Eighteen years after doctors gave the last smallpox vaccination, the United States is preparing for a biological attack.
The defeat of the deadly smallpox virus still stands as one of modern science's most stunning achievements.
The disease covers the body in pustules that itch and ooze and often blind or disfigure survivors. Smallpox killed 500 million people between 1880 and 1980, the year the World Health Organisation declared it "eradicated".
The victory was fuelled by a vaccine that uses a milder but still-dangerous relative of the smallpox virus to provoke an immune response. The vaccine has not been used widely since the early 1980s, but the spectre of bioterrorism has resurrected it.
President George W. Bush has ordered vaccinations for US military personnel in high-risk areas. He also announced plans to offer the shot to healthcare and emergency workers - and eventually to the public.
But does vaccination pose a greater risk than the threat of terrorism? That is a question health officials will be grappling with in the coming months as they debate exactly who should be protected.
Throughout the 1980s and 1990s, the variola virus, which causes smallpox, remained very much alive in Soviet military laboratories, and that stockpile has never been fully accounted for. Many fear that samples could fall into the hands of terrorists - or may have already. Iraq may also possess clandestine samples.
But the vaccine itself poses real hazards. The US Centres for Disease Control and Prevention says 15 of every million people vaccinated for the first time could suffer life-threatening reactions such as encephalitis (brain inflammation), generalised vaccinia (a systemic infection from the vaccinia virus) and eczema vaccinatum (a widespread skin eruption).
Mr Bush acknowledged the dilemma when he stopped short of ordering vaccinations for the public, citing the vaccine's "inherent health risks". By 2004, however, he plans to make the vaccine available to almost anyone who wants it.
Routine vaccination could prove far more dangerous today than before the vaccine went out of use 20 years ago. In an age of Aids, chemotherapy and organ transplants, millions more people now live with compromised immune systems. Those people are all at high risk of complications.
Two leading US experts highlight the debate. In 1969, Dr Donald Millar and Dr Michael Lane wrote a seminal paper on smallpox vaccinations, declaring that they were no longer necessary.
Smallpox had not been seen in the US since 1948, yet thousands of children were suffering bad reactions to the vaccine, and roughly one in a million was dying of complications.
"The benefits of routine ... vaccination no longer outweigh its risks," they wrote in the New England Journal of Medicine. Today the two no longer agree. Dr Millar favours voluntary peacetime vaccination as a strategy for restoring some of America's lost immunity.
His approach could minimise the damage done by the vaccine. During peacetime, health workers would have the luxury of screening people before inoculating them - and caring for those who suffered complications. If even half the population were vaccinated in advance, everyone would be safer because fewer people would be capable of contracting smallpox and spreading it.
"We've just spent millions on airport security," says Dr Bill Bicknell, of Boston University School of Public Health. "We could spend less on smallpox and just take it off the table."
But should the US go to such lengths to eliminate a threat that may never materialise? Dr Lane continues to believe a post-attack strategy is the only one needed.
Under plans in the US Government's new "Smallpox Vaccination Clinic Guide", states and cities must establish clinics that can open quickly during an emergency to screen, counsel and vaccinate anyone who walks through the door.
Most experts believe that is a feasible goal. Smallpox does not spread easily from person to person during its seven to 17-day incubation period, and even infected people can often avoid serious illness by getting vaccinated before they develop symptoms.
Inoculating the nation that quickly would pose big challenges, says Yale health analyst Edward Kaplan, "but it's not impossible".
Can anything be done to make smallpox vaccines less risky?
The US Government is now stocking up on vaccinia-immune globulin, a medicine that can ease adverse reactions to the vaccine. At the same time, it is financing research to develop entirely new smallpox vaccines.
The most promising of these third-generation products - based on a weakened vaccinia strain known as MVA (Modified Vaccinia Ankara) - is already being used as a delivery vehicle in gene-therapy and Aids-vaccine experiments. Even extremely ill patients tolerate it well.
After confirming MVA's safety, says Dr Anthony Fauci of the National Institute of Allergy and Infectious Diseases, researchers will begin testing its efficacy against smallpox. At the very least, he says, it may provide a good booster for people vaccinated decades earlier.
When scientists devise a vaccine that is as safe as MVA and as effective as the vaccines that eradicated smallpox in the 1970s, perhaps we will all take the shot and stop worrying. Short of that, it seems that no plan can keep people completely immune from tough choices that could cost lives.
- AGENCIES
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