Researchers from the the Center for Security and Emerging Technology (CSET) recently mapped “the gain- and loss-of-function global research landscape.” We contextualize the CSET findings relative to the biosafety levels in U.S. biomedical laboratories. A looming question: do other countries have the adequate commitment to health security and biosafety measures in their high risk pathogen research?
Background
The origin of the SARS-CoV-2 (aka Covid-19) coronavirus remains a source of fierce debate. Central to that debate: the role of global partnerships and biosafety in biomedical laboratories in Gain-of-Function (GOF) research. According to the CSET researchers: “Gain- and loss-of-function research have contributed to breakthroughs in vaccine development, genetic research, and gene therapy. At the same time, a subset of gain- and loss-of-function studies involve high-risk, highly virulent pathogens that could spread widely among humans if deliberately or unintentionally released. To maintain U.S. competitiveness in this scientific area, policymakers seeking to regulate gain-of-function (GOF) research will need to develop balanced policies that effectively mitigate varying risk factors without preventing essential scientific studies.”
Understanding the Global Gain-of-Function Research Landscape
CSET analysts identified approximately 7,000 scientific publications that employ GOF or loss-of-function (LOF) research published in PubMed between 2000 and mid-2022.
Key Findings from the Report
- Gain- and loss-of-function research is ongoing, global, and collaborative with U.S.-affiliated researchers contributing to approximately half of identified publications between 2000 and mid-2022.
- Gain- and loss-of-function research frequently co-occur in the same study. That said, LOF research appears in more publications than GOF research.
- Gain- and loss-of-function research is conducted over a range of different experimental methodologies, pathogens, and applications.
- Methodologies: GOF and LOF research does not require cutting-edge gene-editing technologies; 21 percent of all publications we identified for this report use serial passaging instead of other more technically sophisticated techniques such as CRISPR. The use of serial passage is more frequent in GOF publications than LOF publications.
- Pathogens: GOF and LOF research involves pathogens that span the four biosafety levels (BSLs), with nearly all research being conducted on pathogens that are categorized as BSL-2, BSL-2+, or BSL-3.
- Applications: a range of research topics involve GOF and LOF research. For example, approximately 24 percent of the identified publications were related to vaccine development and the most-studied pathogens are those that cause high global health burdens.
HHS: Biosafety Levels 1 through 4
According to U.S. Department of Health and Human Services’ Administration for Strategic Preparedness and Response (ASPR):
Biosafety levels (BSL) are used to identify the protective measures needed in a laboratory setting to protect workers, the environment, and the public. The levels are defined in Biosafety in Biomedical Laboratories (the BMBL).
Risk assessments are conducted by evaluating the way in which the infectious agents or toxin is transmitted and its ability to cause disease, the activities performed in the laboratory, the safety equipment and design elements present in the laboratory, the availability of preventive medical countermeasures or treatment, and the health and training of the laboratory worker.
At any given biosafety level, there will be strict requirements for laboratory design, personal protective equipment, and biosafety equipment to be used. Standard Microbiological Practices are required at all biosafety levels and are good practice for experiments below the BSL-1 threshold.
Activities and projects conducted in biological laboratories are categorized by biosafety level. The four biosafety levels are BSL-1, BSL-2, BSL-3, and BSL-4, with BSL-4 being the highest (maximum) level of containment.
Biosafety Level 1 (BSL-1)
BSL-1 labs are used to study infectious agents or toxins not known to consistently cause disease in healthy adults. They follow basic safety procedures, called Standard Microbiological Practices and require no special equipment or design features. Standard engineering controls in BSL-1 laboratories include easily cleaned surfaces that are able to withstand the basic chemicals used in the laboratory.
Biosafety Level 2 (BSL-2)
BSL-2 laboratories are used to study moderate-risk infectious agents or toxins that pose a risk if accidentally inhaled, swallowed, or exposed to the skin. Design requirements for BSL-2 laboratories include hand washing sinks, eye washing stations in case of accidents, and doors that close automatically and lock. BSL-2 labs must also have access to equipment that can decontaminate laboratory waste, including an incinerator, an autoclave, and/or another method, depending on the biological risk assessment.
Biosafety Level 3 (BSL-3)
BSL-3 laboratories are used to study infectious agents or toxins that may be transmitted through the air and cause potentially lethal infection through inhalation exposure. Researchers perform all experiments in biosafety cabinets that use carefully controlled air flow or sealed enclosures to prevent infection. BSL-3 laboratories are designed to be easily decontaminated. These laboratories must use controlled, or “directional,” air flow to ensure that air flows from non-laboratory areas (such as the hallway) into laboratory areas as an additional safety measure.
Biosafety Level 4 (BSL-4)
BSL-4 laboratories are used to study infectious agents or toxins that pose a high risk of aerosol-transmitted laboratory infections and life-threatening disease for which no vaccine or therapy is available. The laboratories incorporate all BSL 3 features and occupy safe, isolated zones within a larger building or may be housed in a separate, dedicated building. Access to BSL-4 laboratories is carefully controlled and requires significant training.
What Next?
The CSET researchers make clear that regulation of GOF research will be difficult – and create tough risk/reward choices for policymakers relative to research designed to inform a best-in-class pandemic preparedness ecosystem (including proactively creating vaccines based on the most high-risk, virulent pandemic scenarios).
This CSET report contributes clear-eyed findings on GOF research conducted at a global scale – which business leaders should use as a filter to sort through the arduous signal to noise ratio surrounding the future of highly controversial GOF research.
Business strategy issues include:
- The ongoing impacts of dependence on foreign supply chain sources and vendors;
- Employee health and wellness – and crisis preparedness and communications strategies; and
- Operational resilience – in preparation for the “not if but when” probabiliy of another global pandemic (potentially more impactful than even the wily, seemingly unpredictable epidemiological behavioral patterns and variants of SARS-CoV-2).
Difficulties ahead identified by the CSET report include:
- GOF and LOF research are widely used in public health applications. Approximately 24 percent of the identified publications were related to vaccine development and the most-studied pathogens are those that cause a high global health burden, like flu viruses.
- GOF and LOF research are intertwined and difficult to predict, so regulations that restrict GOF research will also restrict the less risky and largely benign LOF research. GOF and LOF employ the same experimental techniques; LOF research is more frequent that GOF research and approximately 29 percent of identified studies involve both GOF and LOF research.
- GOF research can be conducted without access to advanced gene editing technologies. 21 percent of all publications we identified for this report use serial passaging to modify pathogens, which requires only basic laboratory equipment and materials and was more frequent for publications that result in GOF than those that result in LOF.
- Risk varies among GOF studies, and should not be uniformly regulated. Factors like the pathogen and animal model used change the risk level of GOF research. Regulations will need to target the types of research that cause the most risk to account for these vital differences.
Additional Resources (Health Security)
Planning for a Continuous Pandemic Landscape: COVID-19’s geopolitical repercussions are evident, with recent assessments pointing to China’s role in its spread. Regardless of the exact origins, the same conditions that allowed COVID-19 to become a pandemic persist today. Therefore, businesses must be prepared for consistent health disruptions, implying that a substantial portion of the workforce might always operate remotely, even though face-to-face interactions remain vital for critical decisions. See: COVID Sensemaking
Food Security and Inflation: Food security is emerging as a major geopolitical concern, with droughts and geopolitical tensions exacerbating the issue. Inflation, directly linked to food security, is spurring political unrest in several countries. See: Food Security
