Five easy mutations to make bird flu a lethal pandemic

Editorial: "The risk of an influenza pandemic is fact, not fiction"

H5N1 bird flu can kill humans, but has not gone pandemic because it cannot spread easily among us. That might change: five mutations in just two genes have allowed the virus to spread between mammals in the lab. What's more, the virus is just as lethal despite the mutations.

"The virus is transmitted as efficiently as seasonal flu," says Ron Fouchier of the Erasmus Medical Centre in Rotterdam, the Netherlands, who reported the work at a scientific meeting on flu last week in Malta.

"This shows clearly that H5 can change in a way that allows transmission and still cause severe disease in humans. It's scary," says Peter Doherty, a 1996 Nobel prizewinner for work in viral immunology.

H5N1 evolved in poultry in east Asia and has spread across Eurasia since 2004. In that time 565 people are known to have caught it; 331 died. No strain that spreads readily among mammals has emerged in that time, despite millions of infected birds, and infections in people, cats and pigs. Efforts to create such a virus in the lab have failed, and some virologists think H5N1 simply cannot do it.

The work by Fouchier's team suggests otherwise. They first gave H5N1 three mutations known to adapt bird flu to mammals. This version of the virus killed ferrets, which react to flu viruses in a similar way to humans. The virus did not transmit between them, though.

A short journey from hens to humans (Image: Sonny Tumbelaka/AFP/Getty Images)

Then the researchers gave the virus from the sick ferrets to more ferrets - a standard technique for making pathogens adapt to an animal. They repeated this 10 times, using stringent containment. The tenth round of ferrets shed an H5N1 strain that spread to ferrets in separate cages - and killed them.

The process yielded viruses with many new mutations, but two were in all of them. Those plus the three added deliberately "suggest that as few as five are required to make the virus airborne", says Fouchier. He will now test H5N1 made with only those five.

All the mutations have been seen separately in H5N1 from birds. "If they occur separately, they can occur together," says Fouchier. Malik Peiris of the University of Hong Kong, a flu virologist, says this means H5N1 transmissible between humans can evolve in birds, where it is circulating already, without needing to spend time in mammals such as pigs.

Peter Palese, a flu specialist at Mount Sinai Medical Center in New York City who has expressed doubts that H5N1 can adapt to mammals, is not convinced.

"Ferrets are not humans," he says. "H5N1 has been around for a long time" and failed to mutate into a form that can jump between people.

"That it has not adapted doesn't mean it cannot," replies Jeffery Taubenberger of the US National Institutes of Health in Bethesda, Maryland, who studies how a bird flu became the deadly pandemic of 1918.

"It simply means that so far it has not - luckily for us."