WASHINGTON — A DNA sequence-based system to better define when a pathogen or toxin is subject to Select Agent regulations could be developed, says a new report from the National Research Council, which adds that this could be coupled with a “yellow flag” system that would recognize requests to synthesize suspicious sequences and serve as a reference to anyone with relevant questions, allowing for appropriate follow-up.
Select Agents are defined in regulations through a list of names of particularly dangerous known bacteria, viruses, toxins, and fungi. However, natural variation and intentional genetic modification blur the boundaries of any discrete Select Agent list based on names. Access to technologies that can generate or “synthesize” any DNA sequence is expanding, making it easier and less expensive for researchers, industry scientists, and amateur users to create organisms without needing to obtain samples of existing stocks or cultures. This has led to growing concerns that these DNA synthesis technologies might be used to synthesize Select Agents, modify such agents by introducing small changes to the genetic sequence, or create entirely new pathogens. Amid these concerns, the National Institutes of Health requested that the Research Council investigate the science and technology needed to replace the current Select Agent list with an oversight system that predicts if a DNA sequence could be used to produce an organism that should be regulated as a Select Agent.
The committee that wrote the report found that replacing the current list of Select Agents with a system that could predict if fragments of DNA sequences could be used to produce novel pathogens with Select Agent characteristics is not feasible. However, it emphasized that for the foreseeable future, any threat from synthetic biology and synthetic genomics is far more likely to come from assembling known Select Agents, or modifications of them, rather than construction of previously unknown agents. Therefore, the committee recommended modernizing the regulations to define Select Agents in terms of their gene sequences, not by their names, and called this “sequence-based classification.”
The committee was concerned that a dedicated research agenda to improve prediction of Select Agent properties from gene sequence could actually empower those set on misusing synthetic biology, and therefore argued against such security-driven research.
A sequence-based classification system could be used to determine if a DNA sequence might be hazardous and close enough to that of a listed Select Agent — although not falling within the criteria — to raise a cautionary alert or “yellow flag,” the report says. This could help address biosafety goals in addition to biosecurity. For instance, a DNA synthesis company might use the system’s database to screen their orders and investigate who placed a questionable order and why. The committee emphasized that the system would not be regulatory in nature but intended to serve as a resource for information sharing that would not restrict access to the sequence.
Although the sequence-based classification system could be developed and may improve the current practice, the committee noted that such a system does have limitations and potential negative consequences. Therefore, the committee did not specifically recommend that either the classification or yellow flag system be implemented, nor did it address whether the additional administrative structure needed to maintain such a classification system would be justified. Rather, it provided information about what is technologically feasible and emphasized that the potential benefits of such a system should be considered and weighed against the cost and complexity of implementation.
The report was sponsored by the National Institutes of Health. The National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and National Research Council make up the National Academies. They are independent, nonprofit institutions that provide science, technology, and health policy advice under an 1863 congressional charter. Committee members, who serve pro bono as volunteers, are chosen by the Academies for each study based on their expertise and experience and must satisfy the Academies’ conflict-of-interest standards. The resulting consensus reports undergo external peer review before completion. For more information, visit http://national-academies.org/studycommitteprocess.pdf. A committee roster follows.
Copies of SEQUENCE-BASED CLASSIFICATION OF SELECT AGENTS: A BRIGHTER LINE are available from the National Academies Press; tel. 202-334-3313 or 1-800-624-6242 or on the Internet at HTTP://WWW.NAP.EDU. Reporters may obtain a copy from the Office of News and Public Information (contacts listed above).
[ This news release and report are available at HTTP://NATIONAL-ACADEMIES.ORG ]
NATIONAL RESEARCH COUNCIL
Division on Earth and Life Studies
Board on Life Sciences
COMMITTEE ON SCIENTIFIC MILESTONES FOR THE DEVELOPMENT OF A GENE SEQUENCE-BASED CLASSIFICATION SYSTEM FOR OVERSIGHT OF SELECT AGENTS
JAMES W. LEDUC (CHAIR)
Professor of Microbiology and Immunology,
Chair in Global Health, and
Galveston National Laboratory
University of Texas
Department of Epidemiology and Department of Microbiology and Immunology
University of North Carolina
ROGER G. BREEZE
Chief Executive Officer
Centaur Science Group
R. MARK BULLER
Molecular Microbiology and Immunology Department
School of Medicine
Saint Louis University
Janelia Farm Research Campus
Howard Hughes Medical Institute
STANLEY FALKOW 1,2
Department of Microbiology and Immunology
RACHEL E. LEVINSON
Director of Special Projects and Research Initiatives
Office of Vice President for Research and Economic Affairs
Arizona State University
Chairman and Chief Scientific Officer
Blue Heron Biotechnology
ALISON D. O’BRIEN
Uniformed Services University of the Health Sciences
Entomology and Plant Pathology
Oklahoma State University
JANE S. RICHARDSON 1,2
James B. Duke Professor
Department of Biochemistry
Department of Biology
University of Massachusetts
Global Security Program
Lawrence Livermore National Laboratory
RESEARCH COUNCIL STAFF
1 Member, National Academy of Sciences
2 Member, Institute of Medicine