Deadly bird flu may be five steps from pandemic, study finds

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Five genetic tweaks made a deadly strain of bird flu that can infect humans spread more easily, according to a study that the US government had first sought to censor on concerns it could be used by bioterrorists.

The genetic changes made the H5N1 virus airborne among ferrets, the mammals whose response to flu is most like that of humans, researchers from the Netherlands wrote in the journal Science yesterday. The likelihood of those changes occurring naturally is difficult to estimate but there is "no fundamental hurdle to that happening," said Derek Smith, a University of Cambridge researcher who led a second study.

Scientists have been monitoring for pandemic-inducing changes in H5N1 since the strain was recovered from a farmed goose in China's southern province of Guangdong in 1996. The virus has since spread across Asia, Europe, the Middle East and parts of Africa, devastating poultry flocks and causing sporadic infections in people, among whom it doesn't efficiently transmit.

"We now know that we're living on a fault line," Smith said on a conference call with reporters. "It's an active fault line, it really could do something, and now what we need to know is, how likely is that?"

Publication of the paper was delayed after a U.S. biosecurity panel in December asked the scientists to censor some parts of their work to prevent it being used by bioterrorists. Researchers meeting at the World Health Organization in February agreed the full findings should be published to help scientists design vaccines and drugs, and public health officials prepare for a pandemic.

Mixing viruses

More than 600 people have been infected with H5N1 since 2003, and almost 60 percent have died, according to the Geneva- based WHO. Most had direct contact with infected poultry, prompting scientists to question what it would take for the virus to become easily transmissible between humans.

While influenza viruses mutate constantly in a process called antigenic drift, the flu pandemics of the past century, including the 1918 Spanish flu that killed as many as 50 million people, have all been triggered by so-called antigenic shift, the mixing of human and animal flu viruses to create new pathogens to which people have no pre-existing immunity.

Scientists led by Ron Fouchier at Erasmus Medical Center in Rotterdam set out to test whether H5N1 could become more transmissible by antigenic drift alone. The answer: yes.

Infected ferrets

Fouchier and colleagues examined mutations in viruses responsible for previous flu pandemics, and made three such changes to a strain of H5N1 from Indonesia, the country with the most cases and deaths, which they used to infect a ferret. They later took swabs from its nose and throat and used that to infect another ferret, and so on up to 10 animals, to see how the virus evolved.

Sure enough, it developed the ability to replicate in the animals' respiratory tract, suggesting the potential for airborne transmission.

The researchers then put the virus to the test by putting the infected animals next to healthy ferrets in neighboring cages. Six out of eight of the healthy ferrets became infected.

In addition to the three genetic changes introduced by the scientists, they identified two other mutations that enabled the virus to spread, the researchers wrote. Those mutations are now the subject of further research.

The five changes have all been observed in nature, but not in the same virus, they wrote. The mutant viruses were susceptible to Roche Holding AG's antiviral drug Tamiflu.

A similar study led by Yoshihiro Kawaoka at the University of Wisconsin at Madison, which was also delayed, was published in the journal Nature in May. That showed how H5N1 could become highly transmissible by mixing with the H1N1 virus that sparked the 2009 swine flu pandemic.

'Wrong hands'

The two groups agreed in December to suspend their work for 60 days after the US National Science Advisory Board for Biosecurity asked two journals to censor some details of the work to ensure it wouldn't "fall into the wrong hands."

The controversy over the studies triggered a new US government policy for conducting or funding research that could potentially be used for harm, Anthony S. Fauci, the director of the US National Institute of Allergy and Infectious Diseases, and Francis S. Collins, the director of the US National Institutes of Health, wrote in an accompanying article.

"˜Nefarious use'

The benefits of the research "far outweigh the risks of the nefarious use of this information," Fauci said on the conference call. "Being in the free and open literature would make it much more easy to get a lot of the good guys involved than the risk of getting the rare bad guy involved."

Other pathogens studied by scientists are more transmissible and deadlier than H5N1, Fouchier said.

"Anyone with access to the scientific literature can read about all the dangerous pathogens that are more interesting to terrorize the world with than our particular virus," he said on the conference call.

A moratorium on the research will remain in place until the conditions under which the work is done are assessed by authorities, Fouchier said.

The research was funded by the National Institutes of Health.

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