Summary List Placement
In January 2020, an obscure government panel met at the Hyatt Regency in Bethesda, Maryland, to discuss a branch of virology known as “gain of function.” The goal of such research is to take infectious diseases — including the viruses that can cause pandemics — and alter them in ways that make them deadlier or more transmissible, in the hope of getting a jump on outbreaks. It was two days after the United States had its first confirmed case of COVID-19, but the empty seats in the Hyatt conference room were due to lack of interest, not social distancing.
The gathering “couldn’t be more timely,” said David Christian Hassell, a career official at the Department of Health and Human Services, as he began loading slides for his presentation. “We’re seeing this virus reassort and mutate as it spreads. It’s just pointing out the need for doing this kind of work.”
In fact, many critics would soon be pointing to the COVID pandemic as the ultimate proof that gain-of-function research needs to be shut down. At the time, the virus was still widely viewed as a problem confined to China, where it originated. Later, as the US went into lockdown, President Trump would try to rebrand the pandemic as the “China virus.” The city of Wuhan was home to a laboratory conducting “experimental investigations” into what it called the “origin, diversity, capacity to cause illness, and risk of spillover” from bat coronaviruses. If an altered virus escaped from the lab, then gain-of-function research might have accidentally caused the very sort of pandemic it’s intended to prevent.
Trump’s national-security adviser accused the Chinese government of engaging in a “cover-up” of what happened in Wuhan. But as the meeting in Bethesda demonstrated, the Chinese have nothing on the US when it comes to keeping secrets about dangerous viral research.
Discussion at the meeting focused on the government committee that recommends which studies get funded — and which are too dangerous to perform. Its formal name is the P3CO Review Group. The group is cloaked in an opacity even more impenetrable than the one surrounding the military’s drone-strike program or FISA’s wiretapping court. Until that morning at the Hyatt, when Hassell identified himself as chair of P3CO, no one beyond a handful of officials knew who served on the panel. Only federal employees are permitted to take part in its proceedings, which are kept confidential; neither academia nor industry is represented. Even as Trump accused the Chinese of a cover-up, Americans had no way of knowing what their own government was doing to protect them from some of the riskiest science since the development of the atomic bomb.
“This lack of transparency is unacceptable,” two scientists from Harvard and Johns Hopkins argued in The Washington Post. “Making decisions to approve potentially dangerous research in secret betrays the government’s responsibility to inform and involve the public when approving endeavors, whether scientific or otherwise, that could put health and lives at risk.”
Officials insist that the near-total secrecy surrounding P3CO is necessary “to preserve confidentiality and to allow for candid critique and discussion of individual proposals.” A spokesperson for Health and Human Services told Insider that the review group meets “as needed,” and that its membership varies depending on the proposal under review.
At the Hyatt meeting, which was prompted by scientists sounding the alarm over the apocalyptic risks of gain-of-function studies, Hassell said he was open to broadening P3CO’s authority and defended the integrity of its process. “This isn’t some rubber-stamp group,” Hassell said. “Right now, you don’t see evidence of that. But it is a very tough group.”
At the moment, unfortunately, we have little choice but to take Hassell’s word for it. What we do know is that the group weighed in on — and approved — at least one gain-of-function study conducted on American soil. The research, which took place at the University of Wisconsin-Madison in 2019, sought to make the deadly H5N1 bird flu transmissible between mammals. Another study, conducted at the University of North Carolina at Chapel Hill in 2015, created a new “chimeric” hybrid that combined elements from bat and mouse coronaviruses.
We may never know for certain how the coronavirus made the jump from animals to humans. But even the slightest possibility of a lab leak should be worrisome enough to warrant a hard look at whether the benefits of gain-of-function research outweigh the risks, and who gets to make the call about which experiments move forward. Billions of people, after all, would suffer if a risky experiment inadvertently starts the next pandemic. “It is unethical to put the general public at risk,” David Relman, a microbiologist at Stanford, said in a Nature roundtable, “and then minimize inclusion of the public in discussions about the appropriateness and oversight of such research.”
There’s no question that tinkering with infectious diseases in the lab has saved lives. It was passing the yellow-fever virus through chicken cells, for example, that enabled researchers to create a vaccine for humans. And herpes viruses have been altered in the lab to create a treatment for cancer. Today, according to one of the funders of the Wuhan bat studies, hybrid viruses developed in the lab were used as reagents to test possible vaccines.
Michael Imperiale, a professor of microbiology and immunology at the University of Michigan, says that gain-of-function studies have made important contributions to biomedical research. The studies on H5N1 bird flu, he told me, provided vital insights into protein changes that could allow for human-to-human transmission. “The better we get at making these kinds of correlations,” he said, “the further ahead we’ll be in the game of anticipating dangerous pathogens.”
There aren’t many scientists who conduct gain-of-function research. “It’s a very small part of virology,” Richard Ebright, a critic of gain-of-function research who teaches molecular biology at Rutgers University, told me. “Less than 1%.” And it would be wrong to suggest that biomedical research as a whole is unregulated. The federal government has a number of regulations that cover the conduct of scientific research, including special rules for 67 “select agents and toxins.” Among them is SARS-CoV-2, the virus that causes COVID-19.
But what biomedicine lacks is anything approaching a consensus about risk. The potential dangers of gain-of-function research were apparent long before the events in Wuhan drew attention to them. One comprehensive survey found that over a period of 75 years, there were 1,267 documented cases of “laboratory-acquired infections,” or LAIs, caused by exposure to the kind of pathogens used in gain-of-function experiments, which resulted in 22 deaths. Infections by the deadliest agents in high-security labs appear to be far less frequent — there were only 11 self-reported LAIs over a period of seven years.
There is sharp disagreement among scientists about the risk that a deadly gain-of-function pathogen could escape from a lab. Marc Lipsitch, a professor of epidemiology at Harvard, has estimated that it would take only one year of experimenting on a flu virus to put the risk of infecting a single person at 1 in 1,000. But Ron Fouchier, who induced mutations in H5N1 avian flu to make it transmissible between ferrets, calculated that under the safety measures in his own lab, it would take a million years of research to infect a single person — and 33 billion years before an infected lab worker spread the disease to others. “This probability,” he wrote, “could be assigned the term ‘negligible,’ given that the age of our planet is only 5 billion years.”
Whatever the overall risks, there have already been some close calls. In 2014, fears of a lab-spawned pandemic, along with the Ebola outbreak in West Africa, spurred the Obama administration to impose a two-year moratorium on government funding for gain-of-function studies. Unsecured vials of smallpox from the 1950s turned up in a storage room at the Centers for Disease Control. In another incident, the CDC mistakenly sent samples of the virulent H5N1 flu to a lab in Athens, Georgia. And in a third mishap, as many as 75 CDC employees were accidentally exposed to anthrax when they handled samples they thought were inactive.
While none of the incidents involved gain-of-function studies, they underscore the risks inherent to cutting-edge biomedical research and the difficulty of solving for human error. At the time the moratorium was imposed, 19 studies identified as possible gain-of-function research were underway in 11 states. Health and Human Services set about devising a framework for evaluating the risks, which led to the establishment of the P3CO review group.
But even after the moratorium was lifted in 2017, the lab accidents kept coming. In 2019, the CDC briefly shut down the Pentagon’s biodefense lab at Fort Detrick after numerous containment failures. And in April 2020, as the nation went into lockdown, a scientist at the University of North Carolina in Chapel Hill was forced to self-quarantine for two weeks after being bitten by a mouse that had been infected with a strain of the virus that causes COVID-19. Research at UNC — some of which was carried out with the assistance of Shi Zhengli, who led the experiments on bat coronaviruses at the Wuhan Institute of Virology — resulted in four incidents of potential human exposure to SARS coronaviruses. UNC confirmed to ProPublica that the viruses had been created in a lab.
Ralph Baric, who helped lead the UNC research, has denied that it involved gain of function. Zhengli, meanwhile, told The New York Times that the Wuhan lab “never conducted or cooperated in conducting GOF experiments that enhance the virulence of viruses.” (She did not comment on whether the lab was trying to enhance the transmissibility of viruses, which is another key criterion for gain of function.) Dr. Anthony Fauci and the National Institute of Health, which provided funding for the Wuhan experiments, also insisted that the work did not involve any gain-of-function research. The study was “subjected to rigorous peer review and was judged to be very high priority, given how SARS-CoV had already emerged in this bat population,” an NIH spokesperson told Insider.
Experts I spoke with were skeptical of the NIH’s claim that the Wuhan study didn’t involve gain of function, noting that the term is subject to competing definitions. But when it comes to oversight, the NIH’s definition — which is extremely narrow — is the one that counts. The agency told The Washington Post that the Wuhan study was determined to be “outside the scope” of oversight by the P3CO committee.
It’s a telling admission: What turned out to be one of the most controversial and perhaps consequential experiments in history was deemed not to require government oversight. As a result, the grant proposal was never even passed along to the P3CO review group. And there’s no way to know the reasoning behind the decision, or the identities of the officials who made it.
Made in the USA
After much obstruction and foot dragging, most scientists now agree that there is a need to investigate what happened in Wuhan. At the end of May, President Biden ordered the intelligence community to conduct a 90-day review of what they know about COVID-19’s origin.
It’s possible, of course, that the lab-leak scenario will turn out to be wrong. If, as many scientists believe, the virus had a natural origin, then the Wuhan lab — now vilified by everyone from Mike Pompeo to Jon Stewart — was actually conducting critical, prescient research into a soon-to-emerge disease. The lab would be held up as a shining example of the need for gain-of-function research, which proponents view as the last line of defense in humanity’s arms race against nature. Unless we know what could be headed our way, they argue, we won’t have enough time to stop it.
But the relentless focus on China-based research, and what may have gone wrong there, misses a deeper and more disturbing truth. The vast majority of virology — including the Wuhan study and other gain-of-function research conducted outside the US — is supported by American funding. The training, ethical guidelines, and standards for bioscience adhered to by top researchers worldwide are dominated by US institutions. If it becomes demonstrably true that a cutting-edge laboratory caused a pandemic, either now or in the future, America would deserve the blame, regardless of which country happens to be hosting those experiments. And much like the international regulatory regime around nuclear weapons, any effort to create an independent authority capable of overseeing dangerous biomedical experiments would need to be spearheaded by the US.
At the moment, though, we have no way of knowing the number or nature of studies working to change viruses in ways that could lead to the deaths of millions. Even more striking, the public has no way to know who is responsible for reviewing those studies, or how they are making their decisions about funding. Regardless of how COVID-19 emerged, we are being kept in the dark about scientific work that seeks, as its primary objective, to make the most frightening diseases more frightening.
“Everyone on earth has now experienced a pandemic in their lifetimes,” Ebright told me. “Nobody wants to see another. If there’s even a possibility that this category of work caused this pandemic, or could result in the next pandemic, then it needs to be regulated.”