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4 Conclusions and Recommendations INTRODUCTION The preceding chapters have reviewed the nature of the threat asso- ciated with "dual use" knowledge in the life sciences, the current regulatory environment for the conduct and reporting of genetic engineering research in the life sciences, both domestically and interna- tionally, and various information control regimes developed over the last 60 years in the United States. The Committee has concluded that existing domestic and international guidelines and regulations for the conduct of basic or applied genetic engineering research may ensure the physical safety of laboratory workers and the surrounding environment from con- tact with, or exposure to, pathogenic agents or "novel" organisms. How- ever, they do not currently address the potential for misuse of the tools, technology, or knowledge base of this research enterprise for offensive military or terrorist purposes. In addition, no national or international review body currently has the legal authority or self-governance respon- sibility to evaluate a proposed research activity prior to its conduct to determine whether the risks associated with the proposed research, and its potential for misuse, outweigh its potential benefits. After extensive deliberation, the Committee recognized the impor- tance of educating the biotechnology research community about the po- tential dangers posed by dual use of new technologies. Rather than con- sidering methods to identify and prohibit certain areas of research, we believe the community should work together with government agencies to develop communication channels so that both are aware of potential 107
108 BIOTECHNOLOGY RESEARCH IN AN AGE OF TERRORISM problems. The Committee has concluded that a system is needed to build these channels of communication and to provide greater oversight for the research enterprise. The significant increases in funding that will be going to research on biodefense precisely the sort of research likely to pose the most severe dual use dilemmas reinforce the argument for creating such a system. As the case studies discussed in Chapter 1 demonstrate, even experiments that have the greatest potential for diversion to offensive ap- plications or terrorist purposes may also have potentially beneficial uses for public health promotion and defense. To proscribe such experiments without a thorough assessment of their potential risks and benefits carries the possibility for hindering our ability to detect, identify, and defend against the new threat environment. The system we are proposing would establish a number of stages at which experiments and eventually their results could be reviewed to pro- vide reassurance that advances in biotechnology with potential applica- tions for bioterrorism or biological weapons receive responsible oversight. The system relies heavily upon voluntary self-governance by the scien- tific community and expansion of an existing regulatory process that it- self grew out of an earlier response by the scientific community to the perceived risks associated with gene-splicing research. The heart of the system would be a set of guidelines to help identify research that could raise concerns because of its potential for diversion to offensive military applications. The concept behind these guidelines is that they will provide criteria that can assist knowledgeable scientists, editorial boards of scientific journals, and funding agencies in weighing the poten- tial for offensive applications against the expected benefits of an experi- ment in this arena. It is important to realize, however, that identifying these concerns will not prevent a determined nonstate actor or individual from doing harm. Moreover, the Committee was adamant that these concerns should not be interpreted as defining a category of "sensitive but unclassi- fied" research. Rather, like the NIH Guidelines for Research Involving rDNA Molecules established in the 1970s to guide research in a then-new and possibly risky technology, they can serve as the basis for a continuing dialogue between the members of the scientific community, the national security community, and the public. And, like the rDNA Guidelines, they must be applied on a case-by-case basis, with the opportunity for revision as new knowledge and experience in their operation accumulate. KEY ASSUMPTIONS In developing the system outlined in this chapter, the Committee based its recommendations on several key assumptions. Each is discussed in turn.
CONCLUSIONS AND RECOMMENDATIONS 109 Many more experiments will explore the virulence factors of bacteria and viruses. The great majority of experiments on pathogenic bacteria or viruses are performed to ascertain exactly what makes the microbes patho- genic and virulent. Scientists are thus continuously exploring the ways that turning certain genes "on" and "off" enable these agents to be trans- missible or cause disease in an appropriate host organism. Moreover, the concern over bioterrorism has stimulated the government to provide significantly increased funding to help combat infectious disease. The Fis- cal Year 2003 budget passed by Congress and signed into law by Presi- dent Bush in lanuary 2003 added $6 billion-$10 billion, spread across a number of agencies, to biodefense research in the United States. The NIH, for example, received $1.5 billion for biodefense research. Internationally, other countries are also increasing their investments in civilian bioterrorism defense research. These increased domestic and international investments in basic and applied public health and bioterrorism defense research will inevitably create an increased number of research activities that raise concerns about misuse. This increased activity will also un- doubtedly increase the number of research practitioners in this ever-ex- panding field of investigation with a corresponding increase in the num- ber of articles appearing in the peer-reviewed literature. Scientific evaluation of the risks is essential. In Chapter 1 we described and provided brief assessments of the dual use dilemmas presented by three recently published experiments. Although quite different, each of these cases has generated significant controversy. In the judgment of many scientists, the publication of the synthetic poliovirus paper presented no great contribution to the field of virology and no obvious advantages to a bioterrorist.2 The risks for potential misuse generated by the information in the other two papers are certainly greater. This is not to say they should not have been published. Rather, the Committee believes these cases illus- trate that, to balance these risks against the obvious benefits, one must depend upon expert scientific judgment. In fact, the paper describing the engineering of the mousepox was judged both by local scientific officials in Australia and by the editorial board of the Journal of Virology to have scientific merit and, on balance, to provide important information re- quired for progress in fighting diseased The third paper stimulated an accompanying commentary by the journal when it was published. The commentary concluded that the benefits of the original research contribu- tion to the understanding of the complement system far outweighed the risks that the information could be "misused."4 But making such judg- ments requires scientific training and knowledge and expertise in one field may not always provide sufficient understanding of the relevance of research results in another. The qualitative and case-by-case nature of
110 BIOTECHNOLOGY RESEARCH IN AN AGE OF TERRORISM these judgments is a primary reason the committee believes it is better to rely on self-governance to manage this aspect of the problem rather than to attempt to define appropriate or inappropriate research via regulation. As discussed above, key aspects of the system we propose are intended to augment the existing statutory and regulatory framework for controlling biological materials and personnel through voluntary arrangements ad- dressing research issues. Only an international set of standards will help to minimize the misuse of biotechnology. Although the focus of this report is on the United States, this country is only one of many pursuing biotechnology research at the highest level. The techniques, reagents, and information that could be used for offensive applications are readily available and accessible. And the expertise and know how to use or misuse them is distributed across the globe. Without international consensus and consistent guidelines for overseeing research in advanced biotechnology, limitations on certain types of research in the United States would only impede the progress of biomedical research here and undermine our own national interests. It is entirely appropriate for the United States to develop a system to provide oversight of research activities domestically, but the effort will ultimately afford little protection if it is not adopted internationally. This is a chal- lenge for governments, international organizations, and the entire inter- national scientific community. Efforts to meet that challenge are under way, but they must be quickly expanded, strengthened, and harmonized. RECOMMENDATIONS The system we propose for the United States consists of a number of filters for research proposals and publication of results that would cumu- latively serve to protect against potential misuse yet enable important re- search activities to go forward.5 The key initial filter is awareness in the research community of categories of research that should raise concerns and collective community commitment to actively manage such research. Voluntary restraint based on awareness should be supplemented by re- view through existing bodies, namely an Institutional Biological Safety Committee/Recombinant DNA Advisory Committee process augmented to include the assessment of the potential for misuse as a criterion for approval or denial of proposed experiments. At the stage of publication, we recommend enhancing and expanding the process begun by the edi- tors of a number of the leading scientific journals in February 2003. Fi- nally, since this new system relies on both regulatory and voluntary ele- ments, and involves issues and relationships with which the life sciences community has little experience compared to its colleagues in other fields,
CONCLUSIONS AND RECOMMENDATIONS 111 we recommend creation of a National Science Advisory Board for Biodefense (NSABB) to provide advice and assessments to the govern- ment and the scientific community as the system of review we are propos- ing develops. We recognize that successfully implementing the system we propose will require significant additional resources at each stage; we do not attempt to provide an estimate of those costs. Otherwise, concerns for unfunded mandates could be a significant barrier to full consideration of the proposals by the scientific community. In making its recommendations, the Committee has sought to strike a balance and propose processes and mechanisms that will raise awareness and alarms when needed, without unduly constraining the practice, pro- cesses, and products of the life sciences research enterprise. We believe that such a system in the United States could also serve as a model for similar restraint in other countries. Recommendation 1: Educating the Scientific Community We recommend that national and international professional societies and related organizations and institutions create programs to educate scientists about the nature of the dual use dilemma in biotechnology and their responsibilities to mitigate its risks. Adequately addressing the potential risks that research in advanced biotechnology could be misused by hostile parties will require educating the community of life scientists, both about the nature of these risks and about the responsibilities of scientists to address and manage them. At present, awareness of the potential for misuse of biological knowledge varies widely in the research community. Researchers currently working with select agents are already taking steps to contain these agents physi- cally and protect against planned or unplanned harm. But most life scien- tists have had little direct experience with the issues of biological weap- ons and bioterrorism since the advent of the Biological Weapons Convention in the early 1970s, so these researchers lack the experience and historical precedent of considering the potential for misuse of their . . c Discoveries. Fortunately, an extensive national and international network of pro- fessional societies provides the natural basis for increasing knowledge and awareness about the potential risks of research in advanced biotechnol- ogy. These societies hold numerous professional meetings to share the results of research and address issues of concern to the research commu- nity. We recommend that the societies undertake a regular series of meet- ings and symposia at these gatherings, in the United States and overseas, to provide both knowledge and opportunities for discussion. It could be useful for one of the major professional societies or science policy organi-
2 BIOTECHNOLOGY RESEARCH IN AN AGE OF TERRORISM cations to convene a meeting of all the major societies to discuss how best to implement such a program. Industry groups and associations of higher education and research could also usefully undertake the education of their members about the risks and their implications for research prac- tices. Substantive knowledge of the potential risks is not sufficient, how- ever. The Committee believes that biological scientists have an affirma- tive moral duty to avoid contributing to the advancement of biowarfare or bioterrorism. Individuals are never morally obligated to do the impos- sible, and so scientists cannot be expected to ensure that knowledge they generate will never assist in advancing biowarfare or bioterrorism. How- ever, scientists can and should take reasonable steps to minimize this pos- sibility. The Committee believes that it is the responsibility of the research community, including scientific societies and organizations, to define what these reasonable steps entail and to provide scientists with the edu- cation, skills, and support they need to honor these steps. These principles should be added to the codes of ethics of relevant professional societies. Most scientists are familiar with and carefully re- spect the moral norms of their profession that focus on the pursuit of truth and the advancement of science. Often placed under the heading of re- search integrity, prohibitions against fraud and plagiarism, as well as af- firmative duties of openness in the sharing of findings, are well under- stood. Concerns about potential conflicts of interest and respect for intellectual property are similarly well appreciated, if not as clearly delin- eated. The addition of the moral duty we endorse here to those more familiar to the scientific community is not as novel as it may appear at first. As some scientific societies have recognized, scientists also have a general moral duty to use their knowledge and skill for the advancement of human welfare.6 We are only providing a specification of that general moral responsibility. We believe further that scientists have an obligation to inculcate these moral duties in the next generation, both by example and by specific edu- cation and evaluation of their trainees. Other models of training in social responsibilities need to be explored, for example from the law and from medicine. In the law, most students sit for a multistate professional re- sponsibility exam. In medicine, many specialty boards now examine young physicians in ethics as well as in medical skill and knowledge. Sci- entists will need assistance in learning about these other models, but they need to take charge of how best to educate their own next generation. Scientists also should be willing to assist efforts to integrate the ad- vancement of knowledge with the protection of national security by vol- unteering their time to sit on relevant peer review committees and na- tional bodies, much as scientists contribute to advancing science currently
CONCLUSIONS AND RECOMMENDATIONS 113 by serving on study sections and as reviewers for professional journals. Finally, if scientists are to embrace the moral responsibilities outlined here, their home institutions must provide accommodation and support. Ser- vice in review of protocols and in student training must not only be en- couraged but also rewarded. Recommendation 2: Review of Plans for Experiments We recommend that the Department of Health and Human Services (DHHS) augment the already established system for review of experi- ments involving recombinant DNA conducted by the National Insti- tutes of Health to create a review system for seven classes of experi- ments (the Experiments of Concern) involving microbial agents that raise concerns about their potential for misuse. This part of the system includes both the criteria for deciding which experiments will be subject to review and the process by which the re- view will take place. The Criteria for Review The experience with rDNA experiments emphasizes the importance of guidelines developed by the scientific community itself. The guidelines for work with rDNA promulgated after the Asilomar Conference in 1975 have proven remarkably flexible and effective. The logical structure of such a system, keyed to the probability of harm associated with exposures to genetically modified organisms which changed as risk perceptions changed has been integral to their success. The guidelines have prevented any untoward events and have allowed the rapid and efficient progress of the academic and commercial applications of these technologies. We now need to build upon the Asilomar experience to de- velop a uniform set of criteria to manage this new set of risks. The Committee identified seven classes of experiments that it believes illustrate the types of endeavors or discoveries that will require review and discussion by informed members of the scientific and medical community before they are undertaken or, if carried out, before they are published in full detail. These categories represent experiments that are feasible with existing knowledge and technologies or with advances that the Committee could anticipate occurring in the near future. Some of them represent the types of naturally occurring genetic changes in pathogens that have led to disease pandemics such as the "Spanish Flu" in 1917-1918 or the recently recognized disease "severe acute respiratory syndrome" (SARS) but that could now be engineered in the laboratory. Others have been part of the history of biowarfare research and development. Furthermore, carrying out
4 BIOTECHNOLOGY RESEARCH IN AN AGE OF TERRORISM these types of experiments could, in some instances, lead to the potential for great damage without significantly advancing our knowledge in ways that would either greatly increase our ability to defend against them or our ability to promote human health by preventing, diagnosing, or treating common human diseases. The concerns deal with infectious agents or their products because the Committee believes that self-replicating agents or their products pose the most imminent biological threat. The seven areas of concern listed here only address potential micro- bial threats. Of course, modern biological research is much broader, en- compassing all of the health sciences, agriculture, and veterinary science. It also includes diverse industries such as those that manufacture phar- maceuticals, cosmetics (e.g., Botox), and soft drinks (e.g., citric acid pro- duction). Moreover, all of these areas are changing rapidly. The great di- versity as well as the pace of change makes it imprudent to project the potential both for good and ill too broadly and too far into the future. Therefore, the Committee has initially limited its concerns to cover those possibilities that represent a plausible danger and has tried to avoid im- probable scenarios. Over time, however, the Committee believes that it will be necessary not only to expand the experiments of concern to cover a significantly wider range of potential threats to humans, animals or crops but also to include oversight of work conducted for or performed within the private sector as well as non-NIH government facilities and sponsored activities that are not already voluntarily complying with the Guidelines. Experiments of Concern would be those that: 1. Would demonstrate how to render a vaccine ineffective. This would apply to both human and animal vaccines. Creation of vaccine- resistant smallpox virus would fall into this class of experiments. 2. Would confer resistance to therapeutically useful antibiotics or antiviral agents. This would apply to therapeutic agents that are used to control disease agents in humans, animals or crops. Introduction of ci ?rofloxacin resistance in Bacillus anthracis would fall into this class. 3. Would enhance the virulence of a pathogen or render a nonpathogen virulent. This would apply to plant, animal, and human pathogens. Introduction of cereolysin toxin gene into Bacillus anthracis would fall into this class. 4. Would increase transmissibility of a pathogen. This would in- clude enhancing transmission within or between species. Altering vector competence to enhance disease transmission would also fall into this class. 5. Would alter the host range of a pathogen. This would include making nonzoonotics into zoonotic agents. Altering the tropism of viruses would fit into this class.
CONCLUSIONS AND RECOMMENDATIONS 115 6. Would enable the evasion of diagnostic/detection modalities. This could include microencapsulation to avoid antibody-based detection and/or the alteration of gene sequences to avoid detection by established molecular methods. 7. Would enable the weaponization7 of a biological agent or toxin. This would include the environmental stabilization of pathogens. Synthe- sis of smallpox virus would fall into this class of experiments. The Review Process The NIH Guidelines require creation of an Institutional Biosafety Com- mittee (IBC) when research is conducted at or sponsored by an entity receiv- ing any NIH support for recombinant DNA research. Most of the 400 or so IBCs registered with NIH are at institutions that are subject to the NIH Guide- lines and for whom IBC registration is mandatory. While most of these insti- tutions are academic, some industry-based IBCs are registered with NIH as a consequence of receiving NIH support. In other instances, companies volun- tarily comply with the NIH Guidelines as a means of demonstrating a com- mitment to a "gold standard" for safety practices. Several Federal agencies and laboratories have made compliance with the NIH Guidelines a condition of their support of intramural and extramural research projects.8 Further- more, a number of federal IBCs are registered with NIH. All the experiments that fall within the seven areas of concern should currently require review by an Institutional Biosafety Committee (IBC), a process described in detail in Chapter 2. This review should take place regardless of the source of funding, whether the institution doing the re- search is public or private, and whether it is a university, government laboratory, or business. We thus recommend relying on the system of IBCs as the first review tier for experiments of concern. We note that funding agencies also have a potentially important role to play in flagging experi- ments of concern at the proposal review stage. Like the broader life sciences community, the members of the IBCs will require substantial education in the potential risks associated with advanced biotechnology research in order to handle this task competently. Many IBCs may need to add expertise in immunology, virology, pathol- ogy, and epidemiology to undertake this new responsibility. Some of this is already occurring as part of implementing the requirement of the Bioterrorism Response Act, but more will need to be done. To ensure the most consistent application possible of the review process and as a reas- surance to the research scientists subject to the new review regular op- portunities for members of IBCs to gather and discuss the process should be provided on a continuing basis. We recommend that the form researchers now use to submit their
116 BIOTECHNOLOGY RESEARCH IN AN AGE OF TERRORISM experimental designs to the IBC be amended to include another category where researchers would designate whether, in their judgment, their pro- posed projects fit into an area of concern. The IBC would then review that issue along with the other aspects of the project that it is evaluating, care- fully weighing potential benefits versus potential danger. Occasionally, the IBC may discover that what is proposed is forbidden under current guidelines, and would not approve the research. In most cases, however, it would either designate the project as acceptable to move forward or as one raising concerns that need further consideration. Experiments that need further consideration would be referred to an expanded NIH RAC and possibly the Director of the National Institutes of Health for approval or denial of permission to proceed with the pro- posed experiment. We recommend this route because so many of the ex- periments in the area of concern would fall under the purview of the RAC already and because it has an established track record of facilitating re- search while protecting public safety. We propose that when the RAC takes up this new duty, it initially translate our categories of experiments of concern into a set of guidelines for IBCs to use. It should then improve and update these guidelines as needed as its experience with the process grows. The RAC will need substantial new resources to take on this addi- tional task, and both it and the IBCs may need to incorporate new exper- tise to handle the task. Under our recommendation, the RAC would begin to review some projects in the areas of concern from all relevant research institutions. This would be a substantial expansion from its current jurisdiction over re- search funded by the NIH and those institutions that comply voluntarily. The RAC guidelines would thus need to be revised and reproposed in the Federal Register to reflect this expanded scope and mandate. As we envision this review of the experiments of concern, when an IBC refers a project to the RAC, the RAC would carefully weigh the po- tential benefits and dangers of the project, and come to its own indepen- dent judgment. The RAC may approve some projects referred by IBCs to go forward at this point, recommend that the research not be undertaken, or that modifications be made to the research design to minimize the po- tential risks. Recommendation 3: Review at the Publication Stage We recommend relying on self-governance by scientists and scientific journals to review publications for their potential national security risks. By the time a manuscript is submitted for publication, substantial information about the research may have already been disseminated
CONCLUSIONS AND RECOMMENDATIONS 117 through informal professional contacts, presentations of preliminary re- sults at scientific meetings, or consultations with colleagues. This is why the Committee recommends a system that can address research at its earliest stages, and why it is so important to make scientists aware of their personal responsibilities to consider the balance of risks and ben- efits in research they consider undertaking. Nevertheless, publication of research results provides the vehicle for the widest dissemination, in- cluding to those who would misuse them. It is thus appropriate to con- sider what sort of review procedures can be put in place at the stage of publication to provide another layer of protection. The Committee be- lieves strongly that this part of the system should be based on the volun- tary self-governance of the scientific community rather than on formal regulation by government. Proposals to limit publications have caused great concern and con- troversy among both scientists and publishers. The norm of open com- munication is one of the most powerful in science. To limit the informa- tion available in the methods section of journal articles would violate the norm that all experimental results should be open to challenge by others. But not to do so is potentially to provide important information to biowarfare programs in other countries or to terrorist groups. Journals in the life sciences have already responded to the challenge in a variety of ways; the procedures that a number of leading publications have undertaken to screen manuscripts were discussed in Chapter 3.9 The joint statement by editors of four major journals in the life sciences issued in February 2003 was a major step toward developing this part of the system of oversight the Committee believes will be necessary. It was also an important example of the ability of the scientific community to address the potential risks of its activities. Ultimately, any process to review publications for their potential na- tional security risks would have to be acceptable to the wide variety of journals in the life sciences, both in the United States and internationally. The Committee believes that continued discussion among those involved in publishing journals and between editors and the national security community will be essential to creating a system that is considered re- sponsive to the risks but also credible with the research community. The national advisory board recommended in the next section could serve as a forum for such discussions and for creating greater consensus in the sci- entific community about the appropriate role of and process for review at the publication stage. On the broader question of classification, the Committee believes that the principle set out by the Reagan Administration in 1985 in National Security Decision Directive 189 remains valid and should continue to be the basis for U.S. policy. As discussed in Chapter 3, the policy states that:
118 BIOTECHNOLOGY RESEARCH IN AN AGE OF TERRORISM "to the maximum extent possible, the products of fundamental research remain unrestricted.... where the national security requires control, the mechanism for control of information generated during federally-funded fundamental research in science, technology and engineering at colleges, universities and laboratories is classification."~° The Committee's support for self-governance by the scientific community through appropriate re- views by journals and other publication outlets should not be construed as endorsing the creation of "sensitive but unclassified" information in the life sciences. We believe that the risks of a chilling effect on biodefense research vital to U.S. national security as the result of inevitably general and vague categories is at present significantly greater than the risks posed by inadvertent publication of potentially dangerous results. A system of review based in scientific self-governance can, we believe, effectively ad- dress the security risks without discouraging scientists from participating in important biodefense research. Recommendation 4: Creation of a National Science Advisory Board for Biodefense We recommend that the Department of Health and Human Services cre- ate a National Science Advisory Board for Biodefense (NSABB) to pro- vide advice, guidance, and leadership for the system of review and over- sight we are proposing. The NSABB would serve a number of important functions for both the scientific community and the government. At the most general (strate- gic) 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 communication and dissemination of life sciences research infor- mation that is relevant for national security and biodefense purposes. Be- cause of its important bridging functions, its members should include both leading scientists and national security experts, including those with ex- perience in managing scientific research in federal agencies. Particularly in the early phases of its work, it would be desirable to include among the Board's members a few scientists or engineers from research fields long associated with applications to national security. In terms of the regulatory aspects of the operation of our proposed system, we recommend that the Board periodically review and suggest updates to the "Experiments of Concern." We also recommend that the Board review and suggest updates to the list of "select agents" and to policies regarding the international exchange of biological agents. A re- view of the select agents list by DHHS is already required every two years
CONCLUSIONS AND RECOMMENDATIONS 119 but the Board could serve a useful and important function by providing an independent assessment as an input to that process. For the system's self-governing phases, we recommend that the NSABB serve as a resource. This could include aiding the professional societies in developing education programs, as well as providing a con- vening mechanism. It could also include assisting those producing publi- cations in the life sciences. The Board could provide a convening mecha- nism for journal editors, organizing periodic discussions among them as they develop and evaluate their review processes. The Board could re- view and comment on proposed procedures on request, and perhaps serve as a clearinghouse so that journals that have not already adopted review procedures could have ready access to examples of what others are doing. It would be very important for the Board to reach out beyond the United States to the many international publications in the life sciences and to find ways to include their leaders in discussions. The Board might also provide advice on request about particular manuscripts that raise con- cern, perhaps by organizing small groups of experts to assess the trade- offs between the scientific merits of the research, especially that with the potential to advance knowledge relevant to biodefense, and the risks of publishing information that might assist terrorists or proliferatant states. So far, we have only discussed the functions of the Board that relate to the potential risks of research in advanced biotechnology. But we also recommend that the Board have the capacity to advise the government on how the life sciences can contribute to alleviating the risks of bioterrorism and biological weapons through new research in areas such as vaccine and antibiotic development, new detection devices and technologies, and preventative public health measures. This advisory function would serve as a continuous reminder that any system of review and oversight must operate in ways that do not put the United States and the world at risk of losing the great potential benefits of biotechnology. Having a Board that was informed and aware of the latest research developments, even including manuscripts not yet published, would provide the capacity for "early warning," alerting the government to the risks of new findings or techniques that should be met by focusing research resources on appro- priate responses or countermeasures. We considered a number of options for the organizational location for the NSABB. There are clear trade-offs between an independent board that offers its advice to government and one that is a formal advisory body to one or more federal agencies. The relationship between the life sciences community and the national security community is new and still tenuous, with significant potential for suspicion and misunderstanding on both sides. The topics the Board will address are both sensitive and controver- sial within the scientific community, and there is a risk that a formal fed-
20 BIOTECHNOLOGY RESEARCH IN AN AGE OF TERRORISM eral role could raise concerns about the NSABB's capacity to offer genu- inely independent advice. Whatever the home, the organization that houses the Board must have high credibility with the scientific commu- nity, since its engagement is essential to success. But it must also be able to command the cooperation and trust of the national security commu- nity and of the full range of U.S. research facilities, public and private, and publications. A formal attachment to the U.S. government would en- sure access to the relevant high-level decision makers. The host organiza- tion should also have sufficient international standing to gain the neces- sary cooperation from the research communities of other countries. Another important consideration is the suitability of the organization for conducting some closed deliberations, while overall maintaining trans- parency and public trust in the process. No solution meets all the criteria, but on balance we believe that the logical organizational location for the NSABB is within the Department of Health and Human Services providing advice to the secretary of that De- partment.~ DHHS already has a leading role in biotechnology research, particularly that related to the Experiments of Concern. Location within the DHHS would also connect the Board directly to the other parts of our proposed system, the RAC and the IBCs, while not limiting its capacity to work with other relevant agencies or private groups. In addition, this ap- proach would fit within the division of labor created under the Bioterrorism Response Act, where HHS provides tactical advice as the NSABB would do on specific issues and cases and the Department of Homeland Security is charged with formulating overall strategy. We note that the Board will require significant financial resources to carry out its responsibilities, although the Committee did not attempt to estimate an amount.l2 It would be important for the Board to monitor the development and operation of the system we recommend and perhaps of other processes that the government or private organizations may put in place as well. The substantial expansion of funding for research in biodefense now in progress and anticipated suggests that it will be vital to assess how these new resources affect the conduct of research and to be ready to make timely adjustments. The monitoring should be done with the goal of sug- gesting ways to improve the system's operation and efficiency. But it should also include the possibility of proposing that parts of the system be overhauled or even eliminated if they prove ineffective or an impedi- ment to important scientific research. As discussed further in Recommendation 7, international coordina- tion and cooperation will be necessary to make any effort to mitigate the risks of bioterrorism effective. Therefore, the Committee believes that the establishment of an NSABB within the United States can serve as the basis
CONCLUSIONS AND RECOMMENDATIONS 121 for international dialogue aimed at reducing the risks of subversion of legitimate life sciences research efforts. Review systems, comparable to the one proposed involving the IBC and RAC, already exist in many na- tions. These were established as an outgrowth of the Asilomar conference in 1975. In the same manner, other countries should be encouraged to establish counterparts to the NSABB so that the community of life scien- tists globally can work together to reduce the risks of the offensive appli- cations of life sciences research. Recommendation 5: Additional Elements for Protection Against Misuse We recommend that the federal government rely on the implementa- tion of current legislation and regulation, with periodic review by the NSABB, to provide protection of biological materials and supervision of personnel working with these materials. The major focus of the Committee's work has been reviewing the ad- equacy of the current U.S. regulatory system to deal with the increased concerns about misuse of research in advanced biotechnology and recom- mending a system that could better address those risks. But there are other elements of the current regulatory system that the Committee believes should be reviewed and evaluated because of their important impact on the conduct of research. Physical Containment. Absolute containment of organisms with poten- tial for bioterrorism is not a realistic expectation. Many of these agents can be cultured directly from nature or obtained from small animals available at any pet store or exotic animal "swap meet";~3 no genetic modification is required to convert them into weapons. It is, therefore, not feasible- with the possible exception of smallpox to prevent knowledgeable indi- viduals from obtaining any of the agents listed on the CDC select agent list by simply increasing the physical security of the laboratory environ- ment. There may, however, be individuals or rogue groups who lack the expertise either to isolate or grow pathogenic organisms, suggesting that cost-effective efforts should be made to limit access to them. Safeguarding the collections of existing agents is an obvious priority that in large mea- sure has been addressed through recently passed legislation and imple- menting regulations. The CDC's and APHIS's designation of certain pathogens as "select agents" is an appropriate starting point for identify- ing strains and isolates that need to be secured. Additional agents, some of which have only recently been isolated, could be added to the list; agents might also be removed from the list if their potential for misuse is
22 BIOTECHNOLOGY RESEARCH IN AN AGE OF TERRORISM no longer considered a serious risk. Appropriate regulations should be enforced through the existing institutional biosafety committees. It is crucial to avoid well-meaning but counterproductive regulations on pathogens. For example, regulations that force or provide a strong incentive for scientists to purge archival stocks of human, plant, and ani- mal pathogens may deprive of us material that could be critical in the forensic identification of intentionally introduced pathogens into our en- vironment and mounting an effective defense against bioweapons agents. A similar caution exists in assessing the risks of handling DNA fragments from select agents, which may pose no potential risk at all. Rules for con- tainment and registration of potentially dangerous materials must be based on scientific risk assessment and informed by a realistic appraisal of their scientific implications. Moreover, scientific input is essential to ensure that these rules are clear as well as responsive to periodic assess- ment of the current technologies and capacities. We recommended above that the NSABB review the security desig- nations of biological agents. The Board could also be available to provide advice on short notice about revising regulations in response to new de- velopments. Rules governing transfer of materials between laboratories to prevent unauthorized distribution or diversion might also be regularly reviewed by the NSABB so that new threats could be recognized and re- sponded to and unnecessary impediments identified for removal. Trained Personnel. In some areas of technology, the limiting ingredient is the existence of trained personnel. There are two aspects to the technical expertise: general microbiological know-how and knowledge about how to weaponize bacteria or viruses. General microbiological training suffi- cient for culturing and growing pathogenic microorganisms at levels of significant concern is available in high school and first-year college biol- ogy courses; majors in microbiology would be sophisticated enough to grow many select organisms. It should be remembered that the proce- dures used to grow pathogenic bacteria are identical to those used for harmless bacteria, differing primarily in the need for precautions to en- sure the safety of the workers. Moreover, training in basic microbiology is widely available outside the United States. Efforts to identify or control knowledgeable personnel within the United States are, therefore, imprac- tical, and surveillance of such personnel would not, in our opinion, offer much security. The procedures for admitting foreign students and scientists to the United States for study and collaborative research must reflect the impor- tance of keeping universities as open educational environments. This must be weighed against national security concerns for limiting the spread of information to adversarial groups and admitting individuals who pose
CONCLUSIONS AND RECOMMENDATIONS 123 risks to domestic security. Establishing procedures for limiting visas is the role of the Department of Homeland Security and allied government agencies; universities and research scientists may provide information, but they have no investigative powers. It should be borne in mind that scientists and students, in particular those from developing countries, are likely to have a major interest in infectious diseases, because such dis- eases impose a devastating health burden in their home countries. Also, having colleagues and well-trained health workers in other countries in- creases U.S. security by enabling early access to information about emerg- ing infections. In tune 2003 the presidents of The National Academies responded to the growing concerns that new security measures directed against foreign students, workers, and scholars could cause potentially serious damage to the conduct of science in the United States by issuing a statement that read in part: To make our nation safer, it is extremely important that our visa policy not only keep out foreigners who intend to do us harm, but also facilitate the acceptance of those who bring us considerable benefit. The profes- sional visits of foreign scientists and engineers and the training of highly qualified foreign students are important for maintaining the vitality and quality of the U.S. research enterprise. This research, in turn, underlies national security and the health and welfare of both our economy and society. But recent efforts by our government to constrain the flow of international visitors in the name of national security are having serious unintended consequences for American science, engineering, and medi- cine. The evidence we have collected from the U.S. scientific community reveals that ongoing research collaborations have been hampered; that outstanding young scientists, engineers, and health researchers have been prevented from or delayed in entering this country; that important international conferences have been canceled or negatively impacted; and that such conferences will be moved out of the United States in the future if the situation is not corrected. Prompt action is needed.~4 Recommendation 6: A Role for the Life Sciences in Efforts to Prevent Bioterrorism and Biowarfare. We recommend that the national security and law enforcement commu- nities develop new channels of sustained communication with the life sciences community about how to mitigate the risks of bioterrorism. By signing and ratifying the Biological and Toxin Weapons Conven- tion, the United States renounced the use and possession of such offen- sive weapons and methods to disseminate and deliver them. Given the increased investments in biodefense research in the United States, it is imperative that the United States conduct its legitimate defensive activi-
24 BIOTECHNOLOGY RESEARCH IN AN AGE OF TERRORISM ties in an open and transparent manner. This should clear the way for all biomedical scientists to contribute to the development of defensive mea- sures that would mitigate the impact of the use of such weapons against people, plants, and animals. For the scientific community to be a willing partner in biodefense research, there must be trust and understanding between the scientific community and the defense, intelligence, and law enforcement branches of government. The recent experience with anthrax dispersal in the United States made clear that there are individuals or groups in the world who will use the most horrific weapons, including pathogenic organisms, to kill inno- cent people for vague and unstated political goals. Added to the already existing concern about nonstate actors seeking BW capabilities, this has put bioterrorism along with biological warfare on the front burner for both the military and civilian populations. It has also meant that groups of people who had little history of working together, such as basic bio- medical scientists and the FBI and CIA, must now find a way of sharing information and expertise. The nuclear physics/Department of Defense community, which grew from a relatively small group during World War II, has had a long history of participation with intelligence and defense. Biomedical science, as already discussed, has had a different history. The intelligence and law enforcement agencies need the academic scientists both for the expertise they might provide about the nature of current agents and the potential for new ones and for the best advice on limiting the spread of new technologies that would make countermeasures even more difficult. It might be desirable for components of the national secu- rity and law enforcement communities to establish advisory boards of basic scientists and clinicians with expertise in specializations such as vi- ral disease, bacterial pathogens, biotechnology, immunology, toxins, and public health, as well as others in the area of basic molecular biology. These advisory boards could help members of these communities keep current in relevant areas of science and technology and provide trusted sets of advisors to answer technical questions. Recommendation 7: Harmonized International Oversight We recommend that the international policymaking and scientific com- munities create an International Forum on Biosecurity to develop and promote harmonized national, regional, and international measures that will provide a counterpart to the system we recommend for the United States. Any serious attempt to reduce the risks associated with biotechnol- ogy must ultimately be international in scope, because the technologies that could be misused are available and being developed throughout the
CONCLUSIONS AND RECOMMENDATIONS 125 globe. A number of countries and regional and international organiza- tions are already moving forward to develop programs and policies on aspects of the problem; the initiatives include consultations among the parties to the BWC on best practices for the security and oversight of pathogens and toxins.~5 These approaches must be harmonized and widely adopted in order for them to be effective. lust as the scientific community in the United States must become deeply and directly en- gaged, the commitment of the international scientific community to these issues is needed to implement the recommendations contained in this re- port. Diverse groups of scientists, academicians, and policymakers must be brought together for a sustained dialogue in order to develop consen- sus and devise a path forward. We do not expect our recommendations to provide a "roadmap" that could simply be adopted internationally without significant modifications or adaptations to local or regional conditions. But any effective system should include all the issues addressed by our recommendations. The Committee therefore recommends, as a next step, convening an "Interna- tional Forum on Biological Security" to begin a dialogue within and be- tween the life sciences and the policymaking communities internation- ally. Among the topics for this international forum are: · Education of the scientific community globally, including curricula, professional symposia, and training programs to raise awareness of po- tential threats and modalities for reducing risks as well as to highlight ethical issues associated with the conduct of biological science. · Design of mechanisms for international jurisdiction that would fos- ter cooperation in identifying and apprehending individuals who commit acts of bioterrorism. · Development of an internationally harmonized regime for control of pathogens within and between laboratories and facilities. · Development of systems of review to provide oversight of research, including defining an international norm for identifying and managing "experiments of concern." · Development of an international norm for the dissemination of "sensitive" information in the life sciences. The Committee believes that, to be most effective, this and other fo- rums should be sponsored by international organizations with the stand- ing and credibility within both the policymaking and scientific communi- ties. Different topics within this broad agenda may be more appropriate for different organizations. Potential sponsors could include the World Health Organization and the United Nations Educational, Scientific and Cultural Organization (UNESCO) as formal international governmental
26 BIOTECHNOLOGY RESEARCH IN AN AGE OF TERRORISM organizations with direct links to government policymakers. Among non- governmental scientific organizations are the International Council for Science (ICSU), created in 1931 "to identify and address major issues of importance to science and society, by mobilizing the resources and knowl- edge of the international scientific community;" and more recently cre- ated organizations of the world's academies of science such as the InterAcademy Panel on International Issues (IAP) and the InterAcademy Council (IAC) that seek to bring the prestige and convening capacity of these bodies to bear on crucial international problems. Finally, the Committee notes the uncertain international foundation for authoritatively addressing the issues that we have considered. No in- ternational agreement addresses the potential threats posed by the mis- use of research in the biological sciences, and no intergovernmental orga- nization has relevant oversight authority to promulgate guidelines or procedures. The Committee believes that convening an international fo- rum to address these gaps demands international and interdisciplinary mobilization of resources and capabilities. CONCLUSION This report reflects the increasing attention being paid by scientists and policymakers to the potential for misuse of biotechnology by hostile individuals or nations and to the policy proposals that could be applied to minimize or mitigate those threats. The term "misuse of biotechnology" is a phrase that captures a wide spectrum of potentially dangerous activities from spreading common pathogens (e.g., spraying Salmonella on salad bars) to sci-fi plots of transforming pathogens into the next "Andromeda strain." Our Committee addressed one important part of this spectrum of risks: the capacity for advanced biological research activities to cause dis- ruption or harm, potentially on a catastrophic scale. Broadly stated, that capacity consists of two elements: (1) the risk that dangerous agents that are the subject of research will be stolen or diverted for malevolent pur- poses; and (2) the risk that the research results, knowledge, or techniques could facilitate the creation of "novel" pathogens with unioue Properties or create entirely new classes of threat agents. Throughout the Committee's deliberations there was a concern that policies to counter biological threats should not be so broad as to impinge upon the ability of the life sciences community to continue its role of con- tributing to the betterment of life and improving defenses against biologi- cal threats. Caution must be exercised in adopting policy measures to re- spond to this threat so that the intended ends will be achieved without creating "unintended consequences." On the other hand, the potential threat from the misuse of current and future biological research is a chal-
CONCLUSIONS AND RECOMMENDATIONS 127 lenge to which policymakers and the scientific community must respond. The system proposed in this report is intended as a first step in what will be a long and continuously evolving process to maintain an optimal bal- ance of risks and rewards. The Committee believes that building upon processes that are already known and trusted and relying on the capacity of life scientists to develop appropriate mechanisms for self-governance, while greatly expanding the consultation and dialogue between the sci- ence and national security communities, offers the greatest potential to find the right balance. This system may provide a model for the develop- ment of policies in other countries. Only a system of international guide- lines and review will ultimately minimize the potential for the misuse of biotechnology. NOTES ~ Choffnes, E.R. 2002."Bioweapons: New Labs, More Terror," Bulletin of the Atomic Scientists, September/October:29-34. 2 Block, S.M. 2002. "A Not-so-cheap stunt," Science 297 (5582~:769. 3 It should be noted that the American Society for Microbiology, which publishes the journal of Virology, has as a policy to review papers not just for scientific con- tent, but also whether, in the opinion of the Editor-in-Chief and the Publications Board, the manuscript under review describes misuses of microbiology or of in- formation derived from microbiology. If it does, they can decline the manuscript and return it to the author. 4 Lachmann, P. 2002: A Commentary, Proceedings of the National Academy of Sci- ences 99 (13~:8461-8462. 5 A growing number of individuals and organizations are engaged in developing proposals to regulate pathogenic materials and to provide oversight of biotech- nology research activities and information dissemination at the point of publica- tion, both in the United States and internationally. The Committee received brief- ings from many of them and benefited from their ideas in the course of its deliberations (see Appendix C). Among them are Jonathan Tucker, Raymond Zilinskas, George Poste, John Steinbruner, Tara O'Toole, Steve Block, Gerald Epstein, Malcolm Dando, and Mark Wheelis, and organizations such as Johns Hopkins Center for Civilian Biodefense Studies, the Center for International Secu- rity Studies at Maryland, the Center for Nonproliferation Studies of the Monterey Institute for International Studies, the Chemical and Biological Arms Control Institute, the Royal Society, and the International Committee of the Red Cross. See, for example, Kwik, G.; l. Fitzgerald; T.V. Inglesby; T. O'Toole (2003~: "Biosecurity: Responsible Stewardship of Bioscience in an Age of Catastrophic Terrorism," http: / /rudolfo.ingentaselect.com/vl=14455723/cl=15/nw=1 /rpsv/ catchword/mal/15387135/vlnl/s5/p27; Tucker, l. (2003~: "Preventing the Mis- use of Pathogens: The Need for Global Biosecurity Standards," Arms Control Today June: 3-10 at http://www.armscontrol.org/act/2003_06/tuckerjuneO3; Wheelis, M. and M. Dando (2002~: "On the Brink: Biotechnology, Biodefense and the Fu-
28 BIOTECHNOLOGY RESEARCH IN AN AGE OF TERRORISM lure of Weapons Control." http://fas-www. harvard.edu/~hsp/bulletin/ cbwcb58.pdf; Appeal of the International Committee of the Red Cross on Biotech- nology, Weapons and Humanity, http://www.icrc. org/Web/eng/siteengO.nsf/ iwpList515/274D020806432963C1256C3E005C4338 #a3; Moodie, M. (2003~: "Re- ducing the Biological Weapons Threat: New Thinking, New Approaches; January 2003; http://www.cbaci.org/; Steinbruner, l.D. and E.D. Harris (2003~: "Control- ling Dangerous Pathogens," Issues in Science and Technology, Volume XIX, number 3; Spring 2003; Epstein, G. (2001~: "Controlling Biological Warfare Threats: Re- solving Potential Tensions among the Research Community, Industry, and the National Security Community," Critical Reviews in Microbiology, 27~4~:321-354, 2001; Poste, G. (2002~: "Biotechnology and Terrorism," Prospect Magazine, May 2002, http: / /www.prospect-magazine.co.uk...ask?accessible=yes&P%20%20 Ar- ticle=11341; Zilinskas, R. and l. Tucker (2002~: "Limiting the Contribution of the Open Scientific Literature to the Biological Weapons Threat, " Journal of Homeland Security, December 2002, http://homelandsecurity. org/journal; Block, S.M. (2001~: "The Growing Threat of Biological Weapons," American Scientist, 89~1), January-February 2001~:28-37. Statement of the ASM Council Policy Committee: "The Council Policy Commit- tee of the American Society for Microbiology affirms the long-standing position of the Society that microbiologists will work for the proper and beneficent applica- tion of science and will call to the attention of the public or the appropriate au- thorities misuses of microbiology or of information derived from microbiology. ASM members are obligated to discourage any use of microbiology contrary to the welfare of humankind, including the use of microbes as biological weapons. Bioterrorism violates the fundamental principles expressed in the Code of Ethics of the Society and is abhorrent to the ASM and its members." 7For the purposes of this category the term "weaponization" includes experiments that would facilitate the dissemination of a microbial pathogen as a respirable aerosol the optimal means of delivering a putative biowarfare agent over a large geographic area. Experiments that could enhance the aerosol delivery of patho- gens include, inter alla, new techniques for the microencapsulation of fragile mi- croorganisms or the development of aerosol systems for the delivery of therapeu- tic drugs and vaccines. This category would also include the synthesis of viral pathogens. ~ These include the U.S. Department of Agriculture and the Department of Veterans Affairs, as well as Department of Energy laboratories such as the Lawrence Livermore National Laboratory, the Los Alamos National Laboratory, and Sandia National Labo- ratories, and various VA medical centers and military research institutes such as the Uniformed Services University of Health Sciences; the Walter Reed Army Medical Cen- ter and the U.S. Army's Medical Research Institute for Infectious Diseases. See Chapter 2 for further details. 9 See Box 3-3, Chapter 3. in National Security Decision Directive 189. September 21, 1985. Available at http: / /www.fas.org/irp/offdocs/nsdd/nsdd-189.htm. ii One model for the organization and operation of the NSABB is patterned after the Advisory Committee on Immunization Practices (ACIP). The ACIP consists of 15 experts in fields associated with immunization who have been selected by the Sec-
CONCLUSIONS AND RECOMMENDATIONS 129 retary of the U. S. Department of Health and Human Services to provide advice and guidance to the Secretary, the Assistant Secretary for Health, and the Centers for Disease Control and Prevention (CDC) on the most effective means to prevent vac- cine-preventable diseases. The overall goals of the ACIP are to provide advice which will assist the Department and the nation in reducing the incidence of vaccine pre- ventable diseases and to increase the safe usage of vaccines and related biological products. The Committee develops written recommendations for the routine ad- ministration of vaccines to the pediatric and adult populations, along with sched- ules regarding the appropriate periodicity, dosage, and contraindications applicable to the vaccines. ACIP is the only entity in the federal government which makes such recommendations. See further details available at http://www.cdc.gov/nip/acip/ charter.htm. i2 For the ACIP, the estimated annual cost for operating the Committee, including compensation and travel expenses for members (but excluding staff support) is 5151,465. Estimate of annual person-years of staff support required is 2.2 at an estimated annual cost of 5145,222. We would expect comparable funds to be ap- propriated each year for the creation and maintenance of the activities of the NSABB. Details available at http://www.cdc.gov/nip/acip/charter.htm. is "The recent outbreak of monkeypod a relative of smallpox that likely was brought into this country by pet Gambian rats and spread via pet prairie dogs is only the latest example of the multiple dangers that the importation of exotic pets poses to both animals and humans." "Get a Dog." Washington Post, June 13, 2003. Editorial, A28. i4 See the statement on "Current Visa Restrictions Interfere with U.S. Science and Engineering Contributions to Important National Needs," December 13, 2002, by the National Academies presidents. (Revised June 13, 2003~. Available at http://www4. nationalacademies.org/news.nsf/isbn/sl2132002?0penDocument. i5 Tucker, l.B. 2003. "Preventing the misuse of pathogens: The need for global biosecurity standards," Arms Control Today, June: 3-10. i6 Further information about ICSU may be found at http://www. icsu.org/ while further information about the IAP and the IAC may be found at http:// www4.nas.edu/iap/iaphome.nsf?opendatabase and http: / /www.interacademy council.net, respectively.