/ 18 October 2005

Killer 1918 virus exhumed

Only a handful of scientists have security clearance to access the laboratory at the United States government’s Centres for Disease Control and Prevention. Before entering, they must pull on protective hoods, don breathing apparatus and pass through electronic fingerprint and retina scanners to prove their identity.

Inside the lab lies a batch of a virus that more than justifies the extreme level of security. Resurrected nearly 90 years after it spread around the globe, leaving about 50-million people dead, it is a replica of the 1918 Spanish flu virus.

The recreation of the virus, to unravel why the 1918 pandemic was so devastating, has raised as many fears as it has hopes. While the researchers argue that the work will hugely improve protection against natural flu viruses, critics say there is a real danger the virus will escape, with potentially disastrous consequences.

The recreation process was laborious. Scientists collected fragments of the virus from lung tissue taken from victims at the time and preserved in formalin or, in one case, isolated from the lungs of a woman victim whose body had later frozen in the Alaskan permafrost. Using the fragments, they painstakingly pieced together and read the complete genetic code before using the sequence to rebuild the virus from scratch.

By injecting it into mice, the team, led by Dr Jeffery Taubenberger at the Armed Forces Institute of Pathology in Maryland, was able to establish just how ferociously effective it was, compared with more common flu strains. All the mice infected died within a few days; all infected with contemporary strains recovered. ”I didn’t expect it to be as lethal as it was,” Dr Terrence Tumpey, a scientist on the project from the centres told the journal Nature.

By creating flu strains with only certain parts of the 1918 virus, researchers investigated which of the eight genes that make up the virus were most responsible for its virulence. They discovered that they all played a part, which suggests that the virus had completely adapted to cause disease in humans, something they say could happen again with avian flu strains.

In a second paper, published in Nature on October 6, Taubenberger and colleagues at the centres analysed the genetic make-up of the recreated virus. Surprisingly, they found it had no similarities to any of the human viruses in circulation, suggesting that the Spanish strain had jumped from birds to humans, and didn’t mix with a human virus first, as had been believed.

The finding that Spanish flu came straight from birds has raised concerns among scientists. Previously, a pandemic was only thought likely if an avian strain merged with a human flu virus. ”It looks as though an avian strain evolved in 1918 and that led to the deadly outbreak, in much the same way as we’re now seeing the Asian avian flu strains evolve,” said Professor Ronald Atlas, co-director of the Centre for the Deterrence of Biowarfare and Bioterrorism at the University of Louisville in Kentucky.

According to Taubenberger, knowing which mutations gave rise to the 1918 flu virus will help scientists work out whether viruses are evolving to the point where a pandemic is possible. The H5N1 strain of bird flu in Asia is already mutating to make it more suited to humans, he said.

Despite the new insights given by the project, many scientists were alarmed at the recreation itself and, particularly, that the full genetic sequence was to be made public on an online genetic database. ”Assuming this is a replicant of the 1918 flu strain, if it got out, it could initiate infectious disease in humans,” said Atlas.

Viruses have escaped from high-security labs before. During the recent Severe Acute Respiratory Syndrome outbreak, the virus escaped at least twice, once in Taiwan and once in Singapore, when researchers were contaminated.

Other scientists warn that the 1918 virus’s genetic code could easily be misused. ”If the genetic sequence is out there on a database, then that is a clear security risk,” said Dr John Wood, a virologist at the National Institute for Biological Standards and Control in Potters Bar.

According to Dr Julie Gerberding, director of the disease control centres, a pandemic is unlikely even if the virus escapes because of most people’s natural immunities and the availability of antiviral drugs and flu vaccines.

Publication of the research still raises questions about the power of academic journals that take ultimate responsibility for publishing the papers, said Wood. ”That is some responsibility.”

The US National Science Advisory Board for Biosecurity held an emergency meeting last week to discuss the possible publication of the papers. — Â