How risky is 鈥榞ain of function鈥� research? Congress scrutinizes China.
| Washington
As questions mount over whether the COVID-19 pandemic could have started with a Chinese lab leak, members of Congress are shining a bright spotlight on controversial virus research often referred to as 鈥済ain of function.鈥澨�
Lawmakers are increasingly concerned that researchers who experiment with viruses in an effort to understand them and avert future pandemics could end up making them more lethal or transmissible to humans 鈥� potentially causing the types of outbreaks they听were seeking听to prevent. Members of Congress have especially focused on whether U.S. taxpayers funded such research in China.听
At the center of the spotlight is Dr. Zhengli Shi at the Wuhan Institute of Virology, who collaborated on U.S.-funded grants that involved听manipulating coronaviruses to understand their transmissibility to humans. She, her American colleagues, and听National Institute of Health (NIH) officials听have unequivocally rejected allegations that the work involved gain-of-function research or led to the outbreak of COVID-19, denouncing such claims as politicized misinformation.
Why We Wrote This
If a type of scientific research could prevent another pandemic, but also risk causing one if something goes wrong, is it worth it? Questions of scientific freedom, ethics, and public health are in the balance.
Scientists don鈥檛 agree on how exactly to define gain-of-function research, but generally it involves enhancing a pathogen to make it more virulent or transmissible.听Critics say the NIH is听using a narrow interpretation of听what counts as gain of function, and听has听not provided ample transparency into the grant review process for such research.听
Debate over听gain-of-function experiments involving viruses that could cause a pandemic was once largely confined to scientific journals, workshops, and advisory boards. But now, amid heightened concerns about biosafety, lawmakers see a need for greater oversight. A key ethical question is whether the benefits outweigh the risks, and if so, how scientific institutions and governments should best regulate it.
The issue came to a head last month when Republican senators led by Rand Paul of Kentucky grilled Dr.听Anthony听Fauci, director of NIH鈥檚 National Institute of Allergy and Infectious Diseases,听in a congressional hearing about the Wuhan lab鈥檚 U.S.-funded activities. Sen. Roger Marshall of Kansas compared a U.S.-China exchange of such knowledge, which could potentially be used for bioweapons, to working with the Soviet Union on nuclear technology. Two weeks later, Democrats joined Republicans in passing an amendment proposed by Senator Paul permanently banning U.S. funding of gain-of-function research in China, after which the Senate chamber erupted in cheers.
While the House and president would need to approve the measure for it to become law, the support in the Senate indicates lawmakers鈥� level of concern about such research and desire to establish guardrails. On June 22, Rep. Brad Wenstrup, an Ohio Republican, introduced to ban U.S. funding of gain-of-function research in nations considered U.S. adversaries.
But听scientists say it鈥檚 important for their community to take the lead so that the science is not left to Congress.
鈥淵ou can鈥檛 expect a legislative aide in the middle of the night to define the technical features of the kinds of risks we鈥檙e talking about here,鈥� says听David Relman,听a听professor of microbiology and immunology at Stanford University.
鈥淚鈥檓 worried that if we scientists 鈥� together with the NIH 鈥� don鈥檛 get out ahead of this, we鈥檙e going to have this legislated for us,鈥� he adds. 鈥淭he bottom line for me is that we haven鈥檛 pursued this sufficiently. Now would be a pretty good time to do this.鈥�
鈥淥ne of the most dangerous viruses you can make鈥�
In 2011,听an NIH-funded researcher in the Netherlands set off alarm bells with a paper describing how he had made,听, 鈥減robably one of the most dangerous viruses you can make鈥� by enhancing an avian flu virus in a way that made it more transmissible to mammals. Together with a similar NIH-funded study in Wisconsin, it triggered a debate about the risks of conducting such experiments and what could happen if that knowledge got into the wrong hands.听
The work was eventually听published, but a听听from a member of the advisory board that reviewed it raised concerns that the NIH was more focused on extracting itself from controversy听than resolving the underlying issues, a criticism the NIH听.
Several years later,听a series of safety lapses involving avian flu, smallpox, and anthrax听sparked fresh debate. In July 2014, the Cambridge Working Group, headed by Harvard听epidemiologist听Marc Lipsitch, called for experiments involving potential pandemic pathogens听听pending an assessment of the risks. A group calling themselves Scientists for Science pushed back with a听,听arguing that听such research was essential to preventing and treating disease, and听noting that significant resources had already been devoted to ensuring safety, including special lab facilities.
Some听scientists see additional restrictions as more of a hindrance than a protection, hampering academic freedom and potentially blocking scientific discoveries听they say could save lives. Also, absent an international framework involving certification and inspections, any domestic limits could create a competitive disadvantage for the U.S., both intellectually and commercially.听
鈥淲henever you talk about limiting scientific research or controlling scientific research, there are a lot of antibodies that come out,鈥� says听Andrew Weber, former assistant secretary of defense for nuclear, chemical, and biological threats under the Obama administration.听
But concerns were high enough听that, several months later,听the U.S. government put a moratorium on funding gain-of-function research involving influenza, MERS, and SARS, subject to a review period.听
The moratorium was lifted in 2017, and the Department of Health and Human Services (HHS) issued听 for research involving 鈥渆nhanced potential pandemic pathogens.鈥� Under the guidelines, the funding agency is supposed to flag听all grant proposals involving such research. Those flagged are then听subject to an HHS-managed review process that must consider whether the project is ethically justifiable, whether there are any alternative methods that would be less risky but 鈥渆qually efficacious,鈥� and if not, whether the potential benefits outweigh the risks.听
While oversight听proponents see HHS鈥檚 2017 framework as a step of progress,听concerns remain.听
Critics say funding agencies such as the NIH are essentially self-policing when deciding which proposals to flag for broader HHS review, and that the process is subjective and lacks transparency. Even some top experts don鈥檛 know the names and number of individuals on the HHS review committee, how they are appointed, or how they arrive at their decisions about whether proposed research could be 鈥渞easonably anticipated鈥� to create, transfer, or enhance pathogens that could cause a pandemic. There is no independent听biosafety authority outside the government departments听overseeing the research, which increasingly include other departments besides HHS, as well as private-sector actors.听
鈥淭he fact that we have no independent body that can say, 鈥楴IH, CDC, USDA 鈥� hey, don鈥檛 do this,鈥� is a problem,鈥� says Rocco Casagrande, managing director of Gryphon Scientific, which produced a听2015听report at the NIH鈥檚 request on the risks and benefits of gain-of-function research involving influenza, MERS, and SARS in U.S. labs. 鈥淭here鈥檚 no one that is without conflict of interest that can stop risky experiments.鈥�
The Wuhan Institute of Virology
Now, the debate over gain-of-function research and lab safety has gained new urgency over questions about the Wuhan Institute of Virology (WIV).听
Lawmakers and others are pressing for answers on the scope of WIV鈥檚 work with coronaviruses 鈥� particularly whether any of it could have enhanced their virulence or transmissibility, and if so, whether that work was funded by NIH. Growing circumstantial evidence, and particularly China鈥檚 unwillingness to release relevant information, has heightened suspicions that COVID-19 could have started with a leak from the Wuhan lab. So far, no evidence has emerged to definitively prove or disprove the lab leak hypothesis,听but a wide array of scientists and government officials now say it warrants investigation.听
A Trump State Department听听said the WIV had a track record of conducting gain-of-function research and听not being transparent about its work with viruses most similar to SARS-CoV-2, which causes COVID-19. It added that the WIV 鈥渉as engaged in classified research ... on behalf of the Chinese military since at least 2017.鈥澨齌he Biden administration has not walked back any of the fact sheet鈥檚 key assertions.
At the May 11 congressional hearing, Senator Paul questioned the wisdom of U.S. grant money funding collaboration with Chinese scientists on such research.听
鈥淵ou鈥檙e fooling with Mother Nature here. You鈥檙e allowing superviruses to be created,鈥� said Senator Paul听.
Dr. Fauci repeatedly and emphatically denied the senator鈥檚 assertions. 鈥淲ith all due respect, you are entirely incorrect,鈥� he said. 鈥淭he NIH has not ever and does not now fund gain-of-function research in that [Wuhan] institute.鈥澨�
Members of Congress say he is parsing words. They have requested documents that could provide more insight into the kind of work WIV was doing, such as the original grant proposal, but so far the NIH has not released them.听
In a written statement to the Monitor, the NIH said that pre-funding review of grant proposals is not made public 鈥渢o preserve confidentiality and to allow for candid critique and discussion.鈥澨�
鈥淰iruses do not respect borders鈥�
Critics such as Senator Paul have focused on Dr. Shi鈥檚 collaboration with two U.S. scientists: Ralph Baric听of the University of North Carolina at Chapel Hill (UNC), one of the world鈥檚 leading researchers on bat coronaviruses, and Peter Daszak of EcoHealth Alliance in New York, a nonprofit that seeks to prevent pandemics through its research.
In a U.S.-funded study published in 2015, Dr. Baric, using virus sequences provided by Dr. Shi, created a hybrid version of a bat coronavirus that showed the potential to infect humans. The NIH had approved the听, but it听听among some scientists. UNC鈥檚 School of Public Health said in emails to the Monitor that there was no gain of function and the hybrid virus was not sent to China.
Dr. Shi also collaborated听with Dr. Daszak鈥檚 nonprofit on an NIH-funded听听听that created hybrids between a virus which had previously been deemed as having the potential听to infect humans听鈥� and others with听unknown properties.
鈥淭o me, if you鈥檙e already starting with something that is poised for human emergence, you don鈥檛 go messing around with it 鈥� even if the chances of creating something bad are 1 in 100,鈥� says Stanford鈥檚 Dr. Relman.听
In written statements to the Monitor, EcoHealth Alliance and Dr. Baric defended their work as essential to preventing disease outbreaks and developing treatments and vaccines.听听
鈥淭here are many strains of viruses (including SARS-like听betacoronaviruses) that exist in nature, and if we are to develop a drug that is broadly effective against all or most of these strains, we must be able to test such a drug against various strains in the laboratory setting,鈥� said Dr. Baric. He says that his team鈥檚 early work enabled the U.S. to quickly find the first successful treatment for COVID-19 and contributed to the U.S. development of a vaccine.
Even with high safety standards in place,听lab leaks involving viruses have led to outbreaks.听
鈥淚n China, the last six known outbreaks of SARS-1 have been out of labs, including the last known outbreak, which was a pretty extensive outbreak that China initially wouldn鈥檛 disclose that it came out of lab,鈥� said Scott Gottlieb, the former commissioner of the Food and Drug Administration, 听He also noted that 鈥渕ishaps鈥� had occurred in U.S. labs.
From 2007-17,听there were听two dozen incidents and accidents at U.S. labs involving influenza, SARS, and MERS, according to documents obtained through the Freedom of Information Act by Lynn Klotz, a听senior science fellow at the Center for Arms Control and Non-Proliferation, and shared with the Monitor. Ten of those occurred at UNC Chapel Hill, all involving SARS听and featuring a range of scenarios,听including infected mice briefly escaping from a cabinet or a researcher鈥檚 hand.听
In a statement to the Monitor, the School of Public Health said that the听viruses were mouse-adapted strains that pose a lesser risk of infection to humans and that it notified the proper oversight agencies and took corrective action as needed.
鈥淭he University of North Carolina at Chapel Hill takes its responsibility as a leading global research institution seriously,鈥� the statement said. 鈥淐arolina鈥檚 researchers are committed to safety and operate under stringent biosafety and biosecurity procedures and practices.鈥澨�
However imperfect the U.S. biosafety system may be, experts note, the fact that it requires such reporting and corrective actions sets it apart from China.
鈥淭hat鈥檚 what we鈥檙e not seeing in China,鈥� notes Gregory Koblentz,听director of George Mason University鈥檚 Biodefense graduate program,听who is working on developing an international architecture for biosafety standards, certification, and inspections.听鈥淎nd that legitimately feeds concerns about this type of research, because we don鈥檛 see the same kind of mechanisms for reporting and accountability in the Chinese biosafety system as we see in the U.S. and other countries.鈥�听
Amid criticism that U.S. scientists shouldn鈥檛 be cooperating on such risky research with scientists working in China, EcoHealth Alliance stressed the need for a global approach to preventing future pandemics.
鈥淭o isolate ourselves from the rest of the world would be shortsighted,鈥� it said in its statement to the Monitor. 鈥淰iruses do not respect borders 鈥� truly effective research to听identify and characterize them necessarily involves international collaboration. This is exactly the work EcoHealth Alliance does.鈥�
Dr. Fauci also defended U.S. funding of WIV鈥檚 work on bat coronaviruses in a group Zoom call with reporters organized by the Nieman Foundation at Harvard, and said it would have been an abdication of responsibility for health officials not to study the place and animals where SARS originated.
鈥淵ou need to study bat-human interface in the setting where it occurs. That鈥檚 China. ... You don鈥檛 want to study bats in Fairfax, Virginia,鈥� he said on the June 8 call, while reiterating that the research NIH funded in the Wuhan lab had 鈥渘othing to do鈥� with the outbreak of COVID-19.听
鈥淗aving said that,鈥� Dr. Fauci added, 鈥渨e cannot account for everything that goes on in Chinese labs.鈥澨�
