Resurrecting 1918 Flu Virus Took Many Turns

By David Brown
Washington Post Staff Writer
Monday, October 10, 2005

It took a lot of digging to bring back to life the Spanish influenza virus of 1918. Some was done with invisible molecular primers in a PCR machine in Rockville. Some was done with pick and shovel in the frozen ground of Alaska.

Either way, it was a huge amount of work on a project whose chance of success at the start seemed very, very slim. Now, it will go down as one of the most astonishing technical feats in the history of science -- the viral equivalent of bringing dinosaurs back in the fictional "Jurassic Park."

It may also prove to be unusually useful -- not an elaborate biological parlor trick, but a vital service to global public health.

The Spanish flu killed at least 50 million people around the world in slightly more than a year -- late winter 1918 into the spring of 1919. Researchers have never figured out what made the virus so lethal, in part because there were no samples to study. Although viruses had been discovered by 1918, the flu virus was not isolated until 1933.

With the genome of 13,600 nucleotides known and published in the journals Science and Nature, the 1918 virus is already shedding light on its own history. It was a bird virus that appears to have become a human virus through the slow accumulation of mutations, not through the sudden trading of genes with another flu strain.

It is also illuminating the possible future of viruses that are worrying flu experts now. Some of the H5N1 "bird flu" strains seen recently in 10 Asian countries carry a few of the mutations seen in the 1918 virus, suggesting that they, too, may be slowly adapting to human hosts.

With more work, scientists will probably be able to figure out why the 1918 strain was so dangerous. Experiments with the reborn virus began in August at the Centers for Disease Control and Prevention in Atlanta and have already answered some questions, which may lead to better vaccines and drugs.

The story of how this feat came about has several beginnings. In hindsight, it is clear that perhaps the crucial one occurred 55 years ago with Johan Hultin.

Searching in Permafrost

Hultin had taken a break from medical studies in his native Sweden to study for a doctorate in microbiology at the University of Iowa. At a departmental lunch in 1950, he heard a professor make a passing reference to the idea that intact samples of the infamous 1918 strain might still exist in bodies frozen in the Arctic. Hultin was looking for a dissertation project. He proposed to his adviser that he try to recover the virus for use in a vaccine. The idea was approved.

While the percentage of people who became ill and died of the 1918 flu -- the "case-fatality rate" -- was 2 percent to 5 percent in the United States and Europe, it was more than 50 percent in some isolated native groups. In Alaska, some villages were virtually wiped out.

Hultin had spent the summer of 1949 in Alaska, helping a paleontologist named Otto Geist perform excavations. He had driven up on the newly opened Alaska Highway, which he said "was itself a great adventure." He figured there were mass graves from the 1918 pandemic there. He wrote Geist and asked him to contact missionaries working in Inuit villages. Specifically, he wanted to know whether there were records of epidemic deaths in 1918 or 1919, and if so, what the symptoms were.

Hultin heard from seven or eight missionaries. They sent him notes copied from mission record books, often in Norwegian, which he could read. He got a map that showed the extent of permafrost -- land where the ground never thaws. He chose three villages in the permafrost zone that had mass graves containing corpses from an epidemic that sounded like influenza.

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