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UW study hunts for answers in 1918 flu

  University of Washington scientists are embarking on a journey that could help save millions of human lives: They are trying to understand how the 1918 influenza virus, which killed more than 30 million, did its lethal work.

The UW researchers will infect monkeys with separate genes from the virus and analyze the impact — from damage to lung tissue to how the immune system responds.

Scientists at four other institutions across the nation will collaborate in the study, financed by a five-year, $12.5 million grant from the National Institutes of Health (NIH). They will use genes constructed after studies of 1918 flu-virus particles salvaged from the bodies of World War I soldiers and an exhumed Alaska resident from that era.

Ultimately, researchers hope, knowledge gained from the study will be used to develop vaccines, influenza medications and even diagnostic tests.

"The goal of the study is to understand why this virus killed," said Dr. Michael Katze, UW professor of microbiology and lead scientist in the UW portion of the project. "It is the most deadly infectious disease in the history of mankind."

Disease experts have warned for years that the world is due for another flu epidemic that will spread like the 1918 pandemic.

Many public-health officials worry that such an outbreak could occur if the flu virus that has infected millions of chickens in Asia combines with a highly communicable human-flu virus and there is no time to develop a vaccine for the new strain. The avian flu has killed most of the relatively few humans it has infected.

During the study, about 40 to 50 monkeys from the UW Primate Center will be used in the research. After work is completed on each animal to see the genes' effect at certain points in the disease process, the monkey will be euthanized to prevent it from having to live through a full course of the flu, said Dr. Bill Morton, director of the Primate Center and one of the researchers in the new project.

"Our intention is to move very slowly and very methodically," Katze said. "It is very much trial and error."

The UW will use $4 million from the NIH to help finance a $4.85 million renovation of the biocontainment facility in the university's Primate Center, which has been used mostly for HIV research. Most of that $4 million is in addition to the research money.

With guidance from the NIH, the facility will be designed with maximum protection against escape of the virus, officials said. The renovated facility also will be used to study other infectious diseases.

Other institutions participating in the project are the Armed Forces Institute of Pathology, Washington, D.C.; Mount Sinai School of Medicine, New York; Scripps Research Institute, La Jolla, Calif.; and the Centers for Disease Control and Prevention.

Dr. Jeffery Taubenberger, of the Armed Forces Institute of Pathology, sequenced all eight of the virus' genes after studies of the viral particles collected from the 1918 victims. He reported his findings in 1997.

Katze and his UW colleagues already have studied how certain key genes from the virus can devastate the lungs of laboratory mice. And they recently reported that a common, nonlethal form of human-flu virus injected in macaque monkeys causes influenza in the animals that looks much like the disease in humans.

"You can extrapolate relatively easily from the macaque (studies) what to expect in humans," Morton said.

The scientists will test the effects of each of the 1918 flu-virus genes by splicing them one at a time into the common, nonlethal virus and then injecting that new form into a monkey.

The major focus will be on the animals' lungs, because that is where the flu virus replicates and does much of its damage, Katze said. The researchers will examine how the animals' genes react to the invading virus.

The other research institutions will be involved in constructing the new viruses and studying the proteins produced by the monkeys' genes in response to the viruses.