Online Issues

ILAR Journal Vol 46(1)

Administrative Issues Related to Infectious Disease Research in the Age of Bioterrorism

Jerry Jaax

Jerry Jaax, D.V.M., DACLAM, is the Associate Vice Provost for Research Compliance and University Veterinarian, Kansas State University, Manhattan, Kansas.

Abstract

The recent unprecedented growth in infectious disease research funding and infrastructure has resulted in part from an outgrowth of concern about newly emerging and re-emerging diseases and the progressive development of antibiotic-resistant pathogens. However, the most compelling impetus is the suspected and demonstrated capability and will of unknown individuals, groups, or states to use biological agents and/or toxins as weapons. Although the actual number of known victims and fatalities from bioterrorism in the United States has been miniscule compared with many other daily hazards, biological agents have the potential to cause human mass casualties, severely damage segments of our economy or agricultural infrastructure, poison or compromise our food or water supply, and, perhaps most damaging, disrupt our society physically and psychologically. The significant institutional commitment necessary to participate in infectious disease research is described, with a focus on programs that involve research with pathogens thought to have potential for use by bioterrorists. Administrative considerations are described, and include obtaining necessary research funding to offset high operating costs; complying with "select agent" regulations, security screening of employees; building or renovating a biocontainment facility; finding skilled professional and technical manpower; providing adequate physical security in a threat environment; conducting targeted training; overcoming potential internal and external dissent; developing and/or providing sufficient occupational health and safety programs; achieving and maintaining compliance standards in a fluid regulatory environment; mitigating potentially hazardous working conditions; understanding personal and institutional liability; and reassuring and dealing with a concerned, skeptical, or even hostile public.

Key Words: administrative issues; biocontainment; biosafety; biosecurity; bioterrorism; infectious disease; regulatory compliance; select agents

Introduction

Infectious disease research is literally and figuratively "hot." After a steady decline of research emphasis caused by a series of remarkable triumphs such as the eradication of smallpox, the near eradication of polio, and the seeming control of a raft of other historical scourges, infectious diseases have been mounting a steady if not spectacular comeback. In the 1970s and early 1980s in the United States and other developed countries, infectious diseases were thought to be largely irrelevant--soundly defeated by antibiotics, vaccines, nutrition, sanitation, and science. National research emphasis shifted to more seemingly contemporary and pressing health needs such as metabolic diseases, nutritional problems, cancer, aging, and heart disease. However, the disquieting emergence of dangerous new pathogens like human immunodeficiency virus, the filoviruses, hepatitis C, Nipah, monkeypox, and severe acute respiratory syndrome (SARS¹), coupled with the development and increasing prevalence of drug-resistant strains of diseases like malaria and tuberculosis, have clearly signaled that microbes remain a danger. Research with potentially hazardous agents classified as biosafety level (BSL¹)-3 and -4 organisms (Richmond and McKinney 1999) has been the purview of primarily government or industry laboratories, with specialized facilities and missions such as the following: Department of Defense biodefense and infectious disease (ID¹) programs responding to cold war biowarfare concerns and endemic disease threats to deployed military personnel; the National Institutes of Health (NIH¹) and Centers for Disease Control and Prevention (CDC¹) programs in endemic and emerging disease; and the US Department of Agriculture (USDA¹) and Agricultural Research Service research programs focusing on serious foreign and domestic animal and plant diseases.

In the world prior to September 11, 2001 (9/11¹), this equation seemed to be sufficient. However, the security paradigm shifted radically for most Americans in the turbulent days and weeks following the attacks on the World Trade Center Twin Towers and the Pentagon. The nationally traumatizing events of 9/11 fundamentally changed the general public's awareness and perception of collective vulnerability to terrorists in general, and the anthrax letter attacks (CDC 2001) followed by the discovery of ricin toxin in a letter (CDC 2003) dramatically revealed our vulnerabilities to microbes or toxins that might be used as weapons. Unlike other potential weapons of mass destruction (nuclear and chemical weapons), replicating agents pose a unique challenge because terrorists might have the capability to "reload" and perpetrate repeated attacks that could potentially overwhelm defensive or security measures and our public health infrastructure and capabilities (Danzig 2003). Recognizing the potential threat from infectious disease agents and toxins, and in many cases the lack of effective countermeasures, authorities quickly reordered national research priorities. Significant appropriations for new infectious disease research programs rapidly followed, as evidenced by a 30-fold increase in funding for bioterrorism research within the Department of Health and Human Services (DHHS¹) (Bush 2004). Accordingly, organizations in academia, industry, and the government have responded swiftly to the need, and to the opportunities.

The administration and management of new or expanded programs in infectious disease research pose many challenges. Perhaps the most difficult challenge is the possibility that the research itself could directly or indirectly contribute to the threat (DHHS 2004). Such a case could occur through the accidental release or escape of a dangerous pathogen from a research facility or laboratory. Legitimate research activities could be the source of biological threat agents or could provide technical resources and/or capabilities for domestic or international terrorists. To help prevent these unlikely but possible scenarios, the government has enacted strict new laws and regulatory measures, which profoundly affect virtually all research activities that involve a specific list of infectious diseases and toxins called "select agents." These new measures significantly increase the administrative and bureaucratic footprint for organizations performing infectious disease research. However, ensuring that research itself does not somehow contribute to the biological threat is the primary overarching administrative responsibility of any organization performing infectious disease research. Accordingly, participants in infectious disease research must have a realistic understanding of the significant and expandinging organizational administrative and operational responsibilities.

Working with Select Agents

New legislation has increased compliance and administrative requirements considerably for those involved in infectious disease research. The USA PATRIOT Act of 2001 (PL 107-56) and the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (PL 107-188), along with its implementing DHHS regulation Possession, Use, and Transfer of Select Agents and Toxins (42 CFR Part 73: Federal Register 2002b), contain specific provisions that radically affect both the eligibility and the performance of scientists who work with a specifically designated group of "high consequence pathogens"--infectious biological agents and toxins known collectively as "select agents" (Federal Register 2002a). Through the Select Agent Program, the CDC and the USDA have been given the responsibility to regulate the possession, use, and transfer of these select biological agents and toxins that could pose a threat to public and to animal and plant health and safety. Among other requirements, facilities using or transferring select agents, including government agencies, universities, research institutions, and commercial entities, must register in the Select Agent Program with either the CDC or the USDA--whichever is more appropriate for the mission of the facility and the agents used (PL 107-188). The CDC or the USDA then performs on-site compliance inspections for registered facilities (Federal Register 2002b).

Select agents are categorized as human agents, animal or plant agents, and overlap agents (zoonoses that pose a threat to both humans and animals). Much, but not all, of the increased research emphasis and funding of infectious disease research activities involves select agents. The select agent regulations carry significant regulatory safeguards and administrative burdens that did not exist before their passage. As appropriate, these regulations include responsibilities for formal documentation of the following: perimeter and interior security and safety procedures; employee access strategies; threat and risk assessments; agent handling, storage, and transport procedures; sensitive information or data management and protection, biocontainment facilities capabilities; decontamination and waste management procedures; agent transfer procedures; select agent accountability and use; emergency procedures; and employee background investigations. Implementation of the required elements of the select agent program entails a significant institutional investment in compliance and support assets, and often requires the construction or upgrade of biocontainment facilities or equipment that is extremely expensive to purchase, operate, and maintain.

Aside from specialized facilities and procedures for working with most select agents, the select agent regulations require formal background investigations or a security risk assessment by the Department of Justice (DOJ¹) for all persons with access to agents or facilities. Although the DOJ performs the investigations, approval to have access to select agents is ultimately granted by the DHHS Secretary, or the USDA, whichever is appropriate. Persons specifically prohibited from select agent access under the USA PATRIOT Act of 2001 (PL 107-56 2002) include indicted or convicted felons, illegal aliens, those dishonorably discharged from the US armed forces, alien nationals from countries identified as supporters of international terrorism, fugitives from justice, unlawful users of controlled substances, and persons who are mentally defective or have been committed to a mental institution. Additionally, access may be denied to those reasonably suspected by federal law enforcement authorities of being an agent of a foreign power, committing a federal crime of terrorism, or being knowingly involved in an organization that engages in international or domestic terrorism or international criminal violence (PL 107-56 2002). DHHS or USDA approval for an individual's access to select agents is organization specific, therefore personnel who move to a different organization must reapply to the appropriate approval authority for access to select agents in their new job. For employees, preparing and submitting the necessary background information and gaining clearance from the DOJ is a time-consuming task that can delay research activities, frustrate administrators, and intimidate researchers and employees. Additionally, facilities that use select agents may discover that their research programs will be of interest to both state and federal law enforcement agencies.

The most important institutional responsibility is ensuring the safe and judicious use of infectious or select agents in its research programs and facilities, which includes responsibility for the actions of employees. Failure to succeed in this task can have significant undesirable consequences for researchers and the organization, including the possibility of civil and/or criminal penalties. Recently, the reported theft of dozens of pathogenic plague samples from a respected university ID researcher sent shock waves through the country and the research community. Federal investigators swarmed onto the campus, and tension levels were high in the community as national media reported from the scene. The incident resulted in a felony conviction for the scientist, embarrassment and administrative turmoil for the organization, and general dismay in the scientific community (Medical Research Law & Policy 2004). This unfortunate event illustrated the potential administrative, managerial, and compliance pitfalls in executing programs that involve sensitive or potentially dangerous biological agents. It is incumbent on management to ensure that mandated safeguards are adequately implemented, and are not confounded by accident, intent, or chance.

Dual-use Factor

In the context of bioterrorism, the term dual-use reflects the possibility that legitimate research could be misused to threaten public health or national security. Examples of dual-use activities are the theft or diversion of pathogens for malevolent use, or the creation of novel pathogens with unique properties, which creates entirely new classes of threat agents (NRC 2004). Concern about dual-use activities is one of the key drivers of new security regulations affecting ID research, and it will be a continuing issue for research administrators. The National Research Council recently issued a report from an expert committee that developed a number of recommendations for addressing dual-use issues (DHHS 2004; NRC 2004). Based on the recommendations, the DHHS Secretary announced the creation of the National Science Advisory Board for Biosecurity (NSABB¹) composed of nationally recognized experts from across the spectrum of science, medicine, bioethics, veterinary medicine, and law enforcement. The NSABB will be managed by the NIH, and its task is to provide wide-ranging guidance to help improve biosecurity measures related to dual-use research conducted or supported by federal funds without unduly hindering scientific progress.

Immunoprophylaxis

Prophylactic immunizations can provide an important layer of protection for personnel at high risk of biological agent exposure (Richmond and McKinney 1999). Records of use of specialized vaccines to protect at-risk laboratory workers at Ft. Detrick date to the mid-1950s. Since its establishment in 1970, the United States Army Medical Research Institute of Infectious Diseases (USAMRIID¹) has maintained a Special Immunizations Program (SIP¹) in support of their biodefense research on BSL-3 agents (Vander Linden 1998). Additionally, the USAMRIID SIP has provided ongoing support to other DOD, NIH, USDA, and other research or support personnel who have demonstrated a need for special immunizations. Vaccines that are licensed (i.e., approved by the Food and Drug Administration [FDA¹]) and are available in the SIP currently include yellow fever, small pox, hepatitis, Japanese encephalitis, rabies, and anthrax. Investigational new drug (IND¹) vaccines used under an FDA exemption for research and for immunizing laboratory personnel include the following: two Venezuelan equine encephalitis vaccines, Eastern equine encephalitis, Western equine encephalitis, and botulinum toxoid and Rift Valley fever (inactivated). Although not currently available, Q fever and tularemia are expected to be available soon after this issue goes to press (E. Boudreau, SIP Clinic, USAMRIID, Ft. Detrick, Frederick, MD; personal communication, May 14, 2004).

Enrollment and verification of adequate titer development for personnel in the SIP are time consuming and expensive. Government organizations must negotiate a memorandum of understanding, whereas all other organizations (e.g., academia and industry) must negotiate a cooperative research and development form with the USAMRIID SIP clinic. Both require approximately 3 to 4 mo to staff and accomplish. Once the necessary agreements are approved, it can take up to 1 yr to complete the required immunizations, establish adequate protective titers, and receive medical clearance to work with specific agents. This timeframe is variable and greatly depends on the number of required vaccines. Researchers typically need only one or two vaccines, and may complete the immunizations within several months, whereas support staffs such as maintenance personnel or animal care workers, who need an extensive array of vaccines, may encounter a significantly extended timeframe. The SIP, which recovers costs, requires a one-time participation fee and then charges for each immunization received. Costs for participation in the SIP are variable, depending for example, on the vaccine received, the number of boosters needed, and annual titering, if necessary. Additionally, considerable expenses are incurred in meeting the regulatory requirements for using IND vaccines in approved human use protocols. Conversely, charges for receiving fully licensed FDA vaccines are considerably less than for IND vaccines. Annual costs per person for participation in the SIP can range from $10,000 to $15,000 (E. Boudreau, personal communication, May 14, 2004). In general, the cost decreases after the initial series of vaccinations. The SIP clinic at Ft. Detrick is currently the only site for administration of IND vaccines in the SIP program.

In addition to the time and expense involved in the SIP, willingness to participate can be a significant operational and administrative issue. Some employees (e.g., support and maintenance personnel, and animal care staff) may require immunizations for multiple agents because they need access to the entire facility where different agents may be in use. For some employees, participation in special immunizations may be a significant disincentive to working in an ID facility, which can be problematic for research and animal care and use administrators.

Critical Factors in the Administration of an ID Research Program

Coexisting with the Community

The public is understandably nervous about infectious diseases, and dealing effectively with their concerns and perceptions is critical to the success and administration of an ID research program. During the 1990s, "virus thriller" books and movies, sobering revelations about the extent of offensive biowarfare programs in the Soviet Union, and increasing concern about the threat of bioterrorism in this country heightened public awareness and anxiety about infectious agents. Malignant use of anthrax and ricin, coupled with concern about emerging diseases such as West Nile fever, SARS, monkeypox, and Nipah virus, has also raised anxiety levels. Public concern can be especially acute in areas where laboratories that are conducting or plan to conduct ID research are in close proximity to populated areas. Determined community opposition can significantly disrupt ongoing or proposed ID research programs. Diverse special interest groups (e.g., concerned citizens and community groups; animal welfare, environmental, and antibiotechnology groups; antigovernment groups; and business and real estate interests) can form alliances to power opposition to ID and biocontainment operations.

Organizational leadership must be prepared to interact effectively with the community, and answer their questions and concerns about ID research. Some important steps include the following: proactive coordination and information sharing with community leaders; designating competent spokespersons who can represent the facility in the community; developing crisis communication plans for the facility; and close coordination and cooperation with local emergency service providers (e.g., fire fighters, emergency medical staff, and police) who might be involved in an incident. It is critical to anticipate public concerns and possible opposition, and to have realistic plans to build and maintain public awareness, understanding, and support of the program. Organizational confidence, competence, and, when appropriate, transparency are critical to operating a program that is credible to the public.

Biocontainment Construction and Operating Costs

Working with infectious diseases requires an integrated combination of procedures, safety programs, training, compliance, and facilities. Facility standards for working with infectious agents are high, especially for those in the BSL-3 and -4 categories (Richmond and McKinney 1999). Construction costs for high-containment facilities can be as much as three to four times the cost of conventional BSL-2 laboratories. Gross area requirements and efficiency for biosafety levels can range from BSL-2 at 58% efficiency and costs of $250 to $280/gross square foot (GSF¹), to BSL-4 at 25% efficiency and costing $800+ /GSF (M. Schott, Kansas State University Architectural & Engineering Consultant, PGAV, Kansas City, Mo, personal communication, 2004). Depending on the biosafety level, organizational mission, and sophistication of the engineering infrastructure, the ratio of nonassignable (non-revenue-generating) space versus assignable (functional revenue-generating) space in a research facility increases from about 0.3:1 in a conventional building to about 4:1 in BSL-3-Ag (agricultural) and BSL-4 facilities (M. Schott, personal communication, 2004). As a result, biocontainment facilities comprise some of the world's most expensive real estate to build and maintain, and it may be difficult to produce sufficient revenue to be fiscally self-sustaining.

Costly features of containment facilities might include the following: high-temperature autoclaves; specialized animal caging that resists high-temperature autoclave crazing; biosafety cabinets and chemical fume hoods; heating, ventilation, and air conditioning systems that maintain differential air pressure zones; decontamination materials; dunk tanks; airlocks; high-efficiency particulate air filters; liquid and solid waste treatment; redundant utilities; emergency lighting; security equipment such as closed circuit television; personal protective equipment (PPE¹) and laboratory clothing; chemical and personal showers; and contaminated laundering capabilities. Service and maintenance of laboratory equipment that cannot be easily removed from biocontainment present a managerial challenge. Utility costs are high, and interior and external security (equipment and personnel) contribute to overall costs.

Time and Productivity

Administrators are responsible for efficient operation of infectious disease research biocontainment facilities. More research and support staff are required to operate a biocontainment facility than a conventional facility because in general, tasks take longer in biocontainment (Richmond et al. 1997). The higher the biosafety level, the longer it takes, and the more difficult and time consuming the duties become. Performing routine tasks with infectious agents or animals in a positive pressure space suit or in other restrictive PPE usually involves more risk and requires more technical expertise than tasks performed in conventional facilities.

Examples of biocontainment tasks that require excessive time might include the following: security procedures that increase entry times into the building; changing into laboratory-specific clothing and PPE (many facilities conserve space and resources with unisex change and shower facilities, complicating and extending transit times); use of tongs or other devices during animal cage changing, which minimizes the potential for a bite or exposure from an infected animal; procedures to minimize aerosols in potentially contaminated environments; entry of equipment and supplies and exit of waste materials and caging after decontamination in airlocks or autoclaves; additional treatment or scraping of cages before washing for autoclaved caging with baked bedding; transportation of potentially infected animals or materials from one containment area to another (i.e., hot suite to another hot suite, or to a containment necropsy area through noncontainment spaces); and research procedures, clinical treatment, or necropsy of infected animals. Tasks routinely performed by one person in a conventional facility may require two individuals in biocontainment, one on the "hot side" and one on the "cold side" (Richmond et al. 1997). All of these tasks translate into less apparent productivity and the need for more staffing for containment activities compared with conventional research and animal facilities.

Hiring, Training, and Retaining Skilled Personnel

The learning curve for individuals working with infectious materials is steep, especially for those who conduct activities in BSL-3 and -4 facilities. With the increase in ID research emphasis, personnel who have the expertise, experience, temperament, and desire to work in biocontainment facilities will likely be in short supply. Consequently, it is critical to the successful administration of an ID program to attract as well as train and retain the following staff: researchers, administrators, safety personnel, veterinarians, animal and medical technicians, animal caretakers, facilities engineers, security and emergency response personnel, electricians, and possibly others.

Increasingly intrusive security requirements can adversely affect morale and retention in facilities that use select agents. Although tightened security standards are understandable and necessary, their implementation, the psychology of surveillance, and even suspicion by security personnel may affect the productivity and morale of some employees who believe they are the participating in finding a solution to infectious disease issues, and are not part of the problem.

Evolving Compliance Standards

Regulatory and compliance programs for infectious disease research are dynamic. The federal government is scrambling to accommodate the competing goals of proliferating and accelerating ID research programs and products, while at the same time focusing on increased safety and security in the laboratories. Biosafety in Microbiological and Biomedical Laboratories (Richmond and McKinney 1999) is being revised, and additional changes to the select agent program and biocontainment construction guidelines can be anticipated. Keeping abreast of regulatory and compliance changes in response to changing political, threat, and security concerns is a critical challenge for research administrators in ID programs.

Animal Welfare

The use of animals in infectious disease research poses unique challenges. The public is generally supportive of research that has the potential to help protect human and/or animal lives or economic interests from disease threats. However, the very nature of infectious disease research--of purposely infecting animals with diseases that can cause serious and/or potentially fatal conditions--places severe responsibilities and stresses on scientists and technicians, research administrators, and animal care and use programs. Along with other high-risk activities such as toxicology and trauma research, animal welfare proponents can be fundamentally opposed to ID research. Management of pain and experimental endpoints is critical as investigators, technicians, and animal care and use committees balance the scientific need for collecting meaningful and reliable data with the regulatory and moral requirement to minimize unnecessary pain and distress in animals to the greatest extent possible. Regulatory and accreditation standards are not waived for containment activities, so documentation, access, and interactions for compliance committees are decidedly more complex and require additional administrative and managerial attention. These committees can include, but are not limited to, the following: the institutional animal care and use committee, the biosafety committee, the Association for the Assessment and Accreditation of Laboratory Animal Care International, the USDA, the FDA, the NIH Office of Biotechnology Activities, and the Office of Laboratory Animal Welfare.

ID studies can be emotionally taxing for associated personnel because research subjects progress through advancing stages of disease, treatment, recovery, euthanasia, or death. Administrators must always be cognizant of the emotional burden carried by research and animal care personnel, and provide the oversight and support necessary for them to achieve fully the goals of performing quality and meaningful science, and protecting the welfare of the animals.

Physical Security

The significantly increased physical security requirements for biocontainment facilities and laboratories using select agents (Federal Register 2002b) are a direct result of the concern that such facilities could be targets of infiltration or attack. Performance of site-specific threat and risk assessments and carefully designed mitigation strategies are key to implementing acceptable security programs, and existing facilities may require extensive upgrades in building infrastructure. Biocontainment facilities in which research with select agents is performed may incorporate exterior security zones that include vehicular and pedestrian guard stations, vehicle access barriers, a blast-sustainable building exterior, high security fencing, and remote telemonitoring or motion-sensing capability. Examples of interior features are a 24-hr staffed security station to monitor entry and building security, closed circuit television, ID card readers or other more sophisticated personnel recognition devices for controlling access to the facility assets, motion sensors, and emergency alarms and communications systems. It is clear that physical security for select agent programs in both existing and future facilities requires major investments to meet the new standards outlined in 42 CFR 73.11 (Federal Register 2002b).

Emergency Services: Fire, Police, Medical Personnel

Provision of emergency response services during a fire, explosion, chemical spill, medical emergency, accident, or other serious incident that necessitates an emergency response can pose unique problems for ID research facilities. Administrators must carefully coordinate with appropriate first responders to ensure that the responders have all of the pertinent information (e.g., material safety data sheets), agent inventories, standard operating procedures, emergency contact rosters) and emergency response plans and equipment to respond to possible emergencies safely and effectively. Thorough analysis of plausible risks during an emergency must be coupled with a review of emergency procedures, appropriate PPE, and targeted training for emergency responders. It may be necessary for emergency response personnel to enroll in the SIP to gain access to facilities using infectious agents as appropriate.

Occupational Health and Safety

Infectious disease research significantly increases occupational risk to pathogens (NRC 1997) and appreciably increases organizational responsibility for providing employees with targeted training and effective occupational health programs. Organizations may be required to increase practical access to medical or public health infrastructure such as an occupational health physician, nurse, or clinic. Additional occupational health requirements for employees might include, for example, pre-employment physical examinations, baseline serum banking, and special immunizations and antibody titer monitoring. The need may exist for counseling related to individual medical decisions regarding exposure risks in the workplace and reporting of potential exposures. Exposures are possible through a variety of routes such as sharps, skin, oral or ocular exposure, and aerosol or inhalation. Selection of appropriate prevention and control measures for laboratory hazards is based on a hierarchy of elimination and minimization of hazards by engineering controls. The use of PPE is the last resort, for use only when potential exposures cannot be eliminated any other way (Sargent and Gallo 2003). Respirators, which should be used only as stipulated by a respiratory protection program, require strict adherence to provisions of several regulations of the National Institute for Occupational Safety and Health and Occupational Safety and Health Administration, which address respirator safety, fit, cleaning, and effectiveness (NIOSH 1987). For any ID research activity, it is critical to establish and execute effective training programs for the use, maintenance, and replacement of PPE.

Infectious Disease Research in Academia

Although academia has always been involved in infectious disease research, significant initiatives related to national security will involve colleges and universities in new ways. The National Institute of Allergy and Infectious Diseases has recently awarded funding for two new national biosecurity laboratories and 11 regional biosecurity laboratories to address bioterrorism and emerging infectious disease concerns. In addition, the Department of Homeland Security recently created two centers of excellence to address agricultural biosecurity and food safety issues. University consortia will lead the efforts in these new research centers. The diverse intellectual and technological engine of academia makes universities a logical choice for this role, but implementation will involve many difficult hurdles.

A recently published article in the Chronicle of Higher Education (Parker 2004) discusses the "cultural divide" between academia and the intelligence community, an important partner for those involved in bioterrorism or national security-related research. The relationship between these unlikely collaborators has been "dominated by suspicion and mistrust" dating back to the Vietnam War and the Watergate era. Some faculty members in academia, especially those in the social sciences, may be fundamentally opposed to defense-related research on campus. It is probable that this persistent legacy of strained relations and suspicion will be a continuing and complicating factor for administrators on campuses involved in new ID research initiatives. Additionally, strongly held principles of academic freedom and openness can run counter to perceived needs for security and protecting sensitive information. Many universities have long-standing restrictions that prohibit on-campus activities involving "classified research," complicating efforts to engage academia in sensitive ID programs.

The security and background investigation provisions of the USA PATRIOT Act (PL 107-56) restrict certain individuals from working with select agents. These security measures can be especially problematic in academia, where there is a rapid turnover of both domestic and international students. In addition, many graduate students and postdoctoral candidates in the hard sciences are foreign nationals from countries that are suspected to pose a security risk to the interests of the United States.

Summary

Performing infectious disease research in the age of bioterrorism poses many unique challenges for all involved. However, it is clear that the threat of bioterrorism has stimulated a reorder of research priorities by the federal government that has resulted in a substantial investment in new ID facilities, research, and compliance oversight. Hopefully, new research programs will provide the countermeasures needed to overcome the many public health and biodefense challenges confronting our society. The critical task is to strike an effective balance between the need to expand critical ID research programs for our security, and the obligation to provide an effective safety and oversight environment that does not unnecessarily inhibit scientific progress or freedom.

¹Abbreviations used in this article: 9/11, September 11, 2001; BSL, biosafety level; CDC, Centers for Disease Control and Prevention; DHHS, Department of Health and Human Services; DOJ, Department of Justice; FDA, Food and Drug Administration; GSF, gross square foot; ID, infectious disease; IND, investigational new drug; NIH, National Institutes of Health; NSABB, National Science Advisory Board for Biosecurity; PPE, personal protective equipment; SARS, severe acute respiratory syndrome; SIP, Special Immunizations Program; USAMRIID, United States Army Medical Research Institute of Infectious Diseases; USDA, United States Department of Agriculture.

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