ATLANTA - Scientists have made from scratch the Spanish flu virus that killed as many as 50 million people in 1918, the first time an infectious agent behind a historic pandemic has ever been reconstructed.
Why did they do it? Researchers say it may help them better understand — and develop defenses against — the threat of a future worldwide epidemic from bird flu.
Like the 1918 virus, the current avian flu in Southeast Asia occurs naturally in birds. In 1918, the virus mutated, infected people and then spread among them. So far, the current Asian virus has killed at least 65 people but has rarely spread person-to-person.
But viruses mutate rapidly and it could soon develop infectious properties like those seen in the 1918 bug, said Dr. Jeffery Taubenberger of the U.S. Armed Forces Institute of Pathology.
"The effort to understand what happened in 1918 has taken on a new urgency," said Taubenberger, who led the gene-sequencing team.
The public health risk of resurrecting the virus is minimal, U.S. health officials said. People around the world developed immunity to the deadly 1918 virus after the pandemic, and a certain degree of immunity is believed to persist today. Also, in previous research, scientists concluded that modern antiviral medicines are effective against Spanish flu-like viruses.
The virus recreation, announced Wednesday, is detailed in the journal Science. The completion of that gene sequencing was announced in the journal Nature.
The virus was made from scratch, but based on a blueprint from Alaska.
Taubenberger's team sequenced genome information recovered from a female flu victim buried in the Alaskan permafrost in 1918. Then, they shared the data with researchers at New York's Mount Sinai School of Medicine. Using a technique called reverse genetics, the Mount Sinai researchers used the genetic coding to create microscopic, virus-like strings of genes, called plasmids.
The plasmids then were sent to the federal Centers for Disease Control and Prevention in Atlanta, where they were inserted into human kidney cells for the final step in the virus reconstruction.
"Once you get the plasmids inside the cell, the virus assembles itself," said Terrence Tumpey, the
CDC research scientist who assembled the virus. "It only takes a couple of days."
About 10 vials of virus were created, each containing about 10 million infectious virus particles, Tumpey said in an interview with The Associated Press. More may be created, he said, to accommodate researchers' future needs.
The virus particles are being stored at the CDC, and there are no plans to send samples off campus, said Dr. Julie Gerberding, the agency's director.
However, the genetic information sequenced by Taubenberger is being placed in GenBank, a public genetic sequence database operated by the
National Institutes of Health.
Scientists need access to the research as they try to develop vaccines and antiviral medications against potential future pandemic agents, said Donald Kennedy, editor-in-chief of Science.
"We carefully considered the implications of publishing this research and concluded that the knowledge we're gaining to potentially protect public health far outweighs the risk of working with the virus," Kennedy said.
The Spanish flu of 1918 was a terrible pandemic. In a few months, it killed more people than any other illness in recorded world history — an estimated 20 million to 50 million worldwide, including roughly 550,000 in the United States.
In severe cases, victims' lungs filled with fluid and they essentially drowned in a disease process that took less than a week. It was known for being particularly dangerous to young adults, a group usually less susceptible to flu complications than younger and older people.
A flu virus has eight gene segments. Taubenberger and other researchers previously had published the sequences of five of them, but they accounted for less than half of the virus's total sequence. The new work completes it.
The three new segments appear to be crucial in explaining how the bird-based virus became adapted to humans, Taubenberger said.
Tumpey also confirmed the 1918 virus's avian-like characteristics by injecting it in fertilized bird eggs. It killed the eggs, just like the Asian bird flu does. Other modern-day flu strains that are human-based don't kill fertilized bird eggs, he noted.
The researchers also refined their focus on one gene, the HA gene, that encodes the hemagglutinin surface protein that help the virus attach to cells and multiply. The 1918 virus is deadly with the HA gene, but when the gene was replaced, it was not virulent, Tumpey said.
The virus's genetic properties may explain why it was able to settle deeper in the lungs than most current flu strains, causing the drowning condition, he said.
Virologist Yoshihiro Kawaoka of the University of Wisconsin-Madison and the University of Tokyo called the work important.
"We need to understand why this virus was so pathogenic," he said.
He also noted that Tumpey's work had to go through a variety of scientific reviews and approvals — a process Tumpey said took about three years.
"If there was any concern about safety, the experiment would not have been approved," Kawaoka said. Source