In an opinion piece published in The New York Times in March, two leading virologists argued that experiments on a coronavirus found in bats and similar to those that cause Middle East respiratory syndrome (MERS) had been conducted without sufficient safety measures. The experiments involved infecting human cells with the live bat virus to see how the virus behaved1.
Regulatory authorities in many countries where research on potentially dangerous viruses is conducted, including the United States, the United Kingdom, France and Germany, would require such studies to be conducted in biosafety level (BSL) 3 or 4 facilities. (There are four biosafety levels, with BSL-4 being the most stringent.) But for these experiments — which were approved by the equivalent authorities in China — the 25 researchers across 7 institutes and universities in China (including the Guangzhou National Laboratory and the Wuhan Institute of Virology) used BSL-2 procedures. They also used a negative pressure ventilation system designed to prevent microorganisms from spreading outside the laboratory.
In our view, this work and the discussion it has provoked highlights a broader and growing problem that the entire virology community needs to address. On the one hand, the threat posed by emerging infectious diseases is growing2,3 (see ‘A growing threat’), making investigations of potentially dangerous viruses more important. On the other hand, since the COVID-19 pandemic, trust in virology and science more broadly has declined and work on viruses has become more politicized.
To improve trust in science — and to ensure that essential work on viruses can continue — international, standardized and transparent biosafety guidance is urgently needed. Here, we lay out how such guidance might be developed.
Source: Ref. 6
Patchwork regulation
Over the past 30–40 years, various protocols and procedures have been introduced to reduce the risk of viruses escaping from labs, or of people being infected by viruses used in research.
Today, researchers in many countries, including the United Kingdom, Germany, France, Switzerland, Canada and the United States, can work on certain ‘dangerous’ viruses only if they use biosafety cabinets, personal protective equipment and strict standardized procedures for BSL-3 or BSL-4 facilities. The use of negative pressure, which ensures that the air in a facility leaves through a filter that captures pathogens, and strict controls over access to the facility are also required.
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Which viruses qualify as dangerous is decided by the government of each country, and is usually listed as an appendix to the regulations governing the work. In the United States, federal funding for research involving the enhancement of viruses that cause influenza, MERS and severe acute respiratory syndrome (SARS) — whether through the use of genetic manipulation or by harnessing natural evolutionary processes — was banned in 2014. The ban was lifted in 2017, but research is only permitted after a stringent review process and with the use of BSL-3 or BSL-4 facilities4. These rules are likely to change again under the current US administration.
In China, national biosafety laws were updated in 2004 and 2020. These require investigators undertaking studies on potentially pathogenic living organisms to use BSL-3 or BSL-4 facilities, among other strict precautions5. It is unclear exactly how these rules are enforced, however. They don’t seem to have been applied to the experiments on the MERS-like coronavirus found in bats, which were approved by the Wuhan Institute of Virology institutional biosafety committee.
The level of detail included in regulations also varies. For example, Canada uses the Canadian Biosafety Standard, which lays out exactly how containment is to be achieved. The United Kingdom, the United States, the European Union, Australia and New Zealand have similar standards. Many other countries, however, do not provide such detailed information, although they might provide details of the containment levels necessary for certain pathogens.
Avian influenza viruses can infect and spread among domestic poultry, including chickens.Credit: Andres Kudacki/AP Photo/Alamy
This patchwork regulation has led to confusion in the field. And the lack of transparency has probably made it easier for people to spread misinformation and fake news around the handling of live viruses in research.
More than five years on from the start of the COVID-19 pandemic, the controversy about its origins shows no sign of abating. According to the lab-leak theory (now promoted by the administration of US President Donald Trump), research on bat viruses at the Wuhan Institute of Virology led to the accidental infection of lab personnel, which in turn sparked the COVID-19 pandemic. Although the institute is known to have been doing research on coronaviruses before the pandemic, there is no firm evidence that it possessed or conducted work on a SARS-CoV-2 precursor virus. Meanwhile, findings indicating that the pandemic resulted from a natural ‘spillover’ event, the epicentre of which was the Huanan Seafood Wholesale Market in Wuhan, continue to accumulate. (A spillover event is the transmission of what is called a zoonotic virus from other animals to humans.)
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In our experience, virologists are often reluctant to engage in discussions about work that involves the enhancement of live viruses — either genetically or through natural evolutionary processes — for fear of being caught in the crosshairs or of their own work being shut down, even if it is low risk. But now is not the time to lie low.
The number of outbreaks and deaths caused by viruses such as those that cause SARS, Ebola and mpox has been increasing. Data scientists predict that, if current trends continue, Nipah virus, Machupo virus, coronaviruses and filoviruses will, compared with 2020, cause 4 times as many spillover events and 12 times as many deaths by 2050 because of global travel, climate change, tropical deforestation, and wild-animal hunting and trade6,7.
And although virologists now have various ways of studying viruses that can spread between animals and humans, besides growing fully functional zoonotic viruses in the lab, experiments involving live viruses are key to testing antiviral drugs and vaccines. It’s hard to imagine how it would have been possible for researchers to develop COVID-19 vaccines, for instance — estimated to have saved millions of lives since 2021 — without studies on live SARS-CoV-2 (and earlier work on SARS-CoV and MERS-CoV) in animal models.
Given the crisis of mistrust in science and institutions, and an increasingly fractured geopolitical world, unified international guidelines are crucial for protecting essential research involving dangerous viruses.
A global standard
Centralized, standardized guidelines would be analogous to the guidelines for research on human embryos produced by the International Society for Stem Cell Research (ISSCR) — an organization that includes investigators in more than 80 countries. They would be similar to national regulations for research on dangerous viruses, but on a global level. They could lay out what factors might make the use of a particular virus or approach high risk or what benefit-to-cost ratio might justify a research project being pursued or blocked, for example.
Some scenarios should not be allowed to happen. If an investigator is working on the H5N1 bird flu virus in a BSL-3 facility, for instance, they should take strict precautions to prevent viral strains that cause human seasonal flu from entering the facility, even though seasonal flu is not considered a dangerous virus. This is because strains of flu virus can exchange RNA fragments. Such exchange could make H5N1 more transmissible in humans.
