The H5N1 bird flu virus may be five gene mutations away from becoming as contagious as the regular flu, a new study reports. Dutch researchers at the Erasmus University Medical Center tested lab ferrets to see just how many changes were necessary to make the flu airborne and transmissible through coughing or sneezing rather than through birds. Study co-author Ron Fouchier emphasized that the findings do not mean a pandemic is more likely but do highlight the possibility that H5N1 could change itself over time to spread easily through humans. It remains unknown whether these mutations would happen beyond a laboratory setting.

About 386 people worldwide have died and 650 have sickened from the H5N1 bird flu, a disease first discovered 17 years ago in Hong Kong. The bird flu was known to transfer only through contact with sick or dead poultry infected with the virus.

The new study, published Thursday in Cell could help health officials identify and track the gene mutations in birds and eventually prepare in advance for a possible outbreak. In the study, Fouchier and his team placed two ferrets — one with H5N1 virus and one without — in one cage. They designed the cage in such a way that the birds shared the same air but did not come in direct contact with each other — a simulation of airborne transmission. The researchers had sprayed a version of the H5N1 virus strain that they had altered through the nose of the infected ferret.

The healthy ferret began to show a loss of appetite, decreased energy, and ruffled fur — the tell-tale symptoms that the ferret had caught the H5N1 virus from its cage mate. The researchers were then able to identify five key gene mutations in the virus strain. According to Fouchier, two of the mutations helped the virus replicate more efficiently; one increased the stability of the virus, and the last two allowed the H5N1 virus to bind to cells in the upper respiratory tract of mammals.

But these gene alterations — which were produced deliberately by the researchers in the lab — may not necessarily occur naturally outside of the lab.

"The biggest unknown is whether the viruses are likely to gain the critical mutations naturally," Richard Webby, a virologist at St. Jude Children's Research Hospital in Memphis tells The Week. "If they can appear readily, then it is very worrisome. If not, then there's still a major hurdle that these viruses have to get over to become human-transmissible."

The publication of H5N1 research has previously been controversial. In 2011, Fouchier’s research on H5N1 shows how to increase the strength of the virus; these studies were blocked from publication for several months because U.S. officials thought it might be a biosecurity risk. Should the research fall into the wrong hands, it might be used for terrorism.

Currently there have been no reported instances of poultry, birds, or people with H5N1 viruses in the United States, though outbreaks have occurred in the Middle East and parts of Asia. Human infection is rare, the risk being highest for people who come into direct contact with sick or dead poultry. Symptoms include fever, abdominal pain, diarrhea, and shortness of breath, with the most serious cases resulting in seizures, organ failure, decreased mental health, and death.

Source: Linster M, van Boheemen S, de Graaf M, et al. Identification, Characterization and Natural Selection of Mutations Driving Airborne Transmission of H5N1 Virus. Cell. 2014.