THE LIFE-SCIENCE REVOLUTION AND THE DUAL-USE DILEMMA
The life-science revolution that began with deciphering the genetic code has launched biological research into an unprecedented period of productivity. Parallel advances in computational techniques and the widespread use of global computer networks have contributed to the pace of biological research. Within less than 30 years, the entire genomes of many hundreds of organisms, from viruses to bacteria to humans, have been sequenced, and partial sequences from many thousands more organisms have been deposited into databases freely accessible to scientists around the world.
Modern biological research is a thriving international enterprise with enormous potential to benefit society. The synergy created by increasing knowledge and open exchange of ideas and information is accelerating the advance of medicine, industry, and agriculture. Emerging details about the interplay between pathogenic microorganisms and their hosts will allow scientists to continue to develop and deliver new and improved vaccines, stronger infection-fighting drugs, and more-precise diagnostic tools.
However, with its promise, biological research presents a “dual-use” dilemma, in that its technologic advances could also be applied for destructive purposes in acts of bioterrorism or war. Results that have immediate implications for pathogen enhancement or weapons development have been called “contentious research” (Epstein, 2001) or are said to fall
into a gray zone where the benefits of publication may not outweigh the dangers. Any scientist working to develop new treatments for naturally occurring infectious diseases can tap the power of genomics and its globally accessible databases and analytic tools, but so could a malefactor trying to engineer enhanced pathogens for use as biological weapons. Hence, scientists and policy-makers are confronted with the challenging question of how to mitigate the risk of bioterrorism and still foster the research community’s ability to counter current and future biological threats, whether naturally occurring or malevolently deployed.
GENOME RESEARCH IN AN AGE OF TERRORISM
The attacks on September 11, 2001, and the later deadly anthrax letters have focused increased national and international attention on the threat of terrorism. On October 8, 2003, the National Academies released a report, Biotechnology Research in an Age of Terrorism (NRC, 2003a), which examined the dual-use problem in life-science research. The author committee, chaired by Gerald Fink of the Whitehead Institute, offered recommendations on how to confront the potential for misuse of biological agents and technologies without unduly limiting progress in the life sciences. The report proposed modifications of the system of review of biological experiments and stressed the importance of addressing research in subjects of concern early and of educating scientists to be aware of the risks and benefits associated with their research and how to balance them responsibly. The committee recognized the importance of open communication in scientific research as a fundamental practice crucial to continued progress despite the fact that it might make the data accessible to those intent on misuse. A reliance “on self-governance by scientists and scientific journals to review publications for their potential national security risks” was recommended, and a number of major journals that publish life-science research have already committed to implementing such a review process (Atlas et al., 2003a,b,c).
Genome data, the focus of this report, occupy a unique position in the dual-use dilemma in that they are a source of raw material that, although not inherently dangerous, can be enabling for potentially destructive agendas. Furthermore, the culture of genomics is unique in its evolution into a global web of tools and information. The major Internet-based data repositories have policies that mandate free, unfettered, and anonymous access, and most scientific journals require that genome data be deposited into accessible databases as a prerequisite for publication. With the exception of rare cases in which information is classified for national security purposes, the U.S. government itself requires that data, including genome data, resulting from federally funded research be made publicly avail-
able. The committee did not address mechanisms used to determine whether or not information is classified.
CHARGE TO THE COMMITTEE
Members of the National Interagency Genomics Sciences Coordinating Committee (NIGSCC), which comprises representatives of several federal agencies that have an interest in genome research, had discussed the release to the public domain of genome data as they pertain to likely agents of bioterrorism. Given that complete genomes of more than 100 microbial pathogens—including those for smallpox, anthrax, Ebola hemorrhagic fever, botulism, and plague—are already in Internet-accessible databases freely open to all and that the genomes of hundreds more pathogens will be sequenced with the support of government funds in the next few years (Fraser, 2004), representatives of the member agencies discussed whether current policies regarding release of genome sequence data were appropriate. As a result of the discussions, some NIGSCC members decided to seek advice from the scientific community. The National Science Foundation, the National Institutes of Health, the Department of Homeland Security, and the Central Intelligence Agency funded the National Academies to convene a committee, to hold a workshop, and to produce a report about how biological scientists view the potential for misuse of genome sequence data and the policies governing access to databases containing these data.
At the first meeting of the Committee on Genomics Databases for Bioterrorism Threat Agents, the sponsors indicated that they hoped the report would present the perspective of working biological scientists, so that readers in the policy and intelligence communities could use the report when considering potential changes in policy regarding access to genome sequence data. It was understood that the security community would then take this scientific perspective and use it in combination with their own knowledge of security issues to make decisions. The sponsors specifically requested that the report capture input from workshop participants’ presentations and discussions, identify general issues surrounding the release to the public domain of genome data for bioterrorism threat agents, develop a list of pros and cons associated with the release to the public domain of such data, and present recommendations for policy options and decision-making frameworks concerning release to the public domain of genome information.1
The full charge to the committee, the statement of task, can be found in Appendix A.
The National Academies committee organized a 1-day workshop on the public release of genome data on bioterrorism-threat agents, which was held in Washington, DC, on October 1, 2003. About 40 invited scientists and policy experts who work in government, private industry, and academic laboratories attended. Workshop participants were asked to address three questions concerning genome data for possible biological weapons agents:
What categories of genome data present the greatest concern?
What are the pros and cons of unlimited vs. restricted access to such data, including threats posed to the scientific community or to national security?
What are some options for making decisions about release to the public domain?
The workshop agenda and a list of the participants are appended to this report. Although the questions posed to the committee were limited to consideration of genome sequences of bioterrorism-threat agents, these were by no means the only kind of data that workshop participants discussed. The broader context is complex, and there is no clear demarcation between bioterror-agent genome sequences and other genome data, geneexpression data, protein structures, and other kinds of research results. The key advances in modern life science are not readily apparent in any particular piece of genome data. Instead, the growing set of full-length sequences of many organisms can be thought of as “raw material” for modern biological research or as the platform from which research can be launched. Data on one organism often prove to be invaluable for building a better understanding of other organisms, and data from many organisms taken together and compared, analyzed, and applied to new questions will allow new and fundamental insights into biological processes.
GENOME DATABASES TODAY
At the workshop, presentations described genome databases and how they are used to advance research in the life sciences. This report describes two recent success stories—the rapid international response to the 2003 outbreak of severe acute respiratory syndrome (SARS) and the creation of meningococcus B vaccine candidates—that illustrate the power of genomics and openly accessible databases to help improve our understanding of and aid in the development of countermeasures for infectious diseases. The report also considers how genome data and related technologies might be misused for the development of genetically enhanced biological weapons, and it discusses potential malefactors. As access to the knowl-
edge and resources necessary to engineer microorganisms grows, the ability to manipulate pathogen genomes will be far more widespread and accessible than it is today. Such techniques could be used to produce advanced biological agents that are more dangerous, or easier to use, than naturally occurring agents. Although the technical hurdles that would confront a bioterrorist intending to deploy a naturally occurring agent to cause large numbers of casualties are substantial, they are much lower than those associated with enhancing the virulence of a known pathogenic species with genetic manipulation. Thus, an attack with a natural pathogen is more likely; however, given the developments in biotechnology described in this report, a more sophisticated attack with an engineered pathogen is a serious concern.
ISSUES IN THE CONTROL OF GENOME INFORMATION
The committee members and workshop participants discussed a variety of issues as they asked whether and to what degree access to pathogen-related genome data should be restricted. They identified the major domestic stakeholders as the scientific community, the security community, and the general public, and they considered the interests and positions of these groups carefully. The effectiveness of any policy depends on international consensus because databases are globally accessible. The position of the international community and the potential political implications of restrictions imposed by the United States were also taken into account.
The committee was charged with determining which types of pathogen-related genome data present the most concern. Biological agents discussed at the workshop included those on national “select agent” lists and those which could become plausible threats in the future. Genome data from sources other than pathogenic microorganisms were also included, inasmuch as insights about infection processes can come from studying a pathogen’s hosts or nonpathogenic relatives. With the input of workshop participants, committee members discussed whether it was possible to categorize data usefully on the basis of whether they might be misused for bioterrorist purposes. Categories of data that were discussed include primary genome sequences, annotated and analyzed sequences, sequences from select agents, and sequences from engineered microorganisms. In further discussions after the workshop, the committee concluded that assigning data to one of those categories would not be a significant help in determining risks. They reached that conclusion in large part because of the ways that information from one category can inform studies in another category, such as when comparisons are made between closely related organisms. Data on all organisms present some level of
concern; although some organisms are inherently more dangerous, it does not necessarily follow that the genome sequences of the organisms are more dangerous. The organisms themselves are beyond the scope of this study, and many organisms relevant here are governed by the select-agent rules.
Workshop participants also discussed the idea of a gray zone, or a field of contentious research. In a 2001 publication, Gerald Epstein (2001) described contentious research as containing “fundamental biological or biomedical investigations that produce organisms or knowledge that could have immediate weapons implications and that therefore raise questions concerning whether and how that research should be conducted and disseminated.” The conduct of such contentious research is beyond the charge to this committee, but the dissemination of the results falls within our purview.
Workshop participants and committee members also considered possible mechanisms for controlling access to data. Data could be designated as classified so that they would be withheld from people who do not possess a government-issued security clearance. Alternatively, data could be withheld from widespread public release by another mechanism, such as a new screening process that would provide access to those deemed authorized. A third possibility would be to require registration for database access but not to impose any restrictions on who could register; this alternative could provide an opportunity to track database users. Finally, current policies of free access without a requirement for registration could be maintained.
ADVANTAGES AND DISADVANTAGES OF RESTRICTING ACCESS
The committee and workshop participants weighed the possible advantages and disadvantages of the various ways of restricting access to genome data. They considered the potential to thwart efforts to develop genetically engineered bioweapons but recognized that the genome data most likely to be restricted are also the data most relevant to the development of countermeasures and treatments for naturally occurring or engineered pathogens. They noted that restricting access might ease public concern and increase public confidence in the scientific community’s willingness to confront the dual-use dilemma responsibly. However, an open-access policy also has great benefit in that it allows all scientists the opportunity to collaborate and to use all possible information to scrutinize and verify results and conclusions. Given the numerous interconnections between different topics related to life-science research, it is not possible to predict which scientists will benefit from access to which data; this makes restricting access all the more tricky to implement. The group also discussed practical issues that would surround the development and imple-
mentation of a policy to restrict access to genome data, such as who would decide which scientists would have access to which information and whether there are realistic ways to contain digital data.
CONCLUSIONS AND RECOMMENDATIONS
The presentations and discussions at the workshop and their own research has led the committee members to make the following recommendations. In preparing these recommendations, the committee considered the reality that advances 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.
With a growing understanding of microbial pathogens and their interactions with the hosts they infect, national governments, subnational groups, or single individuals could attempt to apply such knowledge to destructive purposes and with potentially grave consequences. However, after careful deliberation, the committee concluded that preserving open access to genome data and free exchange of knowledge and ideas that flow from the data will facilitate scientific and medical advances that will improve health and society’s ability to react to biological threats. That conclusion is supported by the following 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. 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.
Effective Restriction of Genome Data Is Not Practical
As a practical matter, restricting access to genome data would be difficult, expensive, and probably counterproductive. It is notoriously difficult to control access to digital data, and files that contain entire genomes are not particularly large and therefore are easily stored, transferred, and exchanged. Also, 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. In addition, any policy stringent enough to reduce the chance that a malefactor would access data would probably also impede legitimate scientists’ use of the data and would therefore slow discovery and limit 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. Although registration might deter a less determined malefactor or provide a mechanism for tracing his or her activities, 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 sequence. Downloading by pharmaceutical companies, large research centers, and others 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 it is not appropriate to implement a system of registration for the use of genome databases.
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.
The workshop participants considered what categories of genome data present the greatest concern, these categories are described in Chapter 3. The committee did not see evidence that identifying data as belonging to any one of these category would necessarily make them a greater threat. It is important to remember that the focus here is on access to data pertaining to organisms, not on access to the organisms themselves; for example, U.S. government regulations on select agents apply to the possession of the organisms and not to their genome sequences.
There are many reasons why it is difficult to categorize genome data by risk. First, the study of nonpathogenic microorganisms is often closely related to the study of pathogenic species. The ubiquitous soil bacterium Bacillus cereus, for example, is closely related to Bacillus anthracis, the bacterium that causes anthrax; insights gained from the genome of one have been directly applicable to the other (Parkhill and Berry, 2003). Second, biological-weapons developers and those studying ways to counter biological weapons both use model strains to simulate real agents so that they can do development work and trials more safely. One classical model of anthrax is the insect pathogen Bacillus thuringiensis, which is widely used as a microbial pesticide. It could be argued that knowledge of its genome would be beneficial to a malefactor hoping to genetically enhance B. anthracis. Third, data derived from a single microbial species are not the only data relevant to understanding it. Instead, the ability to compare genes, genetic control mechanisms, and protein function among the entire growing and diverse catalog of completely sequenced microbial genomes is what drives many current research efforts (Frazer et al., 2003; Kanehisa and Bork, 2003). Such comparisons among species have already proved to be a productive approach to deciphering how pathogenic and nonpathogenic species function as complex biological systems. Fourth, genome data
that help scientists to clarify how pathogenic microorganisms cause disease are by no means limited to microorganisms. Human gene sequences and sequences from other “host” species are crucial data for those seeking to understand the intricacies of the interactions between the immune system and microbial pathogens, including specific immune mechanisms and vulnerabilities. The gene sequences of humans and other host species and the insights derived from them therefore would be crucial “enabling data” both for those who would work to find new ways to defeat pathogens and for those who might hope to modify pathogens to exploit immune vulnerabilities and create pathogens with unusual or particularly destructive properties.
The committee was charged with determining which types of pathogen-related genome data present the most concern. As described in the report, it is possible to identify categories of data, but it is not clear that types of data can be correlated with a specific risk of misuse for bioterrorist purposes. Data on all organisms present some level of concern but, although some organisms are inherently more dangerous, it does not necessarily follow that their genome sequences are more dangerous. The organisms themselves are beyond the scope of this study, and research on many of the organisms relevant here is governed by the select agent rules.
For the most part, the issues are the same for genetically engineered organisms as for naturally occurring 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 from some genetically engineered organisms could be very useful for a potential bioterrorist attempting to create a more dangerous pathogen. Regulations on the actual conduct of the experiments that might generate such an engineered organism are beyond the charge to this committee, although it is certainly 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. 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 carefully 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 protect us from dis-
ease. In addition, there is some concern that restricting access to this information might lead to a situation in which the mainstream scientific community is unaware of the potential 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.
Since the terrorist attacks of 2001, federal spending intended to improve defenses against bioterrorism and natural infectious-disease outbreaks has increased markedly. 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 in 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 genome 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. Infectious agents that plague agricultural crops and livestock are of critical importance for our economy and our national secu-
rity. The biodefense effort should include both human pathogens and those which might be deployed against agricultural interests.2
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 scientific technology as it affects national security and the health and welfare of all the inhabitants of this planet. Decisions about 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. A well-informed body with both scientific and security expertise should review advances in genome science in case future developments warrant the creation of additional monitoring of or restrictions on access to genome data. 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 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 reviewing body must be part of a network for information exchange among academe, industry, international actors, and U.S. government agencies, including those in the intelligence and security community. Coordination of efforts in all arenas, including the international community and those involved in assessing and responding to threats, would provide a means of evaluating the significance of advances in genome research in terms of both increased threats to security and improvements in understanding of the environment and of 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 many factors to balance in determining where the proposed reviewing function should be based. One option is the newly proposed NSABB announced by the Department of Health and Human Services on March 4, 2004. The NSABB is asked to “advise all Federal departments and agencies that conduct or support life sciences research that could fall into the dual use category (www.biosecurityboard.gov).” However, it may not be feasible for that group to manage the necessary continuing review of genome information while acting on establishing guidelines for the oversight of biological research. In any event, the partnership and full participation of each of the relevant agencies is crucial to ensure that all the available information and insight are used. 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 a clear 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 in order 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 policymaking 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.” An international forum to discuss the potential for the misapplication of life-science research should be convened in the near future to serve as a first step toward achieving harmonized international oversight. The forum should include broad representation of all interested countries. 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 establish an international norm against misuse of genetic information.
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 for 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 to date 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. Professional codes of conduct should 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.