Sequence-Based Classification of Select Agents: A Brighter Line

237 Pages·2010·2.52 MB·English

by  National Research Council, Committee on Scientific Milestones for the Development of a Gene-Sequence-Based Classification System for the Oversight of Select Agents

Sequence-Based
Classifcation of
Select Agents
A B R I G H T E R L I N E
Committee on Scientifc Milestones for the Development of a Gene
Sequence-Based Classifcation System for the Oversight of Select Agents
Board on Life Sciences
Division on Earth and Life Studies
THE NATIONAL ACADEMIES PRESS 500 Fifth Street NW Washington, DC 20001
NOTICE: The project that is the subject of this report was approved by the Governing
Board of the National Research Council, whose members are drawn from the councils
of the National Academy of Sciences, the National Academy of Engineering, and the
Institute of Medicine. The members of the committee responsible for the report were
chosen for their special competences and with regard for appropriate balance.
This study was supported by Contract No. NO1-OD-4-2139 (Task Order #216) between
the National Academy of Sciences and the National Institutes of Health. The content of
this publication does not necessarily refect the views or policies of the National Insti-
tutes of Health, nor does mention of trade names, commercial products, or organizations
imply endorsement by the U.S. government.
International Standard Book Number-13: 978-0-309-15904-3
International Standard Book Number-10: 0-309-15904-0
Additional copies of this report are available from the National Academies Press, 500
Fifth Street NW, Lockbox 285, Washington, DC 20055; [phone] or (202) 334-
3313 (in the Washington metropolitan area); Internet, http://www.nap.edu.
Copyright 2010 by the National Academies. All rights reserved.
Printed in the United States of America.
The National Academy of Sciences is a private, nonproft, self-perpetuating society of
distinguished scholars engaged in scientifc and engineering research, dedicated to the
furtherance of science and technology and to their use for the general welfare. Upon
the authority of the charter granted to it by the Congress in 1863, the Academy has a
mandate that requires it to advise the federal government on scientifc and technical
matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter of the
National Academy of Sciences, as a parallel organization of outstanding engineers. It is
autonomous in its administration and in the selection of its members, sharing with the
National Academy of Sciences the responsibility for advising the federal government.
The National Academy of Engineering also sponsors engineering programs aimed at
meeting national needs, encourages education and research, and recognizes the superior
achievements of engineers. Dr. Charles M. Vest is president of the National Academy
of Engineering.
The Institute of Medicine was established in 1970 by the National Academy of Sciences
to secure the services of eminent members of appropriate professions in the examina-
tion of policy matters pertaining to the health of the public. The Institute acts under the
responsibility given to the National Academy of Sciences by its congressional charter to
be an adviser to the federal government and, upon its own initiative, to identify issues
of medical care, research, and education. Dr. Harvey V. Fineberg is president of the
Institute of Medicine.
The National Research Council was organized by the National Academy of Sciences in
1916 to associate the broad community of science and technology with the Academy’s
purposes of furthering knowledge and advising the federal government. Functioning in
accordance with general policies determined by the Academy, the Council has become
the principal operating agency of both the National Academy of Sciences and the Na-
tional Academy of Engineering in providing services to the government, the public, and
the scientifc and engineering communities. The Council is administered jointly by both
Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest
are chair and vice chair, respectively, of the National Research Council.
www.national-academies.org
COMMITTEE ON SCIENTIFIC MILESTONES FOR THE
DEVELOPMENT OF A GENE SEQUENCE-BASED CLASSIFICATION
SYSTEM FOR THE OVERSIGHT OF SELECT AGENTS
JAMES W. LEDUC (Chair), Professor, Microbiology and Immunology;
Chair, Global Health; and Director, Galveston National Laboratory, The
University of Texas Medical Branch at Galveston
RALPH BARIC, Associate Research Professor, Microbiology and
Immunology, University of North Carolina at Chapel Hill School of
Public Health
ROGER G. BREEZE, Chief Executive Offcer, Centaur Science Group
R. MARK BULLER, Professor, Department of Molecular Microbiology and
Immunology, Saint Louis University School of Medicine
SEAN R. EDDY, Group Leader, Janelia Farm, Howard Hughes Medical
Institute
STANLEY FALKOW, Robert W. and Vivian K. Cahill Professor,
Microbiology and Immunology; Geographic Medicine; and Infectious
Diseases, Stanford University School of Medicine
RACHEL E. LEVINSON, Director, National Research Initiatives, Offce
of the Vice President for Research and Economic Affairs, Arizona State
University
JOHN MULLIGAN, Chairman and Chief Scientifc Offcer, Blue Heron
Biotechnology
ALISON D. O’BRIEN, Professor and Chair, Department of Microbiology
and Immunology, Uniformed Services University of the Health Sciences
FRANCISCO OCHOA-CORONA, Assistant Professor, National
Institute for Microbial Forensics & Food and Agricultural Biosecurity
(NIMFFAB), Department of Entomology and Plant Pathology,
Oklahoma State University
JANE S. RICHARDSON, James B. Duke Professor, Department of
Biochemistry, Duke University Medical Center
MARGARET RILEY, Professor of Biology, Department of Biology,
University of Massachusetts
TOM SLEZAK, Program Leader, Global Security Program, Lawrence
Livermore National Laboratory
Staff
INDIA HOOK-BARNARD, Study Director and Program Offcer
CARL-GUSTAV ANDERSON, Senior Program Assistant
BOARD ON LIFE SCIENCES
KEITH YAMAMOTO (Chair), University of California, San Francisco, CA
ANN M. ARVIN, Stanford University School of Medicine, Stanford, CA
BONNIE L. BASSLER, Princeton University, Princeton, NJ
VICKI L. CHANDLER, Gordon and Betty Moore Foundation, Palo Alto,
CA
SEAN R. EDDY, Howard Hughes Medical Institute, Janelia Farm Research
Campus, Ashburn, VA
MARK D. FITZSIMMONS, John D. and Catherine T. MacArthur
Foundation, Chicago, IL
DAVID R. FRANZ, Midwest Research Institute, Frederick, MD
LOUIS J. GROSS, University of Tennessee, Knoxville, TN
JO HANDELSMAN, University of Wisconsin, Madison, WI
CATO T. LAURENCIN, University of Connecticut Health Center,
Farmington, CT
JONATHAN D. MORENO, University of Pennsylvania, Philadelphia, PA
ROBERT M. NEREM, Georgia Institute of Technology, Atlanta, GA
CAMILLE PARMESAN, University of Texas, Austin, TX
MURIEL E. POSTON, Skidmore College, Saratoga Springs, NY
ALISON G. POWER, Cornell University, Ithaca, NY
BRUCE W. STILLMAN, Cold Spring Harbor Laboratory, Cold Spring
Harbor, NY
CYNTHIA WOLBERGER, Johns Hopkins University School of Medicine,
Baltimore, MD
MARY WOOLLEY, Research!America, Alexandria, VA
Staff
FRANCES E. SHARPLES, Director
JO L. HUSBANDS, Scholar, Senior Project Director
KATHERINE BOWMAN, Senior Program Offcer
ADAM P. FAGEN, Senior Program Offcer
MARILEE K. SHELTON-DAVENPORT, Senior Program Offcer
INDIA HOOK-BARNARD, Program Offcer
ANNA FARRAR, Financial Associate
CARL-GUSTAV ANDERSON, Senior Program Assistant
AMANDA P. CLINE, Senior Program Assistant
AMANDA L. MAZZAWI, Senior Program Assistant
i
Preface
Recent studies by the National Research Council have focused on the
tension between the rapid advances in biotechnology that clearly beneft hu-
mankind and the potential use of the same advances for nefarious purposes.
The 2004 report, Biotechnology Research in an Age of Terrorism helped to
focus attention on the issue, and among other recommendations called for the
creation of a National Science Advisory Board for Biodefense (NSABB) to
serve as a bridge between the government and scientifc communities in raising
awareness of the potential for misuse of biotechnology. A later report, Global-
ization, Biosecurity, and the Future of the Life Sciences carried the discussion
forward with a global perspective and promoted a global common culture of
awareness and a shared sense of responsibility among life scientists. In 2006,
the NSABB issued Addressing Biosecurity Concerns Related to the Synthesis
of Select Agents, which called for expert evaluation to determine whether an
alternative framework based on predicted features and properties encoded by
nucleic acids, such as virulence or pathogenicity, can be developed and used
in lieu of the current fnite list of specifc agents and taxonomic defnitions.
Our committee was tasked with identifying “the scientifc advances that would
be necessary to permit serious consideration of developing and implementing
an oversight system for Select Agents that is based on predicted features and
properties encoded by nucleic acids rather than a relatively static list of specifc
agents and taxonomic defnitions.”
Our committee was populated with persons who had expertise in several
complementary felds. The amalgamation of scientifc backgrounds allowed us
to address our task from different viewpoints and to assess the potential impact
of our recommendations on various sectors. We benefted by having commit-
tee members who were experts in human and animal health and leaders in the
ii
iii PREFACE
development of policy relevant to these felds; leaders in fundamental struc-
tural, evolutionary, and computational biology and bioinformatics; scientists
dedicated to the study of pathogenic viruses and bacteria; and experts from the
commercial biotechnology sector. Many committee members were personally
involved either directly or indirectly in research on plant or animal pathogens
designated as Select Agents and thus had frst-hand experience in dealing with
the relevant regulations and security requirements implemented in recent years
to reduce the risk of misuse. We were especially fortunate to have a senior scien-
tist and executive in the biotechnology industry who was able to offer a unique
perspective on the role of industry in implementation of current and future
steps that might be taken to reduce the risk of misuse of synthetic biology.
We were informed by the shared expertise of many professionals in syn-
thetic biology, security, public health, human and animal medicine, the life
sciences, informatics and several other relevant felds as we grappled with
our challenging task. Specifcally, Julia Kiehlbauch, Robbin Weyant, Claudia
Mickelson, Edward You, and Amy Patterson helped us to understand the
current structure for oversight of Select Agents. Peter Pesenti, John Mulligan,
Marcus Graf, Claes Gustafsson and Stephen Maurer discussed with us the
current mechanisms and criteria for screening and surveillance at the sequence
level. Stanley Falkow, Jeffrey Taubenberger, Michael Katze, Ralph Baric and
Ramon Felciano discussed virulence; and Sean Eddy, Jonathan Eisen, Elliot
Lefkowitz, John Moult and Ian Lipkin addressed gaps, challenges and potential
milestones in predicting pathogenicity from sequence information. In addition,
Carol Linden, Arturo Casadevall, David Relman, Mary Groesch, Jacqueline
Corrigan-Curay and James Blaine all met personally with our committee and
joined in our discussions. We sincerely thank all those who took time from
their busy schedules to meet with us, answer our questions, and guide us in
our deliberations.
Early in our discussions, it became apparent that the criteria historically
used to designate a pathogen as a Select Agent included characteristics that can-
not be determined by sequence alone and therefore cannot be predicted with
the degree of certainty required for regulatory purposes. We soon concluded
that a sequence-based prediction system for oversight of Select Agents is not
now possible, nor is it likely to be feasible in the foreseeable future. We did,
however, recognize that a sequence-based classifcation system for Select Agents
focused on consideration of sequences of concern could be developed and
might help to clarify taxonomic distinctions among recognized Select Agents.
By focusing on “sequences of concern” and coupling that with a cautionary
alert (a “yellow fag system”), one might effectively address both biosecurity
and biosafety goals. Near-term milestone and long-term research objectives
were defned and are discussed in our report. Throughout our deliberations,
we continually tried to balance the need for safety and security, while recogniz-
ing the challenges of potential dual-use applications that arise as the scientifc
PREFACE ix
community improves its understanding of the genomic basis that leads one
organism to be pathogenic, while its near neighbor is not. We were also con-
cerned about the potential burden that such an oversight program might have
on the day-to-day conduct of science and the biotechnology business sector,
and about the opportunities that might be missed. We concluded that a gene
sequence-based classifcation system could be developed. We did not, however,
address whether such as system should be developed or whether the additional
administrative structure needed to maintain such a system would be justifed.
Therefore, we do not specifcally recommend that either the classifcation or
yellow fag system be implemented. Rather, we provide information about what
is technologically feasible, and emphasize that the potential benefts of such a
system should be considered and weighed against the cost and complexity of
implementation.
The Nobel laureate Joshua Lederberg was quoted in Richard Preston’s
1998 article on bioweaponeers in The New Yorker as saying: “There is no
technical solution to the problem of biological weapons. It needs an ethical,
human, and moral solution if it’s going to happen at all. Don’t ask me what the
odds are for an ethical solution, but there is no other solution. But would an
ethical solution appeal to a sociopath? (Preston 1998)” We fnd ourselves today,
more than a decade later, still searching for a technical solution to a challenge
that has grown beyond biological warfare and now encompasses the threat of
bioterrorism as well; a challenge that is ever more complex and threatening as
biotechnology advances and access to it expands. We can attempt to harness
technology to lessen risks, but we would be wise to heed Lederberg’s advice to
couple this with efforts toward an “ethical, human and moral solution.”
The committee wishes to express its sincere thanks and appreciation to
India Hook-Barnard, our study director and program offcer, for her leadership,
guidance and expertise, coupled with good nature and charming personality.
We benefted greatly from her dedication and creativity throughout the study.
She was ably assisted by Carl-Gustav Anderson, senior program assistant, who
ensured that our every need was met during our meetings and conference calls
and worked diligently to coordinate schedules in what must have been a nearly
impossible task. Our project was expertly guided by Fran Sharples as the direc-
tor of the Board on Life Sciences.
Finally, on a personal note, I would like to express my sincere apprecia-
tion to the members of the committee, who generously donated their time and
knowledge to make this project both extremely productive and very enjoyable.
Our discussions were frank, open, and honest, and they benefted greatly from
the diversity of our backgrounds and our complementary experiences. We were
indeed more than the sum of our own individual contributions. It has been my
pleasure and privilege to work with each of you.
James W. Le Duc, Chair