8 Feb 2019 ByJocelyn Kaiser Two “gain of function” projects halted more than 4 years ago have passed new U.S. review process.
Controversial lab studies that modify bird flu viruses in ways that could make them more risky to humans will soon resume after being on hold for more than 4 years. ScienceInsider has learned that last year, a U.S. government review panel quietly approved experiments proposed by two labs that were previously considered so dangerous that federal officials had imposed an unusual top-down moratorium on such research.
One of the projects has already received funding from the National Institutes of Health's (NIH's) National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, and will start in a few weeks; the other is awaiting funding.
The outcome may not satisfy scientists who believe certain studies that aim to make pathogens more potent or more likely to spread in mammals are so risky they should be limited or even banned. Some are upset because the government's review will not be made public. "After a deliberative process that cost $1 million for [a consultant's] external study and consumed countless weeks and months of time for many scientists, we are now being asked to trust a completely opaque process where the outcome is to permit the continuation of dangerous experiments," says Harvard University epidemiologist Marc Lipsitch.
One of the investigators leading the studies, however, says he's happy he can resume his experiments. "We are glad the United States government weighed the risks and benefits … and developed new oversight mechanisms. We know that it does carry risks. We also believe it is important work to protect human health," says Yoshihiro Kawaoka of the University of Wisconsin in Madison and the University of Tokyo. The other group that got the green light is led by Ron Fouchier at Erasmus University Medical Center in Rotterdam, the Netherlands.
In 2011, Fouchier and Kawaoka alarmed the world by revealing they had separately modified the deadly avian H5N1 influenza virus so that it spread between ferrets. Advocates of such gain of function (GOF) studies say they can help public health experts better understand how viruses might spread and plan for pandemics. But by enabling the bird virus to more easily spread among mammals, the experiments also raised fears that the pathogen could jump to humans. And critics of the work worried that such a souped-up virus could spark a pandemic if it escaped from a lab or was intentionally released by a bioterrorist. After extensive discussion about whether the two studies should even be published (they ultimately were) and a voluntary moratorium by the two labs, the experiments resumed in 2013 under new U.S. oversight rules. Scientists Yoshihiro Kawaoka and Ron Fouchier stand together.
Yoshihiro Kawaoka (left) and Ron Fouchier (right) in 2012, after their work with H5N1 bird flu virus sparked a global controversy over research that can potentially make pathogens more dangerous to humans.Martin Enserink/Science
But concerns reignited after more papers and a series of accidents at federal biocontainment labs. In October 2014, U.S. officials announced an unprecedented "pause" on funding for 18 GOF studies involving influenza or the Middle East respiratory syndrome or severe acute respiratory syndrome viruses. (About half were later allowed to continue because the work didn't fit the definition or was deemed essential to public health.)
There followed two National Academy of Sciences workshops, recommendations from a federal advisory board, and a new U.S. policy for evaluating proposed studies involving "enhanced potential pandemic pathogens" (known as ePPPs). In December 2017, NIH lifted the funding pause and invited new GOF proposals that would be reviewed by a committee with wide-ranging expertise drawn from the Department of Health and Human Services (HHS) in Washington, D.C., and other federal agencies.
Now, the HHS committee has approved the same type of work in the Kawaoka and Fouchier labs that set off the furor 8 years ago. Last summer, the committee reviewed the projects and made recommendations about risk-benefit analyses, safety measures to avoid exposures, and communications plans, an HHS spokesperson says.
After the investigators revised their plans, the HHS committee recommended that they proceed. Kawaoka learned from NIH on 10 January that his grant has been funded. Fouchier expects the agency may hold off on making a funding decision until after a routine U.S. inspection of his lab in March.
Kawaoka's grant is the same one on H5N1 that was paused in 2014. It includes identifying mutations in H5N1 that allow it to be transmitted by respiratory droplets in ferrets. He shared a list of reporting requirements that appear to reflect the new HHS review criteria. For example, he must immediately notify NIAID if he identifies an H5N1 strain that is both able to spread via respiratory droplets in ferrets and is highly pathogenic, or if he develops an EPPP that is resistant to antiviral drugs. Under the HHS framework, his grant now specifies reporting timelines and who he must notify at the NIAID and his university.
Fouchier's proposed projects are part of a contract led by virologists at the Icahn School of Medicine at Mount Sinai in New York City (most of Project 5, Aim 3.1, and Project 6 in this letter). They include identifying molecular changes that make flu viruses more virulent and mutations that emerge when H5N1 is passaged through ferrets. The HHS panel did not ask that any proposed experiments be removed or modified. Suggestions included clarifying how his team will monitor workers for possible exposures and justifying the strains they plan to work with, which include H7N9 viruses, Fouchier says.
HHS cannot make the panel's reviews public because they contain proprietary and grant competition information, says the spokesperson. But critics say that isn't acceptable. "Details regarding the decision to approve and fund this work should be made transparent," says Thomas Inglesby, director of Center for Health Security of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. The lack of openness "is disturbing. And indefensible," says microbiologist Richard Ebright of Rutgers University in Piscataway, New Jersey. The critics say the HHS panel should at least publicly explain why it thought the same questions could not be answered using safer alternative methods.
One researcher who has sympathized with both sides in the debate finds the safety conditions imposed on Kawaoka reassuring. "That list… makes a lot of sense," says virologist Michael Imperiale of the University of Michigan in Ann Arbor. "At this point I'm willing to trust the system."
Click here and here to read more of our reporting on the H5N1 controversy.
*Clarification, 9 February, 10:30 a.m.: This story has been updated to clarify that one goal of the controversial experiments is to make the H5N1 virus transmissible in mammals (often ferrets), not humans.