Glaring Gaps in Governance for High-Risk Life Science Laboratories

No state is secure until all laboratories are. The politicization of the debate around the origins of COVID-19 has garnered significant attention from governments, media, and scientists alike. However, this highly divisive debate overlooks a crucial point. The question should not be "Was the coronavirus developed in a lab?" but rather, "How did we reach a point where the lab leak theory is even considered a plausible scenario, and how can policy address this issue?" 

The answer to the latter is straightforward: high-risk laboratory biology is advancing far quicker than common-sense policy frameworks. Present regulatory structures do not sufficiently recognize and address growing research capabilities in the life-sciences. Nonetheless, fearing the potential risks linked with advanced biology research and choosing to prohibit it is not a viable solution. Instead, it is imperative to develop comprehensive reporting mechanisms and establish a "biosafety-by-design" process at local, national, and international levels. Such measures are essential to ensure that international advancements in high-risk life sciences research are conducted safely, efficiently, and transparently. This approach will facilitate innovation while maintaining robust, international safeguards against potential biosecurity threats. 

What are ‘high-risk life science laboratories’?

Life science laboratories are characterized as high-risk based on two primary criteria:

1. ‘Risk Groups’: Categorized depending on certain factors, particularly, the pathogens/toxins they work with, the activities/research performed by scientists with said pathogens, and the availability of treatments/containment measures if something goes wrong.
2. ‘Biosafety Levels (BSL)’: These provide detailed procedures and levels of containment required for working with certain pathogens. Both Risk Groups and BSLs range in severity from 1-4. 

However, BSL laboratories are typically referred to when discussing high-risk laboratories, and this paper primarily refers to BSL laboratories. Below is a table detailing the definitions and sample pathogens associated with each BSL.
 

Table 1: An overview of how Biological Safety Level (BSL) Laboratories are categorized internationally

These categorizations are critical for how governments, international bodies, and the scientific community approach pandemic preparedness and response, as these laboratories typically conduct research on emerging biological threats. Traditionally, most of these laboratories have been located in the US, Russia, and Europe. However, since COVID-19, as states seek to equip themselves with the tools to understand and respond to local threats and future pandemics, the number of operational, under construction and planned (announced by governments or international bodies) high-risk facilities has rapidly increased, particularly in Asia. 

Figure 1: Trends in Operational and Planned BSL-4 Facilities By Region

Why are current regulations insufficient for present & additional high-risk laboratories?

According to the 2023 Global Biolabs Report, roughly 75% of existing operational BSL-4 laboratories are located in cities, and half of all BSL-4 laboratories have an area smaller than a tennis court, exacerbating the risk of an accidental release from these facilities.  These laboratory levels are categorized based on the pathogens they handle, judged primarily on the taxonomic classification of the pathogen. As per international standards, BSL-4 laboratories are designed to have custom-designed airtight doors, dedicated supply and exhaust airflow systems, a negative-pressure environment, and mandatory use of positive-pressure (similar to astronaut) suits. Small laboratories increase the risk of an accidental release by limiting space available for essential containment systems, creating higher density of personnel and equipment, and complicating maintenance of critical safety infrastructure like airlocks and filtration systems. With 3/4th of operational BSL-4 laboratories being located in cities, any accidental release can have devastating consequences.

For instance, anthrax is caused by Bacillus anthracis. Anthrax is a serious disease that produces spores that can enter the body through the skin, inhalation, or ingestion, leading to severe illness or death if untreated. Therefore, almost all countries will have strict restrictions on the use of Bacillus anthracis in laboratories. However, advancements in both gene synthesis and gene editing technologies allow laboratories to evade regulations by altering the genetic makeup of less severe pathogens to mimic more severe ones.

With gene editing, a laboratory can take genes of interest from a more severe pathogen and place them into a less severe pathogen that produce the same outcome. If a laboratory does this, and reports the usage of the less severe pathogen, in a country that regulates pathogen use based on name rather than impact, they can easily evade existing regulations designed to reduce risks. Gene synthesis technologies could be misused in a similar manner with relative ease. Most gene synthesis companies are signatories to the International Gene Synthesis Consortium (IGSC), which encourages companies to voluntarily screen orders from their customers. While most companies would refuse to directly ship a highly pathogenic strain of COVID-19 to a lesser known laboratory, some customers might order a less pathogenic/ non-pathogenic strain of the virus, and using relatively simple synthetic biology techniques, transform the less pathogenic strain to a more pathogenic one.

The question then arises: why would scientists want to evade these regulations? Quite simply, developing and maintaining laboratories suited for BSL-3 and BSL-4 work is expensive and difficult. More concerningly, there are often incidents of near-misses that tend to be downplayed so that laboratories can keep their funding. For example, in 2019, at the University of Wisconsin-Madison, a laboratory was conducting an experiment with a lab-made H5N1 (bird-flu) virus, and when a safety breach occurred, the university never informed local nor state public health officials, let alone the public. The system of federal oversight in the US requires laboratories to report public health officials if there is ‘any potential exposure’ to humans of a dangerous pathogen. However, university officials were the one to determine that there was "no potential exposure." This self-reliant reporting system assumes that scientists will report every near-miss, which scientists may not do so if  they are under risk of losing funding and ability to conduct their research if an incident occurs. The book "Pandora’s Gamble: Lab Leaks, Pandemics, and a World At Risk" details multiple similar incidents where populations only escaped a dangerous disease through luck.

The number of these incidents is only poised to grow as more countries and facilities around the world focus on pandemic resilience efforts, and emerging biotechnologies make conducting high-risk work more accessible. Pandemic resilience efforts, especially after COVID-19, have seen various states scale up their high-containment laboratories and research into dangerous pathogens to develop mitigation strategies, which inherently increases the risk of accidents or breaches. At the same time, states and laboratories want to showcase their competency, and hence, institutions are incentivized to downplay or obscure incidents, fearing reputational damage or restrictions on their work. This combination of increased activity and insufficient transparency poses significant risks to global biosecurity. 

How do we then regulate high-risk laboratories?

Addressing the regulation of high-risk laboratories requires recognizing that current practices cannot continue and that banning all risky life-science research is counterproductive, as it inhibits global capabilities to respond to emerging disease threats, which are only poised to grow in the coming years. Therefore, I believe a ‘biosafety-by-design’ approach is the way forward.

This approach involves looking at biosafety as an opportunity to help unlock the full potential of the life sciences. This would involve various steps such as:

1. Update National and International Regulations on Pathogens: Pathogen classification must be updated to focus on both taxonomy and the potential impact of pathogens used in labs. This dual approach ensures that regulations keep pace with advancements in gene editing and synthesis technologies.
2. Encourage collaboration between Stakeholders on Emerging Biotechnology: Governments, researchers, and the private sector must collaborate to develop clear, concrete, and unified guidelines for companies in gene synthesis, gene editing, and other emerging biotechnology fields to reduce biological risk.
3. Designate National Biosafety Inspection Agencies: Instead of regular international inspections, states with well-established BSL-4 facilities should designate national agencies to inspect high-risk life science laboratories on an annual basis. These agencies should provide reports to international bodies such as the Biological Weapons Convention (BWC) or the World Health Organization (WHO). International agencies, thus, have the option of spreading out inspections and devoting more resources to countries that lack adequate experience or infrastructure for high-risk life science laboratories.
4. Develop Good-Samaritan Reporting Mechanisms: Create local and national reporting mechanisms that allow researchers and scientific journals to express concerns about potentially dangerous research. This encourages transparency and early identification of risks.

Strengthening the BWC

The BWC, while important, is underutilized in addressing concerns with reporting mechanisms. All countries with BSL-4 facilities should be required to comply with the BWC’s confidence-building measures (CBMs) by providing regular reports that should include modernized guidelines to address dual-use research, biosafety risks, and emerging biotechnologies. Existing CBMs solely focus on state-based threats and lack mechanisms to address non-state risks or lab accidents. Additionally, the absence of a legally binding verification system hampers the treaty’s ability to check high-risk laboratories to ensure that no bioweapons or potential bioweapons are in the process of development. An effective verification regime must balance intrusiveness with respect for national security and commercial interests while ensuring legitimacy and agreement among member states. Without greater clarity on acceptable boundaries in balancing commercial/security interests and concentrated international dialogue, progress on these verification systems will remain limited and insufficient. The BWC also requires more funding and resources, as its annual budget of $1.4 million being less than that of an average McDonalds restaurant. Expanding the mandate and resources of the BWC’s Implementation Support Unit (ISU) would enable better enforcement of CBMs and support for member states in implementing biosafety and biosecurity standards. Thus, working to strengthen the BWC through these measures would close critical gaps in reporting mechanisms and ensure safer governance of high-risk biotechnology and life science research.

Conclusion

By recognizing and addressing these gaps in regulation for high-risk life science laboratories, the global community can mitigate the risks posed by emerging biotechnologies and the increasing prevalence of high-containment facilities. Collective efforts such as strengthening the BWC, improving requirements for reporting mechanisms, integrating biosafety-by-design approaches, and investing in biosafety globally, are critical to ensure that life sciences research supports innovation while mitigating biosecurity threats. These steps provide a feasible path for conducting high-risk research safely, responsibly, and in a way that prioritizes global health and security.

The views expressed in this article are those of the author and do not represent those of any previous or current employers, the editorial body of SIPR, the Freeman Spogli Institute, or Stanford University.