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Photo of a nurse and patients at Walter Reed Hospital.

A nurse takes a 1918 flu patient's pulse at Walter Reed Hospital in Washington, D.C.

Photograph by Harris & Ewing, Inc., Corbis

Dan Vergano

National Geographic

Published April 28, 2014

Scientists announced Monday that they may have solved one of history's biggest biomedical mysteries—why the deadly 1918 "Spanish flu" pandemic, which killed perhaps 50 million people worldwide, largely targeted healthy young adults. (Related: "How Flu Viruses Attack.")

The explanation turns out to be surprisingly simple: People born after 1889 were not exposed as kids to the kind of flu that struck in 1918, leaving them uniquely vulnerable. Older people, meanwhile, had been exposed to flu strains more closely related to the 1918 flu, offering some immunity.

Simply put, the Spanish flu owed its ferocity to a switch in dominant influenza varieties that had occurred a generation earlier. (Related: "1918 Flu That Killed 50 Million Originated in China.")

"All a matter of timing," says virologist Vincent Racaniello of Columbia University in New York, who was not part of the study.

Researchers involved in the study looked at the evolutionary history of the components of the 1918 flu, which was built of genes from human and avian flu strains. They unraveled the history of dominant flu strains stretching back to 1830.

The evolutionary biologists found that a worldwide 1889 outbreak of the so-called Russian flu, the H3N8 flu virus, left a generation of children that had not been exposed to anything resembling the Spanish flu, which was an H1N1 strain. (The H and N in the flu designation stand for proteins called hemagglutinin and  neuraminidase, respectively).

The spread of a more closely related H1 flu variety after 1900 provided partial immunity to children born after that time. That closed the window of vulnerability.

"You have the most deadly flu pandemic in history essentially leaving the elderly, its most frequent victims, completely alone," says biologist Michael Worobey of the University of Arizona in Tucson, who led the Proceedings of the National Academy of Sciences report.

Instead, people aged 18 to 29 died in droves during the outbreak, which killed about 1 in 200 of victims.

Experts have suggested that such a window of vulnerability partly explained the 1918 pandemic, Racaniello notes. But the new study provides computational evidence that the 1918 flu's precursor originated around 1907, he says, and explains how the window of vulnerability opened and closed for the disease.

The new finding may help public health officials deal with future pandemics, amid current worries about deadly avian flu strains jumping to humans.

It may also alter how we vaccinate against future flu outbreaks, keying vaccines not to current seasonal flavor, but instead to strains that people didn't gain immunity to as children. (Related: "Influenza—A Killer Cold?")

Flu Fluctuations

Seasonal flu strains typically enjoy decades of dominance in the human population. These periods are often capped by outbreaks of new flu varieties, such as the 2009 H1N1 flu pandemic that led to the current reign of this strain of flu, which killed perhaps 284,000 people worldwide, according to the U.S. Centers for Disease Control and Prevention.

"The seasonal drift is normal and is the reason why we have yearly vaccines produced to protect against these seasonal changes," says immunologist Michael Gale, Jr., of the University of Washington in Seattle.

The key to the team's reconstruction was the realization that flu genes evolve at different speeds in birds, pigs, and people, Worobey says (it's faster in chickens, for example). Once the evolution of flu strains is reset with timing tuned to each carrier species, "the picture came clear," he says.

Rather than a sudden movement of avian flu genes in 1918 explaining the Spanish flu, the study suggests that many of them moved into seasonal flu after 1900. A change in the kind of hemagglutinin used by an already-existent flu strain likely led to the pandemic around 1918.

Universal Vaccine

The overall message of the study is a hopeful one, say the researchers, because the bacterial pneumonia secondary to the 1918 flu that killed most of its victims is treatable with modern antibiotics.

"If there was something particularly deadly about the 1918 strain, then you are out of luck when something like it happens again," Worobey says. "But if this is just the effect of lack of exposure, then we can be more confident of treatment."

If that's the case, the makers of future flu vaccines may want to tune their ingredients to people's ages, aiming to arm them against flu strains they likely missed exposure to during childhood, the prime age for getting the flu.

"It really offers a lot of support for a 'universal' flu vaccine that aims to prevent all varieties of flu," Worobey says. Such a vaccine would be aimed at all strains of flu viruses, not just the current dominant seasonal ones.

Follow Dan Vergano on Twitter.

17 comments
John Swallow
John Swallow

If one wants to read a great, well researched and I do believe true account of this flue, they should obtain a copy of : "The Great Influenza"By John M. Barry.The book, while saying that it is impossible to prove that the influenzastarted in HaskellCounty,Kansas; but,the circumstantial evidence for this is strong and then they make a good case to prove their contention.This is the opposite of many that want to claim that the influenza came from Spain or China.

chris bourke
chris bourke

I can remember my father telling me that my grandmother left her younger children in the care of the older ones during the 1918 flu and went out to nurse those infected in their homes. She used to stand outside a window of home to check on the family each night. she wasn't a nurse just a charitable person married to a policeman

John Delatorre
John Delatorre

@CoughyCup is a new approach to managing the spread of germs & viruses from coughing. Change the lid and it works with sneezing. A Coughy Cup captures, contains, filters and kills 99.9% of cold and flu viruses in 15 minutes or less. 

chris degeer
chris degeer

Fascinating!  I recall being taught that the Spanish flu killed a high percentage of middle-aged people due to the novel environment of trench warfare during WW1.  In that environment, there was selective pressure on the virus to, not only attack middle-aged folk, but also to become extremely virulent, as the host's life expectancy was short, and the trench's population dense.  


Great to experience the evolution of scientific theory!

Lynda Davenport
Lynda Davenport

My great grandmother died in 1918 due to this epidemic, leaving behind a bewildered husband and small children. Glad to see this!

nadine smat
nadine smat

is this related to any kind of geography?

robbie butler
robbie butler

in ireland people survived to be extreme ages because they ate good foood  like cabbage potatoes etc

craig hill
craig hill

It's been well-documented for some years now that the flu at the heart of this particular pandemic first surfaced at an army facility in Kansas.

Dr Bob Rhoda
Dr Bob Rhoda

I have no problem with vaccinations EXCEPT for a few.  Neither Mumps vaccine nor Measles vaccine confer permanent immunity.  If you vaccinate a kid against these childhood diseases then they require periodic boosters all their life.

Most of the time these diseases are transitory, reasonably benign and confer permanent immunity.  I had both as a child and that was the end of it.  My unfortunate brother caught mumps from me when he was around 40 or so.  It is a VERY bad disease in an adult male with the unfortunate, usual result of eliminating the ability of having kids.


There are a variety of strains of Measles and I had them ALL at one time or another during my youth.  I was MISERABLE but never had the same variety twice.


My sons had the usual, routine vaccinations except Measles and Mumps.  We intentionally exposed them to Mumps, Measles and Chickenpox.  The last was not intentional but was due to the fact that I got Chickenpox as an adult because I never had it as a kid.  Let me tell you, adult Chickenpox is NOT PICNIC.  Somewhere I have a couple of pictures taken of me in my undershorts when I had chickenpox.  It is kinda bizarre because I was all polka-dotted.  After the lesions healed and I went back to work my students called me "Dr Connect the Dots" for a while.  (Gotta LOVE STUDENTS!!) 

Anyway, this is a good piece.  I enjoyed reading it.

N A
N A

If this is true, I openly applaud it. Maybe those "evil" vaccinations aren't so evil, after all, mmm?

Hippie Wang
Hippie Wang

@Lynda Davenport  The destiny decides to perish your grandma, instead of your grandpa. Such a fortunate and fabulous girl.

Dave Simmons
Dave Simmons

@nadine smat ""Spanish flu" pandemic, which killed perhaps 50 million people worldwide"

Also see the link in the article: (Related: "1918 Flu That Killed 50 Million Originated in China.")

agnatha hagfish
agnatha hagfish

@Dr Bob Rhoda  No, most vaccines don't confer 'lifelong' immunity. Neither does catching the disease rom another person, no matter what age you are when you catch it.  The immunity wanes.  Your point was?

craig hill
craig hill

@Dr Bob Rhoda  There exists voluminous case studies of vaccines that caused harm and death. The makers of the vaccines do not want you to know that for financial reasons (that must  be spelled out) and the maxim among giant corporations is Do Not Relay Any Such Information, because all of them produce some shoddy or killing products. If all keep quiet, facts stay underground and ignored by superficial media, also corporate and protective of facts detrimental to profit.

Christopher Green
Christopher Green

@craig hill The case studies are much, much larger where lack of vaccines in a population caused indescribable death and suffering.  When a critical mass of unvaccinated kids is reached, polio (or some similar disease) will make a comeback and you can only hope it isn't your kid that is paralyzed for life (or killed by whooping cough).   

Walter Matera
Walter Matera

@craig hill ". . . voluminous case studies . . ."  Either cite your references or go back in the basement, troll

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