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Scientists Resurrect 1918 Killer Flu Virus is Tool to Study Today's Avian Threat

Posted on: Thursday, 6 October 2005, 12:00 CDT

By Gina Kolata

Two teams of federal and university scientists announced Wednesday that they have resurrected the 1918 influenza virus, the cause of one of history's most deadly epidemics, and have found that, unlike the viruses that caused more recent flu pandemics of 1957 and 1968, it was actually a bird flu that jumped directly to humans.

The work, being published in the journals Nature and Science, involved getting the complete genetic sequence of the 1918 virus, using techniques of molecular biology to synthesize it, and then using it to infect mice and human lung cells in a specially equipped secure lab at the Centers for Disease Control and Prevention in Atlanta.

It reveals, the scientists say, a small number of genetic changes that may explain why this virus was so lethal. It also confirms the legitimacy of worries about the bird flu viruses that are emerging in Asia. The new studies find that today's bird flu viruses share some of the crucial genetic changes that occurred in the 1918 flu. The scientists suspect that with the 1918 flu, changes in just 25 to 30 of about 4,400 amino acids in the viral proteins turned the virus into a killer. The bird flus, known as A(H5N1) viruses, have a few, but not all, of those changes.

In a joint statement, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, and Dr. Julie Gerberding, director of the Center for Disease Control and Prevention, said: "The new studies could have an immediate impact by helping scientist focus on detecting changes in the evolving H5N1 virus that might make widespread transmission among humans more likely." The work also reveals that the 1918 virus is very different from ordinary human flu viruses. It infects cells deep in the lungs of mice and infects lung cells, like the cells lining air sacks, that normally would be impervious to flu. And while other human flu viruses do not kill mice, this one, like today's bird flus, does.

But, notes Dr. Jeffery Taubenberger, chief of the molecular pathology department at the Armed Forces Institute of Pathology, the bird flus have not yet spread from human to human. He hopes the 1918 virus will reveal what genetic changes could enable that to happen, helping scientists prevent a new pandemic before it starts.

Scientists said the new work was immensely important, leading the way to identifying dangerous viruses before it is too late and to finding ways to disable them.

"This is huge, huge, huge," said John Oxford, a professor of virology at St. Bartholomew's and the Royal London Hospital, who was not part of the research team. "It's a huge breakthrough to be able to put a searchlight on a virus that killed 50 million people. I can't think of anything bigger that's happened in virology for many years." The 1918 flu showed how terrible that disease can be. It had been, "like a dark angel hovering over us," Oxford said. The virus spread and killed with terrifying speed, preferentially striking the young and the healthy.

Alfred Crosby, author of "American's Forgotten Pandemic: The Influenza of 1918," said that it "killed more humans than any other disease in a similar duration in the history of the world." The story of the resurrection of the 1918 flu began in 1995, when Taubenberger got an idea. He knew about the 1918 flu and the horrors of that pandemic. Medical authorities at the time found it hard even to describe the devastation. They saw, wrote one doctor, Victor Vaughan, young soldiers at Fort Devens dead from the flu whose bodies were "stacked like cordwood." The epidemic, he added, "visited the remotest corners, taking toll of the most robust, sparing neither soldier nor civilian, and flaunting its red flag in the face of science." It had seemed hopeless, though, to discover what that virus looked like. Viruses had not been discovered in 1918, and so no one had isolated and saved the one causing that flu. But Taubenberger recalled that his institute had a warehouse of autopsy tissue, established by President Abraham Lincoln, who had ordered that every time a military doctor examined a patient and took a tissue sample, a sample must also be sent to and stored at the pathology institute. Taubenberger wondered if he could find lung tissue from soldiers who died of the 1918 flu and, if so, if he could extract the virus.

He found tissue from two soldiers, snips of lung soaked in formalin and encased in little blocks of wax. And in that tissue was the virus, broken and degraded just a few molecules of virus, but there.

One of the patients was Roscoe Vaughan, who got the flu when he was 21 years old and training at Camp Jackson, South Carolina. On Sept. 19, 1918, he reported to sick call. He died on Sept. 26, unable to breathe, the air sacs in his lungs filled with fluid. The other patient was James Down, aged 30, who died by coincidence on the same day in Camp Upton in New York. The snippets of their lung tissue had remained, untouched, for nearly 80 years.

Then Taubenberger got a third sample, from a woman who had died in Alaska when the flu swept through her village, killing 72 adults and leaving just 5. The dead were buried in a mass grave in the permafrost, and a retired pathologist, Johann Hultin, hearing of Taubenberger's quest, traveled from his home in San Francisco to the grave site in Alaska at his own expense, dug up the grave with the villagers' permission, extracted the woman's still frozen lung tissue, and sent it to Taubenberger.

Taubenberger and his colleagues spent nearly a decade carefully extracting and piecing together the viral genes, like putting together a jigsaw puzzle. Along the way, they published findings that they and others used to try to understand the 1918 flu, but until now they had only published the sequences of five of the eight genes. The last three, which make up half of the virus's length, were published Wednesday in their paper in the journal Nature.

In August, Terrence Tumpey of the Centers for Disease Control and Prevention and his colleagues used that information to reconstruct the 1918 virus and ask what would happen if they infected mice and if they infected tissue from human lungs.

And, they asked, would the virus remain as lethal if they switched some of its genes with genes from today's influenza viruses?

The scientists took great precautions, Gerberding said, using special labs that were designed to protect the researchers and prevent the spread of the viruses. "We have erred on the side of caution at every step of the process," she added.

And now, the scientists say, the work is starting to unmask that virus's secrets.

Source: International Herald Tribune

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