And now:Ish <[EMAIL PROTECTED]> writes:
June 15, 1999
Smallpox: The Once and Future Scourge?
A Vanquished Plague
A Brief History of a Killer
The following article was reported by Lawrence K. Altman,
William J. Broad and Judith Miller and was written by Broad.
No one has come down with smallpox for decades. But in some respects it is
potentially more dangerous than ever.
Smallpox killed more people over the ages than any other infectious
disease. In the 20th century alone, experts estimate, it took up to a half
billion lives, more than all the wars and epidemics put
together.
Its scars run deep. As long as three thousand years ago, Chinese records
tell of slow deaths and disfigurations. Signs of pockmarks appear on the
mummified head of the Egyptian Pharaoh Ramses V. The disease decimated
Europe and traveled with colonists to the New World, laying waste to tribes
and aiding British soldiers who spread the virus as a biological weapon.
Today, the high fevers, deep rashes and oozing pustules that characterize
smallpox are gone -- a feat of disease eradication so far unequaled in the
history of public health. This banishment is so complete that recent
medical textbooks often skip the disease or give few details of its wrath.
Despite this triumph of modern medicine, Washington and key allies now
fear the scourge could strike anew sometime in the future, unleashed by war
or terrorism. And that worry is raising new alarms and questions.
What makes the virus so deadly? How well do old vaccinations work?
What about new drugs and vaccines? How likely is a smallpox attack?
Some answers are grim. For instance, troubles with quality control are such
that no stored smallpox vaccine in the United States can now be used except
in emergencies, Federal officials say. Stoppers on vials are deteriorating
and a vital ancillary medicine is unusable.
A turning point came on April 22 when the United States -- one of two
official smallpox repositories around the globe, along with Russia --
announced that it would delay its intended destruction of the
virus, reversing years of planning and Washington's previous stance.
The virus was to have been destroyed this month, the first species driven
to extinction by design rather than accident. But the Clinton
Administration, after careful study, concluded that
clandestine supplies probably exist and could cause the disease to emerge
suddenly
in war. And it reasoned that living samples might aid the development of
new treatments and antidotes.
In the wake of that decision, a host of other actions are now taking shape.
Most visibly, top scientists and health experts are now calling for a
Federal program to produce new
vaccine to protect up to 100 million people in the United States --
enough, in theory, to stop any
epidemic in its tracks. More quietly, American and Russian scientists
hope to embark on studies to better understand the killer's ways in an
effort to perfect a cure. And most stealthily of all, intelligence
agencies are stepping up their efforts to better judge the threat of
smallpox attacks.
"It's disturbing, extremely disturbing," said Dr. Donald A.Henderson, the
scientist who led the global campaign that eradicated smallpox and now is
dean emeritus of the Johns Hopkins School of Public Health."I thought the
door had closed on smallpox. I had happily put it away."
Dr. Joshua Lederberg, a Nobel laureate in biology who advises Washington
on germ warfare, called the eradication "one of the great humanitarian
accomplishments of our century." But he added:
"We have no idea what may have been retained, maliciously or inadvertently,
in the laboratories of a hundred countries from the time that smallpox was
a common disease. These would be the most likely sources of supply for
possible bioterrorists."
To the extent that past is prologue, the experts say, the history of
smallpox offers clues to the dangers and opportunities that may lie ahead.
Experts warn that if smallpox returns it could be more deadly than ever.
The effects of the disease on an unprotected population were underscored
by the experience of settlers who set sail from
Plymouth, England, landed on the Massachusetts coast in 1620 and found the
area remarkably free of Indians because a deadly epidemic had just swept
through. Early explorers had already spread the virus.
Over the ages, immunities built up slowly as people survived the infection,
with children usually faring better than adults. Later on, vaccinations
helped keep the scourge at bay.
Today, experts say, such protections are all but gone and people are
generally more vulnerable to the disease, underscoring the need for
intelligent debate and possibly protective action.
"We're all Indians," said Elizabeth A. Fenn, a smallpox historian at George
Washington University. "We're approaching 100 percent susceptibility."
THE MURDERER
As Viruses Go, Huge and Vicious no one knows where smallpox came from.
Viral historians
say it probably began as an epidemic disease 10,000 years ago when human
populations first grew dense. The virus is unusual in that it inhabits only
humans, unlike many whose main home is in animals.
"It had to have evolved from its natural forebears," said Dr. Lederberg, a
president emeritus of Rockefeller University. "Close relatives like
monkeypox are still fairly prevalent in the rain forests,
occasionally reaching humans."
Evidence that the disease has existed for at least three millennia is found
in the scars on the head and shoulders of the Pharaoh Ramses V, who died as
a young man in 1157 B.C., perhaps of the disease.
Deities in India and West Africa are devoted to smallpox, attesting to ages
of devastation.
The disease, probably spread by traders, is said by historians to have
reached Europe sometime in the first millennium.
In 1520, Hernando Cortés, the Spanish conqueror of Mexico, is believed to
have unintentionally brought a smallpox-infected slave with him to the New
World. In the next two years, an estimated 3.5
million Aztecs died.
In 18th-century Europe, smallpox killed 400,000 people a year, peasants and
monarchs alike, a toll proportionately equivalent to more than a million
deaths today. The disease in one 80-year period is
said to have taken the lives of a Queen of England, an Emperor of Austria,
a King of Spain, a Czar of Russia, a King of France and a Queen of Sweden.
And President Abraham Lincoln in 1863 was probably feverish with the
disease when he gave the Gettysburg Address. Two days later,
he broke out in the gruesome rash.
Modern science has found that the smallpox virus, known as variola, is a
monster in size, possessing one of the largest genetic blueprints of any
virus. Whether that helps explain its extraordinary lethality is unknown.
What is clear is that, unlike most viruses, it is highly
stable outside its host and can retain its powers of infection over long
periods of time, aiding its
spread among victims.
After a person is exposed, the virus multiplies rapidly and spreads
unobtrusively through the body's lymph system for about two weeks. Suddenly
the symptoms come on. The head, back and muscles
ache. The temperature spikes as high as 104 degrees, leaving the victim
drained. In these hours, little distinguishes smallpox from garden-variety
flu.
In about two days, fever and aches give way to pockmarks. At first they
dot the tongue and roof of the mouth and then, over a few days, break out
over the face and spread to the arms and legs. Flat and red at first, the
pox over two weeks or so turn into small blisters and fill with pus, after
which scabs form. Sometimes the entire rash becomes bloody.
In its early stages, the disease is often confused with chicken pox, and
one way to distinguish them is that the smallpox rash often spreads
farther, covering the palms and soles.
About a third of the victims die, mainly from blood loss, low blood
pressure, cardiovascular collapse and secondary infections.
Many survivors are scarred and blinded. Others have shortened bones and
other complications.
Smallpox spreads easily once the rash appears in the throat or skin, and
studies have shown that each infected person typically passes the virus to
three or four others in close contact, often by coughing. In hospitals, the
virus has been shown to travel surprisingly far in the air.
THE ERADICATION
Hunting Down an Assassin
In 18th-century Europe, one segment of the population --milkmaids--
attracted medical attention because they escaped smallpox.
Surmising that these workers may have developed an immunity from their
association with cows, who were prone to a related disease, cowpox, Edward
Jenner, a British physician, in 1796 vaccinated a boy with material from an
infected cow, Blossom.
Two months later, Jenner inoculated the boy with smallpox virus, but the
boy did not get sick. He was immune. Jenner had successfully developed the
smallpox vaccine. Jenner sent his report on this
breakthrough to the Royal Society, which promptly rejected it. So Jenner
published the historic paper on his own.
Like any vaccine, Jenner's worked by alerting the body's immune
system to the threat of microscopic invaders, prompting the formation of
antibodies to fight them off. The novelty was that Jenner used one virus to
protect against another, the first being similar enough to trigger the body's
defenses. Cowpox protected against smallpox even though the two viruses,
though clearly related, are distinct species.
Jenner dreamed of eliminating smallpox. But no serious efforts were made
until the 20th century. As late as the 1930's, smallpox struck up to 50,000
people each year in the United States. The last case occurred in 1949 in
Hidalgo County, Texas. Although Jenner had used cowpox virus, a third
virus, vaccinia, became the standard vaccine against smallpox. Experts say
vaccinia is related to the smallpox and cowpox viruses, but its origin is a
major scientific mystery.
Global vaccinations and quarantines began to be envisioned when, after
World War II, the World Health Organization was founded as an arm of the
newly established United Nations.
In 1959, W.H.O. resolved to eradicate smallpox, largely at Moscow's urging.
But little happened until 1966, when the United States and the Soviet Union
proposed $2.5 million for an expanded effort.
That year two million people died of the disease, mainly in Bangladesh,
Brazil, India, Indonesia, Nepal, Pakistan and African countries south of
the Sahara.
Mass vaccinations were not enough to stop all viral transmission. So
planners added strong measures to hunt down hidden cases and quarantine
victims in an effort to create transmission
barriers.
In many countries, tribal healers were hired to perform vaccinations,
eventually doing much good. "They were soon out of a job," recalled Dr.
Henderson, who led the global campaign.
Europe wiped out smallpox early on. But infected foreign visitors still
caused outbreaks so severe that hospitals specifically for smallpox were
built. As late as the 1960's, West Germany constructed two such hospitals.
India was one of the last major hurdles. In 1975 during a
two-week period, 130,000 workers visited 100 million homes there, finding
many smallpox cases. Cash rewards produced others. With each sweep, the
smallpox count dropped.
Once India was free of the disease, attention turned to Ethiopia.
Counts fell and the global effort seemed over. But then cases popped up in
Somalia, on the horn of Africa. After another push, W.H.O. recorded the
last case on Oct. 26, 1977, putting the Somali victim in quarantine.
With that, the person-to-person chain was broken, defeating the
scourge.
In 1980, W.H.O. proclaimed the world free of smallpox and soon
asked for all laboratory samples of the virus to be destroyed or sent to
central repositories. But it had no inspection powers. The heroes of the
eradication effort had to take nations of the world on their word when, one
by one, they said the dreaded virus was gone.
THE THREAT
Dark Evidence of Hidden Arsenal
The deadliness of smallpox has long beckoned to military minds
and was exploited in the New World with relative ease. Settlers and
soldiers from Europe often had immunity because of childhood exposure. And
Indians did not. So the virus tended to kill selectively, overcoming a
general drawback of germ weapons.
During an Indian uprising in 1763, Sir Jeffery Amherst, commander of
British forces in North America (and namesake of the Massachusetts city),
suggested that the disease be sown deliberately. "Could
it not be contrived to send the Small Pox among those disaffected tribes of
Indians?" he wrote a subordinate, encouraging the use of "every stratagem
in our power to reduce them."
In fact, his men at Fort Pitt, today Pittsburgh, had already forged ahead
without his encouragement, giving Indians infected blankets and a
germ-laden handkerchief. Epidemics ensued, but historians are unsure to
what extent the spread was due to natural or deliberate exposure.
Dr. Fenn, the George Washington historian, who is finishing a book on
smallpox epidemics in America, said Amherst and his men's independent
pursuit of smallpox weapons showed the idea's prevalence and wide appeal,
which continued into the Revolutionary War.
"They were willing to use it in nasty ways," she said of British
forces. "But it's almost impossible to determine how effective it was."
Still, she said, George Washington was suspicious enough of the
British using smallpox as a weapon, and had lost so many troops to the
disease, that in 1777 he ordered his men to undergo crude inoculations.
The Americans, in contrast to English soldiers, had typically grown up
without exposure to the disease. Thus, like the Indians, they had no
acquired immunity.
Despite its apparent disuse in the last two centuries, the idea of smallpox
as a weapon has never disappeared. Indeed, evidence has recently surfaced
that many such armaments were made, if not used.
In 1992, a Soviet official named Kanatjan Kalibekov, now known as Ken
Alibek, defected to the United States. In secret debriefings, Alibek,
formerly a top player in Soviet germ warfare, told Washington that Moscow
had made tons of smallpox for war, and he suggested that the virus might
have been sold or secreted away as the Soviet state collapsed and Russian
scientists
sought new ways to support themselves.
Last year he went public, and he followed this year with a book,
"Biohazard" (Random House), which details a nightmare of smallpox weapons
that he says the Soviet Union made, including warheads for long-range missiles.
W.H.O.'s announcement of the disease's eradication in 1980, Alibek wrote,
had prompted the Soviets to redouble their smallpox efforts.
"Where other governments saw a medical victory," he said, "the Kremlin
perceived a military opportunity."
Federal officials say they have confirmed many of Alibek's
smallpox claims and have also found signs that the virus is now hidden in
Iraq and North Korea, although they report seeing no evidence of smallpox
arms or planned strikes. The intelligence, they say, helped drive Clinton's
April
22 decision to forgo destruction of American stocks.
Officially, destruction of the virus has been put off three years, until at
least June 2002, as world health authorities debate the stay.
THE VACCINE
Nagging Doubts About a Life Saver
In 1972, the United States stopped routine vaccinations of
civilians against smallpox, nearly a decade ahead of much of the world.
Thus, about 114 million Americans born since then, 42 percent of the
population, are completely vulnerable.
For people age 27 and older who were vaccinated, the degree of
protection is unclear because scientists have never systematically measured
the duration of immunity. Protection probably drops
with time, but how much is unknown. Lifelong immunity is unlikely, some
experts say. But old vaccinations may lead to milder attacks.
At the end of the eradication program, W.H.O. and a number of countries
independently stored enough smallpox vaccine for 60 million people and kept
a safeguarded supply of the vaccinia virus to
make vaccine in case more was needed.
With its cache, the United States in theory could protect up to
14 million people if each vial of stored vaccine was used to its maximum
potential of 100 doses. The manufacturer, Wyeth Laboratories, holds the
supply of vaccine in Marietta, Pa., under the control of the Centers for
Disease Control and Prevention in Atlanta.
Smallpox vaccine is still needed at C.D.C. for scientists who
work with the virus. But serious problems with quality control have stopped
vaccinations, creating an acute problem for a very select
group of scientists in the United States and, in the event of an
emergency, a much wider group of people.
Crumbling rubber stoppers on vials are letting in moisture, and a
brilliant green dye is inexplicably losing its color, but the vaccine
remains near normal potency, Federal experts say. The bigger problem is
that the American supply of a colorless liquid medicine, known as vaccinia
immune globulin, which is needed to counteract adverse reactions to the
vaccine, has turned pink for reasons no one understands. Federal rules say
the medicine must be on hand before vaccinations are given, and the Food
and Drug Administration has barred its use until the mystery is solved.
A further complication is that new batches of vaccine cannot be
made with the old process, since today that process would fail to pass the
F.D.A.'s more rigorous standards.
In late 1997, prompted in part by Alibek's revelations, the
Pentagon embarked on a $322 million program to make new vaccines for the
military, including smallpox. The earliest it will be ready, officials say,
is 2005 -- if it can pass F.D.A. muster. That will be difficult. Because the
disease no longer exists and the virus is too lethal to unleash on people,
clinical trials cannot be conducted to test whether or not the new vaccine
actually helps humans resist smallpox.
"Ultimately, they're going to have to make a fairly substantial
judgment call," Steve Pryor, president of Dynport, the Pentagon's vaccine
contractor, said of F.D.A. officials.
Civil authorities in Washington want at least 40 million doses of
new smallpox vaccine, and health experts like Dr. Henderson, who now heads
a center for the study of bioterrorism at Johns Hopkins, are calling for
100 million. Talks are under way for Dynport to produce vaccine for
civilian use as well, but nothing to date has been worked out.
Meanwhile, some experts question the whole vaccine approach as a
germ warfare safeguard. Foes, they say, knowing well in advance about
vaccinations, might counter them by switching to a different germ or a
different variant, perhaps genetically engineered.
"Defensive measures are much more difficult than offensive ones,"
said William C. Patrick 3d, who made germ weapons for the United States
before President Nixon outlawed them three decades ago.
Such threats are helping fuel a search for new ways to combat
smallpox and related viruses, including the development of new kinds of
anti-viral drugs. Unlike vaccines, such drugs, if found workable, might be
administered long after exposure to save infected victims, attacking the
virus directly rather than relying on the body's immune defenses.
In March, the National Academy of Sciences released a 108-page
report listing new research frontiers, many of which American and Russian
scientists are already pursuing, such as trying to
understand the genetic secrets that make the virus so deadly. Combined with
the intelligence assessment that other countries were harboring smallpox
for military use, the academy report influenced the Clinton
Administration's decision to forgo destruction of the virus.
The great unknown, experts say, is whether the benefits of such
planning will ever be needed in a crisis and, if so, whether the
protections will work as envisioned. But the consensus is that action is
nonetheless needed.
Early this month, Federal experts meeting in Atlanta reviewed the
germ threats facing the nation. Smallpox came out on top. Second was
anthrax, which causes high fevers and death but is not contagious. In
comparison, smallpox spreads like wildfire.
"It was unanimous that smallpox is the primary threat," said Dr.
Henderson, who attended the Federal meeting. "The likelihood of an attack
is small, but were it to occur it would be a real
catastrophe."
Copyright 1999 The New York Times Company
Reprinted under the fair use http://www4.law.cornell.edu/uscode/17/107.html
doctrine of international copyright law.
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Tsonkwadiyonrat (We are ONE Spirit)
Unenh onhwa' Awayaton
http://www.tdi.net/ishgooda/
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