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Center Articles and Publications Meeting Report Biosecurity and Bioterrorism. Volume 5, Number 1, 2007 © Mary Ann Liebert, Inc. Reprinted with permission. DOI: 10.1089/bsp.2007.0902 Sections: On July 11, 2006, the Center for Biosecurity of the University of Pittsburgh Medical Center (UPMC) convened an invitational meeting to discuss high-containment biodefense research in the United States. Our goal was to analyze whether and how the growing numbers of laboratories could be operated safely, productively, and with respect for the communities in which they are placed. The group was composed of distinguished scientists and experts in biosafety, biosecurity, and public health and included proponents of the laboratories as well as those who oppose the recent expansion. Participants were not asked to reach consensus on the topics discussed; rather, the intention was to spur an open discussion of key issues related to high-containment laboratory research and to seek proposals for constructive actions. Meeting participants are listed in Appendix I. Individual comments were not for attribution, but some quotations that make a compelling case for particular actions are cited without attribution. In this report, the Center for Biosecurity analyzes a number of critical issues related to high-containment laboratories and offers recommendations intended to improve their productivity, safety, and public engagement practices. These recommendations have been informed by pre- and post-meeting discussions with a range of experts, a survey of peer-reviewed literature, press reports, and discussions during the meeting on the issues summarized in this report. Our recommendations are not necessarily endorsed by the participants in the July 11 meeting. Background on High-Containment Biological Laboratories A few years ago, only a handful of laboratories in the world operated at BSL-4, the highest level of containment. In the coming years, BSL-4 capacity will be expanded at least tenfold in the U.S., as laboratories currently under construction begin operations (see Figure 1 for a world map of BSL-4 laboratories, and Table 1 for a list of planned and operational BSL-4 laboratories). Figure 1. BSL-4 Facilities Worldwide
Table 1. BSL-4 Laboratories in the United States Table 2. NIAID-funded Regional Biocontainment Laboratories (BSL-3) A 2005 National Institutes of Health (NIH) survey estimates that there are currently 277 BSL-3 laboratories in the U.S.3 The number may be higher: A 2005 Department of Homeland Security (DHS) and Department of Health and Human Services (HHS) report estimates that there are more than 600 BSL-3 laboratories in the U.S.4 More BSL-3 laboratories are being built specifically for biodefense research, principally funded by the National Institute of Allergy and Infectious Diseases (NIAID) within the NIH (see Table 2 for a list of planned biodefense BSL-3 laboratories funded by NIAID). The rapid expansion of high-containment laboratories has raised a number of policy issues, such as the adequacy of existing biosafety and biosecurity measures, personnel training in biosafety, transparency of laboratory policies and research directions, and the rationale justifying the BSL-3 and BSL-4 laboratory expansion. Additionally, public protests have occurred in many of the laboratory locations, raising the question of how the public should be involved in decision-making processes related to the labs, both in the siting process and once they are operational. Protests may have diminished some universities’ success in receiving federal funding to build a high-containment laboratory.5,6 In addition, public protests against the siting of the Boston University National Biocontainment Laboratory eventually led to citywide regulations on research activities and practice.7 Our meeting focused on these policy issues as they relate to high-containment laboratories in the U.S. However, we recognize that high-containment laboratory expansion is an international phenomenon. For example, in Southeast Asia, newly constructed BSL-3 laboratories are projected to become operational in 2006: in India (16 new laboratories), Thailand (5), Indonesia (2), Bangladesh (1), and Myanmar (1).8 Our premise is that processes that make U.S. labs safer, more productive, and more transparent to the public will be helpful to laboratories and communities elsewhere in the world. Biosafety Training Most research institutions require that all laboratory workers take a short class in biosafety principles. For workers in high-containment laboratories, advanced biosafety is usually taught within a mentor-apprentice relationship. Generally, as trainees improve, they move to higher levels of containment and independence. While there are some training programs available to supplement on-the-job experience (e.g., the Center for Public Health Preparedness and Research program at Emory University11), they are insufficient to build the workforce of researchers, technicians, and biosafety professionals needed to make the newly developed high-containment labs productive and safe. Biosafety training entails more than learning to operate safety equipment, such as the full-body suit worn in many BSL-4 laboratories. Working safely with pathogens requires sound judgment, informed mostly by technical training and experience. As one meeting participant said, “I fear that some of our researchers believe that the engineering controls will provide their safety. And yet . . . it’s the procedural controls and the practices of biosafety within the laboratory, regardless of what kind of building you’re in, that are going to be the most critical in maintaining good safety.” This was demonstrated in the SARS laboratory accidents that occurred in Singapore, China, and Taiwan, which were thought to have been caused not by equipment failure but by human error.12–15 Safety procedures for working with biological pathogens are more complicated and contextual than those for more quantifiable risks, such as radiation. Biological experimentation holds risks that change depending on the details of an experiment. Thus, each experiment requires a separate analysis of potential risks to determine appropriate research procedures. For example, an experiment that could normally be performed at a low biocontainment level may need increased biosafety protections if the researcher is immunocompromised, or if a large volume of infectious material is being handled. Likewise, a procedure that was always conducted at BSL-4 may be performed at BSL-3 if a vaccine becomes available that can protect the laboratory worker. A good biosafety officer can help a researcher determine the best biosafety procedures and practices for these laboratory-specific, experiment-specific decisions, so that the laboratory remains productive and safe. Unfortunately, as one meeting participant said, “I don’t know of any program in the country right now that is really focusing attention on building that body of biosafety professionals that we need.” One exemplary training program for biosafety officers, the National Biosafety and Biocontainment Training Program (NBBTP),16 only graduates one or two biosafety professionals per year. The diverse research backgrounds of the scientists now entering work on pathogens also increases the need for safety training in high containment. As one meeting participant said, “We’re going to have all of these researchers and PIs who have crossed out ‘plant’ on their grants and written in ‘anthrax’ and have gotten funded.”* The causative agent of anthrax can be worked on in a variety of biosafety levels, but the point is that many researchers will be working on potentially lethal organisms for the first time. Participation by scientists with diverse scientific backgrounds can be a positive development for research in new directions in a field and is the norm for scientific discovery. For example, when funding for HIV/AIDS research became available in the 1980s, researchers who had never previously worked with an infectious disease poured into the field. Nonetheless, for many researchers beginning to work with dangerous pathogens, the change in safety culture and safety practices will be serious. In many other areas of biological research, it is more important to protect the experiment from being contaminated by bacteria or viruses in the air than to protect the researcher from the experiment. Scientists coming from these low-risk fields into high-containment research will not be accustomed to the risks of infection and will need additional training. There also may be scientists coming from outside the biological sciences, from such areas as physics and chemistry, who may need additional training. One meeting participant remarked that there are “engineers . . . coming into [biodefense research] now through synthetic biology . . . who don’t think of things as being self-replicating. And they are treating their experimental substrates as if they are not self-replicating.” The workforce that is needed to make the high-containment laboratories productive and safe is not yet in place. To develop the workforce, NIH should first assess how many people will require training for work in the high-containment laboratories, and develop and fund training programs that can supplement on-the-job training. Biosafety professionals with experience in laboratory research will be needed to provide training for and consultations with the researchers. Now that the Pandemic and All Hazards Preparedness Act (S. 3678) has been enacted, the National Science Advisory Board for Biosecurity (NSABB),17 an advisory board to the Secretary of HHS on life science issues, may be directed to give their advice on “a core curriculum and training requirements for workers in maximum biological laboratories.”18 The diverse perspectives and backgrounds of NSABB members will be useful in establishing biosafety training standards on which to base on-the-job training. Ultimately, it is the laboratory director’s responsibility to ensure that all laboratory personnel “demonstrate high proficiency in standard microbiological practices and techniques,” as stated in the Biosafety in Microbiological and Biomedical Laboratories (BMBL) guidebook, published by the Centers for Disease Control and Prevention (CDC) and NIH.2 But relying solely on the mentor-apprentice tradition of training for biosafety will not be sufficient to train the influx of high-containment scientists and technicians. Developing core competencies and standards will be useful in order to conserve mentors’ valuable time and abilities.
Information Exchange Between Laboratories Individuals who wish to work with a wide range of pathogens must abide by the Select Agent Rule, as defined by 45 CFR 72. Under the rule, HHS and the U.S. Department of Agriculture (USDA) keep lists of pathogens that require select agent clearance. The rule regulates the possession, use, and transfer of those agents; imposes security requirements for the facility in which the work will be performed; requires inspections; and can impose criminal and civil penalties on those who do not adhere to the law. Security risk assessments are administered to individuals who work with select agents by the Department of Justice (DOJ), a process that is renewed every five years. Once cleared, an individual is allowed to work with a specific biological agent, but only within a specific laboratory. The specificity of this clearance procedure inhibits the practical exchange of safety-related information and techniques between high-containment laboratory researchers, by preventing, for example, a technician in one laboratory from demonstrating techniques in another laboratory without going through a separate lengthy clearance process. In addition to the clearance barriers that prevent timely sharing of practical safety techniques, there is a perception that laboratories will be liable for accidents that occur to scientists who are visiting for training purposes. Whether or not these perceived concerns are real, they need to be examined in detail and addressed so that experienced scientists can more easily demonstrate techniques and safety procedures developed in one laboratory to another. This would speed up the process for new laboratories to become productive, and, more important, should enhance their safety. As one meeting participant remarked, “As someone who has actually taken a lab hot, I have experience with how you train people. . . . There were no guidelines. There was no checklist. There was nothing. And we reached out to CDC. We reached out to Fort Detrick. We got as much help as they could give. After 9/11, they couldn’t give us as much help as they could give before. And so, now that we’ve been hot, and we’ve worked with animals, and we’ve had to do it on our own with just commonsense rules, people are now coming to us and saying, will you help train us? Well, now our lawyers are saying, no, you can’t let any nonemployee into the lab. I think what we need to do as a group is to try to develop a policy that says we will assist each other in this training procedure.” NIH and CDC should work to make this possible.
Learning from Past Mistakes The record of laboratory-acquired infections at lower levels of containment is less clear, but the meeting participants thought it was much less laudable. In fact, no one knows precisely how many accidents occur at the lower containment levels, including diagnostic clinical laboratories, because laboratory-acquired infections are generally not severe and are not reported. Illnesses may not even be recognized as having been acquired in the laboratory. The Select Agent Rule requires reporting of infections of all select agents, whether they occur at BSL-2, -3, or -4 laboratories. However, there are many infectious diseases that are not on the select agent list, for which there are anecdotes of laboratoryacquired infections but few documented reports. Research institutions are typically required by NIH grants to report any serious accidents or research-acquired infections, but there is no regulatory requirement to report and no penalty for not reporting. The Occupational Safety and Health Administration (OSHA) within the Department of Labor has illness notification requirements,20 but the threshold for reporting is considered to be several infected individuals. The lack of reporting has consequences beyond the individual affected laboratory. Unless someone chooses to write a scientific paper documenting the incident, lessons learned from the experience are generally not reflected in new editions of the BMBL (the biosafety guidebook written by NIH and CDC), so that procedures can be analyzed and future accidents perhaps avoided. There are several explanations for the lack of reporting. Generally, there is a disincentive to report acquired infections and other mishaps at research institutions, because negative publicity or the scrutiny from a granting agency may adversely affect future research funding. In addition, when a scientist acquires an infection in the laboratory, it is almost always his or her fault, and neither the scientist nor the laboratory wishes to advertise the mistake. For example, the mistake may have resulted from a researcher being inattentive, tired, or distracted by other tasks; perhaps the worker had done the procedure many times before and became inured to the risks. Finally, even if reporting were required, once a worker gets infected and becomes ill, he or she becomes a patient—and thus is afforded certain protections and privacy. These barriers need to be cleared so biosafety can be enhanced through shared learning from mistakes, and also so the public may be reassured that accidents are thoroughly examined and contained. One possible analogous mechanism discussed by meeting participants is the reporting system used for aviation incidents, administered by the National Transportation Safety Board and the Federal Aviation Administration (FAA).21,22 Mistakes are analyzed and learned from, but they are not attributed to individuals (except when mistakes result from criminal actions, such as drunkenness). If a similar system were applied to high-containment laboratories, publicizing the names of those involved would be unnecessary; the participants in the meeting agreed that personal anonymity would bolster incentives to report. Participants in the meeting disagreed, however, about whether the laboratory’s research institution could remain anonymous as well after an accident or a near-miss. Some felt that institutional anonymity may be necessary to get robust reporting (the FAA does not include the names of the airlines in their incident reports). As one participant said, “If people are whacked on the head when they report anything going wrong, whether it was an honest mistake or an error or a piece of equipment failing, they will find ways not to report. . . . So the more transparency you have, the fewer penalties you must have.” But as another meeting participant pointed out, “If I live in Seattle and the [researchers] in Seattle that are fooling around with 1918 [influenza] constructs start screwing up and dropping things in the lab, . . . to have a national reporting system that doesn’t reflect or doesn’t inform anybody in and around Seattle . . . is a total letdown to the people.”
Public Engagement NIAID has a great deal of information about all of the biodefense laboratories on its website, including a collective rationale for why the laboratories are being built.1 However, engagement with communities where the laboratories are actually being built is typically handled by the institution proposing the laboratory. Thus, the strategies and outcomes of public engagement, as well as the transparency of laboratory operations to the public, have varied considerably. Public resistance was experienced during efforts to build facilities in Boston, in Davis, California, in Hamilton, Montana, and in Seattle, whereas generally positive support was achieved for the Galveston laboratory administered by the University of Texas Medical Branch. In the end, both the Davis and Seattle facilities were not built, in part due to public opposition. Laboratories that have been accepted by their communities have by and large instituted procedures that not only encourage active reporting of problems but also keep the community informed about operations. Studies have been written contrasting successes and failures of various highcontainment laboratories; this work should be expanded, learned from, and implemented for all laboratories.5,24 Individual laboratories bear final responsibility for their relationships with their communities, but there should be a more aggressive and proactive federal effort to standardize public engagement and transparency of operations and to direct funds to this purpose. A public engagement program needs to address the concerns that have surfaced in siting high-containment laboratories. A fundamental error made by some proponents of these labs is to conflate all protests against the laboratories as a lack of understanding of science (R. Lofstedt, personal communication, July 11, 2006). In the media reports that describe the controversies about the labs, a number of specific concerns appear repeatedly: People fear that weapons will be worked on in the labs, and that the Biological Weapons Convention will be violated; that diseases will be released into the public; that the government could not manage an accident response (as was the case in the aftermath of Hurricane Katrina); and that the lab would make the area a target for terrorism. Some who protest the labs are not against the lab per se, but feel that the location chosen for the lab is unacceptable, or that the lab would not provide jobs or other benefits to locals. Some feel that giving more people access to select agents will lead to an increased chance of accidents or, even worse, an increased risk of terrorism. Each of these issues needs to be actively addressed both by HHS and NIAID and by the institution sponsoring the laboratory. The larger question of whether these laboratories are justified at all also needs to be addressed by focusing on the specific roles of individual laboratories and how they fit into the overall biodefense strategy. The community that surrounds the laboratory should know the strategic importance of their laboratory and why its existence is necessary. The NSABB, in their charge to provide the HHS Secretary with “periodic evaluations of maximum containment biological laboratory capacity nationwide and assessments of the future needs for increased laboratory capacity,” should specifically address the individual role each laboratory should play in the overall federal biosecurity strategy.18 For many years, there was a clear shortage of biological high-containment laboratories.25 Now, after funds have been committed and construction has begun, there should be greater clarity about whether there is enough capacity, the right kind of capacity (e.g., sufficient animal facilities or laboratories that can meet FDA requirements for Good Laboratory Practices), or an excess. Defining the roles of specific laboratories in terms of a larger biodefense strategy will not only help to justify their existence to their neighbors and funders; it will also help to design safety programs for the laboratories and to ensure that the laboratories are doing important, nonduplicative research in the future.
Acknowledgments
Appendix 1: Participants in the July 11, 2006, High-Containment Biodefense Research Forum Kevin Anderson, PhD, Deputy Director (Acting), National Biodefense Analysis Countermeasures Center (NBACC), Science & Technology Directorate, Department of Homeland Security Subscribe to Biosecurity and Bioterrorism at www.liebertpub.com. |
