Scientists re-create 1918 flu pandemic virus

By Scott Allen, Globe Staff | October 6, 2005

Scientists have re-created the virus that caused the horrific 1918 Spanish flu pandemic, then sickened mice with the synthetic virus to gain chilling insights into what made the 1918 flu such an efficient killer.

Federal officials said the breakthrough, based on bits of DNA taken from tissue samples of the flu's long-dead victims, will help them detect signs that emerging flu strains could be particularly dangerous. But critics warned that the researchers may have inadvertently handed terrorists a potential weapon.

The 1918 flu, which killed 30 million to 50 million people worldwide, bears some similarity to the avian flu now circulating in Southeast Asia, said researchers with the Influenza Genome Sequencing Project. But in a telephone briefing, project leader Jeffery K. Taubenberger stressed that current flu strains would have to undergo several important genetic mutations to become as dangerous as the Spanish flu.

Officials at the US Centers for Disease Control and Prevention, the agency that re-created the 1918 virus, said their work will allow other researchers to develop more effective medicines and vaccines.

''We have been able to unmask the 1918 virus, and it is revealing to us some of the secrets that will help us prepare for and predict the next pandemic," said Dr. Julie Gerberding, director of the CDC, during a press briefing on Tuesday.

But the resurrection of the 1918 flu in a federal laboratory -- where it proved at least 100 times more lethal to mice than other flu strains -- set off alarms among some public health specialists, who warned that the world remains unprepared for such an outbreak.

The 1918 flu ''went like Sherman went through Georgia" during the Civil War, said Barry R. Bloom, dean of the Harvard School of Public Health. If a similar strain of flu returns, he added, ''we are very, very vulnerable."

The Influenza Genome Sequencing Project, coordinated by the National Institute of Allergy and Infectious Diseases, has been controversial almost since it began in 1995. No samples of the Spanish flu virus remained, but Taubenberger and other researchers believed that they could still find genetic information about the disease if they could find remains of people who died from it.

They located preserved lung autopsies from victims of the flu as well as tissue from a female flu victim who was buried in the frozen ground of northern Alaska. Researchers from government agencies and New York's Mt. Sinai School of Medicine then painstakingly re-created the virus's DNA. The team published its findings on the last three virus genes in the journal Nature today, and placed detailed genetic information on the Internet.

A separate group, led by the CDC in Atlanta, used the genetic blueprint to re-create the virus in a lab, and test its potency against other flu strains. Their results are being published tomorrow in the journal Science. The researchers found that the Spanish flu could grow without a key chemical ingredient required by other flu viruses, allowing it to burrow deeply into the lungs with lethal results, especially among young, otherwise healthy people.

Critics said it was shortsighted to resurrect such a killer disease, warning that the genetic blueprint could potentially be used to create a bioweapon, and that the flu samples in the lab could be lost, stolen, or accidentally released to the public. ''They are throwing open a door that should remain shut," said Edward Hammond, US director of the Sunshine Project, a group concerned with the proliferation of bioweapons.

Federal officials said they minimized risk to the public by handling the virus under strict safety precautions, including self-contained breathing devices for the researchers. They noted that the Spanish flu is less dangerous to the public than it was in 1918 because people have built up partial immunity through exposure to similar, though less dangerous, flu strains. In addition, they said, two antiviral medicines not available in 1918 appear to be at least partially effective.

Flu viruses require constant monitoring because their genetic structure can mutate rapidly, suddenly allowing the disease to jump from animals to people or giving it new powers to infect or kill. Taubenberger, a geneticist at the Armed Forces Institute of Pathology in Maryland, said the 1918 Spanish flu probably became able to infect people only a couple of years before the global outbreak.

The avian flu strains in Southeast Asia ''could go down a similar path" to cause a major human outbreak, said Taubenberger, but ''they are early on in this process" of genetic mutation. Since 1997, global disease trackers have found strains of avian flu that contain three of the roughly six key genetic changes that launched the 1918 virus, Taubenberger said, but seldom more than one mutation in any single strain.