High-Containment Biosafety Laboratory Safety Breaches a Growing Concern

U.S. Government Accountability Office (GAO) chief technologist Keith Rhodes (Center for Technology and Engineering, Applied Research and Methods, GAO), in his written testimony before the U.S. House of Representatives Subcommittee on Oversight and Investigations, Committee on Energy and Commerce (chair, Democrat John D. Dingell, Michigan, longest-serving member of the House, since 1955), noted that high-containment biosafety laboratories, specifically biosafety levels 3 and 4 (BSL-3 and BSL-4), have been “proliferating” since the September 11, 2001 terrorist attacks. (1)

BSL-3 and especially BSL-4 often contain the most hazardous biological agents, i.e., “any microorganism (including, but not limited to, bacteria, viruses, fungi, rickettsiae, or protozoa) or infectious substance or any naturally occurring, bioengineered, or synthesized component of any such microorganism or infection substance, capable of causing death, disease, or other biological malfunction in a human, an animal, a plant, or another living organism; deterioration of food, water, equipment, supplies, or material of any kind; or deleterious alteration of the environment.” (2) Examples of biological agents handled in BSL-4 laboratories are the small pox virus (Variola major) and the plague virus (Yersinia pestis). Most hospital laboratories are BSL-2 laboratories.

The rationale for the House Committee tasking the GAO with the biosafety laboratory investigation was its “increasing concerns…raised about the safety, as well as operations” of high-containment laboratories. House committee members requested answers to three questions (3):

1. To what extent, and in what areas, has there been an expansion in the number of high-containment labs in the U.S?
2. Which federal agency is responsible for tracking the expansion of high-containment labs and determining the associated aggregate risks?
3. What lessons can be learned from recent incidents at high-containment laboratories?

Rhodes identified two U.S. examples of biosafety laboratory safety/operations issues at the Texas A&M University (TAMU) and Centers for Disease Control and Prevention (CDC) biosafety laboratories.

Some recent exposures in U.S. biodefense laboratories. Source: CDC, as per http://www.sciencemag.org/cgi/content/full/317/5846/1852; accessed October 5, 2007.

Example One: TAMU, College Station, Texas, BSL-3 Laboratory Safety Issues

TAMU, Texas’ first public institution of higher learning (opened Oct. 4, 1876) and one of a select few academic institutions in the nation to hold triple federal designation as a Land-Grant, Sea-Grant and Space-Grant university, initially received funding from the Department of Homeland Security in 2004 during the ramp up of agro-security programs beyond the Plum Island Animal Disease Center at Orient Point, New York. (4) TAMU’s has several BSL-3 laboratories whose staff work extensively on animal diseases, including those caused by “select agents” Brucella melitensis, Brucella abortus, Brucella suis, and Coxiella burnetii. (5)

Select agents are a category of hazardous biological agents regulated by the Select Agent Program, whose origins date to the 1990s. (6) The CDC writes: “The CDC regulates the possession, use, and transfer of select agents and toxins that have the potential to pose a severe threat to public health and safety. The CDC Select Agent Program oversees these activities and registers all laboratories and other entities in the United States of America that possess, use, or transfer a select agent or toxin.” (7) A list of regulated select agents is available elsewhere (7)

Because TAMU worked with select agents, it needed to comply with guidelines published by the Select Agent Program. TAMU belatedly reported a case of human brucellosis that resulted from an accidental exposure when a BSL-3-authorized lab worker, accustomed only to Mycobacterium tuberculosis safety procedures, helped with the operating of the aerosolization chamber in a lab dealing with Brucella (i.e., she was not trained or authorized to be in that lab). (8) The afflicted laboratory worker was correctly diagnosed with brucellosis on April 16, 2006 via the Texas State Public Health Lab. (10) The incident was brought to light through public records requests by Edward Hammond of the Sunshine Project, a watchdog group in Austin Texas. (9) The CDC issued an order to TAMU on April 20, 2007 to “cease and desist all work with select agents and toxins,” as described elsewhere. (10) “In an August 2007 investigation, CDC inspectors found a dozen serious violations, including unapproved experiments, lost samples, improper safety training, and lab workers without select-agent authorization, as described elsewhere. (11)

Example Two: CDC Clifton Road, Atlanta, BSL-4 Safety Issues

On June 15, 2007, lightening struck in and around the CDC’s new $214 million infectious disease building on Clifton Road, Atlanta, including the suite of six BSL-4 laboratories, causing a power surge that knocked out power. Remote backup generators never came on. The outage shut down negative air pressure systems, which keep select agents from escaping the containment areas. (12,13) The BSL-4 labs were uninhabited at the time of the lightning strike/power outage even though construction of the building, which had begun in 2001, had been completed in September 2005. (13) Thus, the public and CDC workers were not placed at any risk as a result of the power outage.

“The new Emerging Infectious Diseases Laboratory occupies a central space on the CDC’s Roybal Campus near Emory University in Atlanta. It consists of two wings: a high-rise lab and office tower (right) and a six-story high-containment lab, vivarium, and glasswash facility (left). (The curved-roofed building at the far right is Building 17, the Infectious Disease Laboratory; Building 15, a containment lab, is the white element behind the new containment wing at the far left.) All photos: Balthazar Korab.” Source: http://www.labdesignnews.com/LaboratoryDesign/LD0605FEAT_3.asp; accessed October 5, 2007.

Necropsy suite at CDC’s new BSL-4 suite of laboratories. Source: http://www.labdesignnews.com/LaboratoryDesign/images/LD0605/RD0605LD_cdc_contlab2_lrg.jpg; accessed October 5, 2007.

Apparently, construction officials warned CDC since 2001 that its backup power system would not keep crucial lab systems from failing in an outage, according to internal documents obtained by The Atlanta Journal-Constitution.” (14) CDC determined that the cause of the failure of its power system servicing the BSL-4 laboratory suite was that “some time earlier, a critical grounding cable buried in the ground outside the building had been cut by construction workers digging at an adjacent site. The cutting of the grounding cable, which had gone unnoticed by CDC facility managers, compromised the electrical system of the facility that housed the BSL-4 lab.” (15) The irony of the situation is that it happened to CDC just as CDC was censuring TAMU for its BSL-3 safety violations.

U.S. Expansion of BSL-3 and BSL-4 Laboratories since 2001

GAO Keith Rhodes and his colleagues determined that the number of known BSL-4 laboratories in the U.S. has grown from 2 (before 1990) to 3 (1990-2000) to 10 (2001-present), which sum up to 15 known BSL-4 laboratories in U.S., as of 2007. (16) Multiple sectors own and operate these BSL-4 laboratories, i.e., federal government (9 labs), academic (4), state (1), and private (1). The two BSL-4 laboratories that existed in the U.S. in 1990 were the federal labs at the U.S. Army’s Research Institute for Infectious Diseases (USAMRIID) in Fort Detrick, Maryland, and at the CDC in Atlanta, Georgia. Between 1990 and 2000, three new BSL-4 laboratories were constructed at Georgia State University in Atlanta (first university BSL-4 lab), the National Institutes of Health campus in Bethesda, Maryland, and a privately-funded lab in San Antonio, Texas.

Map of some BSL-4 and BSL-3 laboratories compiled by the Sunshine Project, Austin Texas. Source: The Sunshine Project at http://www.sunshine-project.org/; accessed October 5, 2007.

Dual-access gloveboxes between the BSL-3 Ag and BSL-4 zones allow split handling of hazardous and unknown samples. The split-sample protocol prevents any material that’s ever been in the BSL-4 zone from entering a BSL-3 area, even if it proves to be a BSL-3 agent. Source: http://www.labdesignnews.com/LaboratoryDesign/LD0605FEAT_3.asp; accessed October 9, 2007.

Many more BSL-3 laboratories than BSL-4 laboratories are believed to exist, according to the research performed by Rhodes, et al. The only definitive data available on BSL-3 laboratories, such as the one at TAMU, exists in a federal database (more below) of laboratories handling select agents. This set of labs must register with the CDC-USDA Select Agent Program, as noted above. The number of BSL-3 laboratories currently registered with the Select Agent Program is 1356. Of the 1356, 1042 are registered with CDC and 314 are registered with USDA (United States Department of Agriculture). (17) Two thirds of the registered BSL-3 laboratories are outside of the federal sector.

According to a survey conducted by the Association of Public Health Laboratories (APHL) in August 2004, since 2001 state public health labs have used public health preparedness funding to build, expand, and enhance BSL-3 labs. In 1998, for example, APHL found that 12 of 38 responding states reported having a state public health laboratory at the BSL-3 level. Today, at least 46 states have at least one state public health BSL-3 lab. (17,18)

Federal Agency Responsibility for Tracking BSL-3/BSL-4 Expansion/Risks

“No single federal agency has the mission to track and determine the risk associated with the expansion of BSL-3 and BSL-4 laboratories in the United States, and no single federal agency knows how many such laboratories there are in the United States. Consequently, no one is responsible for determining the aggregate risks associated with the expansion of these high-containment labs,” notes GAO’s Rhodes. (19)

Lessons Learned about Study of Expansion of BSL-3/BSL-4 Laboratories in the U.S.

Rhodes’ group from GAO learned six lessons from their investigation of the expansion of high-containment laboratories in the U.S., as described elsewhere. (20) Four of the lessons are that barriers to reporting errors exist, clearer definition of what constitutes an “exposure” to a biologic agent is needed, laboratory workers need more safety training, and physical infrastructure of high-containment labs needs maintenance after being built.

Conclusion

The U.S. Congress awarded funding to organizations in many sectors to build high-containment laboratories following the terrorist attack on September 11, 2001 and the anthrax bioterrorism in October 2001. The goal was laudable: to expand the nation’s preparedness and response capabilities in the face of outbreaks of infectious disease. Insufficient thought, however, appears to have been invested in emplacing mechanisms for measuring and improving the ongoing quality and safety of the new high-containment laboratories.

Sources:

1. Government Accountability Office GAO-08-108T: “High-containment biosafety laboratories: preliminary observation on the oversight of the proliferation of BSL-3 and BSL-4 laboratories in the United States,” October 4, 2007. Available online at http://www.gao.gov/docsearch/abstract.php?rptno=GAO-08-108T; accessed October 4, 2007.
2. Ibid, p. 1.
3. Ibid, p. 23.
4. Ibid, p. 2.
5. John Rather: “Lab’s research gets spread around”. New York Times, May 16, 2004. Available online at http://query.nytimes.com/gst/fullpage.html?res=9B0DE0DC113CF935A25756C0A9629C8B63; accessed October 4, 2007.
6. HHS and USDA Select Agents and Toxins. Available online at http://www.cdc.gov/od/sap/docs/salist.pdf; accessed October 4, 2007.
7. More information on the Select Agent Program is available at http://www.cdc.gov/od/sap/ and http://www.selectagents.gov/securitydoc.htm; accessed October 4, 2007.
8. Government Accountability Office GAO-08-108T: “High-containment biosafety laboratories: preliminary observation on the oversight of the proliferation of BSL-3 and BSL-4 laboratories in the United States,” October 4, 2007, p. 17. Available online at http://www.gao.gov/docsearch/abstract.php?rptno=GAO-08-108T; accessed October 4, 2007.
9. The Sunshine Project at http://www.sunshine-project.org/; accessed October 4, 2007.
10. The HHS report of TAMU violations dated August 31, 2007, is available at http://sciencenow.sciencemag.org/feature/data/CDCreport.pdf; accessed October 4, 2007.
11. Jocelyn Kaiser: “Biosafety Breaches: Accidents spur a closer look at risks at biodefense labs.” Science. September 28, 2007, Volume 317, Number 5846, pp. 1852-1854. Available online at http://www.sciencemag.org/cgi/content/full/317/5846/1852; accessed October 4, 2007.
12. Government Accountability Office GAO-08-108T: “High-containment biosafety laboratories: preliminary observation on the oversight of the proliferation of BSL-3 and BSL-4 laboratories in the United States,” October 4, 2007, p. 20. Available online at http://www.gao.gov/docsearch/abstract.php?rptno=GAO-08-108T; accessed October 4, 2007.
13. Allison Young: “CDC lab’s backup power fails during storm.” The Atlanta Journal-Constitution, July 7, 2001, p. A1.
14. Allison Young: “E-mails outline CDC backup power flaws. One expert: Failure to heed warnings a “grave breach of responsibility”. The Atlanta Journal-Constitution, July 24, 2007, p. A1.
15. Government Accountability Office GAO-08-108T: “High-containment biosafety laboratories: preliminary observation on the oversight of the proliferation of BSL-3 and BSL-4 laboratories in the United States,” October 4, 2007, p. 21. Available online at http://www.gao.gov/docsearch/abstract.php?rptno=GAO-08-108T; accessed October 4, 2007.
16. Ibid, Highlights, also p. 9.
17. Ibid, p. 10.
18. Association of Public Health Laboratories website is at http://www.aphl.org/Pages/default.aspx; accessed October 5, 2007.
19. Government Accountability Office GAO-08-108T: “High-containment biosafety laboratories: preliminary observation on the oversight of the proliferation of BSL-3 and BSL-4 laboratories in the United States,” October 4, 2007, p. 13. Available online at http://www.gao.gov/docsearch/abstract.php?rptno=GAO-08-108T; accessed October 4, 2007.
20. Ibid, pp. 15-23.