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Flu Controversy Spurs Research Moratorium

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Science  27 Jan 2012:
Vol. 335, Issue 6067, pp. 387-389
DOI: 10.1126/science.335.6067.387
Taking a break.

Leading flu researchers will halt controversial studies involving H5N1 viruses (blue) for 2 months.

CREDIT: GETTY IMAGES/PHOTO RESEARCHERS

Stung by a growing global controversy over the potential dangers of experiments involving the H5N1 avian influenza virus—and worried about possible government regulation—a group of leading influenza researchers last week agreed to a 60-day moratorium on some sensitive flu studies “to provide time” for international discussions.

“We recognize that we and the rest of the scientific community need to clearly explain the benefits of this important research and the measures taken to minimize its possible risks,” the 39 researchers wrote in a statement published by Science and Nature (see p. 400). During the “voluntary pause,” the scientists—who represent the world's major H5N1 research centers—have agreed to halt several types of studies, including experiments that could create H5N1 viruses that move more easily between mammals.

Flu experts are also helping to organize a summit on the issue, to be hosted by the World Health Organization (WHO) in Geneva on 16–17 February, which is expected to involve about 50 experts. But “it's not going to be a simple one-meeting process,” says Keiji Fukuda, WHO's assistant director-general for health security and environment. “We don't want it to take forever, but [we] can't address all the issues at the same time.”

“Governments and organizations need time to react,” says virologist Ron Fouchier of Erasmus MC in Rotterdam, the Netherlands, who helped craft the agreement and is involved in the research that triggered the global debate (Science, 6 January, p. 20). Investigators on all sides of the controversy, meanwhile, welcomed the move, saying it will help ease tensions and clarify potential risks. But some question whether 2 months is enough time to resolve thorny conflicts between science and security or to institute national or international oversight. Biosecurity expert John Steinbruner of the University of Maryland, College Park, for instance, wonders whether governments can “do anything meaningful within the 60-day period. … What happens if they do not?” And one skeptic calls the moratorium “an empty gesture” designed to fend off stringent U.S. controls on research.

The announcement capped months of rising tension over two studies, in press at Science and Nature, which describe how researchers made the H5N1 virus more transmissible between ferrets, the animal model that most closely resembles humans in flu studies. The researchers say the work offers benefits for preventing flu pandemics, but others are worried that the studies could provide a blueprint for the creation of a bioweapon or lead to an accidental release of the virus. (Although H5N1 viruses readily kill entire chicken flocks and occasionally infect humans, they have not until now transmitted efficiently between mammals.)

In late December 2011, the U.S. National Science Advisory Board for Biosecurity (NSABB) announced that it had taken the unprecedented step of asking Fouchier, the lead author of the Science paper, and Nature lead author Yoshihiro Kawaoka of the University of Wisconsin, Madison, and the University of Tokyo to omit key details. The researchers and the journals reluctantly agreed, provided that the U.S. government, which funded the studies, came up with a way of sharing the details with “responsible” scientists and public health experts.

The deal sparked extensive criticism—with some scientists saying that redaction went too far, and others arguing that researchers should not have conducted the studies in the first place. It also set off shock waves in policymaking circles. In Washington, U.S. officials rapidly restarted a long-stalled process aimed at tightening oversight of so-called dual-use biological research. WHO, meanwhile, warned that the redactions could imperil a nascent global agreement to share flu viruses and the benefits of research on them. On 8 January, The New York Times weighed in with an editorial headlined “An Engineered Doomsday” that questioned the studies and called on scientists to destroy the new H5N1 variants in the name of safety.

Such high-profile attention prompted senior scientists at the U.S. National Institutes of Health (NIH) and elsewhere to warn flu researchers that the controversy could prompt government officials and lawmakers to impose onerous new rules on research. Others argued that the episode exposed the need to address troubling gaps in U.S. and global efforts to oversee research that could be used for good and evil. To give such issues a full hearing, a number of key players in the debate, including NSABB Chair Paul Keim, a microbiologist at Northern Arizona University in Flagstaff, floated the idea of a moratorium. But Keim advocated a stop only on publishing the results; flu scientists have gone much further by halting research. The pause is modeled in part on a landmark 1975 pact reached by scientists in the then-new field of recombinant DNA, who were also facing questions about safety. That moratorium led to a meeting in Asilomar, California, where scientists proposed safety guidelines for genetic engineering.

“I thought it would be a good idea for the investigators themselves to call for a time-out,” says Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, who discussed the idea at length with Fouchier. “I have concerns that people [who are] understandably concerned about security may put restrictions on important research that might go a little bit too far. We have to be extremely sensitive to safety and security, … but what I would not want to see is an overreaction.”

Fact checker.

WHO's Fukuda says a flu summit will help clarify issues.

CREDIT: COURTESY OF WHO

The announcement has drawn mostly positive reviews. “Anything that moves us toward a thoughtful and comprehensive discussion is really helpful,” says flu expert Michael Osterholm, a member of the NSABB and director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Twin Cities.

That view is also shared by an out spoken critic of NSABB's redaction request, virologist Vincent Racaniello of Columbia University. “A dialogue to identify the crucial issues and develop plans to address them, while continuing this important line of research, is certainly welcome,” he says. Indeed, 2 days before the moratorium announcement, Racaniello was one of 18 researchers who signed a letter to Osterholm and other NSABB members, asking them to reconsider its recommendation that the papers be redacted. Such a request “warrants pause and a rational discussion of the scientific facts.” The signers also included Eckard Wimmer of Stony Brook University in New York, the author of a controversial 2002 study that demonstrated how to assemble a synthetic poliovirus (Science, 9 August 2002, p. 1016), and NSABB critics Peter Palese and Adolfo García-Sastre of the Mount Sinai School of Medicine in New York City. (Both also signed the moratorium letter, and García-Sastre leads an NIAID-funded center that subcontracted for Fouchier's work.)

On the other side of the debate, smallpox expert Donald Henderson of the Center for Biosecurity at the University of Pittsburgh in Pennsylvania, who has backed NSABB's decision and criticized the studies, calls the moratorium “wise. … This has to be a societal decision,” and the pause will “provide an interval for [people] other than the laboratory scientists to weigh in,” including political and religious leaders.

Another vocal critic of the flu studies, however, is not impressed, calling the moratorium “pure PR.” It's telling, says Richard Ebright, a biologist at Rutgers University in Piscataway, New Jersey, and the Howard Hughes Medical Institute, that the researchers' statement emphasizes the safety and benefits of H5N1 research but “rejects, out of hand, the need for enhanced biosafety, biosecurity, and dual-use oversight.” If the researchers had proposed a moratorium that lasted until those issues were addressed, “it could be taken seriously,” he says. Without that, the letter “is strictly symbolic. An empty gesture.”

Ebright would like to see all research on H5N1 strains engineered to be transmissible among mammals halted until the WHO discussions produce stringent global controls, including limiting the total number of labs working with the strains to just two. He also supports the creation of a global oversight panel—similar to the WHO panel that oversees smallpox research—to review studies and ensure that experiments occur only under the most stringent safety conditions.

WHO's Fukuda, however, notes that “we are not a regulatory agency. We know we are not going to put out any regulatory framework.” Instead, he says a first step will be simply getting the facts. NSABB members haven't briefed WHO on their reasoning, he notes, and “my overall sense is that most people are pretty confused about what are all the issues. Most people are standing back to see if they should feel one way or another. … One country or research group doesn't reflect the concerns of others.”

Then, he says, he hopes the group will first tackle the most urgent issues, such as deciding how best to deal with potentially sensitive information in the papers. The journals have said that they will not publish the papers until that is resolved, and the U.S. government has reportedly asked to have until at least late February to figure it out. “The first thing I would tell everyone,” Fukuda says, is “convince me that [redacting the papers is] the only option out there. Let's talk about what's the nature of the sensitivity. … What are the concerns, what do we hope for in getting the information out, and then what are the options? We want to go in not prejudging any of the issues.”

One big concern will be how any information-sharing system might affect WHO's new Pandemic Influenza Preparedness (PIP) Framework, agreed to earlier this year after 4 years of often-acrimonious debate. The PIP, which stipulates that countries that provide virus samples should also receive at least some benefits of influenza research, such as vaccines, “is in a vulnerable period,” Fukuda says. “As we work through this quite complicated set of questions, we want to make sure … that the whole global system of providing viruses and sharing benefits doesn't take a pause.” The issue is especially sensitive, other researchers note, because WHO's global lab network provided the H5N1 isolates used by Fouchier and Kawaoka.

Fukuda says other questions may have to wait a bit longer for answers, such as: “How do we make sure we continue research but do it in a way that doesn't cause people and countries undue anxiety?” In the end, however, he is optimistic the group can reach consensus, noting that “at WHO we often deal with tough issues. … We can start the discussions and see how far we get. Starting with 60 days doesn't mean you can't do something afterwards that keeps the pressure down.”

Whether the moratorium and summit will reduce growing pressure for tighter research oversight in the United States, however, remains unclear. A multiagency group has restarted work on formalizing 2007 recommendations from NSABB on procedures for reviewing dual-use research, with a draft statement due sometime this spring. NIH has briefed staff members for several key lawmakers—including senators Joe Lieberman (I–CT) and Susan Collins (R–ME), the top members of the U.S. Senate Committee on Homeland Security and Governmental Affairs. So far, however, Congress has been notably silent on the controversy.

  • * With reporting by Martin Enserink, Gretchen Vogel, and Jon Cohen.

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