The federal government responded to the September 11, 2001, terrorist attacks and the subsequent anthrax attacks with increased focus on and funding for biodefense. A key consideration in this response was addressing capacity shortages for diagnostic, clinical, and research laboratories. Since 2001, the Department of Defense (DOD), the Department of Homeland Security (DHS), the Department of Health and Human Services (HHS), and the Department of Agriculture (USDA) have increased or are in the process of increasing their laboratory capacity for the study of dangerous pathogens. Because stringent protocols and engineering are used to contain the most dangerous pathogens, these facilities are often referred to as high-containment laboratories. High-containment laboratories play a critical role in the biodefense effort, offering the hope of better responses to a biological attack and a better understanding of the bioterrorism threat. However, they could also increase the risk of a biological attack by being a source of materials or training. In addition to increasing laboratory capacity, the federal government invested in research to develop countermeasures, diagnostics, and detectors for dangerous pathogens potentially usable in a terrorist attack. One group has calculated that congressionally appropriated funding for civilian biodefense increased from $690 million in FY2001 to $5.4 billion in FY2008. Much of this funding supports academic and industrial researchers and laboratories that handle these dangerous pathogens. The influx of funds and researchers has exacerbated existing concerns about aging laboratory infrastructure and limited research and diagnostic laboratory capacity. Non-federal entities have also expanded or constructed additional high-containment laboratories. In addition to the threat of bioterrorism, an increasing awareness of the threat posed by emerging and re-emerging diseases has led to the proliferation of high-containment laboratories internationally, as the technologies used are widely available. The increase in high-containment laboratory capacity has raised new policy questions and increased focus on existing ones. How much laboratory capacity is enough? What is the necessary federal investment? Should laboratories be consolidated or dispersed? What is the optimal size and type of high-containment laboratory? With multiple agencies expanding high-containment laboratory capacity, is a plan coordinating these efforts necessary? Does increasing laboratory capacity and the number of trained scientists increase the risk of accidents and/or opportunities for purposeful misuse? What is an acceptable balance between the benefits these laboratories provide and the risks they pose? Policymakers have become increasingly interested in the expansion of these facilities following reports of accidents, regulatory noncompliance, and recent examples of community resistance to the laboratories. The Commission on the Prevention of Weapons of Mass Destruction Proliferation and Terrorism recommended tightening government oversight of high-containment laboratories. These laboratories may also be regulated by state and local laws, regulations, and ordinances. This report focuses on the federal government's regulation of high containment laboratories. It explains the concepts of biosecurity and biosafety, including the mechanisms by which the federal government oversees their implementation; describes the proliferation of high-containment laboratories; discusses issues facing federal policymakers; and identifies policy options for congressional consideration. Biosecurity and biosafety are closely related. Their definitions vary from source to source and sometimes overlap. In this report, biosecurity refers to steps taken to secure pathogens or biological materials from theft, unauthorized access, or illegal use, while biosafety refers to mechanisms or practices employed to lower the risk of unintentional infection in the laboratory or environmental release from the laboratory. While biosecurity and biosafety are clearly related closely, their practices and oversight mechanisms have mainly developed independently. Although biosafety has been a concern of the general laboratory science community for many years, biosecurity has only recently come to the fore. The major federal regulatory program addressing biosecurity is the Select Agent Program. The federal government created the Select Agent Program in order to regulate and oversee commerce in pathogens that might have severe consequences if released into the environment. The Select Agent Program was first established by the Antiterrorism and Effective Death Penalty Act of 1996 ( P.L. 104-132 ). This law required HHS to identify a list of organisms and toxins that could potentially be used for bioterrorist attacks and to regulate their transfer, though not their possession. These pathogens and toxins were to be known as select agents. The 2001 anthrax mailings increased the federal government's interest in the threat of bioterrorism. Congress enacted the USA PATRIOT Act ( P.L. 107-56 ) and the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 ( P.L. 107-188 ) which increased restrictions on the possession of pathogens and toxins that have been identified as possessing the greatest potential for malevolent use. Entities possessing select agents were required to develop explicit security and biosafety plans and procedures to be reviewed and certified by the federal government. The Select Agent Program oversees regulation of select agents possession, transfer, and use. It focuses mainly on two areas: people who have access to select agents and facilities where select agents are used and stored. Scientists who want access to select agents must register with the federal government. Applicants provide information to the Department of Justice (DOJ), which performs background checks to determine whether the applicant may be permitted to handle select agents. Such permits are nontransferable and are valid for five years. Facilities that possess or use select agents must develop and implement a security plan to protect the select agents from theft or improper access. These plans are submitted either to HHS, through the Centers for Disease Control and Prevention (CDC), or to USDA, through the Animal and Plant Health Inspection Service (APHIS). These agencies review them for regulatory compliance and audit their security plan implementation. The CDC performs announced inspections of each regulated facility at least once every three years. Failure to comply with the regulations of the Select Agent Program is punishable by fines. Persons possessing select agents who have not successfully completed the DOJ security risk assessment process or are prohibited from possessing select agents under the USA PATRIOT Act may be in violation of 18 U.S.C. 175, which prohibits the possession of biological weapons. As of February 2009, approximately 390 entities had been issued certificates allowing work with select agents and 15,300 staff had active security risk assessment approvals to have access to select agents. See Table 1 for details. The largest group of certified entities are owned or operated by state or local governments. Many of these entities are state or local public health laboratories. As part of efforts to develop robust testing and response capabilities following a biological attack, the federal government has developed a Laboratory Response Network that links many of these state or local public health laboratories. One of the goals in establishing the Laboratory Response Network was to create a laboratory in each state capable of handling dangerous pathogens. Additionally, the large number of academic entities, and presumably researchers, has increased tensions over the Select Agent Program in academia. This community has a long tradition of openness and has, in some cases, viewed the select agent regulations as too onerous to continue performing research with these pathogens. Approximately 200 entities either transferred or destroyed their select agent inventories rather than registering under the select agent regulations. The performance of the Select Agent Program has been the topic of a number of investigations by agency Inspectors General (IG). These investigations have focused on agency internal controls on select agents, the ability of lead agencies to process researcher and entity applications, and the regulatory compliance of facilities receiving select agent certificates. The HHS IG found that 11 of 15 representative universities investigated did not fully comply with the select agent regulations. It also found that none of the eight representative state, local, private, or commercial laboratories investigated were in full compliance. Three of these entities chose to withdraw their select agent licenses following the investigation. The USDA IG found similarly that APHIS controls over registered entities and registered entities' compliance with select agent regulations were not complete. In 2007, the CDC suspended a select agent entity certificate at Texas A&M University, reportedly because of failure to report occupational exposures in a timely fashion and because laboratory workers lacking a security risk assessment were allowed access to select agents. Other companies, laboratories, and universities have also been cited and fined for violations of the select agent regulations. The HHS OIG has levied a total of $1,887,000 in fines on 12 organizations for failure to comply with the Select Agent regulations. Scientists studying dangerous pathogens generally acknowledge the risk of contracting the disease under study and the potential of accidentally releasing a pathogen into the environment. Over time, scientists have developed best practices to mitigate these risks. In the 1970s and 1980s, the U.S. government began collecting these practices and issuing them as formal guidelines. The most commonly referenced guidelines are disseminated by HHS in the publication Biosafety in Microbiological and Biomedical Laboratories (BMBL). The Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH) have established four main levels of biosafety (BSL-1 to BSL-4) to guide laboratory researchers in the safe handling of biological agents. Each biosafety level is associated with specific physical and procedural protections. See Table 2 . In general, the more dangerous the pathogen is to human health, the higher its recommended biosafety level. Each successive biosafety level consists of the protective measures of the lower biosafety levels, augmented with additional protective measures. Generally, the term "high-containment laboratory" refers to BSL-3 and BSL-4 laboratories. The current BMBL guidelines grew out of earlier efforts by the DOD, HHS, and USDA. These best practices were developed to protect laboratory workers based on the various specific risks posed by different pathogens. The guidelines present criteria to define the different biosafety levels, best practices for safe laboratory operation at these biosafety levels, and mechanisms for identifying the appropriate biosafety level for a given organism and procedure.