By Shannon Brownlee

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Ken Alibek hardly seems like the sort of fellow to have overseen the development of the world's most terrifying biological weapon. A short, stout, moon-faced man in his early fifties, Alibek has a shock of black hair cut straight across his brow, like a schoolboy, and a whispery voice clotted with the round vowels and rolling R's of his native Kazakhstan.

A little more than a decade ago, Alibek was still Kanatjan Alibekov, creator of the world's most potent strain of anthrax bacteria, and second in command of Biopreparat, the Soviet Union's vast biological weapons program. The U.S. intelligence community knew nothing of Biopreparat until 1989, when a mid-level Soviet biologist under Alibek named Vladimir Pasechnik defected to Britain.

Pasechnik detailed for British intelligence officers the existence of clandestine laboratories, scattered around the Soviet Union, devoted to developing such potential biological weapons as anthrax, Marburg virus, tularemia, Q fever, plague, Ebola and, most appalling of all, smallpox.

After British agents passed along Pasechnik's report, the American and British ambassadors in Moscow accused the Soviet Union of violating the 1972 Biological Weapons Treaty, which banned the production and use of biological weapons. The treaty had been signed by 143 nations, including the United States and the Soviet Union.

After some tense negotiations and phone calls among British Prime Minister Margaret Thatcher, President George H.W. Bush and Soviet leader Mikhail Gorbachev, a team of American and British biologists flew to Moscow in January 1991 for the first of several mutual inspections. They found hints of biowarfare research at a number of Soviet laboratories.

But the full scope of the Soviet violation was not known until the fall of 1992. A year earlier, as part of the mutual inspections, Alibek and 12 other Soviet scientists and military officials came to the United States to inspect sites their reconnaissance experts had told them were American biowarfare facilities.

The Soviet contingent found abandoned warehouses, with grass growing at the entrances, and military labs devoted to defensive research, such as finding new vaccines for biological agents.

Alibek realized that Soviet intelligence was either incompetent or lying, and that his American hosts were telling the truth: The United States had long ago abandoned offensive bioweapons research. He and his family defected shortly thereafter, in October 1992.

In a building off I-66, in Virginia, intelligence officers and officials from the departments of State, Agriculture and Defense quizzed Alibek for nearly a year. At first, his American handlers found his reports almost too incredible to be believed.

"When I was talking, people would say, this is Ken's sheer fantasy," says Alibek. Biopreparat, he told them, could mix up batches of deadly viruses in 95-gallon bioreactors, tanks big enough for a microbrewery. Soviet biologists, he said, had modified pathogens to survive delivery by warheads. Engineers had devised a platform that could release canisters of liquid or dry pathogens, smallpox among them, as a missile moved over successive targets.

Slowly, the Americans began to understand the gravity of the security risk Alibek was describing. Smallpox, a savage disease that had killed countless millions throughout history before being eradicated more than two decades ago, once again loomed as a potential threat.

Bioterrorism experts now believe the smallpox virus exists in clandestine biowarfare laboratories in at least three, and possibly more, countries.

The US government has a list of nations that it suspects are harboring secret stocks of the virus, or have tried to buy or steal some. That list is classified, but several public health doctors and virologists who have been briefed say that, along with Russia, it includes Iraq and North Korea. Civilian bioterrorism experts and the press have speculated that China, Libya, South Africa, Israel and Pakistan may also be on the list.

Some of these nations are also suspected of harboring and aiding terrorist groups, including those believed to be involved in attacks on Americans abroad, and now at home. Indeed, when the World Trade Center buildings were destroyed last month, officials feared that the terrorists also might have unleashed biological or chemical agents into the smoking ruins.

It turned out not to be the case, but the risk of bioterrorism was no longer merely academic. What would we do -- could we do -- if smallpox were the terrorists' next weapon of choice?

Before vaccination was invented, in 1796, smallpox epidemics could change the course of history, killing as many as half their victims and crippling entire civilizations. The Aztecs, for instance, were defeated in the 16th century not so much by Hernando Cortes's comparatively puny army as by the smallpox the Spaniards inadvertently brought with them.

In the 20th century, smallpox killed 300 million people, far more than all of the century's wars combined.

The disease is caused by a virus known as variola, from Latin for "speckled." The first signs of illness come 10 days or so after infection, with a splitting headache, backache, vomiting and raging fever. Just as the fever wanes and the patient starts to feel better, the first red spots appear on the face and extremities.

The ability of smallpox to be a potent biological weapon was already demonstrated long ago. During the French and Indian Wars from 1754 to 1767 British forces in North America were able to initiate smallpox epidemics among the American Indians. Blankets used by smallpox victims eventually reached the Indians, and death rates exceeding 50% were seen after some of the tribes were successfully infected.

The rash spreads rapidly as the spots turn to lumps, called pustules, which fill with an opalescent fluid that seeps from capillaries, making them feel hard, or "shotty," as doctors describe them, like BBs embedded just under the skin.

Smallpox causes unspeakable misery. Layers of skin separate as fluid fills the spaces between them. Pustules line the nose, mouth and throat, making swallowing exquisitely painful. Sometimes the lesions are so numerous, the body takes on the texture of a pebbled walkway, and sheets of skin may slough away at the slightest touch -- a blanket, or a nurse's fingers taking a pulse.

In fatal cases, death comes within 10 to 16 days, from organ failure, or maybe pneumonia, or possibly an overreaction of the immune system. Nobody really knows precisely how variola kills.

The planet has not seen a case of smallpox since 1977.

This was two years before the disease was declared eradicated after an intensive 11-year vaccination campaign by the World Health Organization. Within a decade, scientists around the world had turned over their remaining stocks of the variola virus to two designated facilities for safekeeping.

One of these sites is the Centers for Disease Control and Prevention, in Atlanta. Variola's other official resting place is inside a freezer in a Russian laboratory known as Vector, outside Novosibirsk, Siberia.

Several times over the years, WHO officials have scheduled and then called off the destruction of the two legitimate stocks of the virus as scientists debated the wisdom of intentionally destroying a species and doctors argued for eliminating it.

Alibek's revelations, along with the 1991 collapse of the Soviet Union and end of its tight system of political control, have made such lofty debates irrelevant. There is no longer any question that clandestine stocks of the smallpox virus exist; the only unknown is who has them and whether they'd be cruel enough to use them.

A biological attack with smallpox virus -- though perhaps not as unlikely as it was just weeks ago -- is still a "low-probability, high-impact" event, in the parlance of security experts. That means it probably won't happen.

But if it did -- through, say, infected carriers on suicide missions or release into a building ventilation system or, quite unlikely, from a crop-duster -- the result could be a catastrophe. Variola kills between 10 and 40 percent of its victims.

There is no treatment for the disease, and routine vaccination ceased around the world after the disease was declared eradicated. Americans born before 1972 can probably run their fingers over a dime-sized scar on their arms or legs, where they were immunized as children. That vaccination's ability to protect began to wane within a decade after it was given.

Just how vulnerable Americans may be was brought home in a two-day simulation exercise held at Andrews Air Force Base in June. It showed quite clearly that federal and state officials would be ill-prepared for a rogue attack using smallpox.

The exercise began with 24 simulated cases. It ended two imaginary weeks later, with the nation's stockpile of vaccine exhausted, 15,000 people infected and 1,000 dead, and the expectation that every two weeks after that would see a tenfold increase in cases.

Other models starting with just 100 smallpox cases in an American city predict the disease would become a worldwide conflagration in as little as a year, unless a massive immunization campaign were mounted to stop it.

There is not enough vaccine on hand for such an effort. About 60 million doses of vaccine exist worldwide, only a fraction of them in the United States; experts estimate that blocking the spread of smallpox released in a single bioterrorism event in a single American city would require a minimum of 30 to 40 million doses. Which means that unless something is done, a lot of Americans -- and others -- would be vulnerable.

Five sets of locked doors and an eighth of a mile of hallways lie between the main entrance to the Centers for Disease Control and Prevention and the biocontainment laboratories where variola major lives in suspended animation inside a locked stainless steel freezer.

The freezer contains some 400 different strains of the virus, taken from patients afflicted with smallpox during the last century. Each sample of virus is trapped inside a bullet-shaped lump of cloudy, frozen fluid. Together, the vials take up a space no bigger than an oven, but their contents could infect every human being alive.

The reality of what that means is not lost on Jeff Koplan, who has served as the CDC's director since 1998. A tall, balding, wiry man in his fifties, Koplan bears a strong resemblance to Dick Cavett, and has a voice to match.

In 1973, when he still sported a wild mane of strawberry-blond hair and a beard, Koplan was sent by the CDC to Bangladesh, to test a drug that some thought might be effective against smallpox. By that time, Europe and the United States had already eliminated it.

The only remaining pockets of disease were in Africa, South America and on the Indian subcontinent. To find enough patients for his experiments, Koplan headed for Dhaka, Bangladesh, where he was given an empty ward in one of the city's hospitals.

"When I say empty ward, it was empty, it was a concrete shell," he recalls. "I hired an ex-sergeant from the Pakistan army, with a curled mustache and military demeanor, as my right-hand man. We cajoled and borrowed and found some beds, found a place with running water to use as a lab, moved the beds in."

City officials and international health workers steered patients to Koplan's ward, where he gave half the patients the experimental drug, and half standard care, which consisted of trying to keep them comfortable and providing IV fluids and antibiotics for secondary bacterial infections.

The drug was a flop, but Koplan learned to read his patients' futures in the rashes that appeared on their skin. The chances of dying from variola major, the most common form of the virus, depend upon how big a dose of virus a victim receives, and how vigorous a defense his or her immune system mounts.

Most of the patients Koplan saw developed the form of the disease doctors call "discrete" -- the pustules were separated from one another by unaffected skin. Patients usually survived, though they were scarred for life.

In more severe cases, called "confluent" pox, the pustules were so numerous they ran together on the skin, and the patients puffed up horribly with fluid. "I have pictures of people who on admission are recognizable, with a rash," Koplan says.

"Then five days later they're unrecognizable -- they look like they have been burned. They couldn't take anything by mouth. They were comatose. They were extremely uncomfortable." Many of those patients died, usually after suffering for 10 days to two weeks.

Koplan saw two other types of smallpox that were considerably less common, but which killed patients far more efficiently. "Flat" pox, a form of the disease in which the pustules never raise above the skin, kills 75 percent of patients afflicted with it.

"Hemorrhagic" smallpox, or black pox, is mercifully the rarest form of all. Invariably fatal within days after the fever begins, black pox causes blood vessels throughout the body to leak blood, which seeps into the mouth and gut and under the skin, where it leaves dark, bruise-like blotches. Even the whites of the eyes darken with blood. Unable to move or speak, patients with hemorrhagic pox often are aware of what is happening to them almost to the point of death.

"I had one patient in our study group who was hemorrhagic," Koplan recalls. "When I did an exam on him, I remember, it was 5 or 6 in the evening, and I could talk to him. He didn't have much in the way of skin lesions. I came in the next morning, and he was turned to the side and there was a pool of blood next to his pillow.

He bled out into his bed. One day he was sick, febrile, and not well . . . and he was dead the next morning."

The man who best knows the anatomy of a smallpox epidemic is Donald Ainslie Henderson.

Known as D.A. to his colleagues, Henderson is a doctor and the director of the Center for Civilian Biodefense Studies, a think tank run by Johns Hopkins University. From 1966 to 1977, he ran the WHO smallpox eradication program, one of the greatest medical achievements of the 20th century.

When he began his effort, 10 to 15 million people a year were still being infected by smallpox, and between 2 and 3 million were dying, mostly in Africa, Asia and South America. In a little more than a decade, Henderson and his team had bottled up the virus and confined it to vials in laboratories.

The key to eradicating smallpox was a system for choking off outbreaks. Rather than inoculate every last person on Earth, an impractical if not impossible task, Henderson and his team decided instead to track every case they could find, and encircle the virus with people who had been vaccinated.

Past experience had shown that a person who has been exposed to, and even infected with variola, can still be protected by the vaccine, provided it is delivered within five days of exposure. Unlike some viruses, Ebola for instance, smallpox is not carried by animals. Its only host is human beings.

The most common route of infection is through inhaling virus-laden droplets during face-to-face contact with a smallpox victim, although the virus can survive for hours in the air, or for days in the bedding of infected persons. Under normal circumstances, smallpox is not as easily passed from person to person as, say, the flu or measles, which can rip through a classroom in a single morning. But it is far more contagious than HIV, the virus that would cause the AIDS epidemic a decade later.

Henderson's team reasoned that if they could draw the noose tight enough around a smallpox outbreak, they could cut off the virus's path to its next human host. They called their method surveillance and ring vaccination.

The WHO enlisted thousands of local volunteers who, together with doctors from developed nations, scoured villages and cities for active smallpox cases. Doctors identified cases and ordered them quarantined in their homes or in hospitals. Volunteers stood guard, enforcing the quarantines, and tracked down every last one of a victim's face-to-face contacts. Doctors and volunteers alike could vaccinate; all it took was a vial of vaccine and a special bifurcated, or two-pronged, needle.

In October 1975, a WHO team cornered the last naturally occurring case of variola major: in a 3-year-old girl named Rahima Banu, from Bhola Island, Bangladesh. In 1977, Ali Maow Maalin, a Somali cook, became the ultimate victim of a less virulent form of the disease, known as variola minor. Both survived. (The WHO has since lost track of them.)

At 73, Henderson still strikes an imposing figure. He is well over 6 feet tall, barrel-chested, with a craggy face and prominent nose, and a diamond ring on one pinkie. To him, a smallpox epidemic is a terrifying prospect, whether it occurs naturally or as a result of bioterrorism.

A full-blown epidemic comes in waves, rings of infection that spread outward, like ripples on a pond, from each index case. Two weeks after the first round of infected people fall ill, a new wave of cases appears, only to remain steady for another two weeks, when the number of victims escalates yet again. With each wave, the number of victims increases exponentially.

Graphed on paper, the cases rise in little foothills at first, until the number shoots upward, like a viral Mount Vesuvius.

Epidemiologists think of this topography of infection as a road map to disaster. The only hope of containing an outbreak is when it's still in the foothill stage, when the number of infections is low and ring vaccination can be used to choke off the virus.

Failing to catch an outbreak early allows it to erupt. Henderson recalls the smallpox conflagration that was sparked in Bangladesh in 1971 by the savage civil war that led to the country's independence from Pakistan. By then, smallpox had been all but eradicated from Bangladesh. Henderson was at WHO headquarters in Geneva when fighting broke out.

"Refugees were fleeing across the border into India," he says. "I got a call from the US, a guy from the CDC, who had seen pictures of people in an Indian refugee camp. He said it looked like smallpox. I took a plane to the camp and there was smallpox everywhere."

When independence was declared, the refugees began flooding home. "One hundred thousand people poured across the border," says Henderson. "Smallpox exploded across Bangladesh." More than 200,000 people were infected and 40,000 died over the four years it took the WHO team to encircle the disease again.

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