Haunted by the knowledge that influenza killed 50 million people in 1918, scientists and public health officials continue to seek ways to head off the next great pandemic.
They are focused mostly on the lethal avian influenza that's spreading among birds and some of their human caretakers from Asia to Europe and Africa.
The virus is killing humans at a rate of one every four days - 73 this year - or twice last year's pace. And its spread increases the chance it will swap genes with a human flu virus, producing a hybrid that will be easily spread and deadly among people.
So far, the human toll has been relatively small in a global context. The bird flu virus seems to have a difficult time jumping from birds to people.
But scientists are on alert for signs of a genetic shift that could transform the bird disease into something capable of killing millions, disrupting daily life and commerce across the globe.
Others are looking for the best way to construct a vaccine, or antiviral drugs, to prime our immune systems to grapple with the more dangerous virus that may evolve from the avian flu.
And public health officials are working to devise the most effective ways to slow the spread of a pandemic, to hold mass vaccinations and keep essential services running despite absenteeism.
It's an unprecedented mobilization against a virus that doesn't yet exist, officials note. And it's never been done for any influenza virus, despite the substantial death tolls from the annual flu - a complacency that has begun to dissolve.
"The lack of adequate preparation on a yearly basis for a highly predictable seasonal flu is one of the reasons we are now in crisis mode with pandemic flu," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.
Known officially as avian influenza A (H5N1), the bird flu virus is not the same virus that carried illness and death around the planet in 1918 and 1919.
But scientists have found similarities to the 1918 bug, which they have reconstructed from DNA extracted from human tissues saved since the First World War, and chipped from the dead in an arctic grave.
They believe the 1918 virus evolved from an A-type bird flu virus that jumped to humans. Without any past exposure to anything like it, human populations had little or no ready immunity. Nearly everyone was exposed to what was known as "Spanish flu" and death rates reached 8 percent in some places.
The H5N1 avian flu virus is also a Type A avian influenza. Its least-destructive (low pathogenic, or "low-path") form is common in the guts and saliva of wild birds, and easily spread, though rarely fatal to them.
What has scientists worried is that a highly pathogenic ("high-path") strain of H5N1 has emerged. It can kill wild birds and burns through domestic flocks, killing 90 percent to 100 percent of the flocks in a day or two.
That puts the virus in close proximity to people, who are falling ill and dying in increasing numbers. The World Health Organization said this week that 256 people in 10 countries are known to have been sickened by the H5N1 virus since 2003. Of those, 151 have died. That's a 59 percent mortality rate.
Until now, most deaths occurred among people in close contact with sick birds. Among the cases announced this week was a 67-year-old woman who died in West Java, part of Indonesia. She fell ill after her household chickens began to die.
Another was an 11-year-old boy from South Jakarta. He, too, had been fatally exposed to dead chickens in his neighborhood, the WHO said. Indonesia is the current hotspot, with more cases this year than any other nation.
The H5N1 virus is still having a hard time spreading directly between people. But it can, and does.
In June, WHO described a case in Indonesia where one person was infected during contact with infected poultry. He then spread the illness to six family members, and one of those six - a child - infected his own father.
Researchers studying the virus' species-jumping capacity have already reported infections in domestic pigs - frequently a source of illness for humans - wild and domestic cats, dogs and a weasel-like animal in Germany.
So far, the highly pathogenic H5H1 strain has not been found in the Americas. But surveillance continues of migratory bird populations that might bring it here.
The U.S. Centers for Disease Control and Prevention and the federal departments of interior and agriculture said recently that they had found evidence of the H5 and N1 proteins in pintail ducks in Ohio, mallards in Pennsylvania and teals in Illinois. But they said these were likely from separate viruses, or the low-path strain of the H5N1 virus.
"We have done close to 20,000 samples for wild birds in North America ... and none of those samples has been positive for the high-path Asian H5N1 form," said Hon Ip, director of the National Wildlife Health Center's diagnostic virology lab in Madison, Wisc.
Although more samples await testing, he said, "for this summer and fall we can pretty much safely conclude it [high-path H5N1 avian flu virus] is not here."
Acting on the assumption that the bird flu virus, or a human flu virus related to it, will eventually get here somehow, public health authorities and researchers continue to prepare.
Government researchers and pharmaceutical companies have been developing and testing "pilot" versions of a vaccine for the three strains of the H5N1 virus detected in Asia since 1997. And some are being stockpiled on the chance that the pandemic virus, if it emerges, will be closely related.
A study in the New England Journal of Medicine reported, however, that while one of those vaccines worked, it has problems. The dose required is too high, and it worked in only half the people tested, Fauci said.
Subsequent studies have found that compounds called adjuvants, when added to the vaccine, boost the body's immune response - "encouraging data," Fauci said.
Research at the University of Rochester, described this week at a meeting in Toronto, found that "priming" a patient with an H5N1 vaccine - even years ahead of time - will boost the immune response to vaccines given later for another H5N1 strain that evolves.
Hundreds of millions of federal tax dollars have been invested in expanding the pharmaceutical companies' vaccine production capacity. They are also developing new manufacturing facilities based on faster new molecular technologies that would end the need to grow the viral antibodies in chicken eggs.
Fauci said the H5N1 virus has not gotten any more deadly or more easily transmitted to people, even as it has changed its genetic makeup.
To buy more time for people to avoid infection and achieve immunity, the CDC is commissioning $5.2 million in research into the effectiveness of more traditional public health measures.
The CDC is asking the Institute of Medicine and others for advice and hard data on the best ways to slow the flu's spread.
Under scrutiny are such measures as school closings, "voluntary isolation" of the sick and "protective sequestration" of isolated healthy groups. Even the use of face masks and personal hygiene strategies such as sneezing into your sleeve will be re-examined for their usefulness.
The Maryland Department of Health and Mental Hygiene recently formed a Pandemic Influenza Coordinating Committee to plan for the sociological consequences of a pandemic.
Composed of federal, state and local health and safety officials, hospital, industry and faith groups, the PICC will develop plans for keeping vital services, such as police and fire, transportation, utilities and sanitation, functioning despite high absenteeism.
The state Department of Health and Mental Hygiene has held tabletop and field exercises with federal, state and local authorities to develop and troubleshoot pandemic planning.
"There's been a very concentrated effort of exercises for the last 11 months," most recently in August, said Dr. Matthew Minson, director of the office of emergency preparedness at DHMH.
How would they keep the public informed of developments and vaccination clinics? How would the vaccines be distributed? How would the spread of illness be tracked? How would hospital overflows be handled? How can civilian volunteers best be used to augment public officials?
"This is kind of unprecedented ... to get ready for a disease that doesn't really exist yet," Minson said.
At the local level, too, health and public safety officials continue to develop and refine plans.
For example, the Howard County Health Department last weekend conducted what amounted to a pandemic drill, providing more than 2,100 flu vaccinations in six hours at a drive-through clinic in Columbia.
Although the vaccine offered protection against only the annual flu strains expected this winter, the exercise helped expose kinks in the county's pandemic plans.
One Howard resident branded it a "farce" after waiting in line for two hours and 40 minutes, burning a quarter-tank of gas. "If this had been an emergency situation - terrorist attack, bad weather ... flu epidemic - there would have been a riot," Joan Roderick wrote in an e-mail to The Sun.
County health officer Dr. Penny Borenstein acknowledged problems with the design and command structure. And communicating with those in line could have gone better.
"Human nature dictates that you keep people informed every step of the way as to what they can expect," she said. "We did not have enough staff in place to provide that information."
Nevertheless, she said, "this is a mass clinic model we would potentially use," in part because the drive-through format isolates people from each other, providing a measure of infection control.
"In a real emergency," she added, "we think people would be more patient [waiting for a protective vaccination] ... than if it were a normal, sunny Sunday and there was a football game on."
For more avian flu coverage, go to baltimoresun.com/avianflu.