Initially called "the three day fever," it started like any flu, with a cough and a headache, followed by intense chills and a fever that could quickly hit 104 degrees F. It could take a month before survivors felt completely well, and after they emerged from an energy-sapped stupor many said it felt as though they'd been aggressively hit with a club. But for those 650,000 Americans who actually died from the Spanish flu in 1918, the suffering was much worse.

Deep brown spots would appear on a victim's cheeks and a thick, bloody fluid would begin to overwhelm his lungs. Starting at the ears, their faces would gradually turn blue as circulating blood could not get oxygenated. Soon, victims would start to drown in their own fluid -- often coughing up a pinkish froth as they fought to inhale. "It is only a matter of a few hours then until death comes, and it is simply a struggle for air until they suffocate," an army doctor, based outside of Boston at Camp Devens, wrote to a colleague in 1918. "It is horrible."

The influenza pandemic of 1918 killed an estimated 50 million people around the world -- 34 million more than died from the First World War in progress alongside it. Unlike the seasonal flu, a pandemic flu is one for which there is little or no human immunity. And instead of targeting the weak or old, the 1918 flu was particularly deadly among the young and healthy. According to molecular pathologist Jeffrey Taubenberger, almost half of all flu deaths that year were among 20- to 40-year-olds. Their immune systems essentially overreacted, destroying their lungs in an attempt to get to the virus.

Though dubbed the Spanish flu, after millions of early deaths in Spain, the geographic origin of the disease remains unknown. Some hypothesize that it may have been circulating around the world for a few years before developing into a pandemic in 1918. The first confirmed outbreak in the United States, if not the world, was at an army base in northeastern Kansas on March 11, 1918. Just hours after the first soldier reported sick, dozens more began pouring into the infirmary. By the end of the day, hundreds of soldiers had fallen ill. Within a week 500 had come down with the fever.

The flu quickly spread across the country, where 2 million troops were mobilizing for the war in Europe. The soldiers carried the flu with them when they shipped out, introducing the virus to France, England, Germany and Spain. "King George's Grand Fleet could not even put to sea for three weeks in May, with 10,313 men sick," reports Gina Kolata in her book Flu. The virus jumped to China, India, Japan and the rest of Asia. By summer it seemed to have played itself out.

Then, in late August, the flu re-emerged in Boston. This time it was even more deadly. Some people reportedly dropped dead on the street; others managed to hold on for days. By the first week of September, an average of 100 people died every day at Camp Devens. "We have lost an outrageous number of Nurses and Drs., and the little town of Ayer is a sight," wrote one of the camp's doctors. "It takes special trains to carry away the dead. For several days there were no coffins and the bodies piled up something fierce; we used to go down to the morgue (which is just back of my ward) and look at the boys laid out in long rows. It beats any sight they ever had in France after a battle."

By the end of September, 50,000 people in Massachusetts had been infected with the flu. In Philadelphia, 635 people became ill after a large public gathering to raise money for the war. The city tried to staunch the spread by ordering all churches, schools and theaters closed, but by the first week of October, 289 people had died in a single day. In New York, the death tally for one day was 851. San Francisco reported cases, as did Chicago, where there were so many deaths that the city banned funerals

"The morgues were packed almost to the ceiling with bodies stacked one on top of another. The morticians worked day and night," wrote Navy nurse Josie Brown, who was stationed at Great Lakes Naval Station near Chicago. "You could never turn around without seeing a big red truck loaded with caskets for the train station so bodies could be sent home. We didn't have the time to treat them. We didn't take temperatures; we didn't even have time to take blood pressure. We would give them a little hot whisky toddy; that's about all we had time to do. They would have terrific nosebleeds with it. Sometimes the blood would just shoot across the room. You had to get out of the way or someone's nose would bleed all over you."

No place was immune to the disease, though government officials tried their best to protect residents. When ministers in Seattle complained that their churches were shuttered, the mayor retorted, "Religion that won't keep for two weeks, is not worth having." In Ogden, Utah, officials sealed off the town -- no one could go in or out without a doctor's note. In Alaska, the governor closed the ports and posted U.S. marshals to guard them. Even that didn't work: In Nome, just south of the Arctic Circle, 176 of 300 Alaska Natives died.

With 195,000 fatalities from the flu, October 1918 became the deadliest month in U.S. history. But the horror continued through November, when at least 115,000 people in California were stricken ill. Stores canceled holiday sales to keep crowds down, and shoppers were encouraged to phone in their orders. When citizens did go out, many cities required that they wear masks in public. "Obey the laws, and wear the gauze, protect your jaws, from septic paws," warned one jingle. At least one minor league baseball game was played under these circumstances. "It is a surreal image," writes Kolata of a photograph taken at the game. "The pitcher, the batter, every player and every member of the crowd are wearing gauze masks."

By the end of 1918, the flu had killed 57,000 American soldiers -- 4000 more than those killed in combat. But the world war dominated the news, even as Woodrow Wilson reportedly contracted the flu while negotiating the Versailles treaty in Paris. Twenty-five percent of all Americans contracted the virus, before the pandemic was over. The Spanish flu's reach was so complete that its death toll dropped the average life expectancy in the United States by 12 years.

The Aftermath

For more than 80 years after the flu disappeared, epidemiologists still had little understanding of what made the 1918 virus so devastating. Then, in October 2005, researchers at the Centers for Disease Control and Prevention (CDC) and the Armed Forces Institute of Pathology announced that they had isolated, decoded and replicated the entire sequence of the 1918 flu virus now known as H1N1. It was a monumental achievement. Working with tissue samples of flu victims from autopsy archives, and from the infected lung tissue of an Alaskan woman whose body had been preserved in Arctic permafrost, the researchers essentially recreated an extinct virus -- a scientific first.

H1N1, they discovered, arose from an avian strain. A virus that normally affects only birds had developed the ability to jump to humans. Further research revealed why the flu was able to spread so rapidly -- and be so deadly. The structure of the virus's protein coat enabled it to bond efficiently with receptors on human cells and to infect cells deep within the lungs. The enzymes that drive the virus's replication also worked with unusual swiftness.

Since 1918 there have been two other pandemic flus to strike the United States. The Asian flu of 1957 to 1958 killed 70,000 Americans, and 34,000 Americans were killed by the Hong Kong flu of 1968 to 1969. Today, public health officials are concerned about H5N1, which claimed its first fatality 10 years ago. It has since killed nearly 200 people. Like the Spanish flu, H5N1 is an avian flu; however, H5N1 does not yet appear to have evolved the Spanish flu's ability to spread from person to person.

Though the CDC monitors active flu strains in order to develop vaccines for the peak flu season, in many ways the public health response to the pandemic flu of 1918 began in earnest as news of H5N1 spread. In May of 2006, the White House released a 233-page implementation plan for a national strategy for pandemic influenza. The report suggests 30 percent of the population could be infected and 2 million people could die in the United States if a pandemic flu strain emerged in this country today.

The plan calls for $1 billion to be spent on improving the cumbersome vaccine process. Making a flu vaccine is a 50-year-old technology that relies on growing a specific strain in chicken eggs; 900 million eggs are required to create 300 million doses, and the process takes nine months. With the influx of federal money, scientists and pharmaceutical companies are working toward developing cell cultures to grow seed viruses. If successful, the technique could be deployed faster, provide larger quantities and allow researchers to rapidly update vaccines as a virus mutates.

By the end of September, 50,000 people in Massachusetts had been infected with the flu. In Philadelphia, 635 people became ill after a large public gathering to raise money for the war. The city tried to staunch the spread by ordering all churches, schools and theaters closed, but by the first week of October, 289 people had died in a single day. In New York, the death tally for one day was 851. San Francisco reported cases, as did Chicago, where there were so many deaths that the city banned funerals.

"The morgues were packed almost to the ceiling with bodies stacked one on top of another. The morticians worked day and night," wrote Navy nurse Josie Brown, who was stationed at Great Lakes Naval Station near Chicago. "You could never turn around without seeing a big red truck loaded with caskets for the train station so bodies could be sent home. We didn't have the time to treat them. We didn't take temperatures; we didn't even have time to take blood pressure. We would give them a little hot whisky toddy; that's about all we had time to do. They would have terrific nosebleeds with it. Sometimes the blood would just shoot across the room. You had to get out of the way or someone's nose would bleed all over you."

No place was immune to the disease, though government officials tried their best to protect residents. When ministers in Seattle complained that their churches were shuttered, the mayor retorted, "Religion that won't keep for two weeks, is not worth having." In Ogden, Utah, officials sealed off the town — no one could go in or out without a doctor's note. In Alaska, the governor closed the ports and posted U.S. marshals to guard them. Even that didn't work: In Nome, just south of the Arctic Circle, 176 of 300 Alaska Natives died.

With 195,000 fatalities from the flu, October 1918 became the deadliest month in U.S. history. But the horror continued through November, when at least 115,000 people in California were stricken ill. Stores canceled holiday sales to keep crowds down, and shoppers were encouraged to phone in their orders. When citizens did go out, many cities required that they wear masks in public. "Obey the laws, and wear the gauze, protect your jaws, from septic paws," warned one jingle. At least one minor league baseball game was played under these circumstances. "It is a surreal image," writes Kolata of a photograph taken at the game. "The pitcher, the batter, every player and every member of the crowd are wearing gauze masks."

By the end of 1918, the flu had killed 57,000 American soldiers — 4000 more than those killed in combat. But the world war dominated the news, even as Woodrow Wilson reportedly contracted the flu while negotiating the Versailles treaty in Paris. Twenty-five percent of all Americans contracted the virus, before the pandemic was over. The Spanish flu's reach was so complete that its death toll dropped the average life expectancy in the United States by 12 years.

The Aftermath

For more than 80 years after the flu disappeared, epidemiologists still had little understanding of what made the 1918 virus so devastating. Then, in October 2005, researchers at the Centers for Disease Control and Prevention (CDC) and the Armed Forces Institute of Pathology announced that they had isolated, decoded and replicated the entire sequence of the 1918 flu virus now known as H1N1. It was a monumental achievement. Working with tissue samples of flu victims from autopsy archives, and from the infected lung tissue of an Alaskan woman whose body had been preserved in Arctic permafrost, the researchers essentially recreated an extinct virus — a scientific first.

H1N1, they discovered, arose from an avian strain. A virus that normally affects only birds had developed the ability to jump to humans. Further research revealed why the flu was able to spread so rapidly — and be so deadly. The structure of the virus's protein coat enabled it to bond efficiently with receptors on human cells and to infect cells deep within the lungs. The enzymes that drive the virus's replication also worked with unusual swiftness.

Since 1918 there have been two other pandemic flus to strike the United States. The Asian flu of 1957 to 1958 killed 70,000 Americans, and 34,000 Americans were killed by the Hong Kong flu of 1968 to 1969. Today, public health officials are concerned about H5N1, which claimed its first fatality 10 years ago. It has since killed nearly 200 people. Like the Spanish flu, H5N1 is an avian flu; however, H5N1 does not yet appear to have evolved the Spanish flu's ability to spread from person to person.

Though the CDC monitors active flu strains in order to develop vaccines for the peak flu season, in many ways the public health response to the pandemic flu of 1918 began in earnest as news of H5N1 spread. In May of 2006, the White House released a 233-page implementation plan for a national strategy for pandemic influenza. The report suggests 30 percent of the population could be infected and 2 million people could die in the United States if a pandemic flu strain emerged in this country today.

The plan calls for $1 billion to be spent on improving the cumbersome vaccine process. Making a flu vaccine is a 50-year-old technology that relies on growing a specific strain in chicken eggs; 900 million eggs are required to create 300 million doses, and the process takes nine months. With the influx of federal money, scientists and pharmaceutical companies are working toward developing cell cultures to grow seed viruses. If successful, the technique could be deployed faster, provide larger quantities and allow researchers to rapidly update vaccines as a virus mutates.

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