Biocontainment in Gain-of-Function Infectious Disease Research

Lipkin, W. Ian

First, for readers less conversant with biocontainment, it may be helpful to have some insights into Centers for Disease Control and Prevention (CDC) classification criteria (1). BSL-3 is a level of containment used for clinical, diagnostic, research, or production facilities wherein work is done with indigenous or exotic agents that have the potential for respiratory transmission that may cause serious and potentially lethal infection. Design and operational protocols in BSL-3 containment address hazards to personnel related to inadvertent inoculation, ingestion, and exposure to infectious aerosols. BSL-3-Ag, an augmented form of BSL-3 containment, addresses concern about the risk of environmental exposure to pathogens of consequence to agriculture by adding filtration of supply and exhaust air, sewage decontamination, exit personnel showers, and facility integrity testing. BSL-4 containment is used for work with dangerous and exotic agents that pose a high individual risk of life-threatening disease that may be transmitted via the aerosol route and for which there is no available vaccine or therapy. BSL-4 guidelines mandate daily inspection of facilities and equipment, extensive training, and monitoring of personnel for signs and symptoms of infectious disease. They also specifically require date and time logs of when personnel and materiel enter and exit containment. There are no such requirements for work at either BSL-3 or BSL-3-Ag. I do not mean to imply that investigators working at BSL-3 or BSL-3-Ag are nonchalant or poorly trained or that they fail to monitor their staff or equipment; however, training, monitoring, and access controls are not as rigorous as at BSL-4. In 2009, the General Accounting Office reported that the number of BSL-3 laboratories in the United States increased from 415 in 2004 to 1,362 in 2008 (2) . Of these, approximately 300 were BSL-3-Ag (3). We have no accurate information concerning the number of BSL-3 and BSL-3-Ag laboratories worldwide; nonetheless, it is likely to be much larger. In 2011, the National Research Council Committee of International Security and Arms Control reported the existence of 24 BSL-4 laboratories worldwide, with 12 in the United States alone, of which 6 were operational (4). Between 2003 and 2009, the CDC recorded 395 potential release events in U.S. laboratories working with high-threat agents (2, 5) . I am unable to find comprehensive data on similar events worldwide.