When Were the Earliest Cases of the Flu?

It's common to say "I had the flu" for every cold and sniffle. But real influenza is no small malady, and often brings high fevers, severe muscle pains, exhaustion and near delirium that keep sufferers in bed for days.

Influenza outbreaks have caused millions of human deaths around the world over the last few hundred years alone. An estimated 50 million people died worldwide in the 1918 pandemic, including more than half a million people in the United States.

Historians of medicine consider the description of a certain disease in the 5th century B.C. by the Greek physician Hippocrates (of the Hippocratic Oath taken by modern doctors) to be the earliest report of the flu. The "cough of Perinthus," he warned in Epidemics, often occurred in mid-winter and featured "fevers… sore throat, inflammation of the lungs, and other troubles."

In the time of Hippocrates, this "cough" was linked to the ancient Greek city of Perinthus, beside what's now the Sea of Marmara in Turkey. But research indicates that influenza in its many forms has been striking down humans around the world for much longer and that those responsible are birds—specifically birds that live around water.

"The main natural reservoir of influenza A is waterfowl," says biochemist Jesse Bloom, who studies the evolution of viruses for the Fred Hutchinson Cancer Center. "There is a huge diversity of influenza A circulating in waterfowl, and influenza A has almost certainly circulated in those birds for far longer than recorded human history."

One problem is that viruses like influenza are "zoonotic," which means they can spread to some or many other species. Occasionally the influenza A virus crosses from water birds over to other animals, including humans. That can lead to an outbreak, which can lead to mutations of the original strain. The influenza B strain is considered as dangerous to humans as influenza A, while influenza C is generally milder.

Severe influenza outbreaks have happened throughout history. The 1918 pandemic was preceded by a "Russian flu" in 1889, and was followed by an "Asian flu" in 1957. They're thought to have been caused mainly by human transmission of the virus, but it's likely that they originated with people who regularly interacted with birds—on farms or in live poultry markets, for example. Farmed birds like chickens can be infected with influenza they catch from water contaminated by waterbirds. Humans who work with the farmed birds are then exposed to the virus.

"The 1918 pandemic probably originated from an avian virus that either directly jumped to humans or went through another intermediate mammalian host," Bloom says. "There isn’t enough molecular evidence to be fully confident about the exact path it took to humans."

Influenza is far from the only animal-borne disease that infects humans: Shakespeare's "thousand natural shocks" also include several types of plague, malaria, hepatitis, rabies and Ebola. But the influenza virus has several features that make it difficult to deal with effectively. To begin with, influenza is an RNA virus—its genetic code is written in a single strand of ribonucleic acid instead of the double-stranded deoxyribonucleic acid (DNA) used by many other viruses. As a result, it spreads and mutates into new strains relatively quickly, which is why a new flu vaccine is recommended every year. Different strains of influenza can also swap genetic material when they infect the same host, causing additional new strains. Plus, the "reservoir" of birds is always there, ready to reseed the impact of influenza among humans at any time.

But it wasn't always this way. Studies of ancient genetic material recovered from archaic human remains show that our ancestors suffered from several viral diseases—but researchers have found no sign of influenza. The RNA used by the flu virus deteriorates quickly; but some scientists now think humans did not really start getting the flu until they started farming birds, sometime between 10,000 and 5,000 years ago.

"Since the first domestication of birds, influenza has always been one of our most contagious known diseases," says the American physician and public speaker Michael Greger. He warns that an outbreak of a novel strain influenza from birds, like the 1918 pandemic, could happen again. "The last time a bird flu virus adapted to human beings,” he says, “it triggered the worst plague in human history.”