Nature publishes details of bird flu strain that could spread among people
Publication of bird flu study was delayed after warnings that the information could be exploited by terrorists
Controversial research on a hybrid strain of bird flu that could potentially spread between humans was published on Wednesday in Nature after security restrictions on the work were lifted.
Scientists created the virus by merging a mutated strain of bird flu with the "swine flu" virus that sparked a human pandemic in 2009. The hybrid strain spread easily between ferrets the best proxy that flu researchers have for people but was not lethal and could be controlled with antiviral drugs and bird flu vaccines.
The work by Yoshihiro Kawaoka at the University of Wisconsin-Madison was submitted last year to the journal, but was delayed after the US government's biosecurity advisers said key sections of the paper should be struck out to prevent the details being exploited by bioterrorists.
The US National Science Advisory Board for Biosecurity (NSABB) raised similar concerns over a second paper, in which Ron Fouchier at Erasmus Medical Centre in Rotterdam made a mutant strain of bird flu that also spread in ferrets. That article was submitted to the US journal Science.
The intervention of the NSABB led to months of debate among scientists, journal editors and government officials over the risks of publishing the papers. The scientists argued that their work addressed a major unknown factor about bird flu namely whether it could evolve in the wild into a strain that spread easily among humans.
Bird flu was first noticed in poultry more than 1! 6 years ago. The virus rarely infects people, but when it does it can cause serious illness and death. More than half of the 600 or so people known to have caught the virus have died from the infection.
At the end of March the NSABB held a second meeting, which included presentations from US security officials. The advisory panel later approved publication of Kawaoka's paper in full, and voted 12 to 6 in favour of publishing the Dutch research.
Working in a high-security lab, Kawaoka's FBI-screened team created thousands of mutated forms of the H5N1 bird flu virus. From these they selected a mutant able to stick to cells in the human nose and throat. Bird flu usually sticks only to cells deep in the lung, which makes the infections serious but almost impossible to spread through coughs and sneezes.
The scientists then combined the mutant virus with 2009 pandemic flu and infected ferrets with the hybrid strain. After several rounds of infection, where the virus was isolated from animals' throats and noses and used to infect others, they spotted a strain that could spread swiftly in the air between animals in neighbouring cages. None of the ferrets died from the infection.
Studies of the virus revealed that its infectious nature was driven by just four mutations. Three helped the virus stick to cells in the nose and throat, while the fourth enabled the virus to infect them, according to the report in Nature.
"One of the mutations we identified is already circulating in viruses in the Middle East and Asia, so there is concern about these viruses in nature acquiring more mutations and becoming transmissible in mammals," Kawaoka told the Guardian. "If surveillance teams know which mutations are important they can be alert for the emergence of viruses with pandemic potential and inform authorities to ! take app ropriate precautions."
Malik Peiris, a bird flu expert at the University of Hong Kong who was not involved in the research, said it was "absolutely necessary" to publish. "Some people were beginning to say that H5N1 bird flu doesn't have the capacity to transmit in humans. This work doesn't mean it's going to become pandemic, but we certainly can't dismiss it. We now know that can happen," Peiris said.
He said that keeping details of the work secret could have grave implications for surveillance teams who look for early signs of emerging pandemic strains.
"We try to urge people in countries where H5N1 bird flu is endemic to be more active in looking for these viruses. What message do we send out if we say: please do much more surveillance, and by the way, we've found some mutations that are important for transmission in humans but we can't tell you what they are because it's too dangerous That would be the death knell for surveillance," he said.
The mutations in Kawaoka's hybrid strain appeared to have the same effect as those that caused another strain of bird flu, H9N2, to spread in mammals. "This is what is really important and exciting. If we can understand the mechanisms that enable bird flu viruses to become transmissible in mammals, we may be able to generalise to many more, maybe even all, influenza viruses," said Peiris, who has an accompanying article in Nature.
Although the hybrid strain was engineered in the lab, both bird flu and human flu viruses can infect pigs and merge into hybrid forms naturally. One question scientists are now investigating is whether the mutations that made the hybrid virus so transmissible also made it less dangerous.
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