Here’s what it takes to make a deadly virus transmissible through the air: as few as five genetic mutations, according to a new study.

This research, published in the journal Science, is the second of two controversial studies to finally be released that examines how the H5N1 bird flu virus can be genetically altered and transmitted in mammals. Publication of both studies had been delayed many months due to fears that the research could be misused and become a bio-security threat.

Although these particular engineered forms of H5N1 have not been found in nature, the virus has potential to mutate enough such that it could become airborne.

H5N1 influenza can be deadly to people, but in its natural forms it does not easily transfer between people through respiratory droplets, as far as scientists know. The World Health Organization has recorded 355 humans deaths from it out of 602 cases, although some research has questioned this high mortality rate.

The journals Science and Nature had agreed to postpone the publication of the two studies related to the genetically altered virus.

In January, the National Science Advisory Board for Biosecurity recommended that this research be published without “methods or details” that terrorists might be able to use for biological weapons. The board also said the data could assist in preparing for a possible future outbreak, however.

Then in February, the World Health Organization convened a meeting, at which the recommendation was to publish the studies – just not yet. In April, the National Institutes of Health chimed in, also recommending publication.

The first study to be published on the topic was in the journal Nature, and was led by the University of Wisconsin-Madison researcher Yoshihiro Kawaoka. It was released in May.

The other research group, which authored the new study in Science, was led by Ron Fouchier at the Erasmus Medical Center in Rotterdam, Netherlands.

Both Kawaoka and Fouchier’s groups created a mutated version of H5N1 that made it easier to transmit from mammal to mammal. They used ferrets because these animals are a good approximation for how viruses behave in humans.

Fouchier’s study examines what mutations would be necessary to get the virus airborne. He and colleagues found five mutations consistent in a form of the H5N1 flu virus that could spread among ferrets through the air.

None of the ferrets died after developing the flu, the researchers said.

In a separate analysis, researchers looked at the likelihood that an airborne avian flu virus would evolve on its own from the H5N1 currently found in nature.

This study, also published in Science this week, looked at nearly 4,000 strains of influenza virus and frequently found two of the five mutations that appear to be involved in airborne transmission. These two mutations have been found in viruses from both birds and humans, although not in naturally-occurring H5N1 strains.

Derek Smith of the University of Cambridge, who co-authored that study, said at a press briefing that it’s possible that only three mutations are necessary for the virus to evolve.

Smith’s group also did mathematical modeling to look at whether the other mutations could evolve when the bird flu jumps to a human or other mammal.

“We find that it is possible for such a virus to evolve three mutations within a single host,” Smith said during the press call.

If it takes four for five mutations to become airborne, that would be more difficult – but it’s unclear just how likely it would be, Smith said.

While the Nature study looked at how a bird flu virus could become airborne through mutations and re-assortment with other viruses, the latest research in Science suggests mutations alone could do the trick.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told reporters that the benefits from the Science study, in terms stimulating ideas and pursuing ways to understand the transmissibility, adaptability and pathogenesis of the virus, outweigh the risks that someone will use the data for nefarious purposes.

“Does that mean that there’s no risk? No, of course not. I can’t tell you at all
that there’s no risk. But the benefits in my mind outweigh the risks,” he said.

Making the research available generally will hopefully spark input on this topic from researchers in a wide variety of fields, he said.

It is technologically possible to create vaccine based on the genetic code of a flu virus strain including this one, researchers said. Several companies are already making H5N1 vaccines.

Research is ongoing to accelerate the amount of vaccine doses available by using adjuvants, which are agents that modify the effects of vaccines, Fauci said. There is also work ongoing into using computational sequencing to anticipate every possible influenza strain that could emerge, such that a databank could be established to prepare for the outbreak of any one of them, he said.

“Right now we’re in a much, much better position than we were when we had vaccine available after the peak of the 2009 H1N1 two years ago,” Fauci said.