Two rather contrasting videos on synthetic biology this month. In the first videocast, released by TED, Craig Venter exposes his grand vision of synthetic genomics. He insists on the notion of 'combinatorial genomics', that will combine the power of large scale DNA synthesis ('robots that can make a million chromosomes a day') with a database of 20 million genes, 'the design components of the future'. This approach, a pragmatic mixture of rational function-oriented design and empirical large-scale selection, is envisioned to prepare a modern 'Cambrian explosion' of new synthetic species. It is good to see Craig Venter laughing when announcing casually the 'modest goal of replacing the entire petro-chemical industry'. In any case, Craig Venter appears to be more concerned that the technology may not develop sufficiently rapidly to match the urgency and scale of the major ecological and medical challenges faced by our planet than by potential threats represented by harmful biohacking and bioterror.

The second video, admittedly less entertaining, is a recording of the recent deliberations of the National Science Advisory Board for Biosecurity (NSABB). In his presentation entitled 'Assessing Biosecurity Concerns Related to Synthetic Biology', David Relman presents some preliminary findings and recommendations of the Working Group on Synthetic Genomics (jump to 1hr:34min:37sec). It is interesting to see that no consensus definition of synthetic biology exists among the various practitioners of the field, who all use different blends of the typical bottom-up engineering approach assembling circuits from standard components and top-down strategy, based on the modifications of existing genomes. Beyond the lack of definition, the current ability to predict biological functions from sequence (eg virulence) remains very limited complicating the possibility of realistic risk assessment. Finally, the development of synthetic biology can be seen as an extension of the success of 'kit-based' molecular biology, which facilitates access of these technologies to groups outside the traditional Life Sciences communities and institutions, making the mission of oversight, outreach and eduction more challenging. David Relman also clearly emphasizes the importance of not discouraging the enthusiasm directed towards potentially beneficial research and applications by overzealous oversight and regulations.

The intersection between the two talks above was perhaps made when the question of virulence was raised (jump to 1hr:59min:35sec). The fraction of pathogenic agents is very small compared to the number of existing species, a point also made by Craig Venter, and the rate of appearance of new pathogens is low. The idea was then raised as whether it would be possible to roughly estimate the risk of creating synthetic pathogens by calculating the likelihood that the amount of natural recombination responsible for the emergence of new pathogens 'in the wild' could be matched by an equivalent amount of experimental recombination in the laboratory. In other words, is there any way to estimate the probability that new forms of virulence could emerge from the announced synthetic 'Cambrian explosion'?

The Royal Society seeks your views on the emerging area of synthetic biology. This is your opportunity to shape the focus of the Royal Society's policy future work in this important area. We welcome views from individuals or organisations by 27 August 2007.

• Potential developments and applications
• Current research capacity and geographical distribution
• Societal implications
• Ethical concerns
• Biosecurity risks
• Implications for the environment
• Research support and funding
• Implications for human health
• Legal issues and implications for regulation (national and international)
• Ownership, sharing and innovation frameworks (including intellectual property)
• Biosafety concerns
• Education and training
• Governance and oversight of research
• Economic considerations for developed and developing countries

Observations suggest that current climatic models may underestimate how quickly the climate system is changing (in particular for sea level), according to a report in Science a few weeks ago (Rahmstorf et al, 2007). Another Science paper published last week shows that the capacity of the Southern Ocean CO₂ sink is weakening, which may result in increased atmospheric CO₂ levels in the long run (Le Quere et al, 2007).

I remember Hiroaki Kitano calling the systems biology community, in his talk at the ICSB meeting last October in Yokohama, for ideas on how system-level approaches could contribute to address the challenge of global warming. In response to the studies above, a similar call is now sent to the microbiology community by Jonathan Eisen on his blog. Research topics suggested in his post include:

Marine Microbiology

Carbon fixation processes

Hydrogen production

Carbon sequestration

Methane capture

Microbial fuel cells

A similar list of priorities related to energy challenges, environmental remediation and carbon cycling and sequestration can be found on the site of the Genomics:GTL research program from the US Department of Energy.

For all the topics listed above, systems biology and synthetic biology approaches are likely to be crucial not only to accumulate the necessary fundamental knowledge but also to find ways to translate it into technological applications. Proposals, insights and visionary suggestions are more than welcome...

some additional links:
Special issue on Energy and Sustainability
ASM Report on Microbial Energy Conversion
Microbial ecology meets electrochemistry: electricity-driven and driving communities. Rabaey et al, 2007, The ISME Journal 1:9

(via Kaiser-J 2007, Science 316:529 and discuss [AT] syntheticbiology.org)

The National Science Advisory Board for Biosecurity (NSABB) has released a Draft Report (available as pdf) providing recommendations on how to minimize misuse of biological research. This report was discussed publicly on April 19, 2007 (see webcast).

The 50-page draft makes it clear that there is a difficult dialectic between imposing restrictions on research that can be misused for harmful purposes on one hand, and, on the other hand, the necessity of facilitating open and rapid information exchange to accelerate scientific progress, for the benefit of society in general, but also to precisely counteract potential threats. The report insists on the prime importance of openness in scientific research and clearly states that unrestricted progress and communication should be the "default position".

One major recommendation of the draft report is that Principal Investigators should carry the responsibility for the initial evaluation of the potential for misuse of their own research. Concrete implementations could be inclusion of check boxes in grant proposal forms and annual reports to the researchers institution to formally certify that risk assessment has been performed.

Dual Use Research of Concern is defined as follows:

Research that, based on current understanding, can be reasonably anticipated to provide knowledge, products, or technologies that could be directly misapplied by others to pose a threat to public health and safety, agriculture, plants, animals, the environment, or material.

To aid identification of research that might be qualified as "dual use research of concern", seven categories are listed (inspired from the National Research Council "experiments of concerns", in Biotechnology Research in an Age of Terrorism):

1. Enhance the harmful consequences of a biological agent or toxin.
2. Disrupt immunity or the effectiveness of an immunization without clinical and/or agricultural justification
3. Confer to a biological agent or toxin, resistance to clinically and/or agriculturally useful prophylactic or therapeutic interventions against that agent or toxin, or facilitate their ability to evade detection methodologies.
4. Increase the stability , transmissibility, or the ability to disseminate a biological agent or toxin.
5. Alter the host range or tropism of a biological agent or toxin.
6. Enhance the susceptibility of a host population.
7. Generate a novel pathogenic agent or toxin, or reconstitute an eradicated or extinct biological agent.

The philosophy of self-regulation by researchers appears to be in line with the stated purposes of raising awareness on dual use research issues and promoting a culture of responsibility within the scientific community. The report recognizes however major difficulties in defining a threshold at which dual use research would be clearly "of concern", which makes it difficult to come up with clearcut and concrete recommendations. In the report, NSABB provides "tools" to assist the formulation of an appropriately balanced response via a risk/benefit assessment in research management and communication. The final decision will influence content, timing and distribution of publications reporting "dual use" research. As such, scientific journals will play an important role in developing a "Code of Conduct for Dual Use Research in the Life Sciences":

Those who play decision-making roles in the process of communicating scientific information have an ethical responsibility to consider whether the information being considered for publication could be used to endanger public health, agriculture, plants, animals, the environment, or materiel. Depending on their analysis of the risks and benefits of communications regarding information or technology that meet criteria for dual use research of concern, they may choose to proceed in a way that mitigates or manages the risks associated with communication – for example, by adding contextual information not found in the original article, or delaying communication until a time at which the risks would be reduced.

1. What entity should be in charge of reviewing research identified by PIs as dual use of concern?
2. Is the definition of dual use research of concern appropriate in terms of its "specificity" and "sensitivity"?
3. Are the listed seven categories of potentially dual use research appropriate?
4. Should the PI be the sole and prime responsible to identify his own research as dual use of concern?
5. What additional guidance is required?
6. What burden does these recommendations (eg necessity to review research identified as dual use of concern) represent for your institution?

see also:
Statement on the consideration of biodefence and biosecurity (2003) Nature 421:771
Nature journals' policy on biosecurity
BIODEFENSE: Proposed Biosecurity Review Plan Endorses Self-Regulation. Kaiser-J (2007), Science 316:529
Will Bioterror Fears Spawn Science Censorship? Granick-J (2007) Wired