The Joint Genome Institute's synthetic biology internal review process

Abstract

Serious concerns have been raised over the possible intentional use of synthetic biology approaches to engineer pathogenic organisms as well as the possible accidental environmental release of genetically engineered organisms. Scientists pursuing synthetic biology research must diligently consider issues such as these. As such, the U.S. Department of Energy (DOE) Joint Genome Institute (JGI) has developed a Synthetic Biology Internal Review process to assess, beyond technical and scientific merit, certain broader aspects (e.g. environmental, biocontainment, biosafety, or biosecurity) of the research proposals associated with the JGI's DNA synthesis program.

Keywords:

• synthetic biology
• environmental
• biocontainment
• biosafety
• biosecurity

Serious concerns have been raised over the possible intentional use of synthetic biology approaches to engineer pathogenic organisms as well as the possible accidental environmental release of genetically engineered organisms. Scientists pursuing synthetic biology research must diligently consider issues such as these. As such, the U.S. Department of Energy (DOE) Joint Genome Institute (JGI) has developed a Synthetic Biology Internal Review process to assess, beyond technical and scientific merit, certain broader aspects (e.g. environmental, biocontainment, biosafety, or biosecurity) of the research proposals associated with the JGI's DNA synthesis program (http://jgi.doe.gov/our-science/science-programs/synthetic-biology/). The purpose of this internal review process is twofold: (1) to assess the broader aspects of the research, request proposal modifications if issues of concern are not sufficiently addressed in the proposal, reject research proposals where issues of concern are not or cannot be satisfactorily addressed, and output a paper-trail audit of the review process; and (2) to encourage and educate researchers to more extensively consider the broader aspects of their research, including beyond the immediate research itself.

All JGI DNA synthesis proposals (including those from the JGI Community Science Program and from the DOE Bioenergy Research Centers) contain a broader implications section dedicated to a brief discussion of these broader aspects. This broader implications statement should address not merely the possible rewards but also a considered statement of the risks associated with the work. These statements serve as a useful tool to protect not only the public, but the Investigators (and their institutions), as well as JGI itself. These statements are examples of consideration and deliberation of the responsible application of science. As members of the research community, we must consider risks, and be able to show our consideration of those risks – even if they are demonstrably small.

After a synthetic biology research proposal has successfully passed technical feasibility and scientific merit review, the proposal enters the JGI's Synthetic Biology Internal Review process. A JGI system administrator uploads the proposal to the Synthetic Biology Internal Review System (SBIRS, http://jgi-sbirs.jgi-psf.org) and assigns a minimum of three Reviewers to it. Each Reviewer reads the full proposal, makes comments on the proposal in the SBIRS, and votes in the SBIRS to either approve the proposal or to discuss it further with the other assigned Reviewers. If not unanimously approved, the assigned Reviewers discuss the proposal in person or via telephone, and decide to approve or reject the proposal, or to require that modifications be made to the proposal to address the Reviewers’ concerns. The Reviewers email the decision to a system administrator, who records the decision in the SBIRS. If the Reviewers decide to approve the proposal after discussion, a JGI Director is required to approve the proposal before work begins. A JGI Director can reject any proposal, and can require that additional modifications be made to any proposal. The entire Synthetic Biology Internal Review process should take three weeks or less (unless modifications are requested, which could delay the process by an additional three weeks or more).

Investigators are strongly encouraged to use the broader implications section of the proposal to make it clear to the Reviewers that the Investigators are actively thinking about the broader implications (noted above, primarily environmental, biocontainment, biosafety, or biosecurity) of their research, and that they have mitigation strategies in place to address outstanding issues of concern. Note that Investigators are not expected to provide an in-depth analysis (e.g. full socio-economic analysis) of their early-stage research, but Investigators should demonstrate that they are currently considering the implications of their research, and that more in-depth analyses can and will be pursued as their research matures. Investigators should not merely write “None” or “All research will be conducted in a safe manner according to Federal regulations” in the broader implications statement, as this will lead to the Reviewers asking for proposal modifications.

Following Dual Use Research of Concern guidelines, Investigators must explicitly state if their proposed research would:

1. Demonstrate how to make a vaccine ineffective

2. Confer resistance to antibiotics or antiviral agents

3. Enhance a pathogen's virulence or make a non-virulent microbe virulent

4. Increase transmissibility of a pathogen

5. Alter the host range of a pathogen

6. Enable a pathogen's ability to evade diagnostic or detection modalities

7. Enable the weaponization of a biological agent or toxin

Investigators are encouraged to think broadly about the aspects of their research, as this will start to nudge the collective research community's cultural mindset in the right direction. Reviewers should assess whether Investigators are actively thinking about the broader implications of their research, and whether the Investigators have mitigation strategies in place to address outstanding issues of concern. Reviewers should request proposal modifications if issues of concern are not sufficiently addressed in the proposal, and reject research proposals where issues of concern are not or cannot be satisfactorily addressed.

JGI Synthetic Biology Internal Review Process Statistics (as of 18 November 2014):

• 25 proposals reviewed

  1. 13 from DOE BioEnergy Research Centers

  2. 11 from the JGI's Community Science Program

  3. 1 from the JGI/EMSL (Environmental Molecular Sciences Laboratory) joint Community Science Program

• 97 Reviewer comments

  1. General [43], BioSafety [21], BioSecurity [8], Ethical [4], Legal [3], Social [8], Environmental [10]

• 13 proposals unanimously approved by Reviewers

• 6 proposals discussed and approved by Reviewers

• 6 proposals discussed and modifications requested by Reviewers

  1. 3 revised proposals unanimously approved by Reviewers

  2. 3 proposals pending modification and resubmission

• 22 proposals approved by the JGI Director

Concerning the above statistics, we note first that the distribution of comment topics may reflect Reviewer demographics, with Reviewers to date perhaps more confident in commenting on matters of biosafety and environmental concerns. Second, roughly 50% of proposals are discussed, and roughly 25% of proposals require modification, demonstrating that proposals are being considered and deliberated to a great extent.

Our hope is that through demonstrating the efficacy of Internal Review process at the JGI, and (in the near future) by making our guideline materials and software embodiment of the process publicly available, that other institutions may more easily adopt a similar process.

Acknowledgements

We thank Dan Drell, Elizabeth (Libby) White, Pablo Rabinowicz; Caroline Ajo-Franklin, Harry Beller, Samuel Deutsch, Samuel Evans, Hector Garcia-Martin, Karmella Haynes, Katherine Louie, Aindrila Mukhopadhyay, Trent Northen, Pilar Ossorio, Megan Palmer, Sarah Richardson, Steven Singer, Laurie Zoloth, Ronald Zuckerman; John Gladden, Blake Simmons, Ellen Ford; Christa Pennacchio, Jim Bristow, Jan-Fang Cheng, Len Pennacchio, Ray Turner; Stephen Maurer; and the Berkeley Lab Community Advisory Group (CAG) for feedback and suggestions that have greatly assisted us as we continually improve the JGI's Synthetic Biology Internal Review Process.

ORCID

Nathan J. Hillson http://orcid.org/0000-0002-9169-3978

Notes on contributors

Lisa Simirenko is a software engineer in the Synthetic Biology Informatics Group at the Department of Energy's Joint Genome Institute.

Miranda Harmon-Smith is Project Manager at the Department of Energy's Joint Genome Institute. She was previously a Senior Research Associate at the University of California, San Francisco.

Axel Visel is the Strategic Planning Lead at the Department of Energy's Joint Genome Institute. He also holds appointments as a Staff Scientist at Lawrence Berkeley National Laboratory and as an Associate Adjunct Professor at the School of Natural Sciences at the University of California, Merced.

Edward M. Rubin, MD, PhD, is the Director of the Department of Energy's Joint Genome Institute and a geneticist and medical researcher at the Lawrence Berkeley National Laboratory. He sits on the scientific advisory boards of several technology companies and public research organizations, and is a member of the Jackson Laboratory Board of Trustees.

Nathan J. Hillson is the Group Lead of Synthetic Biology Informatics at the Department of Energy's Joint Genome Institute. Hillson is also the Director of Synthetic Biology Informatics, Fuels Synthesis and Technologies Divisions, at the Joint BioEnergy Institute; Biochemist Staff Scientist in the Physical Biosciences Division at Lawrence Berkeley National Laboratory; Affiliate Investigator at the Synthetic Biology Engineering Research Center (Synberc); and co-founder and Chief Scientific Officer at TeselaGen Biotechnologies. He holds a PhD in Biophysics from Harvard.

Additional information

Funding

This work, conducted by the U.S. DOE JGI, a DOE Office of Science User Facility, is supported under Contract No. DE-AC02–05CH11231.