Concerns regarding unexpected biological incidents and their public health implications were discussed in a 2014 Domestic Preparedness biosecurity and bioterrorism article. From the improper possession and storage of decades-old live smallpox virus in a former Food and Drug Administration laboratory (lab) on the National Institute of Health (NIH) campus to the possible exposure to live Bacillus anthracis (anthrax) by Centers for Disease Control and Prevention, agencies experienced lab accidents and made serious human errors. The biosafety lab concerns were not limited to these two serious incidents.
These biosafety incidents – and others involving Ebola, high-pathogenic avian influenza, and anthrax – were relevant when considering the findings of a 2014 Government Accountability Office (GAO) report. The report on biosafety lapses at high-containment labs indicated that no federal entity was responsible for strategic planning and oversight of these essential research labs. The expansion of labs was not based on a government-wide coordinated strategy but on the availability of congressional funding for each requesting agency. Lab oversight was reportedly fragmented and largely self-policing. The report recognized the value of national standards and a government-wide strategy. Many other GAO biosafety products since 2007 also documented these insufficient practices.
The biosafety challenges have continued in the decade since the publication of the 2014 Domestic Preparedness article. The worldwide debate of an accidental or intentional biosafety lab leak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, demonstrates the continued threat of non-existent, insufficient, or ignored biosafety policies and practices in high-containment labs. The continued ignoring of these vulnerabilities could produce even more severe consequences, which may be difficult to truly comprehend even after the past three years of the COVID-19 pandemic. However, the biological threats may not be just international.
Biosafety labs (BSL) range from BSL-1 (least secure) to BSL-4 (most secure) rating. As the threat of the agent (pathogen) increases, so does the level of biosafety training, procedures, and equipment required to properly handle them. BSL-3 and -4 are often considered high-containment labs. The number and complexity of BSL-4 labs have expanded since the 1970s but are still rather limited in number in the United States.
Fort Detrick was established in Frederick, Maryland, in 1931 as part of the Maryland National Guard. In the early 1940s, a research program and lab were developed at the fort to study biological agents and infectious diseases. The fort expanded into developing medical countermeasures in the 1950s, including therapeutics and diagnostic procedures. The facility became a leader in the early study of respiratory diseases and the operation and sterilization of biological labs. The research involved offensive biological warfare until the program ended in 1969 and transitioned to defensive in nature.
The U.S. Army Medical Research Institute of Infectious Diseases was created in 1969 at the fort to address biological threats to military personnel. Additional military and similar organizations were also moved to or originated at Fort Detrick to strengthen medical support and planning for global military operations. Through its various operations and expansions, Fort Detrick helped lead the way in developing high-containment labs.
The Centers for Disease Control and Prevention (CDC) opened its first permanent high-containment lab in 1969 to handle dangerous infectious pathogens, specifically the recently emerging Marburg virus and Lassa fever. The hemorrhagic fevers required enhanced facilities for their safe handling and research. A second was opened in 1978 that utilized positive pressure suits to protect the researchers. The CDC opened the first high-containment biosafety level (BSL)-4 lab in 1989 as one of only two nationwide. The number of federal government BSL-4 labs grew from two in 1990 to nine in 2007. The total number of BSL-4 labs in the United States increased from 2 to 15 by 2007. In 2008, CDC operated four different BSL-4 labs in one building to handle the deadly pathogens for which no approved treatment or vaccine exists.
There were reportedly 14 BSL-4 labs in the United States in 2023. BSL-3 and -4 labs can be found in other governmental agencies as well as in academia and the private sector. The CDC plans to build a new High Containment Continuity Laboratory in Atlanta, Georgia, by 2025. The BSL-4 facility will have 160,000 square feet to accommodate approximately 80 researchers.
Lack of National Strategy
The GAO issued a 2007 report with preliminary observations on overseeing high-containment BSL-3 and -4 labs across the federal, state, academic, and private sectors. Generally, BSL-3 labs handle agents that can be transmitted through the air and cause lethal infection using air-tight enclosures. BSL-4 labs handle high-risk agents and diseases for which no therapy or vaccine is available and require BSL-3 standards along with full-body suits with an outside air supply and shower upon exit of the facility. The auditors found that no single federal agency was responsible for tracking the BSL-3 and -4 labs or the associated risks.
The auditors reported that the limited federal oversight for the high-containment labs was fragmented across several agencies and often relied on self-policing their activities. It created unnecessary risk. The findings recommended establishing a single federal entity to conduct government-wide strategic planning for high-containment lab requirements, including assessment of risks. There was also a need to develop national standards for designing, constructing, commissioning, operating, and maintaining such sensitive labs.
In a more detailed 2009 report, GAO again addressed the need for a national oversight strategy. With no single federal agency overseeing the expansion of high-containment labs, there was no common operating picture or global understanding of the aggregate risks. GAO identified that:
If an agency were tasked or a mechanism were established with the purpose of overseeing the expansion of high-containment laboratories, it could develop a strategic plan to (1) ensure that the number and capabilities of potentially dangerous high-containment laboratories are no greater or less than necessary, (2) balance the risks and benefits of expanding such laboratories, and (3) determine the type of oversight needed. (p. 66)
The report emphasized that recent biosafety incidents at high-containment labs and their causal factors were not unique. Those incidents and other biosafety lab accidents involved similar factors and involved the failure to maintain adequate biosafety. GAO recommended that the federal government identify a single entity for the government-wide evaluation of labs.
GAO stressed in a 2013 report that an assessment of the nation’s need for high-containment labs was absent. The report showed that, as lab expansion occurred, no single federal agency was responsible for assessing the nation’s overall needs. It also found no national standards for lab design, construction, operations, and maintenance, which increased accident risk. With the lack of national standards and uncertainty regarding the number of high-containment labs required to support the country’s needs, the auditors believed the nation was exposed to considerable risk.
In 2014 testimony of biosafety lab lapses, the GAO began with their finding that no federal entity was responsible for strategic planning and oversight of high-containment labs. As a result, there was no government-wide strategic evaluation of research requirements based on public health or national security requirements. They believed this failure may have been more critical five years later in 2014 due to budget constraints.
The GAO released a 2015 report for primary observations on federal efforts to address weaknesses exposed by recent safety lapses. The report addressed several 2014 and 2015 Department of Defense (DOD) and CDC lapses that raised biosafety and biosecurity policy and procedure questions. DOD and CDC reportedly improved their operations to better manage high-risk biological agents in high-containment labs. The level of improvement may have been insufficient compared to the level of risk.
A follow-up 2016 report addressed the continued need for more robust policies and oversight for high-containment labs to improve safety. GAO continued to find deficiencies in internal controls for the management of labs. The reviewed policies were not as comprehensive because they lacked vital safety elements or did not apply to the specific labs. In addition, many of the policies were not up to date. The report provided 33 recommendations for federal departments and agencies.
In a 2023 report, the GAO found that the Department of Health and Human Services (HHS) could improve research oversight involving enhanced potential pandemic pathogens. HHS developed a framework in 2017 that required funding agencies to refer proposed research involving enhanced potential pandemic pathogens to HHS for additional review and associated risks and benefits. However, the report found that the framework did not fully meet the key elements of effective oversight, leaving HHS without assurance that the department was reviewing all necessary research proposals. These findings may be more relevant in the future.
GAO discussed high-containment labs in numerous other reports, testimonies, and products related to biosafety and biological threats and risks. The need for a national oversight strategy and enhanced management and coordination remained essential for the current and future high-containment labs.
Risk of Lab Leaks
According to a 2020 analysis by Lynn C. Klotz at the Center for Arms Control and Non-Proliferation, the risk of a pandemic from an enhanced influenza virus via an accidental lab leak was unacceptably high. The concern stemmed from the amount of viral enhancements conducted by scientists in various countries. Research that modified avian influenza to be more transmissible to mammals was a substantial concern. According to Klotz, there are at least three ways this could happen:
(1) An undetected or unreported laboratory-acquired infection where the infected lab worker leaves the lab and goes into the community at the end of the workday. This is the one release scenario for which there is considerable data, so it is possible to estimate the probability of release from a lab.
(2) Mischaracterization of a virus as harmless, so it is removed entirely from biocontainment or removed to labs with lower biosafety levels (e.g., from biosafety level 3 to biosafety level 2) for further research.
(3) Purposeful release into the community by a mentally unstable lab worker or by someone with evil intent.
The concerns and risks to humans were real, with 14 facilities reportedly conducting research with lab-created, highly pathogenic avian influenzas transmissible to mammals. The analysis indicated that lab-enhanced avian influenzas were among the more worrisome pathogens since they could cause a deadly worldwide pandemic. Research involving gain-of-function activities may not receive the appropriate review and oversight, causing significantly more serious vulnerabilities.
According to research in 2019 by Klotz, human error caused 67-79% of incidents that led to potential BSL-3 lab exposures. The percentages came from an analysis of years of incident data from the Federal Select Agent Program and NIH. Klotz found that the first step in calculating the likelihood of a pandemic was to understand the probability of human error – knowledge, rule, or skill-based – in releasing the pathogen. Beyond human error, there are equipment or mechanical failures and incomplete inactivation of a pathogen for a BSL-2 lab (which could be linked to human error).
During the 2017 meeting of the Biological Weapons Convention, an analysis estimated a 20% probability of a mammalian-airborne-transmissible, highly pathogenic avian influenza virus release from one of 10 labs over 10 years. The release could initiate a pandemic of the novel pathogen. Unfortunately, human error remains a continued vulnerability for future lab incidents and possible leaks, no matter the quality of the labs’ facilities, training, and procedures. As the number of labs and technology expands, so does the risk. The research and analysis by Klotz may have been prognostic in analyzing possible lab leaks and the emergence of SARS-CoV-2 and the COVID-19 pandemic.
A review of the information above, along with emerging information and research, provides an interesting assessment of the possible source of SARS-CoV-2. The United States government and its intelligence community appeared to be shifting toward the more significant possibility of a lab leak in Wuhan. The Federal Bureau of Investigation believed that the virus most likely originated in a Chinese government lab. Other intelligence community members concurred with that belief with varying levels of confidence.
The Overton Window for the virus origination theory shifted from a wet or seafood market toward a lab leak in Wuhan, China, since its emergence in 2020. However, the debate continued:
If a lab leak, was it accidental by human error or intentional by the government or a bad-actor employee?
Either way, did the government of China intentionally conceal its escape or encourage the pathogen’s spread after it entered the local population?
All the answers may never be known or trusted by the impacted world. However, what was known was that a lab leak could produce severe, if not catastrophic, consequences well beyond the public health environment.
Both houses of Congress unanimously passed the COVID-19 Origin Act of 2023 to mandate the declassification of COVID-19 origin-related intelligence and information. The president signed the bill with a statement to continue to review all classified information and its links to the Wuhan Institute of Virology. It remains to be seen how much information will be transparently and timely shared with the public.
Oversight and Action
Regardless of the location, the threat of a highly pathogenic public health threat escaping from a high-containment lab is a grave risk. The United States has limited control or influence over foreign labs beyond supplied funding and political pressure to adhere to treaties and norms. The United States does have a level of control over domestic labs, where there appears to be room for improvement to enhance safety and security to include a national strategy and oversight.
The number of high-containment labs may increase domestically and worldwide in response to the COVID-19 pandemic. These biosafety labs may utilize controversial procedures and methods with terms such as gain-of-function or directed evolution to conduct their research. The results may range from beneficial to cataclysmic. To reduce the possibility of a lab leak, enhanced oversight and coordination in the United States are overdue. Lab accidents have occurred in the past, and there will be more in the future with even more dangerous pathogens. Humans will err. Procedures will fail.
Bioterrorism and biowarfare remain at the top of the list for what keeps many homeland defense and security experts up at night. However, the biological threat may not stem from outside the United States. The next lethal outbreak or pandemic could be home-grown from a lab leak and much more deadly than COVID-19. It is time for expanded high-containment lab oversight and action to address this possible internal threat along with a very serious discussion about gain-of-function and directed evolution research.
Robert C. Hutchinson
Robert C. Hutchinson was a former police chief and deputy special agent in charge with the U.S. Department of Homeland Security (DHS), Homeland Security Investigations in Miami, Florida. He retired in 2016 after more than 28 years as a special agent with DHS and the legacy U.S. Customs Service. He was previously the deputy director of the agency’s national emergency preparedness division and assistant director for its national firearms and tactical training division. His numerous writings and presentations often address the critical need for cooperation, coordination, and collaboration between public health, emergency management, and law enforcement, especially in the area of pandemic preparedness. He received his graduate degrees at the University of Delaware in public administration and Naval Postgraduate School in homeland security studies. He is a long-time contributor to Domestic Preparedness and serves on the Advisory Board.