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Unravelling the mystery of one catastrophic respiratory ailment while another continues to run rampant Similarities between avian flu mutations and 1918 virus fuel fears of next pandemic

Similarities between avian flu mutations and 1918 virus fuel fears of next pandemic

MEDICAL REPORTER

The avian flu killing people and poultry in Southeast Asia has sprouted some of the same genetic mutations that made the 1918 flu virus the most deadly in human history.

U.S. scientists discovered the similarities after piecing together the full genetic code of the historic virus, which circled the globe and killed perhaps more than 50 million people in less than a year.

In a separate report, American researchers also reveal that they have used the genetic code to reconstruct a live version of the 1918 Spanish flu, betting the world's best defence against a new pandemic is to learn the secrets of an old one.

As a result, finding common mutations between the two viruses fuels the widespread fear that Asia's H5N1 avian flu could be the culprit behind the next pandemic.

So far the virus does not seem to be spreading from person to person, but it has killed at least 60 people who likely caught it from chickens.

"[H5N1] may be going down a similar path that led to 1918," said Jeffery Taubenberger, a pathologist with the U.S. armed forces in Washington who led the effort to sequence the genome of the 1918 flu virus and is lead author of the report published today in Nature.

No sample of the 1918 virus had ever been stored. Instead, Dr. Taubenberger and his team spent nearly 10 years piecing the strain's eight genes together from viral bits they fished out of preserved autopsy tissues and the frozen lungs of an Inuit woman who was recovered from Alaska's permafrost in 1997.

Unlike other virulent flu strains that began as human viruses and acquired bird-flu genes along the way, the 1918 flu was "an entirely avian-like virus," Dr. Taubenberger said. It went on to acquire several mutations, likely those that allowed it to outwit the human immune system, which enabled it to spread easily among people and become a pandemic strain within a couple of years.

Some of these same mutations can be seen in the H5N1 flu. But since not all of the mutations are present, he said, H5N1 may be "early on in the process" of mutating into a form that can spread efficiently between people.

Knowing which genetic changes to watch for, however, could give experts a checklist, or "molecular clock," by which to assess the pandemic nature of a strain.

At the U.S. Centers for Disease Control and Prevention in Atlanta, where the 1918 virus was rebuilt in August, researchers have found that H5N1 can kill a lab mouse at much lower doses than the 87-year-old Spanish flu.

Microbiologist Terrence Tumpey, who led the reconstruction and is lead author of the report in tomorrow's edition of Science, also found the 1918 flu was no longer virulent in animals after replacing just one gene, a trait known as HA, or hemagglutinin, which allows the virus to break through a variety of defences and into the cells of a host.

Dr. Tumpey said the HA gene now stands as a strong target for new drugs or vaccines in development.

CDC director Julie Gerberding played down concerns that rebuilding the 1918 virus could unleash a man-made pandemic. During a teleconference this week, she said people today have at least some immunity to the H1 family of viruses to which the 1918 strain belongs.

In fact, Dr. Taubenberger noted that many flu viruses circulating today are direct descendants of the 1918 killer flu. And Dr. Gerberding said lab tests have shown "the 1918 virus was sensitive to drugs we have on the shelf today."

This was one reason the CDC opted to rebuild the Spanish flu virus in an enhanced Biosafety Level 3 Lab instead of a Level 4 lab. A Level 4 lab runs on the strictest containment standards to house pathogens for which there are no effective drugs or vaccines.

Dr. Gerberding said the agency would be open to inviting investigators to Atlanta, but added, "We have no intention of releasing this from CDC."

Yet, with the publication of Dr. Taubenberger's report, the genetic code of the 1918 flu virus has been uploaded to GenBank, a U.S. government repository of genetic sequences that anyone can access freely on-line.

Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Disease, said careful thought was given before the information was made public.

It was decided, he said, that "knowledge can be shared so that the very best and brightest scientists can join the team . . . in developing countermeasures."

The feeling, Dr. Fauci said, "is that the benefit, scientifically, outweighs any risk of this being used in a nefarious way."

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