Researchers Make Headway in Solving Anthrax Riddle
Last Updated: October 01, 2001 06:37 PM ET
By Will Dunham
WASHINGTON (Reuters) - Amid heightened concern over a biological weapon
attack involving anthrax, scientists said on Monday they had made important
headway in understanding the molecular events triggered by the bacterium's lethal
toxin and developing an antidote for it.
Writing in the journal Current Biology, researchers at Harvard Medical School
identified a gene found in mice that in some forms made mice resistant to anthrax.
These gene variations -- which the researchers speculate also exist in people --
seemed to work by augmenting the response of the body's immune cells to the toxin
released by the bacterium.
In the aftermath of the Sept. 11 attacks on New York and Washington, experts
have warned of U.S. vulnerability to attacks against civilian populations involving
disease-causing germs or chemical weapons.
Anthrax -- a deadly bacterial disease spread by spores and generally confined to
sheep, cattle, horses, goats and pigs -- is seen as a likely agent in any biological
warfare attack because it can be deployed relatively easily and kills about 90
percent of the people it infects.
An existing vaccine can provide some protection, but very few people have been
vaccinated and there are scant supplies available. While some researchers have been
toiling to develop a better vaccine, others have been searching for different ways to
prevent death in those exposed to anthrax, perhaps through an antidote to the
bacterium's toxin.
Anthrax produces a toxin that kills white blood cells called macrophages that are
responsible for fighting off bodily intruders. Researchers have wondered why some
strains of mice are more resistant to this assault than others. Researchers led by
Harvard geneticist William Dietrich found that variations in a gene called Kif1C
provided the answer.
"We found the gene that in mice determines whether mice are susceptible or not to a
particular aspect of anthrax pathogenesis," Dietrich said in an interview.
How a certain variation of the gene works to reduce susceptibility in mice is unclear,
the researchers said. After the anthrax toxin invades a macrophage, the immune cell
launches a burst of inflammatory and oxidative activity in a counter-attack.
But many of these cells self-destruct in the process, spewing bacteria and damaging
inflammatory and oxidative agents into the blood stream. This triggers a system-wide
state of shock that eventually kills the infected host.
Dietrich said the gene may guard against the self-destruction by ferrying the anthrax
toxin to a part of the cell where it can be attacked more effectively. The gene
variants that confer resistance may play their role in this sequestering process more
efficiently, he added.
"For one of the first times, we have a real, concrete molecular foothold on what's
going on inside the cell in response to this toxin," Dietrich said.
Anthrax is virtually untreatable once symptoms develop. Initial flu-like symptoms
develop two to three days after the bacteria is inhaled. This is followed by high fever,
vomiting, joint ache, labored breathing, internal and external bleeding, lesions and
usually death.
Dietrich said the insights provided by the research into the molecular events triggered
by anthrax infection could aid scientists looking for a way to protect people.
"My sense is this gets us closer to an antidote to the intoxication that's an important
part of the pathogenesis," Dietrich said. "It also potentially gives us an avenue to look
for and think about differences in susceptibility in the human population to the toxin."
Dietrich said if scientists can disrupt the anthrax bacterium with antibiotics and
disrupt the toxin with an antidote, then "hopefully we would be able to stop the
disease course in a patient who was unvaccinated."
Like mice, people who carry a certain genetic variation might be naturally more
resistant to anthrax than others, Dietrich said. He added this knowledge could be
used to determine which civilians who have been exposed to anthrax need the most
urgent attention. It also could allow the military to know which soldiers might be best
able to tolerate an anthrax attack on the battlefield. |
