Smallpox was officially wiped out 22 years ago, but Tara O'Toole, a bioterrorism expert at Johns Hopkins University, can imagine how the ancient disease might quickly come back.

Her scenario begins on an April day, with the FBI deciding not to tell other agencies about vague rumors that bioterrorists will strike during the vice president's visit to a Northeastern city.

By mid-June, there are 15,000 U.S. smallpox cases, including 2,000 deaths. Dramatic footage of pox-covered children fuels public panic, and emergency rooms are overwhelmed by demands for inoculation.

By year's end, smallpox has taken hold in 14 countries, and the World Health Assembly is contemplating a new global campaign to try to eradicate the disease again.

O'Toole's provocative scenario was published in 1999 in a journal of the Centers for Disease Control and Prevention. Now, shaken by the Sept. 11 and anthrax attacks, U.S. officials are avidly debating exactly such grim what-ifs - and how best to prepare.

Yesterday, a CDC advisory committee recommended "pre-attack" vaccination of up to 510,000 hospital workers. That is more extensive than the panel recommended in June but less ambitious than the administration's latest proposal, which would gradually phase-in vaccinations of most Americans.

Over the last year, the United States has stockpiled about 153 million doses of smallpox vaccine and readied response plans for an outbreak of the deadly virus, which some experts believe may be part of Iraq's arsenal. But there is sharp disagreement about how many people should be inoculated in preparation for a calamity that may never happen and whether to offer vaccination to the public.

Some people may find the debate overwrought, given that almost half of Americans alive today were vaccinated as youngsters. Why not just resume the routine inoculation program that ended in 1972?

But much has changed since then. Americans are less willing to tolerate the vaccine's sometimes life-threatening complications, and the number who would be at high risk of complications has grown.

While there is not a final plan for inoculation - either before or after an attack - these are key issues and quandaries that officials must consider:

The likelihood of a smallpox attack.The only acknowledged smallpox virus remaining in the world is locked away in U.S. and Russian labs. There are concerns that Russia had - or has - a bioweapons program and that some of its smallpox stocks may have found a way to the black market.

Whether a terrorist with the technology to spread the virus - presumably in an aerosol - would be suicidal enough to try to do so is impossible to gauge. Smallpox is normally spread in airborne droplets from an infected person or direct contact with the rash or scabs.

Meryl Nass, a Freeport, Maine, physician and authority on bioweapons, believes any smallpox outbreak would soon go global.

However unlikely, such a smallpox epidemic would be horrific. Almost a third of unvaccinated victims would likely die, and many survivors would be scarred, blind or deformed.

The safety of the vaccine.In 1796, a British physician, Edward Jenner, figured out that inoculation with vaccinia - a virus that caused the cow version of smallpox - protected people from smallpox. Science has not improved on this approach.

Dryvax, the smallpox vaccine in government stockpiles, was made decades ago by Wyeth Laboratories. It is a live cowpox virus vaccine, administered by needle pricks on the shoulder. A nearly identical vaccine made by the French firm Aventis is also in the U.S. stockpile.

While modern vaccines for other diseases are made with disabled viruses that cannot cause infection, Dryvax can be spread - elsewhere on the vaccinated person or to an unvaccinated person - because the vaccination site sheds the live virus as it heals.

Although accidental infection is rare - a few cases for every 100,000 vaccinations - Dryvax can be dangerous or even deadly for people who should not be vaccinated, including pregnant women and those with chronic skin conditions or weakened immune systems.

Studies from the 1960s suggest 15 people of every million vaccinated will have life-threatening skin complications or brain swelling, and one or two will die. The CDC warns the rates could be higher today because of the prevalence of immune-suppressing HIV, cancer therapy and organ transplants.

Complications are "very rare, but in this day and age, even a rate as low as that isn't tolerated by our society," said Steven R. Rosenthal, a vaccine evaluator at the Food and Drug Administration. "The oral polio vaccine caused a rare paralysis that occurred to one in 3.3 million [people]. Even that has caused us to switch" to a safer polio vaccine.

The CDC has contracted with Acambis-Baxter Pharmaceuticals of Cambridge, England, for a new supply of smallpox vaccine, scheduled for delivery by the end of the year. It will still be a "live" type.

The effectiveness of the vaccine.Studies show Dryvax - a powder that is reconstituted with a liquid - built immunity in more than 90 percent of vaccinated people. To stretch existing supplies of the vaccine, the government plans to use it at one-fifth the intended concentration. Will it still work? Yes, according to recent tests.

Protection against smallpox fades over a 10-year period. People vaccinated before 1972 may have some residual immunity - but not full protection, studies show.

Vaccination strategies.Experts agree that even a single confirmed case of smallpox would signal a bioterrorism attack because the disease no longer occurs naturally.

But how to respond? As O'Toole's scenario illustrates, human factors, from the FBI dropping the ball to infected people flying abroad, could turn a manageable emergency into a global disaster.

The good news is that vaccinating people within four days of exposure can often prevent infection or reduce its severity. Also, the disease is generally not contagious during the first 12 to 14 days of infection.

Considering all this, CDC advisers and the American Academy of Pediatrics, among others, have recommended that an outbreak be controlled by isolating and vaccinating infected people and their contacts. If that kind of limited vaccination proved inadequate, widespread voluntary inoculation might be warranted, despite the risk of vaccine side effects.

The CDC has developed a 48-page guide, complete with informed-consent forms, for setting up mass-vaccination clinics to respond to an attack.

But the pediatricians do not believe the benefits of routine pre-attack vaccination outweigh the risks.

"At this point, we have real reservations about voluntary mass vaccination," said Robert S. Baltimore, a Yale University pediatrician on the academy's advisory committee. "The public is not well-informed about the side effects."

CDC advisers, who initially advocated pre-attack inoculation of only about 20,000 hospital workers, yesterday said they changed their recommendation because of more study and feedback - not political pressure.

Earlier this month, in the latest of a series of proposals, top federal health officials said they favored a three-phase vaccination program that would initially inoculate up to 10 million health-care workers, police and paramedics, then extend voluntary vaccination to the public.

Whatever plan is adopted and enacted, it won't solve a basic problem.

"What does a perpetrator do when the nation is immunized against anthrax or smallpox?" Nass, the Maine physician, asked rhetorically. "He simply picks another agent, like tularemia, plague, Ebola, or an encephalitis virus."

Contact Marie McCullough

at 215-854-2720 or mmccullough@phillynews.com.

About the Vaccine

A "live virus" vaccine contains a living virus that is able to give and produce immunity, usually without causing illness.

Because the virus in the vaccine is live, it can be transmitted to other parts of the body or to other people.

For most people with healthy immune systems, live virus vaccines are effective and safe.

Sometimes a person getting a live vaccine has mild symptoms of the virus in the vaccine.

Other live virus vaccines used in the United States include measles, mumps and rubella, and chicken pox.