By David N. Leff

In 1918, a young woman boarded the New York City subway at its Coney Island station. By the time the train reached Columbus Circle, 45 minutes later, she was dead.

All this passenger had previously complained of was slight fatigue.

Her death was one of some 675,000 in the U.S. alone, slain by the same swift, silent killer -- the influenza virus. Around the world, between 1918 and 1919, that pathogen took the lives of 20 to 40 million people, mostly young men and women in their 20s and 30s, as well as children.

"The fact that World War I was going on," observed molecular biologist Ann Reid, "certainly exacerbated the 1918 flu pandemic. One of the odd things about that outbreak," she added, "was that the influenza affected young people — almost, it seems, preferentially. The death rate was highest among young adults, which is very unusual for flu. Usually, it's the elderly who are at highest risk."

She pointed out the highly susceptible, healthy young adult males who were preselected as the troops being mobilized for war. Troopships were jam-packed to the gunnels with recruits, which facilitated the airborne viral contagion. So did horrendous overcrowding, as at bond rallies and parades on the home front.

Reid also speculated this congestion "may have been a factor in causing the virus to mutate to such an unprecedented virulence." She is a research biologist at the U.S. Armed Forces Institute of Pathology, in Washington, D.C.

In January 1976, at Fort Dix, N. J., it seemed as if history were repeating itself. An 18-year-old private, David Lewis by name, reported to the base dispensary with flu-like symptoms — nausea, dizziness, fever, aching muscles. But he insisted on joining his fellow recruits on a night-long, full-pack training hike through the New Jersey winter. Along the way Lewis collapsed, and died some hours later.

His blood serum carried antibodies to swine flu, which had flared during the 1930s and was suspected of marking the 1918 pandemic. This led to the government mounting a $135-million crash vaccination operation, which never got off the ground.

In an eerie historic parallel, a 21-year-old army private (name withheld) died in September 1918 of the flu then raging. He was stationed at Fort Jackson, S. C., presumingly awaiting shipment overseas to the World War I front.

At post mortem, the Armed Forces Institute of Pathology (AFIP) added microscope slide sections and paraffin blocks of his lung tissue to the archive of such specimens it has preserved since the Civil War, at its National Tissue Repository, in Silver Springs, Md.

Now, 80 years later, that soldier's archived specimen has helped settle a divided opinion as to the viral etiology of that 1918 flu pandemic. It's reported in today's Science (dated March 21, 1997), in an article titled: "Initial genetic characterization of the 1918 'Spanish' influenza virus." Reid is one of its two lead authors.

She surmised it was called "Spanish" because the World War's main fighting nations kept their own flu ravages under wraps, whereas Spain, a non-combatant, made no secret of its pandemic suffering.

"The AFIP archives," Reid told BioWorld Today, has about 70 cases containing slides and blocks of victims of the 1918 flu. We looked specifically for those whose disease course and pathology appeared consistent with having died of the disease very quickly, of a primary viral infection."

Most of the people who died did so from secondary bacterial infections, she pointed out, "and since the influenza virus does its replication and gets out of there within two or three days, we didn't think any of those archived cases would contain viral RNA.

Summing up the immediate result of their analysis, Reid observed: "There were two competing theories out there about where this 1918 virus had come from. The natural reservoir for influenza virus is wild birds. They fly widely in the world, and sow the virus in their infected droppings.

"Most flu viruses that have emerged since viruses could be characterized," she continued, "seem to have come through pigs. Swine are susceptible to avian viruses that adapt to mammalian systems in pigs, and then become infectious to humans. That was one hypothesis.

"There was some indirect evidence to support it from the 1930s. Looking at peoples' serum who had survived the 1918 flu in those years indicated that pandemic had been very similar to swine flu. And the results of our RNA genetic analysis," Reid said, "would indicate that these genes were already adapted to grow in mammals. They are most closely related to pig viruses, not avian.

"The other theory," she continued, "was that maybe this virus jumped directly from avian sources into humans. That would be unprecedented, but perhaps it would explain why that pandemic was so bad. There is one avian virus mutation that is extremely virulent, and kills a lot of birds. So it was thought that maybe the 1918 virus had that particular change.

"But we sequenced that region, and found that it does not. We were able to rule that out as a cause of its virulence, but we didn't uncover any other smoking gun."

Still ahead, Reid and her co-authors "would like to immortalize the case we have, somehow make a library from its RNA that would be abundant and accessible. And making libraries from 80-year-old paraffin blocks," she concluded, "is not an off-the-shelf technology!" *

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