The New Defenders

An explosion of federal funding has Bay Area researchers at the forefront of America's counter-terrorism program. Will the money make us safer - or just make science a military secret?

Marks is quick to point out, in no uncertain terms, that his lab does not possess any actual spores of botulism. His researchers have managed to do their work by collaborating with AMRIID, which does have the live agent. At some point, however, he and his colleagues are going to have to decide whether to move forward into more advanced work that would require housing actual infectious agents. Marks is not as concerned about security -- they already work behind locked doors that are behind locked doors -- as he is unenthusiastic about the risk of becoming a "person of interest" to government terrorism investigators.

Jim Marks is the exact sort of bright mind that the United States government desperately needs. A practical man with graying hair and a caterpillar mustache, Marks is at home in both the hospital and the laboratory.

In 1992, he returned to San Francisco from the Laboratory of Molecular Biology at Cambridge University in England, where he'd worked on antibody research as part of his doctoral studies in molecular biology. He resumed a place on the faculty of the University of California at San Francisco, which was familiar territory, given that Marks had learned to be a doctor at UCSF and had gone on to head the Intensive Care Unit at S.F. General, a teaching hospital for the university.

Still, Marks wanted to continue his research on antibodies -- proteins that the human body makes to fight the presence of a foreign substance -- with the idea of producing them through genetic engineering to combat diseases. So, at the suggestion of a scientist friend at UC Berkeley, Marks pursued grant money from the Department of Defense.

As is the case in most scientific discovery, the process in this research was just as important as the end result. Basically, Marks and his group used a method of introducing human antibodies directly into the patient, rather than waiting for the body to make its own. This is particularly important to fighting botulism, a fast-acting virus that can produce symptoms within two hours of infection.

The group isolated parts of the DNA of particular antibodies that mice and humans produce in response to the botulism toxin and then replicated them. They combined three antibodies in the laboratory, making sort of an antibody cocktail. Each antibody attacks a particular part of the toxin; the three together bind tighter to, and therefore attack more of, the botulinum toxin molecule. "I always thought this work was important, but I never thought it would be applicable during my lifetime," Marks says, pausing from an explanation of the intricacies of antibodies.

The Defense Department had good reason to be interested in Marks' research. Long before anthrax was sent through the mail, botulism was a biological agent sought by terrorists and Saddam Hussein. The Journal of the American Medical Association's Working Group on Civilian Defense notes that a single gram of crystalline botulinum toxin, if evenly dispersed and inhaled (a big if; such widespread dispersal is not easily achieved), would kill more than 1 million people.

Following the Gulf War, Iraq admitted to United Nations weapons inspectors that it had successfully produced and weaponized more botulinum toxin than any other biological agent. Perhaps more disturbing: Some 19,000 liters (or three times the amount needed to kill off the entire human population) remains largely unaccounted for.

The botulism threat is not entirely theoretical. Aerosol versions of botulinum toxin have been dispersed by terrorists in Japan at least three times since 1990.

And botulism is a nasty bug. Within 12 to 72 hours its victims may become violently nauseated. An infected person usually also has blurred vision and loses the ability to speak and swallow. As time progresses, the botulinum toxin begins to paralyze facial muscles, limbs, and then the rest of the body, in some cases leading to respiratory failure.

This is where Marks brings a particular perspective to the laboratory bench.

In his work at hospital bedsides, Marks saw real people suffer from botulism. (Food contamination can produce naturally occurring botulism.) This experience makes him a lot less patient than many scientists with the slow bureaucracy that moves bench science to drugs that help sick people. Even so, actual production of a drug for botulinum toxin based on Marks' research is, in the best-case scenario, three to four years away.

The ultimate San Francisco terrorism nightmare: Some sort of nuclear device is hidden inside one of the more than 1 million cargo containers that come through the Golden Gate on ships each year. The device is detonated. The blast destruction far exceeds what happened to the World Trade Center, and dangerous fallout contaminates much of the Bay Area for years, or even decades.

"We're all very acutely sensitive about airport security, but the threats of what can be brought into a cargo container are much more sensitive," says Lawrence Berkeley's Barletta.

"The amount of damage that you saw in the World Trade Center would be dwarfed, and the number of casualties that would continue to occur in the following five years would be even more," Barletta says.

Even before last September, the lab was already developing neutron tubes for use in a handheld device that scans for nuclear materials on an airplane or deep inside a cargo container. The device can detect radioactive materials virtually anywhere. After September, research on a neutron detector became a priority.

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