On a spring day in 1997, Dutch virologist Jan De Jong received an unusual specimen of influenza from a colleague in Hong Kong. The sample had been harvested from a sick 3-year-old boy and matched no known human flu strain.
Tests at a colleague's lab in Rotterdam found that the boy had been sickened by a bird flu virus. It was the first evidence that birds could give influenza directly to people.
Two days later, De Jong was on a plane to Hong Kong.
"We had to act very, very quickly," recalled De Jong, now a senior investigator at Rotterdam's Erasmus University. "We realized this could be a pandemic situation."
Authorities eventually ordered the eradication of every chicken, duck and goose in Hong Kong. All told, six people, including the boy, died before the outbreak of avian flu faded.
But the troubling findings in the Dutch lab continue to haunt health authorities worldwide.
The virus -- dubbed H5N1 -- has now spread throughout Asia.
Although it is innocuous in wild waterfowl, it is so unfamiliar to the human immune system that scientists fear it could seed a deadly influenza pandemic. All it needs is to transform itself so it can be transmitted between humans -- a possible scenario if enough people are infected.
Once inside human cells, it could mutate on its own or merge with pieces of human influenza already adapted to spreading among Homo sapiens. Influenza assails its victims with high fevers and aches that, in the most serious cases, can lead to secondary infections, pneumonia and death.
"Past epidemics have been limited to a few million chickens," De Jong said. "But we are now talking about the whole area of Southeast Asia -- so we have to multiply the risk by hundreds of thousands."
The discovery in 1997 "was a profound moment," said influenza researcher Kennedy Short- ridge, emeritus professor of the University of Hong Kong. "What really hit me was the sudden realization ... that the next pandemic could arise, doing so right on our doorstep."
H5N1 resurfaced in 2001, 2002 and 2003. Last year, while the world was focused on the SARS virus, two Hong Kong residents who had visited China were infected with H5N1, and one died.
The latest outbreak has engulfed 10 countries throughout Asia. Authorities have exterminated millions of domestic chickens and ducks to contain the bird epidemic. At least 21 people have died in Vietnam and Thailand.
So far, scientists believe nearly all the human victims contracted the disease from birds. In two cases, however, investigators haven't ruled out human-to-human infection.
"It's incredibly troubling," said Richard Webby, influenza researcher at St. Jude Children's Research Hospital in Memphis. "The more chance that virus has of interacting with humans and human viruses, the more danger we're in."
If the virus succeeds in tweaking its genome to become a far-traveling human scourge, it will join a rogue's gallery of killer influenza viruses that have struck humanity through the millennia.
Influenza's History
The earliest-known reference to flu probably comes from the writings of the ancient Greek physician Hippocrates, who in the 5th century BC described an outbreak of coughs and pneumonia in the city of Perinthus.
It was centuries before the illness came to be known as influenza (Italian for "influence" or "visitation"). People believed the disease was caused by inauspicious alignments of the stars.
Pandemics have swept the world 31 times since 1580, the first clearly recorded case. The most infamous was the 1918 Spanish flu outbreak, which claimed the lives of 20 million to 40 million people before it was over.
All the pandemics' viruses belonged to a large family known as Influenza type A. The virus looks like a sphere studded with hundreds of tiny spikes. Inside the sphere's core are eight strands of genetic material carrying building instructions for a modest 10 proteins -- all the virus needs to infect, replicate and spread.
The spikes on the outside, comprised of two proteins known as H (hemagglutinin) and N (neuraminidase) act like hooks to help the virus get into and out of cells. Hs and Ns come in many different forms, and the major subtypes are all assigned numbers.
How Disease Spreads
A cough from an infected person can send a droplet of fluid packed with millions of flu particles through the air to the next victim's nasal passages. The virus attaches to the victim's cells using its hundreds of spikes. Once inside, it diverts the cell's machinery for its own nefarious purpose: the mass production of more viruses.
Errors accrue as the virus' genome is copied, causing a gradual "drift" in the structure of its proteins. Especially important are slight changes in H and N. This drift is why people can get flu over and over, and new vaccines are needed each season. Immune systems can't entirely keep up with the changes, but these flus are usually not lethal because our bodies have been exposed to similar viruses.
