Just a “small subset” of studies that manipulate dangerous pathogens to give them new abilities pose potentially grave risks to the public, an expert advisory group to the U.S. government concludes in a new draft report released today. But the current patchwork of U.S. policies aimed at regulating such risky experiments “is not sufficient,” and “may require supplementation,” the report concludes. And it says there are still some so-called gain of function (GOF) experiments that may never justify the risk.
Some outside scientists, however, say the report’s apparent endorsement of greater government oversight of such studies may not be enough to ensure public safety. “As usual the devil is in the details,” Harvard University epidemiologist Marc Lipsitch wrote in an email to ScienceInsider. “I am pleased to see an acknowledgment that some experiments should not be done, but fear that the exaggerated perception of benefits, and the flaws in the existing processes to weigh risks and benefits, would together neutralize that acknowledgment into a de facto ‘anything goes’ approach.”
The 70-page document, released today by a working group of the National Science Advisory Board for Biosecurity (NSABB), is the latest contribution to a long-running debate over how best to regulate potentially risky research with infectious agents. Such studies are needed to develop treatments and vaccines, but accidental or intentional release of modified pathogens is always a risk.
That debate gained prominence in 2011, when two groups of researchers announced that in experiments seeking to understand what makes flu viruses spread, they had modified the deadly H5N1 avian influenza virus to make it transfer more readily between mammals. Some researchers opposed publication of the results, fearing they could aid bioterrorists, while others worried about the risks of a pandemic if such new viruses escaped from a lab. The controversy eventually led researchers around the world to voluntarily declare a 1-year moratorium on these GOF experiments.
The GOF work ultimately resumed, but the debate took a new turn in late 2014, when the U.S. government made the unprecedented decision to halt 18 U.S.-funded GOF studies that involved making the viruses responsible for influenza and newer diseases such as Middle East respiratory syndrome (MERS) or SARS more pathogenic or likely to spread among mammals. The National Institutes of Health (NIH) later exempted some of the studies from the funding ban, but government officials said it would remain in place while NSABB and the National Research Council (NRC) reviewed the risks and benefits of GOF studies.
That discussion began with an NRC meeting in December 2014 where all sides aired the issues. And earlier this year, NIH commissioned a private firm to conduct a risk-benefit analysis of GOF studies; that some 1000-page document was released earlier this month and is scheduled to be discussed at an NSABB meeting on 7-8 January in Bethesda, Maryland.
Risks and benefits
The draft report released today aims to inform and guide that discussion. It concludes that the risk-benefit report, conducted by Gryphon Scientific of Takoma Park, Maryland, is “[o]verall … comprehensive, objective and reasonable, and generally extensively documented.” The Gryphon report includes an examination of the probability of both lab accidents and security breaches, the draft report notes. After examining a number of scenarios, it concluded that “[o]nly a small fraction of laboratory accidents would result in a loss of containment; of those, only a small fraction would result in a laboratory acquired infection, and of those, only a fraction would spread throughout the surrounding community (or global population).”
The Gryphon report also suggests that some kinds of GOF experiments are not likely to pose significant risks to the public, the NSABB report notes. That category includes experiments aimed at improving the growth of influenza viruses for vaccines, and efforts to adapt human strains to animal models.
Still, the Gryphon analysis “has some weaknesses and limitations,” the NSABB working group concludes. Data on GOF risks are often sparse, it notes, and some analyses may “obscure significant risks associated with GOF studies.” For example, some scenarios compared the risks posed by potential manipulations of some human flu strains with the flu virus that caused a 1918 pandemic and killed millions of people. But using the 1918 flu as a yardstick could make even relatively lethal new flu strains seem tame by comparison, the report notes.
The risk-benefit study also highlighted potential gaps in the current patchwork of U.S. regulatory systems that have evolved over the past few decades to oversee risky research. Some pathogens are regulated as “select agents,” for instance, with work restricted to labs with certain security and safety systems. But others are covered by less stringent systems, and GOF studies involving a few—including the MERS virus and seasonal influenza viruses—don’t appear to fall neatly into any single regulatory scheme. “Oversight policies vary in scope and applicability, therefore, current oversight is not sufficient for all GOF studies that raise concern,” the NSABB draft concludes.
Is it "of concern?"
To reduce any risks, the draft report proposes a multistep approach to evaluating GOF studies before they are funded. In the first step, reviewers would determine whether a GOF study meets three criteria that would make it “of concern” and in need of special evaluation. The pathogen a researcher aims to create would have to be “highly transmissible” and “significantly virulent” in a relevant mammalian model, “likely resistant” to existing treatments, and more “capable” of spreading in human populations than existing strains.
GOF studies determined to be potentially problematic would then undergo a review that considers seven criteria. Reviewers would determine whether the study was “scientifically meritorious,” for example, and whether the benefits outweighed the risks. They’d also examine whether the sponsoring institution could carry out the study safely, and whether there were safer alternatives for gaining the same knowledge. “Proposals not meeting these criteria should not be funded,” the NSABB proposal states. In a final step, funded studies would be routinely revisited and reviewed by the sponsoring institution and federal funding agencies.
That framework, and the many other issues raised in the draft report, are likely to draw extensive comment at the upcoming NSABB meeting. Lipsitch, who helped catalyze the current moratorium on U.S.-funded GOF research because of concerns about biosafety, says he’s still absorbing the document. But his first take is that NSABB and Gryphon “accept very credulously the unvalidated statements by those who do and fund GOF of concern studies that these studies offer unique practical benefits … [T]he NSABB draft report seems to show much more optimism than I think is warranted that existing structures can take care of the issue. If that were the case there would have been no need for the funding pause.”
With reporting by Jon Cohen. Background material drawn from prior reporting by Jocelyn Kaiser.