Tommy G. Thompson's schedule for Sept. 11, 2001, had penciled into the 9:30 a.m. slot: "flu vaccine briefing."
Experts from several federal agencies were going to tell the new secretary of Health and Human Services what to expect in the upcoming flu season -- and give him a status report on preparations for a possible worldwide outbreak of influenza, a pandemic.
"He wanted to know why the pandemic plan wasn't finished," a person who was there recalled recently. "He was very annoyed -- having been convinced pandemic flu was a danger -- that it had been allowed to languish." Another participant remembers Thompson as "livid."
As the news of that morning's terrorist attacks trickled in, Thompson at first insisted the meeting proceed before dismissing the group, saying they would meet later.
The aborted briefing that morning symbolizes the tortuous route that the issue of pandemic influenza has taken as it has ascended the national agenda -- a place it occupies today in a way few health issues ever do.
Last week, President Bush asked Congress for $7.1 billion to confront the threat, and the administration released a massive and long-awaited flu preparedness plan. Today, U.S. health officials and experts are in Geneva for a three-day international meeting on how to stop the spread of a potential pandemic virus that has begun spreading around the world.
But it took more than an earnest and angry Cabinet secretary to get the country's attention. It took four more years of cajoling, the reappearance of "bird flu" in Asia with a chilling trickle of human deaths, a vaccine debacle, Bush's summer reading, migrating birds and a hurricane. Ironically, the events of Sept. 11 may also have prompted action.
Whatever the reasons, pandemic flu has now arrived -- not the disease, but the issue. The latest milestone in its march into the public eye was last week's release of the "pandemic influenza plan" -- 396 pages of dire prediction and advice. It is the plan Thompson was asking about four years ago.
"There is no question that the tipping point has finally arrived," Thompson, now a private consultant, said recently. "I'm sorry it wasn't two years ago."
But the seemingly overnight appearance of worries about pandemic flu on the front pages and in water-cooler conversations is misleading. The subject has been evolving out of sight for years -- much like the virus itself.
"I think there was always rather intense interest at the level of the [HHS] department," said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases and a chief adviser of the past two secretaries. "Influenza has always been at the very top of my short list of things to be concerned about."
"The idea that pandemic flu has just gotten traction is not strictly accurate," said Martin G. Myers, former head of the National Vaccine Program Office and now a professor of pediatrics at the University of Texas Medical Branch in Galveston. He said a draft was presented in 1998 to Donna E. Shalala, HHS secretary in the Clinton administration.
An influenza pandemic occurs when a strain of flu virus emerges that has the capacity to be transmitted easily from person to person but is so different from previously circulating strains that just about everyone is susceptible to it. It occurred only three times in the 20th century -- 1918, 1957 and 1968.
Over a long enough period of time, a flu pandemic is inevitable. But the intervals can be long enough that an entire generation reaches maturity with no recollection of one.
"Flu people have a saying: 'The clock is ticking. We just don't know what time it is,'" Myers said.
A hint that pandemic hour might be nigh occurred in 1997 when an unusually virulent form of avian influenza called A/H5N1 appeared in Hong Kong. The virus swept through chicken flocks causing close to 100 percent mortality. More troubling, it occasionally infected people who came into contact with the birds. Over several weeks, 18 people got it and six died.
It was the first time flu viruses of the broad H5 subtype had been known to infect people. Hong Kong authorities ordered every bird in the territory killed to stop the outbreak and prevent further adaptation of the virus to human hosts.
Myers was one of many scientists already convinced that pandemic flu was no idle threat. He convinced Stewart Simonson, HHS deputy general counsel, and Simonson in turn helped convince Thompson.
Thompson soon had pandemic flu and food safety at the top of his list of 20 high-priority issues. The events of Sept. 11, however, and the anthrax attacks that followed, forced pandemic flu down the agenda.
Nevertheless, when Bruce G. Gellin, a physician and epidemiologist from Vanderbilt University, arrived in late summer 2002 to replace Myers, Thompson told him "his first, second and third jobs were to get the pandemic plan out," according to an HHS insider.
The issue took on new urgency in February 2003, when two members of a Hong Kong family that had recently visited mainland China became ill with H5N1 flu, and one died. But what really concerned public health officials was the appearance that same month of a new disease initially mistaken for flu -- SARS, or severe acute respiratory syndrome.
Also arising in China, SARS eventually spread to more than 30 countries over six months. It infected 8,000 people, killed about 800, and cost the world $80 billion. Yet the control of SARS was an unprecedented success. A report by the National Academy of Sciences' Institute of Medicine in 2004 said that "the quality, speed, and effectiveness of the public health response to SARS brilliantly outshone past responses to international outbreaks of infectious disease."
Experts knew a fully human-adapted influenza virus would be far more contagious than the SARS microbe. If a pandemic strain of flu emerged and spread even half as far as SARS, it would be unstoppable. They also knew the only really good tool to stop influenza would be a vaccine.
In 2003, HHS requested $100 million for "pandemic vaccine development" in the 2004 budget. It asked the Office of Management and Budget for more than that, although how much more Thompson will not say. Congress appropriated $49.7 million. The most resistance came from House Republicans.
"I think it was the lack of knowledge and information that people had," Thompson recalled. "This was a new idea and they figured, 'Give them half.' I don't think they understood the science and the probabilities and the possibilities."
The next year HHS again asked for $100 million. Congress again prepared to give it less, with the House appropriations bill calling for $60 million, the Senate's for $75 million. But before the two houses could decide on a final number, the nation's flu vaccine supply was cut in half overnight because of contamination at a Chiron Corp. plant. That led to a panicky search for vaccine by high-risk patients and government-directed rationing of the diminished supply.
The Chiron debacle had nothing to do with pandemic flu. But suddenly congressional committees wanted no part of cutting money for flu vaccine. The full $100 million request was appropriated.
When Thompson resigned last December, the HHS pandemic plan still was not out. In his exit speech, he warned that bird flu was "a really huge bomb that could adversely impact the health care of the world."
The man who replaced him, former Utah governor Mike Leavitt, quickly became a believer, too. Days after his arrival, Simonson handed his new boss a copy of what has become the cause's proselytizing text -- John M. Barry's 2004 bestseller "The Great Influenza," a 546-page history of the 1918 pandemic.
Leavitt read the book in February. He then read it again, tagging and underlining a half-dozen key passages -- all great eye-openers, he said recently. He gave nearly 100 marked copies of Barry's book to Cabinet members, administration staffers and Capitol Hill leaders.
The president himself read "The Great Influenza" during his summer vacation in Crawford, Tex. At a news conference in September, Bush referred to the book when asked a question about pandemic flu.
But something other than persuasion began to make people pay attention to the subject.
In December 2003, the H5N1 virus appeared in Southeast Asia for a third time. Since then, it has led to the death of 140 million birds and infected about 125 people, killing half of them.
In August, the virus showed up in Mongolia, Kazakhstan and Siberia, apparently carried by migrating birds. Last month, it reached Europe, infecting flocks in Romania, Croatia and Greece.
"People realized it was no longer an Asian problem," Charles H. Riemenschneider, an official of the U.N. Food and Agriculture Organization, said in an interview.
Last month, scientists completed a 10-year project in which they reconstructed the 1918 virus from the frozen and chemically preserved tissue of three victims. It showed that Spanish flu was a bird virus that adapted to man, and that the H5N1 strain that has been killing people in Asia bears genetic similarities to it.