Conclusions and Recommendations
The conclusions and recommendations presented here are the results of deliberations of the committee. The recommendations are not intended to indicate a consensus of the workshop participants. They are based on information from the workshop, the expertise of the committee members, and published references. In committee discussions after the workshop, the members of the committee analyzed the information and debated among themselves on appropriate recommendations. In preparing the following recommendations, the committee considered the reality that advances in and technologies of life-science research could potentially be misused by individuals, groups, or nations to create agents capable of causing great harm. However, given that society has reason to fear natural outbreaks and intentional attacks, the committee concludes that biosecurity would be better served by policies that facilitate, not restrict, scientists’ ability to understand infectious disease and to develop countermeasures to both naturally occurring pathogens and biodefense threats.
Recommendation 1: Policies with regard to release of genome data on microbial pathogens should not change. Rapid, unrestricted public access to primary genome sequence data, annotations of genome data, genome databases, and Internet-based tools for genome analysis should be encouraged.
Mechanisms currently exist to cope with sequence data obtained during criminal investigations or for specific intelligence or national-security reasons. The committee did not address any criteria presently used by
investigative or security organizations in control of genome data. Those situations are beyond the scope of the committee’s charge. In situations where these specific exceptions do not apply the committee calls for unrestricted public access to genome data.
At the outset of the 21st century the possibility that life-science research might be perverted for destructive ends and that a pathogen could be deliberately enhanced and released to significant harm must be taken seriously. As understanding of host-pathogen interactions grows, national governments, subnational groups, or even individuals might well attempt to apply the growing power of biological science for destructive purposes, and it is possible that they could succeed. By the same token, as our understanding grows, the global health community has a greatly enhanced ability to produce new anti-infective drugs, vaccines, and diagnostic reagents.
The primary question before this committee is which policies regarding release of genome data about pathogens will provide the greatest overall biological security. That question takes into account both the possibility of deliberate pathogen enhancement and release and the fact that new and dangerous pathogens will continue to emerge naturally. After careful deliberation, the committee concluded that preserving open access to genome data and free exchange of knowledge and results that flow from the data will, by a substantial margin, increase biosecurity. Therefore the committee recommends no expansion in the amount of genome data which is classified and no change in the extent of material withheld from widespread public release, they also recommend that no registration system be imposed. The committee’s reasoning as it came to that conclusion focused on three sets of arguments:
Current Policies Are Effective. Unfettered, free access to the results of life-science research is the historic norm and has served science and society remarkably well. Open access allows life scientists everywhere to evaluate, interpret, adapt, and extend results from many fields of inquiry for use in their own work and thereby accelerates research and speeds the delivery of life-saving benefits that biological and medical research are so rapidly creating. Science builds on itself, and the sharing of methods and data allows scientists to learn from the work of others and to make unexpected connections. There is no obvious way to predict which scientists will benefit from access to which data, so restricting access poses a risk of slowing the progress of research. The current vigor in the life sciences depends on the free flow of data and ideas, and it is necessary if science is to deliver needed new biodefense capabilities.
Current policies allow for the most rapid and effective scientific response possible during an infectious-disease crisis, such as the SARS outbreak of 2003. At such times, when scientific and public-health
resources must be rapidly mobilized to combat a poorly understood emerging disease, free and rapid exchange of data, results, and ideas is essential to allow scientists to communicate effectively and to build on one another’s findings. Restrictions on the flow of information in such circumstances would slow the acquisition of understanding of the emerging infection and the development of countermeasures against it.
A security-classification mechanism already exists to deal with specific and unusual cases in which genome data should be withheld. The committee has not examined the current system used to determine which information should be classified, but it believes that a government system of classification should be adequate for restricting disclosure and that an additional system of control is not necessary to address security needs.
Some genome-sequence data acquired with federal funds have not been released immediately. For example, anthrax sequences that were obtained during the criminal investigation of the anthrax attacks of 2001 have not yet been released and might not be for some time, perhaps not until a legal case is resolved. Some sequence data have been classified, such as the sequences of certain PCR primers designed to be used in environmental sensors; this was done to reduce the likelihood that pathogens would be altered to make the primers useless. Mechanisms now in place to cope with sequence data obtained during criminal investigations or for specific intelligence or national-security reasons should not be used to limit scientific research but may be necessary to cope with unusual situations in the future.
Effective Restriction of Genome Data Is Not Practical. As a practical matter, restricting access to genome data would be difficult, expensive, and probably counterproductive. First, it is notoriously difficult to control access to digital data. Files that contain entire genomes are not particularly large—generally, several megabytes—and are easily stored, transferred, and exchanged. Second, in the absence of a uniform international agreement to impose similar control measures worldwide, potential users who are denied access because of U.S. policy could direct their Internet browsers to genomics sites in other countries that have the same kind of data. A global consensus on how to implement policies that would be strong enough to keep relevant data out of the hands of potential malefactors would be difficult to achieve. Third, any policy stringent enough to reduce the chance that a malefactor would access data would probably also impede legitimate scientists in using the data and would therefore slow discovery. Penalties would be required to ensure that restrictions were obeyed, and an oversight organization would have to be created to monitor compliance. The international framework needed to make the policies workable would be cumbersome and expensive. It is possible that the
harm done during a process of negotiating such an agreement—through building walls of mistrust between peoples—would be greater than the benefit gained through the sense of security that such a regime might provide. Finally, such a restrictive regime, the committee believes, could seriously damage the vitality of the life sciences.
At the outset of the workshop, the concept of requiring all users of genome databases to register to gain access seemed to many participants to be a reasonable policy compromise. Under such a policy, anyone could gain access but only after stating a name, address, and institutional affiliation. After additional discussion, however, the committee concluded that a registration requirement of this kind would not be an effective way of protecting society from bioterrorism. Registration would not prevent a determined malefactor from accessing genome databases. Registration might deter a less determined malefactor or provide a mechanism for tracing his or her activities, but it would also raise many troubling questions about who could use registration information and under what circumstances. In addition, the lack of an international consensus that registration should be required would render such measures futile. It seems unlikely that a uniform agreement could be generated between all public and private database managers and others who generate genome data, which would be necessary to track those with access to genome sequences. In addition, scientists are wary of efforts to track their use of genome data, especially in the competitive field of biological research. Some are concerned that another laboratory will figure out what they are working on and be the first to publish. Pharmaceutical companies are cautious about protecting their early-stage investigations from competitors; companies’ willingness to invest in drug discovery could decrease if others could determine what data they are using. In addition, the fact that pharmaceutical companies, large research centers, and others download many of the available data onto their own networks so that they can be used privately would hinder the usefulness of attempts to track discrete queries to databases. Many of the data have been in the public domain for years and may well be stored in dozens or even hundreds of locations around the world. Given the international availability of the data, many people could access sequence information without relying on a database that requires registration. For all the above reasons the committee feels that the benefits of registration do not outweigh the costs to society from the resulting slowdown in research on infectious diseases.
Pathogen Genome Sequences Are Not Uniquely Dangerous. Primary sequence data on pathogens become dangerous only if the user has a sophisticated ability to exploit them and a malevolent goal. Mere possession of the sequence of a pathogen does not confer the ability to
enhance the virulence of the organism to which it pertains, nor would it help to solve the demanding technical problems associated with conducting a terrorist attack. Although a potential malefactor might be able to adapt published research results that reveal genetic manipulations that would enhance the virulence of a pathogen, discovering which genetic change would enhance virulence is difficult and would require a substantial and sophisticated effort.
Pathogen genome sequences are not uniquely dangerous, because sequence data from non-pathogenic organisms could also be used to enhance a pathogen’s virulence or create a new pathogen. For example, sequence data from a close relative of a pathogen, such as Bacillus cereus, could be useful to a potential terrorist. Alternatively, sequence data from a pathogen’s host could be used to engineer a microorganism. For example, mousepox virus has been shown to become more virulent when engineered to contain the gene for the mouse version of interleukin-4, an immune regulator. Moreover, many nonpathogenic symbiotic or commensal microorganisms could conceivably be made pathogenic by the addition of genes that encode human immune system signals; this would disrupt the normal immune response and allow otherwise harmless bacteria to cause harm. Access to all pathogen and host sequences could not be restricted without severely damaging the fabric of the entire global scientific enterprise; such information is essential to current life-science research efforts. In the end, the availability or nonavailability of a pathogen’s genome sequence will not deter a dedicated actor from using a naturally occurring infectious strain in a terrorist attack.
The above discussion focuses mainly on naturally occurring organisms. For the most part, the issues are the same for genetically engineered organisms. Information on the altered sequences and the resulting phenotypes can provide insight into basic biology, and most alterations are not particularly useful to a potential bioterrorist. However, sequence data on some genetically engineered organisms could be useful for a potential bioterrorist attempting to create a more dangerous pathogen. Regulation of the conduct of the experiments that might generate such engineered organisms is beyond the charge to this committee, but it is an important issue. Decisions on the appropriateness of conducting particular experiments should ideally be made before the experiments are begun. Local institutional review boards (IRBs) play a large role in that process, and the newly announced National Science Advisory Board for Biosecurity (NSABB), discussed in detail in Recommendation 3, will play a growing role in that regard. The guidelines for IRBs and codes of conduct for individual scientists that the NSABB envisions should help to ensure that appropriate consideration is given to the potential implications of research
approaches before they are begun. In addition, journal editors have a responsibility to consider the national-security implications of the papers they publish. Given all those caveats, if an experiment is published, the accompanying genome data should not be restricted by regulations. The data are essential for others to understand the significance of the research and may be crucial to future experiments that could help to protect us from disease. There is some concern that restricting access to this information might lead to a situation in which the mainstream scientific community is unaware of dangers that may threaten us. And some have proposed that observing changes in the frequency of publications (and conference presentations) of potential malefactors can provide useful clues as to whether they are conducting secret experiments.
For all those reasons, the committee concluded that maintaining the current standard of free access to all genome data is the best policy choice. The problem with which the committee has been charged is not to strike the correct balance between security and openness. That is a false dichotomy; openness has enhanced security in the past and is the best way to ensure security in the future. Instead, the most important task is to be as well prepared as possible to cope with the serious infectious-disease threats that society is sure to face in the coming century, both natural and human-made. The committee believes firmly that the policies currently in place for genome data—immediate release and free access—are correct because openness is essential to maintain the progress needed to stay ahead of those who would attempt to cause harm.
Recommendation 2: Genomics and genome sequence data should be exploited fully to improve our ability to defend against infectious agents of all types, including those which contribute to epidemic diseases and infant mortality and the naturally occurring or genetically enhanced organisms that could be used in a bioterrorist attack.
Maximizing the benefit from research on infectious diseases is important for both public-health and national-security reasons. Even before the increase in attention to national security that followed the attacks of 2001, the U.S. government had considered infectious disease as a security issue. For example, in testimony to Congress on June 29, 2000 (Gordon, 2000), a national intelligence officer discussed the possibility of bioterrorism; the threat to public health from importation of diseases; the impact of troop health on U.S. military readiness; the ability of tuberculosis, malaria, and AIDS to slow economic development and undermine social structures in some regions; and the potential harm from infectious-disease-related embargoes and restrictions on travel.
Since the terrorist attacks of 2001, federal spending intended to improve defenses against bioterrorism and natural infectious-disease out-
breaks has increased markedly. For FY 2003, the total expenditure for bioterrorism preparedness was $5.9 billion (http://www.niaid.nih.gov/biodefense/about/nbe.htm). Of that total, about $1.75 billion was spent on biodefense-related research, most of it channeled through the National Institute of Allergy and Infectious Diseases (Fraser, 2004). Indeed, many of the pathogen whole-genome sequencing efforts that have been recently completed or begun have been funded with money earmarked for biodefense.
Research exploiting the revolution in genomics has an important role to play in increasing our ability to defend against infectious agents of importance to biodefense and global infectious disease. Indeed, research on many of the currently important societal infectious threats, such as antibiotic-resistant bacterial pneumonia and antibiotic-resistant staphylococcal disease, will benefit enormously from the genomic revolution. Extensive sequence comparisons between pathogenic and nonpathogenic organisms, studies of changes in the pattern of gene expression in pathogens and their hosts as they interact, and sequencing of multiple strains of specific pathogens will all contribute to the development of new diagnostics, vaccines, and therapeutics for disease-causing organisms, including those which might be used in a bioterror attack. It is important to maintain policies that allow all medical and agricultural scientists, including those who focus on biodefense, to use genome data to the fullest extent possible in their research. The genomics revolution includes not only human pathogens and their hosts but also the infectious agents that plague agricultural crops and livestock. These are also of critical importance for our economy and for our national security. The biodefense effort should include both human pathogens and pathogens that might be deployed against agricultural interests.1
Recommendation 3: Future advances in genome science should be regularly reviewed to keep all relevant government departments and agencies apprised of new developments that may affect national security. Regular meetings of scientific and security experts should be held to discuss the implications of new developments and to develop coherent responses. The newly formed National Science Advisory Board for Biosecurity or another appropriate entity with the ability to connect with diverse federal agencies would be a suitable home for that function.
The pace of scientific progress creates a need for continuous and thorough evaluation of science and technology as they affect national security
and the health and welfare of all the inhabitants of the planet. Decisions about policies related to pathogen genomes cannot be properly made unless they are considered in the context of other scientific advances. New developments in law enforcement, forensics, and public health based on continued research may provide better approaches to improving biosecurity than attempts to restrict access to genome data. However, a mechanism is needed to ensure adequate communication between the scientific and security communities. People in the scientific and security communities bring to the table their own cultures and experiences. Extensive discussions are necessary for each to be able to understand the other’s perspectives. This sharing of perspectives is crucial if future policy decisions are to reflect the best possible input. Improved communication will help to guide scientific research in fields that will facilitate biodefense, and it will help security experts base their actions on the latest science.
A well-informed body with both scientific and security expertise should provide an accessible link between the scientific and security communities and review advances in genome science in case future developments warrant the creation of additional monitoring of or restrictions on access to genome data. The new body would serve as a communication mechanism between the scientific and security communities and help to decrease the likelihood that new developments will come as a surprise. Extensive participation of the security community in this activity would be a concrete action that could be taken as part of its data-gathering work.
Review should be scientifically broad because the effect of genomics on biosecurity goes far beyond the biology of biothreat organisms and includes both biomedical topics, such as drug and vaccine development, and topics pertaining to forensics, intelligence, agriculture, and the environment. Limiting the evaluation to direct studies on genomes of pathogens would not adequately address threats to biosecurity. Knowledge of the genomes of infectious agents that might be used as weapons of bioterror is obviously important, but the genomes of potential hosts (humans, other animals, and plants) also offer opportunities for manipulation. Over the next 10 years, scientists may learn at least as much about the genetic and molecular basis of genetic resistance and susceptibility to infection as about specific microbial virulence factors and their function. The perspective of those involved in basic research related to humans, plants, animals, and microorganisms is essential for staying on top of new developments that may affect biosecurity. Continuing review of new technology could include the use of functional genomics as it pertains to understanding microbial virulence; host susceptibility and resistance to infectious diseases of plants, domestic animals, and humans; and relevant aspects of the development of new drugs, vaccines, and anti-infective therapies.
To be well informed, the review body must be part of a network for information exchange among academe, industry, international actors, and U.S. government agencies, including those in the threat-response community. Coordination of efforts in all arenas, including the international community and those involved in threat response, would provide a means of assessing the significance of advances in genome research in terms of both increased threats to security and improvements in understanding of the environment and human health and disease. As an additional benefit, providing a network for information exchange would help to further research in disease diagnosis and epidemiologic surveillance on a national and global basis and facilitate communication of information required for the unambiguous identification and attribution of pathogens in forensics.
There are several options for implementing action on the functions described above. For example, a new entity could be created or an existing entity modified. The committee is not aware of any existing entities that would have access to both the scientific expertise and the broad network described above. However, the newly announced National Science Advisory Board for Biosecurity (NSABB) might be a suitable home for those tasks, depending on the focus it takes as it is established. On March 4, 2004, the Department of Health and Human Services (DHHS) announced at a press conference and on its Web site (www.biosecurityboard.gov) the creation of the NSABB to “advise all Federal departments and agencies that conduct or support life sciences research that could fall into the dual use category. The NSABB will be managed by the National Institutes of Health.” In announcing the creation of the board, John Marburger, director of the White House Office of Science and Technology Policy, said that “it is imperative that we develop this new framework to address serious concerns that range from personal responsibility to national security.”
The NSABB was created in response to Recommendation 4 in the recent National Research Council report (2003a) Biotechnology Research in an Age of Terrorism.
We recommend the formation of a National Science Advisory Board for Biodefense (NSABB)2 to provide advice, guidance, and leadership for the system of review and oversight that we are proposing. The NSABB would serve a number of important functions for both the scientific community and the government. At the most general (strategic) level, it would serve as a point of continuing dialogue between the scientific community and the national security community and as a forum for addressing issues of interest or concern. At the operational (tactical) level, it would provide case-specific advice on the oversight of research and the
The name of the board announced on March 4 differs slightly from that proposed in the 2003 National Research Council report.
communication and dissemination of life sciences research information that is relevant for national security and biodefense purposes.
The DHHS announcement states that the NSABB will
Advise on strategies for local and federal biosecurity oversight for all federally funded or supported life sciences research.
Advise on the development of guidelines for biosecurity oversight of life sciences research and provide ongoing evaluation and modification of these guidelines as needed.
Advise on strategies to work with journal editors and other stakeholders to ensure the development of guidelines for the publication, public presentation, and public communication of potentially sensitive life sciences research.
Advise on the development of guidelines for mandatory programs for education and training in biosecurity issues for all life scientists and laboratory workers at federally-funded institutions.
Provide guidance on the development of a code of conduct for life scientists and laboratory workers that can be adopted by federal agencies as well as professional organizations and institutions engaged in the performance of life sciences research domestically and internationally.
The NSABB will have up to 25 voting members, to be appointed by the DHHS Secretary in consultation with the heads of relevant federal departments and agencies. Members will be experts in a broad range of fields, including molecular biology, microbiology, infectious diseases, laboratory biosafety and biosecurity, public health/epidemiology, health physics, pharmaceutical production, veterinary medicine, plant health, food production, bioethics, national security, biodefense, intelligence, law and law enforcement, and scientific publishing. The board will also include nonvoting ex officio members from at least 15 federal departments and agencies.
The following agencies were included in the announcement and are expected to be involved in the NSABB: the Executive Office of the President, DHHS, the Department of Energy (DOE), the Department of Homeland Security (DHS), the Department of Veterans Affairs, the Department of Defense, the Department of the Interior, the Environmental Protection Agency, the U.S. Department of Agriculture, the National Science Foundation (NSF), the Department of Justice (DOJ), the Department of State, the Department of Commerce, and the National Aeronautics and Space Administration. The intelligence community is also expected to participate.
There are pros and cons to locating the responsibility for review of genome data in the NSABB. For example, it may not be possible for the NSABB to manage the necessary continuing review of genome information while establishing guidelines for the oversight of biological research. A dedicated subcommittee of the NSABB might be formed to review developments and keep the NSABB as a whole informed. Another issue in assigning the above functions to the NSABB is that the board will be managed by the National Institutes of Health (NIH), and this may hamper its ability to view biosecurity-related issues from all the necessary perspectives. The review of genome research envisioned will require the gathering and analysis of diverse opinions. The partnership and full participation of each of the agencies is crucial to ensure that all the available information and insight are used.
A useful example of cooperation between agencies already exists in the National Interagency Genomics Sciences Coordinating Committee (NIGSCC), which meets on an ad hoc basis and has proved effective in maintaining close contact between the various government agencies with interests in genome research, including NSF, NIH, the Federal Bureau of Investigation, DOJ, the Centers for Disease Control and Prevention, the Central Intelligence Agency, the Defense Advanced Research Projects Agency, DOE, DHS, the U.S. Army, and USDA. The NIGSCC provides a useful model of how the understanding of interdisciplinary issues can be advanced and profited from by successful collaboration among individuals and agencies with diverse perspectives. The NIGSCC, however, has no formal authority to carry out actions that it deems necessary, nor does it include representatives of academe, industry, or international bodies; so it is not ideal for the purpose the committee suggests. The entity that becomes responsible for reviewing scientific advances in genome science for their potential effect on national security must be scientifically respected, have the ability to integrate information from diverse sources, and have the ability to influence discussions in numerous federal departments and agencies.
Recommendation 4: The committee endorses Recommendation 7 of Biotechnology Research in an Age of Terrorism, which calls for an international forum to unify the discussion on the effect of genomics on biosecurity.
Life-science research is global, and no single nation can successfully implement policy concerning access to and release of life-science data and results without reference to the rest of the international community. For that reason, it is of the utmost importance that the international community establish a common understanding of security concerns and shared
resources to make the most efficient and safest use of genome data and experimental results, some of which might suggest how pathogens could be successfully enhanced. The committee therefore strongly endorses Recommendation 7 of Biotechnology Research in an Age of Terrorism, which calls for “the international policy-making and scientific communities [to] create an international forum on biosecurity to develop and promote harmonized national, regional, and international measures that will provide a counterpart to the system [recommended] for the United States.” If conducted openly and in the proper spirit, the process of discussing these issues might actually build understanding, and some trust, among the nations involved and eventually help to establish an international norm against misuse of genetic information.
Since the release of Biotechnology Research in an Age of Terrorism, plans have begun for the International Forum on Biosecurity. The event will be coordinated by the Policy and Global Affairs Division of the National Academies and funded by the Sloan Foundation and the Nuclear Threat Initiative. An international steering committee will be formed to develop plans for the forum. The committee membership will include experts with current or past ties to existing international organizations working in this field. The details of the forum will be worked out by the members of the committee as they engage in several outreach activities. Its three key objectives are as follows:
To advance awareness in the life-science community and the international scientific community about the critical challenges posed by the dual-use dilemma.
To solidify the commitment of leading scientific organizations to make biosecurity issues part of their regular programming. The forum will also serve as a showcase for the results of other meetings on biodefense and for the programs of major organizations.
To serve as a major convening and coordinating mechanism for the scientific and policy-making communities. For example, a number of organizations already have or will be developing codes of conduct, some with an eye to the meeting of Biological Weapons Convention States Parties in the summer and fall of 2005 and some for their own purposes. The forum will provide the opportunity to bring these efforts together and to think strategically about how to maximize their impact.
The committee applauds the new initiative and encourages all parties to participate in the activities of the forum to advance the goal of promoting coordination and synergy by linking other efforts headed by established organizations with developed constituencies. In the same way that the
United States should maintain an endeavor in this field (see Recommendation 3), it will be important for international cooperation and coordination to be maintained.
Recommendation 5: The committee endorses Recommendation 1 of Biotechnology Research in an Age of Terrorism, which calls for national and international professional societies and related organizations to work to educate scientists about the risk that life-science research results will be misused and about scientists’ responsibility to mitigate the risk.
Recommendation 1 of Biotechnology Research in an Age of Terrorism calls for national and international professional societies and related organizations and institutions to create programs to educate scientists about the dual-use dilemma in biotechnology and their responsibilities to mitigate its risks. As noted under our Recommendation 1 above, we believe that although the risk that the growing power of biological and medical research could be applied to destructive purposes is unknown, it is not zero. All life scientists must be sensitized to the potential for the harmful misuse of the knowledge they create.
The committee recognizes and applauds the efforts of numerous professional societies to educate their members and the public about these issues, and it suggests that such professional societies are the natural home for further efforts in this respect. They should expand efforts to engage their members in discussion of the potential benefits and dangers of the widespread availability of genome sequences and functional genomics data.
At this writing, the U.S. government has announced that the mission of the NSABB will include the development of professional codes of conduct for scientists and laboratory workers that can be adopted by professional organizations and institutions engaged in life-science research and the development of materials and resources to educate the research community about effective biosecurity (www.biosecurityboard.gov). The work of the NSABB will provide an important opportunity for the professional societies to work with the government so that the educational opportunities provided and the guidelines produced will be most effective.
The committee recommends that professional codes of conduct explicitly require scientists to act to mitigate the risk of misuse of scientific progress to cause environmental or medical harm and require them to carry out their research with integrity to minimize the risk of misuse of life-science research for destructive purposes.