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Discovery gives scientists edge in race to reduce anthrax danger

In an important step toward finding drugs to protect against some biological weapons, researchers have discovered how anthrax toxin destroys cells and rapidly causes death.

Now that science knows the target for the anthrax toxin, researchers should be able to find a drug that will block its action, said Dr. George F. Vande Woude, a National Cancer Institute researcher and co-author of a study to be published in the journal Science.

"An inhibitor drug would make anthrax as a weapon as useful as a water pistol," said Vande Woude.

Experts consider anthrax weapons a major threat to both military personnel and civilians. Bioterrorism weapons using anthrax or other bacteria are easier to make and distribute than nuclear weapons. Anthrax bombs are a major concern of United Nations weapons inspectors working in Iraq.

Attorney General Janet Reno and FBI Director Louis J. Freeh warned Congress last week that U.S. civilian targets are vulnerable to biological terrorism. Some in Congress have said classified studies suggest such an attack could occur within a decade.

The military is inoculating all of its troops against anthrax, using a vaccine that would prevent infection from the disease. However, the vaccine is not 100 percent effective and most civilians do not receive these shots.

Anthrax is a rapid and highly effective killer. When it infects, the bacteria produces a toxin, or poison, that attacks cells.

"The only treatment now for anthrax is to give massive, massive amounts of antibiotics," said Nicholas S. Duesbery of NCI. "You have to give it almost immediately after exposure. If you give it 24 hours later, it is too late. Your patient is dead."

Anthrax toxin consists of three proteins, and early research showed that one of the proteins, called Lethal Factor, or LF, was the major cause of cell death. But what science didn't know until now is how LF actually killed the cells.

Vande Woude, Duesbery and their colleagues found that LF disrupts a signaling system in cells called the MAP-Kinase-Kinase pathway. When this system is blocked, Duesbery said, a cell "is cut off from the world." Its metabolism shuts down and it can no longer divide. The toxin also causes the massive release of an inflammation protein and destruction of immune system cells.

The result, said Duesbery, is rapid shock and death.

Now that researchers know the target of Lethal Factor, said Duesbery, "this gives us the first clues of what we need to develop an antitoxin. We can look at the protein structure of the target and come up with (a protein molecule) that will block Lethal Factor from chopping up its target."

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