Researchers tinker with bird flu: Are enough safeguards in place?

A new study and one to be published soon on Asian bird flu have prompted debate about safeguards during research and how much access others should have to research details.

A new study involving a genetically modified flu virus has put a spotlight on calls for tighter international oversight of biomedical research whose bugs pose a high risk of global disease outbreak if released accidentally, by terrorists, or by a rogue individual.

It's one of two such studies – the second to be published soon – that have been at the center of a debate over how heavily to censor research results to avoid publishing details that could make it easier for individuals or countries to increase a virus's ability to spread among organisms it currently can't infect.

The study aimed to answer the question: How radically would a virus that scientists have linked to Asian bird flu need to evolve in order to readily spread among humans, something it rarely does now? To answer the question, the scientists genetically modified the virus until they hit on a combination of changes that could enable it to spread readily among ferrets – a lab stand-in for humans.

A team led by University of Wisconsin virologist Yoshihiro Kawaoka found that only four changes to the virus's genetic makeup give it the traits to spread among ferrets.

The virus's potential for spread among humans is of keen interest to public-health officials. Since 2003, the World Health Organization has recorded 600 cases involving the Asian bird flu virus in humans. While the number is small, of those cases, nearly 60 percent were fatal, according to the WHO data.

With such a high fatality rate, researchers and public-health officials are concerned that if the virus mutates, the consequences could eclipse those of a global flu pandemic in 1918, a touchstone event in the annals of infectious disease. The pandemic is estimated to have killed between 20 million and 50 million people worldwide, according to the Centers for Disease Control and Prevention in Atlanta.

Understanding the potential for such genetic mutations in the virus, which can evolve rapidly, could help scientists spot a more virulent form early and point to vaccines and other treatments tailored to halt its spread, the study's researchers say.

Dr. Kawaoka's team worked with a lab-created hybrid version of the virus. None of the ferrets affected died. Even so, the genetic changes that appear to ease its spread could plausibly appear in strains outside the lab, other researchers say.

The formal report on the results appears in Thursday's issue of the journal Nature. A second research paper on the topic, from a team led by Ron Fouchier, a scientist at the Erasmus Medical Center in Rotterdam, Netherlands, is slated for publication in an upcoming issue of the journal Science. Dr. Fouchier's team reportedly has used the original virus for its experiments, instead of a hybrid.

Much of the debate surrounding the papers has focused less on whether such work should be done and more on safeguards during the work and access to the details.

After reviewing drafts of the papers last fall that the two teams aimed to publish, the US National Science Advisory Board for Biosecurity (NSABB) recommended last December that the papers be published, but with key details removed to make it harder to use the information to turn the virus into a weapon. At the end of March, the board reversed its recommendation after a panel of experts convened by the World Health Organization reviewed the studies and supported the global public-health case for publishing the papers in their full form. Also, the teams revised their papers to clarify points, including biosafety measures that the researchers used to guard against accidental release.

Discussions about adequate oversight of research into contagious diseases with the potential for global reach in the post 9/11 era have been “perking along, but nothing has happened," says Lynn Klotz, senior science fellow with the Center for Arms Control and Non-Proliferation in Washington. Meanwhile, the research itself has moved ahead.

“The truth of the matter is that we never hear about these things” until the research “is done and published,” he says.

At the end of March, the US government adopted policies to more closely monitor “dual use research of concern” involving 15 organisms or toxins that are deemed to pose the greatest potential threat to people or economic sectors such as agriculture. But those policies apply only to studies that the federal government conducts or funds.

While terrorism remains a concern, Dr. Klotz and others argue that accidental release poses the more significant immediate risk.

Testifying April 26 before the Senate Committee on Homeland Security and Governmental Affairs, Tom Inglesby, director of the Center for Biosecurity of the University of Pittsburgh Medical Center, noted that in 2004, when memories of the SARS outbreak were still fresh, researchers at three labs in Asia inadvertently infected themselves with that virus. In one case, he told the panel, the researcher passed the virus along to others outside the lab, which had many layers of biosecurity measures to prevent organisms from escaping.

“Clearly, mistakes are made and accidents happen, even at high-containment labs during times of extraordinarily heightened awareness and caution,” he said.

The work done on Asian bird flu “is of scientific interest,” Klotz acknowledges. “But since the potential of pandemic would be so horrific, it's a scientific interest that shouldn't be pursued except under the most extreme safety conditions.”

For instance, Klotz argues for designing high-biosecurity lab facilities with a space-station-like approach to staffing. Scientists conducting the research would rely on teams of highly trained, well-paid technicians working at a lab for two to three weeks at a time before rotating out. At the end of a research stint, the outgoing team would remain in quarantine inside the facility for another week to ensure they are not inadvertently carrying the organisms they were working with.

Given the global nature of a pandemic, John Steinbruner, director of the University of Maryland's Center for International and Security Studies at Maryland, calls for the World Health Organization to regulate research into the pathogens that scientists have deemed the deadliest. He cites WHO oversight of smallpox research as an example already under way. Only two labs in the world – one in the United States, the other in Russia – are sanctioned to conduct the research.

Dr. Steinbruner's approach calls for an international panel of scientists that would approve research proposals, identify the people who should have full access to the methods and results, and “hold those vetted individuals accountable for what they do with the information,” he wrote in Nature in January, as the debate over the initial NSABB recommendations heated up.

“We really do need to bring research on potential pandemic pathogens under international monitoring, and there probably should only be two or three labs in the world that do this kind of stuff,” Klotz says.