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BY BRIAN W. SIMPSON
PHOTOS BY JOHN DEAN AND TAMARA HOFFER
STUNNED AND FRIGHTENED BY ANTHRAX TERRORISM ATTACKS, THE NATION
TURNS TO D.A. HENDERSON AND THE SCHOOL'S CENTER FOR CIVILIAN BIODEFENSE
STRATEGIES FOR ANSWERS.
September 11th marked the beginning of a dark autumn.
From the moment the second hijacked passenger plane pierced the
World Trade Center's south tower in an attack that would ultimately
kill thousands, researchers at the Center for Civilian Biodefense
Strategies realized its deeper significance. What D.A. Henderson
and his colleagues had spent years talking about, warning about,
and preparing for — bioterrorism — suddenly burst from
the realm of the purely hypothetical.
As she watched the first television images of fire and collapsing
glass towers, Tara O'Toole, MD, MPH '88, understood the attack's
implications for bioterrorism. "We were thinking about it right
from the beginning," says O'Toole. The attack "demonstrated
immediately these terrorists were sophisticated, organized, and
capable of doing complex activities and using high technology. That
seemed to us to counter directly the opinion of some that bioweapons
were beyond the reach of terrorists.
"The other line crossed was they were clearly able and willing
to kill large numbers of people," says O'Toole, who became
the Center's director on Oct. 30 following Henderson's departure
to become director of the Office of Public Health Preparedness (see
Welch Wanderings).
The terrorists also proved they were willing to fight America in
a new way: using targeted attacks at vulnerable points on U.S. soil,
while avoiding U.S. military might — a concept called asymmetric
warfare. And biological weapons, according to O'Toole, are a
"classic asymmetric type of weapon."
Anthrax:
Filling in the Blanks
Almost everything we know today about anthrax outbreaks
has been inferred from a 1979 epidemic. In Sverdlovsk, Russia,
a germ warfare facility accidentally released an aerosol
of the pathogen, killing scores of people. Casualties were
relatively light because the wind had blown the anthrax
away from Sverdlovsk, toward the countryside. (One Russian
bioweapons expert has estimated that if the wind had been
blowing toward the city that day, hundreds of thousands
would have died.)
But the Sverdlovsk data are sketchy
because the Russians waited 13 years before allowing in
a U.S. investigative team (which included Alexander Langmuir,
MD, MPH '40).
Last year, D.A. Henderson, MD,
MPH '60, then-director of the School's Center for Civilian
Biodefense Studies, decided to lay out all that was known
about the Sverdlovsk incident for Ronald Brookmeyer, PhD,
an expert in using biostatistics to monitor and track epidemics.
He hoped Brookmeyer could wring some additional information
from the skimpy facts:
The spores were leaked April 2, 1979.
The Russians had mounted a tardy public health response
by mid-month.
At least 70 people died.
The dates of death of all known victims were learned
through photographs of their tombstones.
Some dates of the onset of symptoms were known.
Brookmeyer, a professor of Biostatistics, wasn't fazed
by the dearth of data. "Ideally," he now says,
"you of course want good surveillance data, but that's
the exception rather than the rule. Often you have to
settle for incomplete numbers — and that's when biostatistics
can sometimes fill in some blanks."
The investigators decided to
work from two main assumptions: that all the deadly spores
had originated with the April 2 leak, and that, over time,
the anthrax cases would have naturally distributed themselves
along a log-normal curve (a curve with a long right tail
that signifies the cases with long incubation periods).
Tweaking the data, they hit
pay dirt. The scientists' model showed the disease's average
incubation period — that is, the median time for
onset of inhalation anthrax — was 11 days after exposure:
an incubation period nearly twice as long as any previous
estimate. Further, they were able to show that 1 percent
of those exposed on April 2 could have fallen ill as long
as 58 days after the accident.
Brookmeyer had confirmed that,
in any future anthrax outbreak, antibiotics would have
to be kept on hand for a much longer time than hitherto
imagined, and that those exposed to the pathogen should
continue to receive treatment for 60 days.
— RG
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So, on Oct. 4, when the anthrax stories first began trickling in
about the infection of a photo editor in Florida and then his coworker,
and later an NBC employee in New York, and staff in the U.S. Senate
majority leader's office, and postal workers in Washington, the
deeper meaning dawned on us all: this fall would be unlike any other.
* * *
In 1995, the year that sarin gas attacks in the Tokyo subway killed
12 and sickened thousands, President Bill Clinton made counter-terrorism
a top priority. Millions of federal dollars poured into the departments
of Justice and Defense and other agencies to strengthen counter-terrorism.
But bioterrorism was a poorly understood, minor concern at the time.
"In fiscal year 1998, I think the whole budget for bioterrorism
in the Department of Health and Human Services was about $2 million,"
says Henderson. (It has since grown to $175 million. Estimates for
next year's allocation start at $1.4 billion.)
From 1993 to 1995, D.A. Henderson was a deputy assistant secretary
at the Department of Health and Human Services (HHS) and served
on various defense and intelligence committees. "The thing
that was of great concern to me was there was nobody there from
medicine or public health. Almost nobody," says Henderson.
"They were not doing anything in preparation for an epidemic,
which was what bioweapons would cause."
A mere 100 kilograms of anthrax released from a plane above a metropolitan
area could spread an invisible, odorless cloud of spores that could
kill 130,000 to 3 million people, according to one government study.
Large outbreaks of anthrax, plague, botulism, tularemia, or smallpox
could cripple cities.
Henderson knows epidemics and brought the highest possible public
health credentials to the committees. He led the successful global
smallpox eradication campaign from 1966 to 1977, and subsequently
was the School's dean from 1977 to 1990. Familiar with the devastating
power and sweep of epidemics, he set out to spur government officials
to start thinking about and preparing for biological terrorism.
At a 1997 symposium sponsored by the Infectious Diseases Society
of America, Henderson led a presentation on the threat of biological
weapons. The meeting drew more interest and more requests for speaking
engagements. With funding from the School and the School of Medicine,
Henderson, MD, MPH '60, started the Center for Civilian Biodefense
Studies. O'Toole and Tom Inglesby, MD, joined him in a mission to
influence government and public policy regarding bioterrorism. The
Center would be part think-tank, part research center, and part
bioterrorism information clearinghouse.
"We were pretty much lone voices," Henderson recalls.
"The idea that this was a real problem or could be a real problem
was just not appreciated at all. There was nobody doing anything
on this at the Centers for Disease Control, the National Institutes
of Health. There was nobody in the secretary's office [at HHS] doing
anything about it."
From the beginning, they devoted much of their time to raising national
awareness of the bioterrorism threat through congressional testimony
and debriefings, publication in scientific journals, and lectures.
They also organized elaborate bioterrorism response training events.
In June 2001, one such event called Dark Winter posited a
smallpox bioterrorism attack on U.S. citizens. Former government
officials acted as members of the National Security Council dealing
with the attack. The exercises revealed key gaps in the nation's
bioterrorism preparedness, months before it would have to respond
to the real thing.
 Now,
Henderson and the Center are international focal points of information
on bio-terrorism. They draw diverse pleas for information: a U.S.
Army master sergeant wants to know how much radiation it takes to
kill anthrax spores, or a Union Pacific railroad official has questions
about environmental control for critical buildings. At a House intelligence
committee meeting, O'Toole recently testified on the use of microchips
to medically diagnose bioweapons pathogens. Media interview requests
flood in daily from Newsweek, CBS News, the Japanese newspaper
Asahi Shimbun, The Economist, Reuters, and dozens of others.
"We can't even begin to return 10 percent of the phone calls,"
Henderson says.
With a dearth of solid information about anthrax, the response to
this fall's anthrax attacks — which at press time had killed
four and infected 17 — revealed the lack of federal government
preparation. Law enforcement and public health authorities have
not cooperated seamlessly. Tom Ridge, newly installed director of
the Office of Homeland Security, initially downplayed the danger
posed by the letter to Senator Tom Daschle. And the Bush administration
has been criticized for not protecting postal workers sooner, two
of whom have died from anthrax.
"It's not surprising they aren't performing like a well-oiled
machine," says O'Toole. "We're learning as we go. We haven't
invested enough in bioterrorism preparedness to really know what
we're dealing with."
Anthrax is a particularly difficult challenge because so little
is known about it. Inhalation anthrax has historically been associated
with people who have inhaled its spores while working with contaminated
animal hides, wool, and fur. There have been only 18 cases of inhalation
anthrax in the U.S. in the 20th century, and most of those occurred
before the age of antibiotics. More information about inhalation
anthrax was gleaned from an anthrax release at a Russian bioweapons
facility in 1979 (see Anthrax: Filling in the
Blanks). Local, state, and federal law enforcement and public
health officials, therefore, had little experience to draw on.
 Most
doctors only knew of anthrax infections from textbooks. "How
much clinical experience do we have treating people with anthrax
in the U.S.? There's none," says Inglesby, now the Center's
deputy director. "Clinicians are not trained to look for it.
We have limited diagnostic tests in the tool kit to tell us it is
or it isn't anthrax."
While clinical experience with anthrax is limited, knowledge is
being acquired daily, Inglesby says. "We actually know enough
to make some serious recommendations and we have made them,"
he says.
What's been lacking in the government's bioterrorism response has
been a sound strategy for communicating the risks and dangers to
the public, notes Monica Schoch-Spana, senior fellow at the Center
and a medical anthropologist. "You know how they screwed up?
Their first message was, 'Don't panic,'" Schoch-Spana says.
"It's paternalistic. It's not helpful." People want an
honest assessment of the situation so they can make informed decisions
to safeguard their families, says Schoch-Spana, PhD, who has done
extensive research on the 1918 Spanish flu epidemic, scouring the
history for clues to how the public and medical and public health
communities respond to a devastating outbreak of infectious disease.
 "There
is an assumption that the dominant response of the public is panic,"
Schoch-Spana says. "That is a myth." To help overturn
that misconception, Schoch-Spana organized a rapid response research
team to study World Trade Center volunteers who flooded Ground Zero.
She hopes the study will document for government officials how the
public can adjust and respond to new threats. In a worst case scenario
of bioterrorism involving mass casualties that overwhelm medical
facilities, the government would have to turn to the public for
help anyway, argues Schoch-Spana. People would have to treat family
members and themselves at home in that situation, and they would
depend on public health officials to clearly articulate the problem
and provide practical information on infection control and medical
care.
The Scoop on
Cipro
 How
did the public come to believe that ciprofloxacin is the
be-all, end-all antibiotic defense against anthrax?
It arose from a misunderstanding, according to D.A. Henderson,
MD, MPH '60. A working group was convened about 3 years
ago at the School's Center for Civilian Biodefense Studies
to evaluate biological agents that could be used for bioweapons.
Anthrax was on the list, and the Russians reportedly had
developed a form of anthrax resistant to some unspecified
antibiotics. It was believed that the Russians would have
difficulty making anthrax resistant to ciprofloxacin. So
the group decided to recommend ciprofloxacin, a powerful
antibiotic, to treat anthrax-exposed patients for up to
5 days. During that time, antibiotic sensitivities could
be tested and another, less expensive antibiotic could then
be prescribed.
Anthrax used in this fall's attacks
has been shown to be susceptible to other antibiotics, according
to Henderson. However, "now cipro-floxacin has got
the cachet of being the antibiotic," Henderson says,
despite the fact that doxycycline is just as effective at
about one-tenth or one-
twentieth the cost of ciprofloxacin. And doxycycline is
thought to be less likely to cause side effects.
"This is how things get out
of hand," Henderson says. "I try to make it clear
that ciprofloxacin is not the only thing you can use! Doxycycline
and other fluoroquinolones seem to be equally effective
as the ciprofloxacin."
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Inglesby agrees that an effective communication strategy is essential:
"As [former Senator] Sam Nunn said in Dark Winter, 'There's
no way to demand 300 million people do something unless they're
absolutely persuaded that it's in their best interests, and you're
doing everything possible to help them.'"
In addition to researching better communication strategies, the
Center is guiding other long-term government responses through briefings
to key congressional committees, the vice president, and high-level
officials at the departments of Defense, State, and HHS. "We've
been trying to get them to understand in specific terms, with price
tags attached, what the medical and public health systems need in
order to respond to a biological or chemical attack," says
O'Toole.
The Center, respected for its independent, objective views in partisan
Washington, has helped shape the current debate in Washington on
how best to prepare the nation for future bioterrorist attacks.
(A bill sponsored by Senators Bill Frist and Edward Kennedy is currently
being drafted that will spend an estimated $2 billion or more on
improvements to the National Pharmaceutical Stockpile, Centers for
Disease Control and Prevention laboratories, vaccine research, and
public health infrastructure.)
In the future, the Center will also be working with scientists whose
legitimate discoveries can be twisted for darker purposes. "As
we learn of the virulence of microorganisms, we have the capacity
to make better drugs and vaccines," says O'Toole. "We
also have the capacity of building more virulent microorganisms.
"Biology is losing its innocence as it grows in power,"
she says. The Center has recently secured funding to start a dialogue
in the scientific community about keeping science advancing while
protecting against its deliberate misuse.
* * *
For D.A. Henderson, the genie is out of the bottle. Anthrax, plague,
botulism, tularemia, and the disease he defeated in 1980 —
smallpox — will remain threats for many autumns to come.
He has felt no grim satisfaction that others now understand the
dangers of bioterrorism. Shuttling between endless meetings and
briefings in Washington, tackling his new responsibilities at HHS,
and patiently handling rounds of interviews at the office and at
home, he only has time to help direct the current concern over bioterrorism
to the most effective results.
On a recent, harried Saturday morning at home, he fielded phone
calls from the BBC, a Japanese reporter, and the chief of staff
for the secretary of HHS, all while being photographed and interviewed
by yet another reporter. The book he's been meaning to write on
the smallpox campaign waits for his attention. The bioterrorism
papers he wants to write have been shelved. His new position requires
a 24-hour-a-day commitment.
Like everyone else, Henderson longs for the way things were before.
"I really was rather enjoying where we were until this hit,"
he says.
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