The H5N1 bird flu virus that has killed several hundred people worldwide would have to undergo complex genetic changes before it would be easily transmissible from person to person, and thus capable of triggering a pandemic, laboratory experiments with ferrets suggest.

Findings are published in the Proceedings of the National Academy of Sciences.

In an effort to learn how bird flu might mutate and become easily transmissible among humans, researchers attempted to combine the H5N1 strain with a common human flu virus. They found that the altered virus did not spread easily and was less potent than the original.

Alarm Level Reduced

Many health experts believe that a worldwide flu pandemic is inevitable, and fears that H5N1 would set it off have mounted in recent years. Most people have no immunity to the strain, and it is highly pathogenic. The only thing preventing it from sweeping the globe -- and possibly taking millions of lives -- has been its inability to spread easily from one person to another.

If H5N1 were to mutate by swapping genes with a human strain of flu, it could develop that ability, scientists have warned.

The CDC team engineered flu viruses that contained genes from H5N1 and H3N2 -- the most common variety of human flu currently circulating.

Ferrets exposed to the human flu, H3N2, passed the infection easily from one animal to another when they were housed in adjacent cages. However, ferrets injected with either H5N1 alone or with the reassorted virus containing genes from both the human and bird flu strains did not spread the diseases among themselves. Furthermore, the disease-causing ability of the newly engineered strains was much less potent.

While the study suggests that a simple gene exchange may not be enough to transform H5N1 into a global killer, the CDC researchers intend to investigate other other possible mutations. Their work thus far does not indicate that a mutated H5N1 will never be dangerous to humans. However, it does suggest that the likelihood that a mutated virus will seriously threaten global public health is less than once feared. There are 50 possible virus combinations.

Valuable Research Methodology

"This important science has established a new research method to help us learn more -- in advance -- about the genetic changes that enable new influenza viruses to spread efficiently and in a continuous manner among people," said CDC Director Dr. Julie Gerberding.

"H5N1 viruses continue to spread among birds worldwide and their genetic properties are constantly changing. There is an urgent need to better understand how these viruses could acquire the ability to spread efficiently between people. This research increases our knowledge, and may enable us to more quickly identify H5N1 viruses and other influenza viruses that have the potential to cause a pandemic," she added.

Humans can, of course, contract the H5N1 virus from close contact with sick birds -- and it can be deadly. Unlike other flus, it does not infect the upper respiratory tract. Rather, it does its damage deep in the lungs. Victims often don't realize they're sick until the disease has progressed, which is one reason the death rate among those who become infected with bird flu is so high.

Vigilance Still Necessary

"This study provides for the first time an assessment of the risk of an H5N1 pandemic strain emerging through reassortment with a human influenza virus. However, there is still much we do not know about the molecular changes the virus would need to cause a pandemic," said Dr. Jackie Katz, a branch chief in CDC's Influenza Division and one of the lead researchers in the study.

"Influenza viruses are constantly changing, so we need to be vigilant and continue our work using this research method to better understand if there are other possible virus combinations or emerging changes in the H5N1 viruses that would increase the risk of a pandemic strain emerging," Dr. Katz added.

It is impossible to predict which flu strain will emerge as the next pandemic, when it will occur or how severe it will be. As of late July, H5N1 had caused more than 230 cases of disease in humans worldwide and is widespread in bird populations in Asia, Africa and Europe. However, the virus has only rarely passed between humans and does not currently transmit easily from human to human. H5N1 avian viruses have not been found in the United States in either birds or humans.

It is worth noting that the virus that caused the pandemic that killed more than 40 million people in 1918 most likely evolved from the mutation of a bird flu strain rather than recombination with a human virus.