Vials of terror

One hundred years ago a smallpox epidemic swallowed whole towns in America. In Kansas, a doctor and his bride exchanged vows at a March 1901 wedding by megaphone, both being in quarantine with the deadly disease. Since that time smallpox has killed more than 300 million people-but now, a global vaccination program has successfully wiped it out.

Smallpox, viewed as eliminated, has fallen off medical radar screens. Health clinics no longer carry the vaccine. Immunizations in the United States ended 30 years ago, leaving the population at large unprotected should the disease ever strike again. Smallpox eradication is one of modern medicine's greatest success stories-but use of the virulent virus in germ warfare could represent one of terrorism's greatest horror stories.

Six weeks ago at a government lab in Great Britain, researchers revealed that a vial of another toxin-foot-and-mouth disease-was missing. That lab also holds secret caches of tuberculosis, anthrax, ebola, and smallpox, all raising the specter that a disease heist could unleash human tragedies far worse than the livestock deaths that have swept the United Kingdom.

Debate over germ warfare will accelerate, too, because President George W. Bush is signaling that he may part ways with Britain and other allies on how best to manage specimens of viral vials. Mr. Bush is likely to reject the protocols, now more than six years in the making, for enforcing a 1972 germ-warfare treaty. A group of advisers is uneasy with inspection provisions that could give America's enemies access to private labs, without strong enough guarantees that the United States could keep an effective eye on activities of terrorist states. When the White House leaked that position to reporters last week, European allies accused the United States of reversing progress in the germ war.

Only a small handful of laboratories are known to possess smallpox virus specimens: a Russian state laboratory known as Vector, the British lab at Porton Down in Wiltshire, and the U.S. Centers for Disease Control in Atlanta. U.S. intelligence analysts believe other countries want to acquire it, or may already have secret stocks. These include China, India, Pakistan, North Korea, Iraq, Iran, Israel, Cuba, and Yugoslavia. It is no coincidence that most are already listed on the State Department's list of known sponsors of terrorism, and it is no secret that they want to build a biological weapons program. After the fall of the Soviet Union, then president Boris Yeltsin admitted that his country had a longstanding biological weapons program, including the manufacture of 20 tons of smallpox.

When unleashed, the potency of the smallpox virus makes it an instant and widespread killer. Airborne, the virus can easily infect other victims 30 feet away. It requires no special injection or equipment; a simple cough will do. A suicide germ-warfare terrorist could carry the disease onto a plane or into a sports arena and infect thousands within a day. "Biological weapons will strike us unaware. A terrorist only has to open a vial instead of setting off a loud bomb," said Robert Maginnis, vice president for policy at the Family Research Council.

"I think the likelihood of a biological weapon being used is a lot higher than a ballistic missile coming across the Pacific," said Tara O'Toole, deputy director of Johns Hopkins University's Center for Civilian Biodefense. "Yet we are spending an awful lot more on missiles than on bioweapons."

In presentations, Ms. O'Toole likes to hold up a photo of a uranium enrichment plant for comparison. When it was first built it had the largest roof structure in the world, she tells an audience of defense experts. To make one kilogram of plutonium, the plant must process 100 tons of uranium. By contrast, the world's deadliest bugs-smallpox, plague, anthrax, tularemia, botulin toxin, and ebola-are contained in vials each no larger than a thumb. They can be stored in liquid nitrogen or cryogenic freezers and grown in fermenters the size of a desktop copier.

"You can't see a fermenter, or anything that you would need to make a biological weapon, via satellites," Ms. O'Toole pointed out. "It is going to be hard to see a biological weapon, it is going to be hard to track it before it's used, and it is going to be very hard to interdict before it's released," Ms. O'Toole told a gathering of policymakers in Washington last year.

This may sound apocalyptic, but a wide range of medical experts and scientists take the threat seriously. Johns Hopkins, whose research teams pioneered the smallpox vaccine, hosts smallpox war games to test whether medical communities are prepared to deal with a sudden outbreak. In a simulated terrorist attack conducted in 1999, health workers could not halt the spread of the disease. More than 15,000 hypothetical cases developed within two months.

Even at cutting-edge facilities like Johns Hopkins, reports Ms. O'Toole, it would be hard to treat 100 patients suddenly needing isolation and special care. She and other specialists want to see joint projects among the Pentagon, pharmaceutical manufacturers, public-health officials, and other private health organizations. They want to focus on discovering better medical responses to smallpox, as well as other pathogens, and improving hospital care in the event of a bioterrorist attack. They envision a surveillance system-a germ-warfare defense shield of sorts-that could detect a terrorist-sponsored outbreak before doctors do.

Such a system would rely on microchips that could identify specific pathogens by deciphering the molecular genomes, something already under construction in the biotech community. By deciphering the genomes of the first 50 pathogens most likely to be used as bioweapons, they could set up alerts at the first sign of an attack.

The government's Centers for Disease Control (CDC) also projects new urgency. In February, after theft of the foot-and-mouth vial in Britain, the CDC announced plans to better prepare for a bioterrorist attack. It was the first time in 10 years CDC officials made changes to guidelines covering "bioterrorism preparedness." Citing "heightened international concern for the potential use of smallpox virus as a bioterrorism agent," the new plan calls for increasing the production of vaccine and finding ways to make the vaccine more effective after a bioterrorist attack.

Heightened alerts will improve the medical care system and advance new drugs and vaccines in the United States, researchers like Ms. O'Toole believe. Along the way, Americans become less attractive targets for a bioweapons attack, and everyday medicine can partake in the new advances from a biological defense shield.

Still, smallpox could be a particularly tough weapon. It can remain dormant for 14 days, then victims show symptoms that begin with sudden high fever, headache, vomiting, and stiffness. A rash that develops into painful blisters and can lead to permanent scarring follows this. In the worst cases, smallpox leads to death within three or four days. Between one-third and one-half of victims die without vaccination, which must be given within the first days of infection (often before symptoms appear) to be effective. The disease scars or blinds most of those who do survive. In the past, one smallpox victim could infect up to 50 others. No known treatment exists for smallpox.

Part of the urgency stems from progress. The same advances in bioscience that could bring about better vaccines, even a cure, will make it easier to manipulate gene structure to produce more virulent strains of biological weapons.

Political deadlines loom as well. International negotiators want to perfect the enforcement aspect of the germ-warfare treaty by November. But a review team involving key federal defense and health agencies set up by the Bush administration will unanimously recommend that the agreement-in the works for more than six years-be tabled again. The United States wants to limit inspections of its own biodefense labs, as well as protect private pharmaceuticals from international spies. It is also concerned that terrorist states with a professed interest in biological weapons-like Iraq and Iran-as treaty signatories would negotiate their own way out of inspections.

Ms. O'Toole said abandoning the biological weapons convention would be "bad news, but understandable." She believes "the Bush administration thinks it is important, but whether that message gets through if we opt out of the process is not certain."

Rejection of the treaty protocols will put Mr. Bush at odds with allies already distressed by his rejection of the Kyoto environmental agreement. Mr. Bush is likely to argue, however, that the stakes in germ warfare are too high to run with the herd.