Scientists study revived 1918 flu virus

Terrence Tumpey stepped into the laboratory and glanced at the dead mice. Suddenly it hit him — the significance of what scientists were attempting.

A few days earlier, Tumpey had infected the mice with genes from the 1918 influenza virus. The virus killed 40 million to 50 million people in the worst infectious disease outbreak in recorded history, then vanished.

For years, scientists had attempted to decipher the virus’ genetic code from snippets of lung tissue preserved from flu victims.

At this point in 2001, they had identified two of the virus’ eight gene segments and wanted to test the effect on mice. There was no mistaking the result.

“It brought a chill down my spine because I knew that I had this deadly virus,” said Tumpey, a research scientist for the national Centers for Disease Control and Prevention. “I didn’t have the whole thing, but I knew I had parts of it.”

Virus Revived

In October, Tumpey and a team led by Dr. Jeffery Taubenberger of the Armed Forces Institute of Pathology announced they had achieved a remarkable feat. Not only did they discover the virus’ entire genetic code, they brought it back to life in a tightly controlled laboratory at CDC offices in Atlanta.

The virus that had swept the globe, infecting more than one-fourth of the world’s population, existed on earth once again.

Scientists hope to use the virus to discover how to prevent new pandemics, or at least lessen their devastation.

In the best-case scenario, the scientific advances would come in time to help fight the avian influenza now spreading through Asia and parts of Europe.

Scientists worry that if the avian influenza mutates so that it is easily transmissible among humans, it could rival the 1918 virus in its deadliness.

Researchers say they already have some initial insights about why the 1918 flu spread so rapidly and what made it so deadly, although more work remains.

Safety Concerns

While lauding the researchers’ goals, critics question the wisdom of reviving the virus. They fear it could be accidentally or deliberately let loose into the population.

“That can come about if a disgruntled or disturbed laboratory worker releases it,” said Richard Ebright, a chemistry professor at Rutgers University.

“That can come about if a person of ill intent follows the procedures in the published work and reconstructs and releases it. It’s worth bearing in mind that this virus killed 1 percent of the earth’s population.”

The scientists insist they have imposed tight security measures and say the potential to save lives makes the risk worthwhile.

“The 1918 virus appeared as a natural outbreak and we need to understand why it behaved the way it did if we’re ever going to prevent something like that from happening again,” Taubenberger said.

Unimaginable Toll

It may be hard for modern-day Americans, used to the milder seasonal flu, to comprehend the devastation wrought by the 1918 virus.

So many people died, including 675,000 Americans, that it lowered the average life expectancy in the United States by more than 10 years.

Unlike the seasonal flu, which strikes the elderly and young children the hardest, the 1918 virus was particularly deadly to healthy young adults ages 15 to 34.

The pandemic ripped the nation’s social fabric, overwhelming hospitals, morgues and health care services.

In the East Bay, Concord shut down its saloons and businesses banned people from entering without masks.

Oakland set up a 300-person special police force to ensure its residents wore masks. Livermore officials closed schools and discouraged churches from holding services to make it tougher for the virus to spread.

Unique Origins

One of the more surprising insights from reviving the virus is that the 1918 flu had a different origin from other recent flu pandemics.

A pandemic, or worldwide outbreak, occurs when a new flu strain is so different from previous ones that people have no immunity to it.

Milder flu pandemics hit in 1957, killing two million people, and in 1968, when 1 million died.

In both instances, a human flu strain acquired a few genes from a bird flu virus. The blended human-avian strain then sparked the outbreak, Taubenberger said.
This apparently did not occur in 1918. “We think this was an entirely new, avian-like virus that got into humans directly without mixing with a human strain,” Taubenberger said.

“So that means that pandemics can form in more than one way, and that certainly is important in terms of preparing for another one.”

In analyzing what made the 1918 virus so lethal, scientists have zeroed in on two genes — the haemagglutinin and polymerase genes.

They also have noted that the 1918 virus appears to have attacked deeper areas of lung tissue than the flu that is prevalent today.

Unusual Behavior

One reason it was so deadly may be that it prompted an overly aggressive immune response. The chemicals produced by white blood cells in response to the infection may have caused much of the lung damage, Taubenberger said. There is some evidence the current avian influenza acts in a similar way.

“So this may give a whole new clue as to why certain influenza viruses are very virulent and might lead to new targets of drug design, where you might be able to actually dampen immune response a bit,” Taubenberger said.

Once scientists revived the virus, federal officials quickly added it to the U.S. health department’s list of select agents and toxins, which includes such deadly threats as smallpox, Ebola and foot-and-mouth disease.

Stringent Controls

Anyone desiring to work with these agents must register and undergo federal background checks.

Tumpey is believed to be the only person in the world now working with the fully reconstructed 1918 virus.

To enter the high-containment laboratory, he uses a keycard and places his finger on a keypad reader to confirm his fingerprint.

Once inside the laboratory, he positions his eye in front of an iris scanner. Only then can he unlock the freezer where the virus is kept.

To protect himself while working with the virus, Tumpey takes the antiviral drug Tamiflu daily and monitors his body temperature.

Critics such as Ebright believe officials should impose even tighter security measures.

Ebright argues that scientists should work with the virus only in the highest-security laboratories, known as biosafety level 4. Now, scientists can work with it under the second-highest safety precautions, or biosafety level 3-plus.

The virus should have been put on a restricted list within the select agent list, Ebright maintains. That would require additional approvals before anyone can do experiments with it.

He noted that 15,000 investigators in the United States are authorized to work with select agents. He also pointed out that the virus’ genetic sequence is now available in published literature.

Tumpey and Taubenberger stress that before they revived the virus, they obtained approval from several review committees, as well as the directors of the CDC and National Institute of Allergy and Infectious Diseases.

The virus qualifies for the second-highest safety precautions, they say, because experiments have shown that current antiviral medications lessen the severity of the virus’ symptoms in mice.

Weakene Legacy

Research also has shown that current flu vaccines provide some protection against the virus, the scientists add. They believe this is because the influenza viruses that circulate today are highly mutated forms of the 1918 virus.

Even critics agree that if it were to get into the population today, the 1918 virus would probably not wreak the kind of havoc it did decades ago. But it would almost certainly be more deadly than the seasonal flu, and no one wants to witness what would happen.

It was necessary to recreate the virus, rather than just determine its genetic sequence, Tumpey said, because the genetic sequence alone did not reveal what made it so deadly.

“There wasn’t a smoking gun, so to speak,” he said.

Many influenza experts hold great hope that the recreated virus will shed new light on disease and eventually lead to strategies and drugs that can help prevent future deadly outbreaks.

“Without the 1918 virus as the guide map for us, we really wouldn’t have the clues as to which mutations are going to be important for jumping species from birds to humans, or the mutations that would be responsible for causing disease,” Taubenberger said.

“It really required having the sequence of the virus before this line of investigation could even be attempted.”