An unthinkable number of people worldwide—more than 50 million—died from the 1918-1919 flu pandemic commonly known as the “Spanish Flu.” It was the deadliest global pandemic since the Black Death, and rare among flu viruses for striking down the young and healthy, often within days of exhibiting the first symptoms. In the United States, the 1918 flu pandemic lowered the average life expectancy by 12 years.
What’s even more remarkable about the 1918 flu, say infectious disease experts, is that it never really went away. After infecting an estimated 500 million people worldwide in 1918 and 1919 (a third of the global population), the H1N1 strain that caused the Spanish flu receded into the background and stuck around as the regular seasonal flu.
But every so often, direct descendants of the 1918 flu combined with bird flu or swine flu to create powerful new pandemic strains, which is exactly what happened in 1957, 1968 and 2009. Those later flu outbreaks, all created in part by the 1918 virus, claimed millions of additional lives, earning the 1918 flu the odious title of “the mother of all pandemics.”
Deadly Virus Struck in Three Waves
Jeffrey Taubenberger was part of the pioneering scientific team that first isolated and sequenced the genome of the 1918 flu virus in the late 1990s. The painstaking process involved extracting viral RNA from autopsied lung samples taken from American soldiers who died from the 1918 flu, plus one diseased lung preserved in the Alaskan permafrost for nearly 100 years.
Now chief of the Viral Pathogenesis and Evolution Section at the National Institutes of Health (NIH), Taubenberger explains that genetic analyses of the 1918 flu indicate that it started as an avian flu and represented a completely new viral strain when it made the leap to humans shortly before 1918. Lab tests of the reconstructed 1918 virus show that in its original form, the virus’s novel encoded proteins made it 100 times more lethal in mice than today’s seasonal flu.
The 1918 pandemic struck in three distinct waves over a 12-month period. It first appeared in the spring of 1918 in North America and Europe largely in the trenches of World War I, then reemerged in its deadliest form in the fall of 1918, killing tens of millions of people worldwide from September through November. The final wave swept across Australia, the United States and Europe in the late winter and spring of 1919.
But did the 1918 flu simply “go away” after that third wave? Absolutely not, says Taubenberger.
Virus Mutates Into Seasonal Flu
Since the whole world had been exposed to the virus, and had therefore developed natural immunity against it, the 1918 strain began to mutate and evolve in a process called “antigenic drift.” Slightly altered versions of the 1918 flu reemerged in the winters of 1919-1920 and 1920-1921, but they were far less deadly and nearly indistinguishable from the seasonal flu.
“The 1918 flu definitely lost its real virulence by the early 1920s,” says Taubenberger.
But what’s truly incredible, according to genetic analyses, is that the same novel strain of flu first introduced in 1918 appears to be the direct ancestor of every seasonal and pandemic flu we’ve had over the past century.
“You can still find the genetic traces of the 1918 virus in the seasonal flus that circulate today,” says Taubenberger. “Every single human infection with influenza A in the past 102 years is derived from that one introduction of the 1918 flu.”
Welcome to the Pandemic Era
The 1918 flu pandemic was by far the deadliest flu outbreak of the 20th and 21st centuries to date, but it wasn’t the only one to qualify as a pandemic. Even with the advent of the first seasonal flu vaccines after World War II, the flu virus has proven capable of some unexpected and deadly genetic tricks.
In a normal flu season, vaccine scientists can track the most active viral strains and produce a vaccine that protects against changes in the human flu virus from year to year. But every so often, viral genes from the animal kingdom enter the mix.
“If one animal is infected with two different influenza viruses at the same time,” says Taubenberger, “maybe one virus from a bird and another from a human, those genes can mix and match to create a brand new virus that never existed before.”
That’s what happened in 1957 when the 1918 flu, which is an H1N1 virus, swapped genes with another bird flu giving us the H2N2 pandemic, which claimed a million lives worldwide. It happened again in 1968 with the creation of the so-called “Hong Kong Flu,” an H3N2 virus that killed another million people.
The so-called “Swine Flu” pandemic of 2009 has an even deeper backstory. When humans became infected with the 1918 pandemic flu, which was originally a bird flu, we also passed it on to pigs.
“One branch of the 1918 flu permanently adapted to pigs and became swine influenza that was seen in pigs in the US every year after 1918 and spread around the world,” says Taubenberger.
In 2009, a strain of swine flu swapped genes with both human influenza and avian influenza to create a new variety of H1N1 flu that was “more like 1918 than had been seen in a long time,” says Taubenberger. Around 300,000 people died from the 2009 flu pandemic.
All told, if 50 to 100 million people died in the 1918 and 1919 pandemic, and tens of millions more have died in the ensuing century of seasonal flus and pandemic outbreaks, then all of those deaths can be attributed to the single and accidental emergence in humans of the very successful and stubborn 1918 virus.
“We’re still living in what I would call the ‘1918 pandemic era’ 102 years later” says Taubenberger, “and I don’t know how long it will last.”