With extreme care under tight conditions, scientists in New York City and Georgia have constructed a bug that resembles the deadly virus that caused the disastrous 1918 worldwide influenza pandemic.

Hoping to find ways to protect people if the natural virus returns, microbiologist Christopher Basler and his colleagues recently made new copies of several genes that rendered the 1918 flu so dangerous. These few genes were engineered into infectious viruses for testing at a U.S. Department of Agriculture laboratory in Athens, Ga.

The results showed, fortunately, that existing drugs such as amantadine, zanamivir and oseltavir seem to work, protecting mice against big doses of engineered virus.

"These data suggest that current anti-viral strategies would be effective in curbing the dangers of a re-emergent 1918 or 1918-like virus," Basler and his colleagues announced Sept. 23 in the Proceedings of the National Academy of Sciences.

The lead author, Terrence Tumpey, works for the U.S. Department of Agriculture's Southeast Poultry Research Laboratory, in Athens. Ga. Basler's team works at the Mount Sinai School of Medicine in Manhattan.

The researchers said the drugs that are already available could be used as a stopgap measure while work began on creating protective vaccines against 1918 flu. Their tests in animals show that the drugs can be used to protect against infection or to treat infections that are already under way.

Biochemist Eckard Wimmer, at SUNY Stony Brook, said, "I believe this kind of work is extremely important, because we would like to know why these viruses caused such an enormous rate of death. This in turn would allow us to protect ourselves against outbreaks of similar strains."

Wimmer, who recently announced construction of whole polio virus "from scratch" using off-the-shelf materials and publicly available information, added that the 1918 bug is especially important. "We're all afraid that the influenza virus may come up again with a new mixture of genes, against which we are not protected, and we might have a disaster."

The Mount Sinai researchers emphasized that their new experiments were done using extreme care not to let any engineered viruses escape the laboratory. And the laboratory itself was a high- security facility maintained by the USDA near the University of Georgia. It is specifically designed to keep dangerous microbes from getting out.

The reconstructed flu viruses were made by stringing together chunks of DNA to create the specific "virulence" genes that apparently made the 1918 pandemic so lethal. These special genes were engineered into infectious flu viruses, which were then tested in mice and shown to be surprisingly lethal.

The special genes are of great interest because the original flu virus that came armed with such genes was far more deadly than "ordinary" flu viruses, various types of which strike year after year. The complete 1918 flu bug has never been isolated, but chunks of its DNA have been found in old tissue samples and are being studied.

As a result, researchers have deciphered the chemical "spelling" of several virulence genes from the 1918 virus. This allowed Basler's team to make new copies of the genes, plug them into viruses and try to re-create the 1918 bug. It's not clear they've succeeded, but perhaps they're close.

Such work is important because infectious disease experts fear that the 1918 bug might return to again wreak havoc. Or, the Mount Sinai team suggested, a similar virus might be used as a bioterrorism weapon, with large impact.

"The influenza pandemic of 1918-19 resulted in the deaths of millions of people worldwide," the researchers said, "and an estimated 550,000 excess deaths in the United States."

Worse, unlike most flu outbreaks, the 1918 pandemic was especially hard on the healthiest people, striking and killing many young adults. This might be explained, in part, by the pandemic emerging during World War I, when many young men were gathered in barracks and aboard military ships.