ASHINGTON,
March 19 Two years ago, long before most Americans gave much thought to
bioterrorism, a small group of scientists began a series of experiments they
hoped would yield a treatment for smallpox.
It seemed a highly theoretical task, because smallpox was effectively
wiped out in 1980 and the possibility that it would recur as a biological
weapon appeared slim.
On Wednesday, nearly six months after the anthrax attacks made the
prospect of smallpox seem frighteningly real, the researchers will report
the early fruits of their work: a medicine that stops replication of the
smallpox virus in the laboratory dish and that prevents symptoms in mice
infected with a cousin of smallpox.
Because the drug has yet to be tested for safety in people, it may be
years before it will be considered for government approval.
And one leading expert said the experiments did not address the critical
question of how the medicine might work in someone already exhibiting the
characteristic smallpox lesions.
Still, the studies are generating excitement among scientists, who see a
possible therapy for one of the world's most dreaded scourges.
"Although it's too early to say that this is, quote, a breakthrough,
there are some very encouraging components about this," said Dr. Anthony S.
Fauci, director of the National Institute of Allergy and Infectious
Diseases. "We are pushing very vigorously to get this into a trial in
humans, to see if it would work."
The drug, developed by scientists at the University of California at San
Diego and the Army's bioterror defense laboratory at Fort Detrick, Md., is a
potent derivative of an existing antiviral medicine, cidofovir
[sigh-DOFF-oh-veer]. Marketed by Gilead Sciences
of Foster City, Calif., the medicine is ordinarily used to treat a
complication of AIDS, and was recently approved by the Food and Drug
Administration as an experimental treatment for smallpox in the event of a
bioterror attack.
But cidofovir must be administered intravenously, making it impractical
in a fast-moving outbreak. The derivative, which is made by adding a lipid,
or fat, to cidofovir, is 100 times as powerful as the original drug and can
be given in pill form, said Dr. Karl Y. Hostetler, a professor of medicine
at the University of California at San Diego who developed it.
"If it tracks all the way through, it could be a very useful addition to
our armamentarium," Dr. Hostetler said. "People could self-administer it
instead of having to go to places and stand in line."
The research has not yet been published in an academic journal, so it has
not been subjected to the independent evaluation known as peer review. Dr.
Hostetler and his chief collaborator, Dr. John Huggins of Fort Detrick, plan
to announce their results on Wednesday at a medical conference in Prague.
Smallpox is highly contagious and kills 30 percent of its victims.
Although the disease was officially declared to be eradicated in 1980, the
United States and Russia still keep stocks of the smallpox virus, and
defense experts believe certain other nations may be developing it for use
as a weapon.
In this country, routine vaccination against smallpox ended in 1972. But
last fall, after the Sept. 11 terrorist attacks, the federal government
began to stockpile the vaccine.
The vaccine can prevent smallpox up to four days after exposure to the
virus. But it does not work for everyone. Once people develop symptoms, it
is too late. And the vaccine is risky for people with weakened immune
systems.
So Dr. Huggins said he envisioned the cidofovir derivative as "a second
line of defense for those people who are vaccinated too late or cannot be
vaccinated."
Because the drug has also shown promise against herpes and
cytomegalovirus, a complication of AIDS, Dr. Huggins and Dr. Hostetler said
they hoped the drug would be marketed for those conditions and stockpiled in
the event of a smallpox attack. The University of California at San Diego,
which holds the patent on the derivative, said today that it was negotiating
with a pharmaceutical company interested in licensing the drug.
Dr. D. A. Henderson, who led the worldwide effort to eradicate smallpox,
said he was skeptical of any stockpiling plan.
Dr. Henderson, who directs the federal office charged with preparing the
public health response to bioterrorism, opposes efforts to stockpile the
original cidofovir because animal studies show the drug is effective only
immediately after exposure to smallpox, but not once symptoms appear. If the
derivative works the same way, Dr. Henderson said, he saw little advantage
over the vaccine.
"I know I look like some kind of troglodyte, as though I am not
interested in anything novel or new," he said. "But you can see why I am a
little lukewarm about this."
In any event, Dr. Henderson and Dr. Hostetler said the conversation about
stockpiling was premature. The next step is to test the derivative in
monkeys, and then people. For Dr. Hostetler, at least, the terrorist attacks
of Sept. 11 and the anthrax attacks that followed have given the work a
profound sense of urgency.
"It was all very theoretical," he said, "until those planes crashed into
the buildings."