ATLANTA — It sounds like a sci-fi thriller. For the first time, scientists have made from scratch the Spanish flu virus that killed millions of people in 1918.
Why? To help them understand how to better fend off a future global epidemic from the bird flu spreading in Southeast Asia.
Researchers believe their work offers proof the 1918 flu originated in birds, and provides insights into how it attacked and multiplied in humans. On top of that, this marks the first time an infectious agent behind a historic pandemic has ever been reconstructed.
The scientists involved in the project contend there’s no real risk to public safety. The vials of this frightening germ — about 10 of them — are locked away at the federal Centers for Disease Control and Prevention in Atlanta, said Terrence Tumpey, the CDC research scientist who constructed the virus.
However, at least one ethicist thinks there should be a broader public discussion before scientists take such bold steps.
“There isn’t much input from the public. I think there should be,” said Dr. Arthur Caplan, director of the University of Pennsylvania’s Center for Bioethics.
'A big day for science'
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 infected and 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 earlier 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 team that did the gene-sequencing for the project.
The research involved everything from excavation of human remains to application of the latest laboratory technology. “It’s the sort of story you could tell high school students to get them excited about science,” said Dr. William Schaffner, a vaccine specialist at Vanderbilt University.
“It is a big day for science,” said Schaffner, who was not involved in the project.
The Spanish flu of 1918 was a worldwide contagion that in a few months killed 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 older people.
Some public health experts believe the virus was also devastating because of the malnutrition and poor living conditions that existed in that period at the end of World War I.
The reason the scientists believe their reconstructed virus poses no public health threat is that based on previous research, modern-day medicines are effective against the 1918 flu. And they think most people today are already at least partially immune.
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The subtype of virus that caused the 1918 pandemic is now common, and so it would not be as unknown to the immune defense systems of people today. In other words, it would not be as deadly, said Adolfo Garcia-Sastre, microbiologist at the Mount Sinai School of Medicine in New York.
“In each pandemic, it’s been a new subtype of virus,” not an existing one, said Garcia-Sastre who participated in the effort to reconstruct the virus.
In their research detailed Wednesday in the journals Science and Nature, the scientists explained how they reconstructed that 1918 virus.
Using the remains of a female flu victim buried in the Alaskan permafrost in 1918, federal researchers sequenced the virus’s genetic information. They shared it with Garcia-Sastre and others at Mount Sinai, who used the coding to create microscopic, virus-like strings of genes, called plasmids. The plasmids then went to the CDC, 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 Tumpey, the CDC scientist. “It only takes a couple of days.”
A flu virus has eight gene segments. Taubenberger and other researchers previously had published the sequences of five of them; 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.
Scientists had already believed the 1918 virus was a bird-adapted agent. This offers evidence of that, Tumpey 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.
Why the virus was so deadly
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.
The gene sequencing information from the new research is being placed in GenBank, a public database operated by the National Institutes of Health. Sequence information for smallpox and other deadly infectious agents is also stored there. It is accessible to scientists and others, including some who may have harmful intent.
But it won’t be simple for terrorists or anyone else to reconstruct their own versions of the 1918 virus, said Diane Griffin, chair of molecular microbiology and immunology at Johns Hopkins University’s Bloomberg School of Public Health.
“These are not easy viruses to reconstruct,” she said. “You’re not going to do this in a cave in Afghanistan.”
Researchers say their work was carefully reviewed before they were allowed to complete the reconstruction. Among the sign-offs was an approval from the National Science Advisory Board for Biosecurity, a panel created last year to advise federal health officials on biological research that might threaten public health.
That panel includes appointed experts who are outside government, so there was important public involvement in the pre-approval process, Garcia-Sastre said.
Caplan, the ethicist, said he’d like to see more, but he added that the public until now hasn’t been particularly interested in the kind of science that allows reconstruction of infectious agents.
“The power of synthetic genomics to make and recreate life is astounding,” he said. But policy-makers and the public have been far more interested in human cloning — a scientific development believed to still be years away.
“We’re arrogant. We tend to focus on what doctors and engineers can do to genetically engineer us. We tend not to worry as much about what they’re doing with tiny little critters that we can’t see. But science is much more advanced in terms of microbial engineering,” Caplan said.
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