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Last summer, the Johns Hopkins Center for Civilian Biodefense Studies simulated a bioterrorism attack. They called the game Dark Winter.

In the simulation, a terrorist released smallpox in Oklahoma City in the winter of 2002. Over the next 13 days, government, health care and media representatives watched the disease spread to 25 other states and 15 other countries. Game players concluded that government is incapable of dealing with a crisis of such magnitude. Containment proved impossible.

The alarming conclusion has taken on new significance since September 11. After a series of anthrax cases, bioterrorism is much closer to home for the American public.

"If there's a silver lining at all, it's that with a small number of deaths we're ramping up to become concerned about more serious things," said Dr. Steven Block, a Stanford professor of Applied Physics and Biological Sciences and an expert on bioterrorism.

Block is a member of JASON, a group of academics who advise the U.S. government on technical matters relating to national security. He realizes that while the threat of bioterrorism has only just become prominent in the public sphere, biological weapons are nothing new.

In the 14th century, the Tatars proved that biological weapons are simple to unleash but difficult to control. The Tatars catapulted the bodies of bubonic plague victims over the city walls of Kaffa, a Black Sea port. Some of the city's inhabitants escaped to rat-infested sailing ships, spreading the bubonic plague across Western Europe.

During the Cold War, the Soviets created a bioweapons program of frightening magnitude. From 1970 to 1992, 60,000 Soviets were involved in the research and testing of biological weapons.

"This is a project which dwarfs the Manhattan Project," Block said.

Following the breakup of the Soviet Union, foreign nations recruited the scientists. Some, like Ken Alibek, joined private companies in the United States and exposed secrets about the bioweapons program. One of the Soviets' most deadly projects was an attempt to create the chimera virus. Half smallpox and half Ebola, the chimera virus could perpetuate as rapidly as smallpox and kill with the force of Ebola. The Soviets considered the best biological agents to be those with no prevention and no cure.

It is unknown whether defecting Soviet scientists have sold their research to nations which harbor terrorists, but American scientists and government officials are preparing for the possibility.

The Center for Disease Control (CDC) in Atlanta has created a smallpox response team which could diagnose cases early in an outbreak. The team includes Dr. Lawrence Brilliant, who worked to eradicate smallpox in India during the 1970s. Brilliant believes that a smallpox outbreak would dwarf the recent anthrax scare.

"Anthrax is kindergarten stuff," Brilliant said. "Smallpox is the worst I could think of."

Although smallpox has a 35 percent death rate - compared to 80 percent for inhalation anthrax - the disease is highly contagious. If someone is exposed to smallpox, it is 70 percent likely that they'll become infected. Painful lesions on the skin and inside the body make it difficult to breathe and eat.

"Anyone who has ever seen a case of smallpox will go anywhere and do anything to stop it," Brilliant said.

Brilliant has seen plenty of smallpox cases. He came to India as part of a hippie commune, intending to offer relief to cyclone victims in Bangladesh. Commune members were denied permission to enter Bangladesh because 10 million refugees were streaming across the border the other way. Brilliant stayed in India, and eventually settled in with a guru in the Himalayas.

After a year a spiritual learning, the guru told Brilliant that it was his dharma to serve the poor and sick. India was suffering from massive smallpox outbreaks, and this American doctor needed to help.

When Brilliant first showed up at the offices of the World Heath Organization (WHO), officials didn't know what to make of him.

"I had a white dress and hair down to the middle of my back," Brilliant said. "They thought I was the nuttiest thing."

After cutting his hair and purchasing Western clothing, Brilliant managed to convince WHO that he was serious about joining the smallpox eradication team.

India and Bangladesh were the last nations to eradicate smallpox due to difficult working conditions. Population density fosters the rapid spread of disease and superstitions lead to fear of vaccination. Brilliant was vaccinated more than 300 times in demonstrations to ease Indians' worries about the shot.

Brilliant witnessed the last naturally occurring case of smallpox in Bangladesh in 1975. Due to WHO's persistence in tracking the disease and vaccinating those who had been exposed, the world was declared smallpox free. Today, the only known smallpox samples exist in laboratories in the CDC and Moscow.

If a smallpox outbreak occurred in the United States, Brilliant and the CDC advocate the vaccination method used by WHO in the 1970s. Since vaccination is effective even after exposure to the virus, tracking the disease after an outbreak is preferable to mass inoculations.

"It's morally challenging calculus," Brilliant said. "We have to look at which will kill the most people or make the most people safe."

According to Brilliant, if 300 million Americans were vaccinated for smallpox, 1,000 would die, 30,000 would be left blind, and 100,000 others would suffer other serious side effects.

"That amount of pain for the hypothetical doesn't make sense," Brilliant said.

Although the CDC is developing strategies to contain an outbreak, Brilliant worries about how the American public would respond to a crisis. For religious or moral reasons, a variety of groups in America don't believe in vaccination.

"These guys are nuts," Brilliant said. "They don't understand what they're dealing with."

Brilliant also fears reaction to quarantine or closed borders following a serious smallpox outbreak.

"We're a very violent country and we have a lot of guns," Brillant said. "People will do anything to keep disease away from them."

Block points out that quarantines also raise serious civil liberty and logistics questions. The CDC plan for a smallpox outbreak acknowledges that containment "may require suspension of large public gatherings, closing of public places, restriction of travel." In the most extreme case, federal and state authorities would erect barriers around an entire city.

As the CDC develops its first response team, bioterrorism preparations are underway close to home. The Stanford Hospital has created a bioterorism task force to build upon existing emergency procedures. Although the 300-bed hospital is too small to handle an influx of patients in the case of an outbreak, Stanford's sophisticated scientific community is key to preparing for bioterrorism.

"We've got some of the greatest scientific minds here who know more about the agents," said Lou Saksen, vice president of general services at the hospital and co-chair of the bioterrorism task force.

The task force, which includes representatives from all hospital departments, has developed a response plan called Code Zebra. The name refers to an old medical saying - if it sounds like hoof beats, it's probably a horse. In other words, don't look for everything else in a diagnosis. But with new threats of bioterrorism, doctors may have to consider zebras when they hear hoof beats. Flu symptoms could indicate more than the flu.

"Anthrax, smallpox, Ebola - all start with flu-like symptoms," Saksen said.

In a Code Zebra, medical staff would prevent infected patients from entering the emergency room.

"If someone comes in covered in white dust, the whole area is exposed," Saksen said in a reference to anthrax.

The quarantine period for smallpox is 16 days. If someone infected the emergency room, the hospital would shut down and be unable to provide trauma care for over two weeks.

Suspected cases would be decontaminated in the triage area and given the appropriate antibiotics. Hospital staff would shut down one wing and use it as the incoming area for patients with flu-like symptoms.

Saksen considers non-contagious anthrax to be at one end of the bioterrorism spectrum, with smallpox as a worst case scenario.

"One smallpox patient is a disaster," Saksen said. "It's hard to believe that any country would unleash something so devastating."

Saksen would like to believe that the uncontrollable nature of smallpox would prevent someone from triggering an outbreak, but realizes that terrorists aren't always rational.

"We're not expecting a big mushroom cloud, but it could be delivered with a very low-tech method," Saksen said. "If you're committed to dying, just inject yourself with bacteria and you could infect a lot of people."

Although smallpox symptoms are obvious during the contagious stage, Saksen believes that terrorists could hide behind clothing and makeup long enough to expose people.

"If you walked through the lobby of the San Francisco airport, you've done your damage," Saksen said.

Fearing that terrorists could obtain bacteria with ease, government officials have opened the debate on laboratory security. According to Saksen, Stanford works with biological agents that could be used in a terrorist attack. Anyone using the labs must go through several sets of checks, and labs are inspected regularly.

California Senator Dianne Feinstein has proposed stricter background checks on university lab workers and more extensive security safeguards. Scientists are concerned that new regulations will hinder studies on biological agents - studies which could lead to new vaccines.

"The paperwork burden is already horrendous," Block said. "If we make it so difficult to study these pathogens, we could shoot ourselves in the foot."

The scientific community is debating whether to publish experiment results which could help terrorists design biological weapons. This year, Australian scientists Ron Jackson and Ian Ramshaw discovered a genetically engineered strain of mousepox that kills even vaccinated mice. They decided to publish the results to warn the scientific community of the need to strengthen protections against biological weapons. Restricting the information flow between the scientific community, argue some scientists, could do more harm than good.

"You don't know if your unborn babe will turn out to be Hitler or Ghandi," Block said. "How can you know what will come of published results?"

Biological terrorism has created new questions of ethics, and scientists agree that there is no easy answer. Although the death toll from the recent anthrax outbreak is small, bioterrorism experts worry that it unleashes new standards for terrorists. As Brilliant says, once the genie is out of the bottle, it's hard to put back.

"Biological terrorism is a violation of an unwritten taboo," Block said. "It sets a precedent which is hard to come back from."