative biological systems designed to produce a range of practical interventions in health, energy, and the environment; although, the application areas are far less certain than for the first-generation developments.
Dr. Venter’s team used digitized genome sequence information to synthesize an artificial bacterial genome, which was then inserted into an existing cell from another bacterial species, and then it was induced to take charge of its metabolism. The synthetic cell is an organism with a synthesized natural genome—rather than a new life form (or artificial life form) created from scratch. This bacterial transformation is an impressive technical feat, even if it does not quite represent the creation of artificial life. The authors of the Science paper anticipate that "this work will…raise philosophical issues," and Dr. Venter has described the work as "a philosophical advance as much as a technical advance" and "the first self-replicating species we’ve had on the planet whose parent is a computer."8
Emerging benefits and risks
Synthetic biology challenges our everyday understandings of nature, and the place of humans within it; however, philosophical and bioethical issues are not the only ones that need to be addressed.9 Concerns about creating novel life forms are not necessarily related to religious and philosophical anxieties about allowing humans to play God. There are also practical and political concerns about the ability of organizations and regulatory systems to manage the risks from synthetic organisms. Synthetic biology may offer the potential for economic growth through trans-sectoral impacts, in areas such as energy, health, and the environment. Developments currently envisaged include10:
Green energy companies are using the nascent field of synthetic biology to modify bacteria into creating hydrocarbons for gasoline, diesel, and jet fuel. Image: Treehugger.
- environmental applications, such as detecting environmental contaminants using biosensors and removing such contaminants using specifically tailored plants or microorganisms;
- health-related applications, such as diagnosing, monitoring, and responding to disease conditions in humans and animals and developing and manufacturing new drugs and vaccines;
- industrial applications, such as employing plants, microorganisms, and specifically tailored enzymes for developing biofuels, as well as devising more efficient biomanufacturing and synthesis processes using chemical technology.
At the same time, many concerns have arisen about the risks of synthetic biology. Emerging risks tend to be discussed under four main headings: biosafety; biosecurity; intellectual property and trade; and ethical concerns. Some of these issues include:
the release into the environment of novel, genetically modified organisms—either accidentally or deliberately (e.g., for bioremediation)—potentially resulting in harmful consequences for ecological systems and/or human health;
the possible misuse of synthetic biology for bioterrorism—including the construction of modified or novel microorganisms with lethal or incapacitating effects. The synthesis of several pathogenic viruses from scratch, such as poliovirus and severe acute respiratory syndrome (SARS), has led to concerns that the current level of regulatory oversight is not commensurate with the risks;
the increasingly routine nature of many synthetic biology procedures, which makes them more readily accessible to those without specialized training;
the ability to recreate existing, extinct, or eradicated pathogens of humans, animals, or plants;
patenting strategies, potentially creating monopolies that could inhibit basic research and restrict product development to large companies;
trade and global justice issues, such as preventing the exploitation of indigenous resources by enabling the chemical synthesis of valuable products in industrial countries (e.g., the production of the antimalarial drug artemisinin in genetically engineered bacteria rather than extracting it from a plant source);
claims that synthetic biology is involved in creating artificial life, raising philosophical and religious concerns.
In considering these emerging risks, it is important also to pay attention to potential benefits and to make a balanced assessment of the costs (and benefits foregone) associated with different approaches to risk governance, including setting standards for research practices or for product or process safety. Another important consideration is the extent to which new developments could render some current risks obsolete (for example, through the more rapid development of new vaccines).
There is currently ignorance or uncertainty about the risks of synthetic biology among all stakeholders (including scientists, regulators, and citizens). As with other life sciences, it is also difficult to disentangle beneficial and hostile applications at the level of basic research—a phenomenon known as the "dual-use" dilemma. How can policy makers begin to address the challenges raised by synthetic biology and make informed decisions at such an early stage of development and in the face of incomplete knowledge?
The appropriate risk governance of innovative technologies
The success or failure of any innovative science, and the products and processes developed from it, will depend on the outcomes of a complex series of interactions among11:
- scientists, professionals, and engineers developing the technology;
- policymakers and regulators involved, either in promoting science and innovation, or in regulating its products; and
- citizens and advocacy groups with concerns—either positive or negative—about the implications of the technology concerned.
In the early stages of development, policy and regulation can influence the future development of the science, guide product development, and either generate or diminish conflict among the stakeholders and the public. A key issue, for example, is how and when to reach closure on a particular regulatory framework, as this will be one of the factors shaping future patterns of innovation. Decisions taken in the early stages may have unforeseen outcomes that are then difficult to change and may close down options too early. There is the danger of compressed foresight, whereby highly uncertain futures are presented as imminent and known.12
Policy and regulatory responses should ideally be based on the concept of appropriate risk governance to ensure a balanced consideration of relevant risks and benefits. This approach integrates the in-depth understanding of:
- science and innovation strategies in public and private sector organizations;
- regulation and governance of new technology; and
- public and stakeholder perspectives.
An appropriate approach to risk governance can be defined as one that is enabling of innovation, minimizes risk to people and the environment, and balances the interests and values of the public and the stakeholders.13
Decision-making needs to be informed by an understanding of how risk governance and engagement approaches interact with innovation processes. In addition to the usual focus on the science and potential risks, the optimal form of debate about technologies such as synthetic biology may include discussions about innovation and regulatory processes. The emphasis is on the need to base risk governance as far as possible on evidence of harm, and to consider the values and interests of all societal groups. In a heterogeneous field with many potential applications, reliance on a single risk reduction or prevention principle would restrict the scope for choice among a range of technology options.
The potential benefits, potential risks, and speed of emergence of new developments in synthetic biology mean that it is a prime case for concerted international consideration of the three elements described above and the systemic interactions between them.14 Policy makers need to support the development of internationally applicable principles to avoid the difficulties that arise from piecemeal and divergent national approaches to the governance of innovative technologies in the life sciences. Although specific governance mechanisms will vary according to local and regional contexts, the need for international harmonization is particularly urgent with respect to biosafety and biosecurity risks.
The International Risk Governance Council (IRGC) has recently published a concept note on synthetic biology and is developing policy recommendations.15 There have also been reports from other national, international, and non-governmental bodies, and the debate will intensify following the recently reported advances in the field.16 Due to the wide range of potential applications, synthetic biology will be subject to different forms of oversight, using standards and guidelines, as well as legally binding instruments. It is impossible to predict how the field will develop; nonetheless, the pace of change in life science research is rapid. Appropriate governance mechanisms should be knowledge-sensitive and include effective provisions for the ongoing revision of risk assessment and management practices based on new evidence.
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