Synthetic biology promises a new breed of industry—and new potential for security challenges.

Synthetic biology is a hybrid effort of biology and engineering that has only recently emerged from academic research laboratories onto industry platforms. “Synbio” is in part premised on the idea that if genetic materials could be standardized in their construction—much like electrical circuit components, for example—they could be used to construct “genetic machines”. Whereas DNA is the building block of life, synthetic biologists seek to make that moniker more literal. Man-made DNA might become a building block of industrial engineering.

The possibilities for research and development are wide-ranging. But, as the spotlight on synbio grows brighter, so do concerns about biosecurity. The very advances that create the potential to manufacture drug-secreting biomachines might also allow development of virtually undetectable bioweapons.

The concerns are legitimate; any time science discovers a new area of inquiry, it must question whether opening new doors to discovery will also open new doors to danger.

When the first restrictive enzymes became available in 1970, for example, there were widespread concerns that genetically-engineered life-forms might threaten public health or cause undesirable social change. A group of scientists convened at Asilomar, Calif., to discuss how potential risks might be minimized. It was there that the Recombinant DNA Advisory Committee (RAC) was conceptualized and granted jurisdiction, under the National Institutes of Health (NIH), to review research involving the use of recombinant DNA.¹ 

RAC’s Guidelines for Research Involving Recombinant DNA Molecules (the “NIH Guidelines”) was first published in 1976. They remain one of the only review processes to specifically address the risks unique to genetic engineering.

The emergence of biotechnology in the early 1980s also raised challenging policy questions in response to public concern that the products of advancing biotechnology and genetic engineering techniques might pose greater risks to public health and safety than those developed through traditional techniques. An intra-government agency committee concluded that existing regulations were sufficient to address any biosecurity issues as they might arise. Nonetheless, to offer further guidance on how existing government agencies might work together to provide appropriate regulatory oversight, The Coordinated Framework for the Regulation of Biotechnology was published by the committee in 1986.²

New age, new concerns
Synthetic biology, however, presents new areas of concern. And what might be more significant is that synbio is coming of age in an era that is very sensitive to the potential dangers of discovery. It is not surprising that the US federal government has initiated consideration of changes to existing research policies, in response to the potential threat that synbio represents.

In this age of war, of 9/11 and anthrax attacks, policy makers and the public alike understand that bioterror is an area of potential imminent danger. With respect to preventing bioterrorism by regulating scientific research, policy makers have focused their attention specifically on dual-use research—biological research with legitimate scientific purpose, the products of which could be misused to threaten to public health and safety. Synthetic biology is considered to be “dual-use research of concern” by the federal government.

Dual-use research presents a unique concern, in that nearly every experiment carries some malevolent potential. But to prevent the danger entirely would be to stop the science from progressing. Can policy makers find an acceptable (and safe) path to continued development?

The question of how to handle the threat inherent in dual-use research gained momentum after the publication of a 2003 report by the National Research Council of the National Academy of Sciences, Biotechnology Research on an Age of Terrorism: Confronting the Dual-Use Dilemma.³  It was after the publication of this report that the Department of Health and Human Services (HHS) moved to charter the National Science Advisory Board for Biosecurity (NSABB).⁴

The NSABB is tasked to provide advice, guidance and strategic leadership to HHS, the NIH, and the heads of all federal departments that conduct or support life sciences research regarding the conduct of dual-use research—taking into consideration both national security concerns and the needs of the research community.

To date, the Board has produced two reports regarding the risks of dual-use research and potential mechanisms for its oversight.

The first NSABB report, Addressing Biosecurity Concerns Related to the Synthesis of Select Agents (December 2006),⁵   focuses on whether or not existing regulations might provide adequate safeguards against the misuse of synbio research and concludes that existing regulations lack the flexibility needed to encompass everything that synbio is capable of producing, namely, reconstructed Select Agents⁶  de novo.

Current regulations apply only to certain organisms, as defined by their DNA sequence and taxonomy.⁷  But the greatest concern raised by the practice of synthetic biology is its inherent potential to produce novel and taxonomically-unclassified agents with properties equivalent to, or more harmful than, current Select Agents. Thus, the current regulatory system, which is built on restricting a classified system of agents, becomes inadequate.

To redress the identified inadequacy, the NSABB concludes that, given the wide spectrum of potential agents with the possibility for causing harm, future standards for oversight of synthetic biology research should be based on presumed or predicted functionality, rather than sequence homology or taxonomy. (Nonetheless, the report also emphasizes a need for a comprehensive screening program to track DNA sequencing orders and to develop and promote standards of practice for screening DNA orders.)

The most recent report from the NSABB, Proposed Framework for the Oversight of Dual Use Life Sciences Research: Strategies for Minimizing the Potential Misuse of Research Information (June 2007),⁸  builds upon the Board’s previous conclusions. The framework is not a collection of delineated regulations, but rather a delegation of broad responsibilities to research institutions and researchers themselves. It invites a close reading.

The framework’s Guiding Principles for Oversight, as well as its Seven Key Features, emphasize the responsibility expected from the scientific community. One Principle suggests that “the foundation of oversight of dual-use research includes investigator awareness, peer review, and local institutional responsibility.”⁹  Four of the Seven Key Features—staff and researcher awareness, dual-use education, local evaluation and review of research, local risk assessment and risk management—place the burden of responsibility at the local level.

The Guiding Principles suggest that for researchers to accept this liability “demonstrates to the public that scientists are taking responsibility for their research.”¹⁰

Culture of shared responsibility
As NIH Director Dr. Elias Zerhouni argued at a meeting of the NSABB, it is this culture of shared responsibility—and shared liability—that will allow any oversight framework to evolve over time.¹¹  And this shared responsibility must not place undue restrictive burdens on scientists and their governing institutions, lest it hamper the evolution of scientific discovery.

In consideration of these open intentions, it is worth noting that the Proposed Framework categorizes potential dual-use activities rather broadly. The NSABB suggests research should be closely assessed for its dual-use potential if it includes knowledge, products, or technologies that could lead to any of the following:
• the enhanced harmful consequences of a biological agent or toxin;
• the disrupted immunity or ineffectiveness of an immunization without express justification;
• the conferred resistance, to any biological agent or toxin, against therapeutic interventions or the conferred ability to evade current methods of detection;
• the increased stability or transmissibility of a biological agent of toxin;
• the altered host range of a biological agent of toxin;
• the enhanced susceptibility of a host population;
• the generation of a novel pathogenic agent or toxin;
• or the reconstruction of an eradicated or extinct biological agent.¹²

The framework, therefore, proposes to oversee a potentially broad area of scientific discovery.

Despite claiming wide jurisdiction, the NSABB has been careful to protect the free flow diffusion of scientific information, recognizing that the spread of knowledge is critical to scientific progress. In 2005, for example, the Board unanimously decided to allow the publication of the 1918 Spanish influenza virus genome.¹³ The potential for malicious misuse is evident, but Board argued that publication of the report was critical, both to validate the findings' significance and to support future research on the development of diagnostic tests, treatments, and preventative measures.

The NSABB is doing its best not to construct barriers, but rather to facilitate communication and understanding regarding dual-use research. The Board has been careful to emphasize its dedication to an open scientific environment as well as its potential risks, and notes in the Proposed Framework that no national or international review body has the legal authority or self-governance responsibility to determine whether the risks for misuse of a given research project outweigh its potential benefits.

The Proposed Framework offers guidance and recommendations to those scientists whose research might be classified as dual-use. It is not regulatory in nature, but the Framework reflects the principles which might underlie a regulatory plan if one were to be adopted—namely, the principle of researcher accountability. Those scientists that work in areas of dual-use research will likely shoulder the responsibility of determining, communicating, and mitigating potential risks. But by bearing this burden of responsibility, scientists might escape more restrictive regulations. The developing policy space should be closely watched.

About the Author
J. Mark Waxman is a partner in the Boston office of Foley & Lardner LLP. Mr. Waxman is the chair of the firm’s health care industry team and a member of the white-collar defense and corporate compliance practice group.