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 this kind of research.
One of the projects has already received funding from the National Institutes of Health (NIH)’s National Institute of Allergy and Infectious Diseases (NIAID) and will start in a few weeks; the other is awaiting funding.
The outcome may not satisfy scientists who believe that certain studies that aim to make pathogens more potent or likely to spread in people are so risky that they should be limited or even banned.
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 Yoshi Kawaoka of the University of Wisconsin, Madison, and University of Tokyo. The other group that has gotten a green light is led by Ronald Fouchier at Erasmus Medical Center in Rotterdam, the Netherlands.
In 2011, Fouchier and Kawaoka alarmed the world by revealing that 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 be published (they ultimately were), and a voluntary moratorium by the labs, the two labs’ experiments resumed in 2013 under new U.S. oversight rules.
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 MERs or SARS 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” or ePPPs. In December 2017, NIH lifted the funding pause and invited new GOF proposals that would be reviewed by an HHS committee with wide-ranging expertise drawn from the Department of Health and Human Services (HHS) and other federal agencies.
Now, the HHS committee has approved the same 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. (She said the agency cannot make the reviews public because they contain proprietary and grant competition information.)
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 be holding off on making a 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.
Fouchier’s proposed projects are part of a contract led by virologists at Mt. Sinai School of Medicine in New York City (most of Projects 5, Aim 3.1 and and Project 6 in this letter). They include identifying molecular changes that make H5N1 more virulent and mutations that emerge when it 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.
This story will be updated.
Click here and here to read more of our reporting on the H5N1 controversy.