Lab leak hypothesis renews calls to restrict gain-of-function research

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Renewed public interest in whether the pandemic started with a Chinese laboratory experiment gone wrong has also thrown a spotlight on a controversial form of research that some experts say may not be worth the risk.

Known popularly as the innocuous-sounding gain of function, these kinds of studies involve enhancing a virus to make it more infectious to understand how it spreads better.

“This is a debate we’ve been having for 10 years,” Gregory Koblentz, director of the Biodefense Graduate Program at George Mason University, told the Washington Examiner. “Even though there’s new attention because of the purported relationship between research at Wuhan Institute of Virology and COVID-19, this is not a new issue.”

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A robust discussion within the scientific community over how to approach gain-of-function experiments emerged in 2012 when a group of scientists took a strain of the virus that causes bird flu and modified it to spread between mammals by respiratory drops.

The experiment raised ethical concerns among scientists who argued the risks may have far outstripped the possible benefits of creating a virus that, at the time, did not occur in nature and was not an active threat to humans.

“It is easily possible that this lab-engineered … strain would constitute a novel danger for humans if ever it escaped,” Simon Wain-Hobson, a French microbiologist, argued in a strongly worded paper at the time.

In 2014, dozens of scientists called on the Obama administration to halt gain-of-function research following a string of accidents in top labs across the United States involving deadly pathogens, including anthrax and smallpox.

“An accidental infection with any pathogen is concerning. But accident risks with newly created ‘potential pandemic pathogens’ raise grave new concerns,” wrote the group of scientists, who called themselves the Cambridge Working Group.

“Laboratory creation of highly transmissible, novel strains of dangerous viruses, especially but not limited to influenza, poses substantially increased risks. … An accidental infection in such a setting could trigger outbreaks that would be difficult or impossible to control,” they continued.

The U.S. government paused its funding for gain-of-function research in October 2014 amid public concerns, vowing to initiate a “deliberative process” to develop new rules for conducting future studies.

After years of discussion, the National Institutes of Health lifted the ban on funding gain-of-function research in December 2017 and imposed rules requiring a new layer of review for each experiment. But concerns remained among some scientists who thought the rules may not be sufficient.

“I still do not believe a compelling argument has been made for why these studies are necessary from a public health point-of-view; all we have heard is that there are certain narrow scientific questions that you can ask only with dangerous experiments,” Marc Lipsitch, a Harvard University epidemiologist, told the Lancet in 2017.

Koblentz noted the NIH’s rules in 2017 only applied to research funded by the Department of Health and Human Services. This left room for privately funded research at universities and other institutions, as well as studies funded by other parts of the government, to escape the more rigorous approval process.

“I definitely think there needs to be more oversight,” Koblentz said. “This policy really should apply to any lab in the U.S., whether it is funded by NIH or not, that is engaging in research that is designed to enhance the lethality or transmissibility of any pathogen.”

Republicans on Capitol Hill pushed to block U.S. funding to all gain-of-function research in China late last month. Sen. Rand Paul, a Kentucky Republican, successfully led the charge to pass a measure that would stop such studies — citing, among other things, the lack of transparency that Chinese authorities have provided investigators looking into conditions at the Wuhan lab.

Scientists at the Wuhan Institute of Virology have denied they were conducting gain-of-function studies in the months before the pandemic, and the NIH has denied that any of its financial support for Wuhan research was used for those types of experiments.

But skeptics have pointed to previous research by Dr. Shi Zhengli, the top coronavirus expert at the Wuhan lab, that involved experimenting with bat coronaviruses to argue China should share more information about what Shi and others were doing, given the remarkable coincidence a novel coronavirus sparked a pandemic so close to the location of the lab.

Koblentz said a key piece of information that NIH officials have not provided is how they evaluated Shi’s grant proposal in the context of the 2017 rules, given that some of her funding came through a U.S. research group called EcoHealth Alliance.

Other scientists believe the virus jumped from a bat population to humans near Wuhan, where wild animals such as bats were often sold in outdoor markets.

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Proponents of gain-of-function research argue it is necessary to stay ahead of the next pandemic. Other major outbreaks, such as SARS in 2003 and MERS in 2012, spread through human populations after viruses native to animals mutated enough to make the jump to people.

Without studying the mechanical changes behind such jumps, gain-of-function supporters say scientists may not be able to predict or control future viral outbreaks that emerge naturally.

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