The United States remains woefully unprepared to protect the public against terrorists wielding biological agents despite dramatic increases in biodefense spending by the Bush administration and considerable progress on many fronts, according to government officials and specialists in bioterrorism and public health.

Although administration officials have spoken at times about bioterrorism's dangers, they are more alarmed than they have signaled publicly, U.S. officials said. As President Bill Clinton did, President Bush and Vice President Cheney have thrust themselves into the issue in depth.

"There's no area of homeland security in which the administration has made more progress than bioterrorism, and none where we have further to go," said Richard A. Falkenrath, who until May was Bush's deputy homeland security adviser and is now a fellow at the Brookings Institution.

Unlike many other areas of domestic defense, which are centralized in the Department of Homeland Security, responsibility for biodefense is spread across various agencies. It is coordinated by a little-known White House aide, Kenneth Bernard, whose power is relatively limited.

Biological and nuclear attacks rank as officials' most feared types of terrorist attacks. Because of the technical difficulties in creating such weapons, they reckon the chances of a devastating attack are currently small. But the consequences of a big biological strike could be epically catastrophic, and rapid advances in science are placing the creation of these weapons within the reach of even graduate students, they said.

Given the escalating risks, many public health and bioterrorism experts, members of Congress and some well-placed Bush administration officials express mounting unease about what they believe are weaknesses in the nation's biodefenses:

* The great majority of U.S. hospitals and state and local public health agencies would be completely overwhelmed trying to carry out mass vaccinations or distribute antidotes after a large biological attack. Hobbled by budget pressures and day-to-day crises, many health agencies say they cannot comply with federal officials' urgent demands that they gear up for bioterrorism.

* Overlapping jurisdiction among federal agencies working on biodefenses -- including the departments of Homeland Security and Health and Human Services -- leads to confusion inside and outside government about who is in charge of preparations for, and response to, bioattacks.

* In tabletop exercises, missteps by top administration officials reveal that more work is required to plan how the government should communicate with the public after an attack and manage the potential flight of perhaps millions of people from city centers.

* Despite considerable progress since the 2001 attacks, the National Institutes of Health, which has the lead role in researching biological warfare vaccines and antidotes, remains largely wedded to its traditional role of doing basic research and is not producing enough new drugs. Large drug firms with track records of developing medications have little interest in making bioterrorism vaccines and treatments.

* Because of the scientific complexities, no technology exists to detect a biological attack as it occurs. Under the most advanced current program, called Biowatch, technicians remove filters from air-sniffing units in about 30 cities once a day and carry them to labs for computerized analysis in search of about 10 biological agents.

In this way, a biological attack could be discovered within a day. Without Biowatch, no one would know about a smallpox attack, for example, until the first symptoms appeared about 10 days later.

Though it clearly has far to go, the Bush administration has sharply stepped up biodefense efforts. Spending has increased 18-fold since the Sept. 11, 2001, attacks, from $414 million in fiscal 2001 to a proposed $7.6 billion this year, according to a study by the University of Pittsburgh Medical Center's Biosecurity Center.

Administration officials say that in each area where critics note weaknesses, they already have made great progress. "There is no comparison between where we are today and where we were before 9/11," said Stewart Simonson, assistant HHS secretary for public health emergency preparedness. "On 9/11 we had 90,000 doses of smallpox vaccine ready to go. Today we have 300 million."

The government "is on a wartime footing," said Anthony S. Fauci, the NIH official who heads biodefense research. "People who say we haven't made progress are not well informed about what it takes to make vaccine," he said, citing steps to develop vaccine for the ebola virus since 2001. "This is light speed. . . . Usually vaccines can take many years or decades."

The government also has launched other initiatives. One gives officials early warning of a biological attack by correlating pharmacy data about, for example, cough medicine sales with spikes in symptoms such as high fever and rashes observed at medical clinics. Another plan calls on mail carriers to deliver drugs after an attack.

Administration officials say most gaps in U.S. biological defenses result from the sheer vastness of the task ahead -- radically transforming entire sectors of society to mount defenses. They cite the need to induce an intensely skeptical drug industry to invest in biowarfare research, and the challenge of redirecting cash-starved hospitals and local health agencies into the unfamiliar field of mass casualty response.

In this age of bioterrorism dangers, long-tolerated weaknesses in the U.S. health care system have become serious national security vulnerabilities.

Daunting Array of Bioagents

The list of biological agents available to terrorists is daunting: smallpox, plague, tularemia, botulism and viral hemorrhagic fever, to name a few. Experts believe the most likely biological attack would be small, like the anthrax attacks that killed five people three years ago. But as that incident showed, even a few grams of microbes can cause widespread disruption.

Anthrax bacteria remain among the easiest microbes to manufacture and weaponize. The government has little in the way of defenses, primarily a few million doses of an old vaccine that requires six injections to confer immunity weeks later. A planned newer vaccine requires several inoculations. In the event of an attack, health officials foresee being swamped not only by crowds demanding inoculation, but also by paperwork on who has been treated.

Deepening their alarm is the prospect of new genetically engineered pathogens that could be both more deadly and more difficult to detect and treat. A 2003 CIA study described the effects of these genetically altered strains as potentially "worse than any disease known to man."

Because of "explosive growth" in biotechnology, the skills needed to make microbes resistant to antibiotics and vaccines are widely available, the CIA report said. Unlike nuclear weapons research, which is more detectable and can generally be conducted only by large government labs, bioweapons can be made by individuals in secret.

"The diversity of new BW agents could enable such a broad range of attack scenarios that it would be virtually impossible to anticipate and defend against," the CIA review said.

Although many in the scientific community are skeptical about the prospect of genetically altered superbugs, barriers to the creation of new pathogens have been falling rapidly. "We are at a transformative moment in science," said Tara O'Toole, director of the University of Pittsburgh Center for Biosecurity.

Terrorism experts believe the capacity to produce sophisticated bioweapons is still beyond the grasp of terrorist groups such as al Qaeda but easily within the reach of states such as Iran, as well as microbiologists in countries where extremist sympathies run deep. And terrorists need little expertise to mount a potentially devastating attack on livestock or crops, experts note.

"You don't need to manipulate genetics to spread foot-and-mouth disease in cattle," said David Franz, who headed the military's top biodefense research lab at Fort Detrick, Md. "You can see economic damage that adds up not to millions, but to tens of billions of dollars."

Drill Led to Breakdown

In a May 2003 exercise, the victims of a mock bioterrorism attack began to trickle into Chicago's emergency rooms complaining of fever and chills -- first in twos and threes, then by the dozens and hundreds. Soon it was thousands, and people were dying of respiratory failure all over the Midwest. But at least physicians were able to diagnose the microbe afflicting the actors in the drill: the plague.

Over the next several days, the telephone networks crashed at some Chicago hospitals and at government offices taking part in the "Topoff 2" exercise, and one was forced to use ham radios. Hospitals ran out of beds, equipment and nurses. Civic leaders gave conflicting advice on what to do. Three days later, Chicago's health system was close to collapse. Thousands of untreated people were on the streets infecting others, and 47,000 were dead or dying.

The scenario is not as far-fetched as it sounds. The government's real-world test involved thousands of emergency personnel and mock patients responding to the imagined release of aerosolized germs at O'Hare International Airport and at a Chicago Blackhawks hockey game on a Saturday night.

Just as conceivable is the breakdown of the U.S. public health system after an actual, large-scale biological attack, experts say.

According to former White House official Falkenrath, the U.S. government's reliance on state and local health agencies to speedily distribute vaccines and drugs is "the Achilles' heel" of U.S. biodefenses.

"The single biggest problem is the nonperformance of state and local public health agencies" in drawing up plans that U.S. officials have requested on how they would respond rapidly to a biological attack, he said. The plans would detail how officials expect to deliver medicine to people after the drugs are flown to airports. "From tarmac to bloodstream, their time frames are way too lackadaisical," he said.

Federal officials have given state health agencies and hospitals $4.4 billion in the past three years to develop such plans. But experts say that beyond buying computers or walkie-talkies and hiring some staff, the funds have hardly helped them prepare for large-scale bioterrorist strikes.

"This won't be solved by money alone," said Elin Gursky, a biodefense specialist at the private Anser Institute for Homeland Security.

Federal statistics show that among the 50 states, only Florida, Illinois and Louisiana are close to being ready to swiftly distribute vaccines or antidotes from the national stockpile, according to the nonprofit Trust for America's Health, which studies public health issues.

Local and state health officials say their underfunded agencies, which focus mostly on caring for the poor, have received inadequate federal funds and guidance on what the states should address in their bioterrorism master plans.

"The public health system has been running full steam without a break since 9/11," said Georges Benjamin, executive director of the American Public Health Association. "To do added things that are being requested, it's going to need more resources."

Most U.S. hospitals also lack the "surge capacity" to respond to a bioattack -- the ability to rapidly bring in hundreds of trained medical professionals to care for a huge influx of very sick people. Expanding staffs runs counter to the decades-long trend of hospitals reducing staff sizes because of budget pressures.

"The main priority of our biodefense program should be enlisting hospitals and private doctors to prepare [for bioattacks], but hospitals and private doctors are not now in the game," said a federal official with direct knowledge of the shortcomings. "This issue has completely fallen through the cracks. . . . No part of the federal government can deal with mass casualties."

"There's a lack of an overarching federal game plan in biodefense," said Shelley Hearne, executive director of the Trust for America's Health. "States aren't being told, 'Here are the things you need to do, and why.' . . . Nobody's in charge."

But in some respects, too many are in charge. The jurisdictions of the departments of Homeland Security and Health and Human Services overlap in many areas of biodefense. Overall, HHS handles health matters, while Homeland Security handles crises. But the two departments, for example, offer sometimes indistinguishable biodefense training for local health agencies.

Administration officials say the two departments mesh well, with their roles delineated in a recent presidential directive. But bureaucratic bottlenecks persist, as the two departments' lawyers and contracting officers hash out turf, experts said.

One such case involved the Strategic National Stockpile, set up in 1999 as an arm of HHS's Centers for Disease Control and Prevention. It is a repository of tons of biodefense drugs and vaccines that can be flown anywhere in the nation within 12 hours.

Experts said the CDC did a good job managing the stockpile, and its employees grumbled when they were moved into Homeland Security last year, where officials have no expertise handling drugs or fashioning emergency medical doctrine. Every time CDC wanted to add drugs to the stockpile, the permission of Homeland Security lawyers was needed, slowing even basic functions. So with no public fanfare, the stockpile was returned to CDC in August.

The administration's most prominent action in bioterrorism -- the initiative last year to inoculate 500,000 health workers against smallpox -- fizzled. The plan was hatched in late 2002 as the country prepared to invade Iraq. Officials feared Iraq or terrorists might attack this country with the bioterrorism agent.

But workers, concerned about health risks, refused to sign up. Officials had failed to line up legal guarantees that the government would compensate workers sickened by immunizations. The worries gave way to complacency when U.S. troops failed to find smallpox or other biological weapons in Iraq.

In the end, about 40,000 people were inoculated -- 8 percent of the goal. The episode suggests the government continues to have trouble communicating with the health community and the public about bioterrorism dangers.

"The biggest consequence is the loss of credibility," Jerome M. Hauer, former director of HHS's Office of Public Health Emergency Preparedness, said of the episode. "How do you get people to trust you again?"

New Drugs Slow in Coming

To counteract the attack that officials are nearly certain will come one day, the nation needs long lists of new biowarfare antidotes and vaccines. But despite intense effort by NIH, the arrival of usable drugs has been slow, experts and U.S. officials said. Besides the complex science involved, NIH's tradition of academic-oriented basic research, and a lack of focus on creating new drugs are responsible, they said.

NIH's bioterrorism budgets have jumped from $53 million in 2001 to $1.7 billion in 2005, as Congress and other parts of the administration increased pressure on the agency to change.

"Some of the criticism of the past was valid," NIH's Fauci said. "But we've already shown we've been successful" in pushing scientific concepts toward becoming reality, he said. "This is a change in the culture."

Experts said NIH drags its feet researching such areas as skin patch vaccines, which could be given more quickly than shots, and vaccine-boosting compounds called adjuvants, which allow limited stocks to be used on more people. Fauci said NIH is working on these questions.

Even so, officials said, a top priority is persuading large drug firms to make big investments in biological warfare research -- in essence, creating a biodefense industry from scratch.

"Big pharma" is now not interested for several reasons, industry and government officials say. Big firms are accustomed to huge profits on their drugs for arthritis, ulcers, impotence and the like, and foresee returns a fraction of that size for biodefense work.

The industry also fears lawsuits against firms developing such drugs, and government temptation to nationalize patents on biodefense drugs in a crisis.

In July, Congress approved Project Bioshield, which allocates $5.6 billion over 10 years to induce the industry to begin investing in these drugs. But industry executives say they are waiting for much larger sums, as well as stronger legal liability and patent protections.

"The measures the U.S. government has taken to date (including Bioshield) will not be enough to entice pharmaceutical industry leaders into this field," according to a recent study by the University of Pittsburgh biosecurity center based on interviews with 30 top industry and government officials.

Health experts say that the recent loss of half the nation's flu vaccine supply because of contamination in a British plant does not bode well for future efforts on the more daunting scientific challenge of bioterrorism.

Some believe that Bush should publicly declare the seriousness of the government's bioterrorism concerns, name a bioterrorism "czar" to focus public attention, and initiate vastly expanded research into new drugs. Administration officials said that such steps are unnecessary and that the current arrangement works fine.

But the biosecurity center's O'Toole disagreed.

"The country cannot do what's needed to get prepared for bioattacks without very visible national leadership from the president," said O'Toole, who worked in the Clinton Energy Department. "We're not yet treating this like a national security emergency."

In May 2003, children await medical attention at Advocate Illinois Masonic Medical Center during a mock bioterrorism drill in the Chicago area.Chris Schmidt, an emerging infectious disease fellow in the Centers for Disease Control and Prevention's poxvirus section, shows the use of a biohazard suit.