The Worst Pandemic in History

After years of sometimes bizarre research, why are scientists still baffled by the 1918 Spanish flu?

Historical photo of the 1918 Spanish influenza ward at Camp Funston, Kansas.
A ward at Camp Funston, Kan. showing the many ill patients who caught the 1918 Spanish influenza

Photograph by an unkown U.S. Army photographer.

Ninety-five years ago in the little town of Brevig Mission, Alaska, a deadly new virus called Spanish influenza struck quickly and brutally. It killed 90 percent of the town’s Inuit population, leaving scores of corpses that few survivors were willing to touch. The Alaskan territorial government hired gold miners from Nome to travel to flu-ravaged towns and bury the dead. The miners arrived in Brevig Mission shortly after the medical calamity, tossed the victims into a pit two meters deep, and covered them with permafrost.

The flu victims remained untouched until 1951, when a team of scientists dug up the bodies, cracked open four cadavers’ rib cages, scooped out chunks of their lungs, and studied the tissue in a lab. But they were unable to recover the virus and threw out the specimens. Nearly 50 years later, scientists dug up another victim from the same site, this time a better preserved, mostly frozen, obese woman, and successfully extracted viral RNA. In 2005, a team of scientists finally completed the project, sequencing the full genome of the viral RNA. But they still don’t know exactly why it caused the Spanish flu pandemic.   

There’s no single reason why the deadliest pandemic in modern history is still mysterious. Scientists have pinpointed the origins of recent influenza outbreaks like swine flu and bird flu with relative ease, arming the international health community with an arsenal of tests and vaccines to fight back. And a flu virus isn’t particularly complex; it’s just a stretch of RNA transmitted between animals, human and nonhuman, that has evolved to mutate quickly enough to outpace any long-term immunity.

But one stretch of RNA can wreak a lot of havoc. Spanish influenza killed about 50 million people (estimates vary), including 675,000 in the United States, and up to 40 percent of the world’s population was stricken with the flu. Unusually for the flu, the pandemic afflicted the young more than the old. Scientists have since established that the disease triggered an overreaction by the immune system, thus turning a young person’s robust immune system against itself. (Bird flu and swine flu were similarly more deadly in young people.) Victims’ lungs overflowed with fluid while their skin, deprived of oxygen, became mottled and discolored. Many sufferers came down with severe nosebleeds—some spewed blood out of their nostrils with such force that nurses had to duck to avoid the flow. Those unable to recover eventually drowned in their own bodily fluids.

Horrifying as the flu was, its reign of terror was mercifully brief: By late 1919, the flu had largely disappeared. Although its survivors and their children faced lifelong health problems, those dark years were largely struck from cultural memory. (Downton Abbey did kill off a character with Spanish influenza, primarily as means to wiggle out of a messy love triangle.)

Scientists, however, never forgot the mysterious pandemic, and research into the 1918 flu experienced something of a renaissance in recent years. In addition to the exhumed Inuit, scientists have studied the organs of flu-suffering soldiers, including a long-forgotten piece of lung tissue stored at a military pathology institute in Washington. Just five years ago, British scientists exhumed the body of Sir Mark Sykes, a British diplomat who was buried in a lead coffin after dying of Spanish influenza in 1919. The scientists had hoped Sykes’ special casket might have preserved his body, allowing his organs to be studied and more potential flu RNA to be extracted and sequenced. But the coffin had caved in on the diplomat sometime between 1919 and 2008, and his body tissue was decomposed.

Where does that leave scientists? Still largely uncertain about the details of the Spanish flu—and fairly anxious about it. John Oxford, who led the team that exhumed Sykes, hoped to study the disease in order to prevent a similar flu pandemic—which he thinks is just around the corner. Ideally, the better we understand previous pandemics, the better able we’ll be to treat and prevent future ones. That’s the goal of Jeffrey K. Taubenberger, chief of viral pathogenesis and evolution at the National Institutes of Health’s Laboratory of Infectious Diseases. Taubenberger, who led the research team that recovered the Inuit victim’s lung tissue, speculates that humans have been facing influenza pandemics for longer than most realize, probably millennia. He’s uncovered annals from monasteries in England and Italy in 1070 that describe maladies with identical respiratory symptoms—probably the flu by another name. And Taubenberger has traced about 14 discrete pandemics since the 1500s, the most recent being the swine flu outbreak of 2009.

But Spanish flu was a pandemic of a different magnitude compared to swine flu, bird flu, or any other recent outbreaks. And perhaps because of its worldwide prevalence, it became the foundational flu of modern times. Before 1918, another influenza virus was surely being passed from human to human. When Spanish flu emerged, it out-competed this virus, mutating with greater celerity and spreading with ease. And though it has since mutated further, Spanish flu remains the basic strain of influenza being spread today. If you had swine flu, or even a standard-grade seasonal flu, you almost certainly contracted a mutation of Spanish flu.

It might sound pretty horrifying to know you’ve had Spanish influenza, but it could be worse. As long as we’re dealing with the same basic virus, Taubenberger says, it’s fairly easy to study the flu and develop vaccines, building upon a sturdy foundation of research and resources already in place. The problem comes along when a completely new influenza virus emerges, one that knocks Spanish flu off its throne. Such fears have thus far been fodder for horror movies and science fiction, but we may be closer to flu doomsday than we realize.

“You can say with almost complete certainty that humans will face future pandemics of influenza,” Taubenberger said. “And at the moment, we can’t predict them in advance.” That could change eventually: Taubenberger dreams of a day when scientists are able to spot a newly developing pandemic in its earliest stages and even develop a universal vaccine for all future mutations of the influenza virus. Right now, though, “the virus mutates so fast that it’s impossible to make a vaccine with broad universality.” In other words, the flu is out-evolving us.

In the meantime, Taubenberger and his team will keep studying the old virus in an attempt to uncover a pattern in its genetic structure that might explain its particular virulence. As for its animal origin? “It’s possible we’ll never actually know,” Taubenberger conceded. “We don’t have these missing links. There’s no surveillance [of flu-prone animals] going on before 1918. We don’t have any animal samples” to trace the development of the virus.  

What they may have, however, are human samples. The Armed Forces Institute of Pathology, which served as the largest pathology institute in the world before it was disbanded in 2011, has preserved tissue samples going back to the Civil War. If Taubenberger can get his hands on a few flu-infected pieces of lung from before 1918, he might be able to sequence the pre-1918 influenza virus. A comparison of the two viruses could reveal how Spanish flu mutated its way to the top, giving us a greater understanding of influenza in general—and possibly even paving the way for the development of the mythical universal vaccine.

For now, the flu will keep adapting year after year, usually as a seasonal annoyance, occasionally as a 2009-level menace. Scientists like Taubenberger will continue to sequence both fresh and old influenza viruses, while the international community remains vigilant against the next pandemic. Perhaps when it comes, we’ll have gleaned the secrets of the Spanish flu and be prepared to fight against influenza’s endless mutations. If we aren’t—well, we’ll have a whole new set of human samples to study before the next flu comes around.