October 10, 2005

Resurrecting 1918 Flu Virus Took Many Turns

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.

A Key Institution
One of Washington's more obscure but important institutions is the Armed Forces Institute of Pathology in Rockville. It provides pathology services for the military, including autopsies of war dead. It also functions as a kind of Supreme Court for difficult cases. Pathologists unsure of a diagnosis, for a small fee, can consult its experts and send them microscopic slides or other samples for review. Part of the institute's value lies in its pathological specimens dating to 1862 -- 3 million pieces of preserved human tissue.
Jeffery K. Taubenberger is a civilian pathologist who heads the institute's division of molecular pathology. His laboratory is one of the few in the country with expertise in rescuing and restoring genetic material from damaged or decayed tissue. In 1995, Taubenberger wondered whether it might be possible to get the 1918 virus out of dried and fixed tissue from the Spanish flu pandemic. "I really wanted to see if there was some way we could make use of this vast, wonderful collection for this," he recalled.
He and his colleagues reviewed slides of lung tissue from 78 soldiers who had died in the pandemic. They narrowed the search to 10 slides in which the microscopic appearance showed that the men died only of viral pneumonia, not of a secondary bacterial infection that was more often the cause of death.
They tested preserved, leftover pieces of lung tissue from all 10. Two came up positive for influenza A, the broad family that includes Spanish flu. One was from a 21-year-old private who died in South Carolina on Sept. 26, 1918. The other was from a 30-year-old private who died in Upstate New York on the same day.
Using polymerase chain reaction (PCR) technology to amplify the genetic material, and primers -- short, important stretches of genetic material -- from human, animal and bird viruses, Taubenberger, Ann H. Reid and Thomas G. Fanning fished out fragments of the 1918 microbe. There were multiple copies of the virus in the sample, but they had broken into small pieces. Matching the overlapping ends of the fragments, the researchers reassembled the fragments in the right order.
The first gene they recovered, called NS, was virtually identical in the two cases.


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