* Bird flu transmissible in humans could evolve in nature
* Experts see "no hurdle" to that happening
* As few as 5 mutations needed to form human pandemic strain
* Two of those mutations already exist in viruses in nature
By Kate Kelland
LONDON, June 21 (Reuters) - The world has yet to see a form of the deadly bird flu virus that could spread easily between people and cause a global outbreak - but that doesn't mean it won't happen, scientists said on Thursday.
After studying 15 years of data on bird flu viruses in the wild, researchers said some strains were already part way along the road to acquiring a handful of mutations needed to change into a form that could cause a devastating human pandemic.
"The remaining... mutations could evolve in a single human host, making a virus evolving in nature a potentially serious threat," Derek Smith of Britain's University of Cambridge, who led the research, told reporters.
Currently, bird flu, or H5N1 avian flu, can be transmitted from birds to birds, and birds to humans, but not from humans to humans. When it does pass from birds to humans, it is usually fatal.
Two earlier studies by researchers in the United States and Europe have found that with as few as five mutations, H5N1 flu can become transmissible in the air between mammals, including potentially from person to person.
Their work was highly controversial because they manipulated viruses in the lab to produce the new mutated strains.
MUTATIONS ARE ALREADY OUT THERE
Until now, scientists were not sure whether it was possible these same mutations could evolve in nature.
But Smith's co-researcher Colin Russell said their study, published on Thursday in the journal Science, showed it was.
"Viruses that have two of these mutations are already common in birds, meaning that there are viruses that might have to acquire only three additional mutations in a human to become airborne transmissible," he told reporters.
So far, the H5N1 virus, which was first detected in Hong Kong in 1997, has infected tens of millions of ducks, geese, chickens and other birds. People who have been infected - so far there have been 606, of whom 357 have died - are mostly those who came into close contact with birds.
Last year, teams led by Ron Fouchier at Erasmus Medical Center and by Yoshihiro Kawaoka at the University of Wisconsin managed to create laboratory-enhanced versions of the virus that spread like ordinary flu between mammals.
This type of research is seen as vital for scientists working to develop vaccines, diagnostic tests and anti-viral drugs that could be deployed in the event of an H5N1 pandemic.
But opponents said the work could be misused by terrorists or that the virus might somehow escape from the lab and spread. An international row over the publication of the two papers blew up, leading to a temporary moratorium on such research.
"ACTIVE FAULT LINE"
Smith likened scientists' current position on the likelihood of an H5N1 human pandemic to that of researchers trying to predict an earthquake.
"We now know that we're living on a fault line," he said. "And what we have discovered in this working collaboration with Fouchier and Kawaoka is that it's an active fault line. It really could do something. We've seen no fundamental hurdle to that happening."
But he said it was impossible to assess the exact risk. "We know it is in the realms of possibility ... and what needs to be done now is to assess the risk more accurately."
In a second H5N1 study published as part of a series on bird flu in Science on Thursday, Rino Rappuoli, a researcher at the Swiss drugmaker Novartis's vaccines and diagnostics unit in Italy, outlined how the world could better prepare for a potential bird flu pandemic.
Among the most important steps, he said, would be to immunise as many people as possible with existing H5N1 vaccines to prime their immune systems and reduce the severity of illness if a pandemic were to happen. There was also a need to ensure manufacturers could make large quantities of a pandemic vaccine quickly by sharing strains and scientific knowledge swiftly across the world.