The search for answers about the origins of Covid-19 has focused global attention on a controversial corner of science that previously operated far from public view.
The work, known as “gain of function” research, involves manipulating pathogens, often to make them more lethal. Proponents argue it is vital for understanding how viruses behave and how they might become resistant to vaccines and treatments. Critics say the risk of one of the viruses escaping and leading to a pandemic is too great.
The debate is so fraught that former US president Barack Obama in 2014 stopped federal funding for gain of function research on Sars, Mers and flu viruses, while officials drew up stricter approval guidelines. The ban was lifted and new rules were finally put in place in 2017 by the Trump administration.
“If you are going to do an experiment that carries an appreciable risk of starting a new pandemic, there should be a very good public health justification for doing it,” explained Marc Lipsitch, professor of epidemiology at Harvard.
And yet gain of function research, or very similar work, continued after the ban at laboratories around the world, often with US funding, and most importantly at the facility now at the centre of the coronavirus origins debate: the Wuhan Institute of Virology.
A multinational group of 15 scientists working at the Wuhan Institute received $600,000 of US public funds between 2015 and 2020 to investigate whether bat coronaviruses posed a risk to humans, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told a US Senate hearing this week.
As part of the work, the team — including the renowned Chinese virologist Shi Zhengli, known as China’s “batwoman” — spliced together two different coronaviruses, creating a more dangerous version, which they found had the potential to infect humans, according to a 2015 paper the scientists published in the journal Nature.
Fauci on Tuesday denied that the experiments constituted gain of function research. However, the 2015 paper carried a stark warning: “Scientific review panels may deem similar studies building chimeric viruses based on circulating strains too risky to pursue.”
“These data and restrictions represent a crossroads of GOF [gain of function] research concerns,” the scientists wrote. “The potential to prepare for and mitigate future outbreaks must be weighed against the risk of creating more dangerous pathogens.”
The warning has taken on greater resonance since some scientists, still lacking definitive proof that Sars-Cov-2 jumped naturally to humans from bats or via an intermediate animal host, have refocused their attention on the possibility it leaked from the Wuhan Institute.
“We must take hypotheses about both natural and laboratory spillovers seriously until we have sufficient data,” a group of scientists including Ralph Baric, one of the authors of the 2015 paper, wrote in an open letter this month.
A World Health Organization investigation, facilitated by China, found earlier this year that it was “extremely unlikely” Sars-Cov-2 had leaked from a research facility. But the conclusion was challenged in March by countries including the US and the UK, and by Tedros Adhanom Ghebreyesus, director-general of the WHO, who said the investigation had not been “extensive enough”.
US president Joe Biden this week ordered his intelligence agencies to review the evidence for the lab leak hypothesis and come to a conclusion within 90 days. Chinese state media has repeatedly denied that a lab leak was possible and described the theory as a “conspiracy”.
The renewed attention has raised difficult questions for the US National Institutes of Health about its relationship with the Wuhan Institute and the research. Baric and the EcoHealth Alliance — a non-governmental group through which NIH channelled its funding — have, like Fauci, previously denied that their work at Wuhan constituted gain of function research, in part because it was not intended to increase infectiousness in humans.
Baric, NIH, the EcoHealthAlliance and the Wuhan Institute did not respond to requests for comment.
But however the NIH-funded work at Wuhan was classified, some experts, including Richard Ebright, a professor of chemical biology at Rutgers University, argue it should not have been done.
“Irrespective of whether the Covid-19 pandemic was a result of a lab leak, the very fact that such an outcome is plausible means this is a category of research we should not have been funding or helping to carry out,” Ebright said.
Ebright also questioned the security standards at the Wuhan facilities. In 2016, some of the scientists including Shi and the EcoHealth director, Peter Daszak, used the NIH funding to conduct experiments in Wuhan on live coronaviruses in a biosafety level 2 lab, according to published details of the work. BSL-2 facilities are usually used for work of only moderate risk, where researchers can experiment at open benches wearing only lab coats and gloves.
“If this work was happening, it should definitely not have been happening at BSL-2,” said Ebright. “That is roughly equivalent to a standard dentist office.”
China’s first biosafety level 4 lab, where the most high-risk biological work is undertaken, was opened at Wuhan in 2018. Daszak did not respond to a request to comment.
Ebright is not alone in his concerns. In 2018, American diplomats in China reportedly sent cables to Washington warning: “The new lab [at Wuhan] has a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory.”
While scientists say the world may never know for sure whether Covid-19 originated naturally or at the Wuhan lab, many believe that the pandemic has highlighted why such research should not have been taking place at all.
Milton Leitenberg, an expert in biological weapons at the University of Maryland, said: “Whatever we classify this work as, it should not have been taking place at the Wuhan Institute of Virology.”
Additional reporting by Yuan Yang and Nian Liu in Beijing