Can We Stop the Next Killer Flu?

Resurrecting a Killer

FINDING THE FIRST SCRAPS of the 1918 virus took a full year. Any flu virus is tricky to recover, because it tends to vanish under the onslaught of the body's immune system. In many cases the 1918 victims died of secondary bacterial pneumonia that flared in their ravaged lung tissues.

Taubenberger and his assistants searched scores of autopsy samples and finally came across one from a soldier who died at Fort Jackson, S.C., with pneumonia in just one lung. Taubenberger had a hunch: The soldier would have died with live, intact virus still in his "healthy" lung. Sure enough, in tissue from that healthy lung he found, and painstakingly recovered, remnants of the 1918 virus.

Then he got more of the virus from an unexpected source. After he published a paper in the journal Science in 1997 reporting his initial results, he received a call from an elderly pathologist named Johan Hultin. Hultin knew where to find bodies of native Alaskans who had died of the virus and were still preserved in the permafrost of Alaska. What happened next has been oft-told in recent years: Hultin returned to Alaska and, hacking into the frozen ground, found the corpse of a woman whose tissues preserved the killer virus. Eventually, Taubenberger teased out the entire genome.

Then came something unimaginable even a decade ago: Taubenberger, Terrence Tumpey of the federal Centers for Disease Control and Prevention, and their collaborators brought the 1918 virus back to life. Or more precisely, they re-manufactured it. They followed the genetic recipe and cooked it up.

The procedure involved a technique developed in 1999 called reverse genetics. Scientists can synthesize stretches of DNA, putting the chemical bases in a desired order. Genes can then be converted into a useful chunk called a plasmid and inserted into a cell culture. If all goes well, and if the scientists have stamped This End Up in all the right places, the virus will reassemble itself inside the cell.

Tumpey and his colleagues took antiviral medication and wore protective hoods as they rebuilt the virus in Atlanta. They actually made a number of variations of the 1918 virus. Some viruses had a few of the 1918 genes. One version had all the genes. The scientists infected mice with the different strains, and the strain with all the genes proved by far the most lethal, quickly killing all the infected mice.

This fall, the scientists published the genome and their test results in the journals Nature and Science. One syndicated columnist declared that we had just given our terrorist enemies a lethal weapon. It's certainly true that mad scientists could conceivably re-create the 1918 pathogen and combine it with some kind of warhead. Back in the day, the Soviets were enthusiastic about putting biological agents such as anthrax into their missiles.

But the 1918 virus wouldn't be the ideal bioweapon. Flu strains currently in circulation are descendants of that virus, so people carry some immunity to that subtype of flu. There are biological agents, such as anthrax, that would be easier to obtain, easier to weaponize.

The upside of publication is clear. Scientists can try to figure out where the 1918 germ came from and what made it so lethal. The paper in Science stated that all 11 genes, contained in eight gene segments, play a role in making an "exceptionally virulent virus" in the mice. To Taubenberger, that suggests that bird flu viruses need a small number of mutations on each gene, possibly in a certain order, to reach the elite level of a 1918-style killer. He thinks perhaps 25 mutations all told are necessary. He bases this on what appear to be some common mutations that differentiate human flus such as 1918 from ordinary bird flus. Alarmingly, strains of avian flu in Asia already show some of these mutations on four of the eight gene segments. On the three genes necessary for viral replication, for example, some avian flu strains already have two of what Taubenberger believes are 10 mutations common in human flus. "I am moderately worried," he says. "We don't know exactly what the rules are."

Sure, bad guys might somehow figure out how to use the published data about the 1918 virus to invent a new version of flu that can kill lots of people. But a simpler scenario is that Mother Nature will do it by herself.

She's got a bigger lab.

A Planet of Germs

GERMS COME IN MANY FORMS, from viruses to bacteria to protozoa to fungi, and we prejudicially lump them into a group called microorganisms, or "microbes," as though being a bulky, fleshy hunk of animated meat is the norm for life on Earth. But the microbes had dominion over the planet long before there were any humans, and they'll surely be here when we're gone.