Corvallis lab comes up with drug to combat smallpox

Corvallis lab comes up with drug to combat smallpox

Scientists in a Corvallis laboratory, backed by $100 million in federal contracts, have concocted a drug they hope will never be needed, against a deadly virus that hasn’t infected anyone in more than 30 years.

The drug would treat smallpox, an ancient scourge eradicated by global vaccination. The last case of smallpox in the United States occurred in 1949; the last worldwide, in Somalia in 1977. It is the only infectious human disease ever erased.

But since the 2001 terrorist attacks, concern that human error or bioterror could unleash the small remaining quantities of smallpox virus has renewed interest in drugs against such a disaster. With that interest, U.S. spending on biodefense has multiplied twentyfold, to about $8 billion in 2005.

Siga Technologies Inc. in Corvallis is a beneficiary of that fear.

Siga’s search for an antiviral smallpox drug started before 2001, but Sept. 11 accelerated its work and opened the federal spigot for research and development to counter biological warfare.

The drug is named ST-246. Siga hopes the Food and Drug Administration will approve it “sometime in 2010,” says Dennis Hruby, chief scientific officer.

“It’s phenomenal that we’re able to develop a drug that potentially could have global impact,” Hruby says. “It’s a real shot in the arm for Oregon.”

Smallpox is one of many devastating illnesses — including malaria, yellow fever, measles, typhus, typhoid fever and diphtheria — introduced to the Americas by Europeans.

Collectively, the diseases decimated Native tribes, who had no natural immunity to them.

About 54 million people lived in the New World when Columbus arrived in 1492, including 25 million Aztecs and 12million Incas, estimates geographer William Denevan, an emeritus professor at the University of Wisconsin.

By 1700, that population had plummeted by nearly 80percent. Denevan calls the early American disease epidemics “possibly the greatest demographic disaster in the history of the world,” saying it eclipsed the Black Death of medieval Europe.

Still, Native cultures in the Northwest thrived into the late 1700s. But a century later, “These cultures were shattered,” anthropologist Robert Boyd has written.

Their numbers, throughout what is now Oregon and Washington, fell from 180,000 to about 40,000, Boyd says in his book, “The Coming of the Spirit of Pestilence: Introduced Infectious Diseases and Population Decline Among Northwest Coast Indians, 1774-1874.”

By statehood, Oregon’s Native population had dwindled to an estimated 7,000, says Judy Chambers, research librarian at the Museum of the Oregon Territory in Oregon City. Smallpox was a factor, along with war and violence.

How much of the infection was an early example of bioterror — intentional pollution of wells or distribution of infested blankets — remains a matter of fierce historical debate. But throughout the Americas, smallpox spread like wildfire.

“They didn’t have to pass out contaminated blankets,” says Stephen Greenberg, a researcher at the National Library of Medicine. “They just had to sit down and have dinner with those folks — and, bang, smallpox and measles would spread.”

A generation after smallpox’s eradication, society has become lax and naive about it, Siga’s Hruby warns.

Smallpox is as contagious as the common cold, spreading via airborne saliva droplets from the infected person, or contaminated clothes and bedding. Symptoms include high fever, fatigue, body aches and a rash. About 30 percent of those exposed die.

The federal government ranks biological warfare threats — A, B or C — by how lethal and contagious they are.

“A is for the really bad guys,” Siga’s Hruby says. Smallpox is one of six A-team “bad guys,” along with anthrax, botulism, hemorrhagic fevers (such as Ebola), plague and tularemia.

Smallpox is “one of the most dangerous potential biological weapons because it is easily transmitted from person to person, and because few people carry full immunity,” Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases told Congress seven weeks after the 2001 terrorist attacks. People vaccinated before 1972, when the immunization requirement was lifted in the United States, “very likely have diminished immunity,” he testified.

The vaccine, discovered by English physician Edward Jenner in 1796, is made from a related pox virus and does not contain smallpox. CDC says it has enough vaccine stockpiled to immunize the U.S. population in an emergency.

Small quantities of the smallpox virus are kept under tight security in two laboratories, one in Russia and the other at the Centers for Disease Control and Prevention in Atlanta. The World Health Organization, which originally recommended the stocks be destroyed, now favors their preservation for developing new vaccines, antiviral drugs and diagnostic tests.

U.S. spending on biodefense has its critics. They consider the threat to public health overblown and the money it gets disproportionate to the need. Meanwhile other needs, from HIV to diabetes research, get shortchanged.

It’s not cheap, fast or easy to measure the effectiveness of a drug for possible use against a disease pronounced dead.

Siga’s ST-246 smallpox drug cannot be tested for efficacy in people because no human being has the disease. Monkeys are the closest animal match. But the drug can be tested for safety and side effects in humans without smallpox. Siga tested the drug against the actual smallpox virus in tissue culture and animals at the CDC lab, which is under top-grade security.

“The virus never leaves Atlanta,” Siga’s Hruby says.

The Corvallis lab, which employs about 50 people, has no direct financial ties with Oregon State University. But the two share what Hruby, an OSU graduate, calls “a close working relationship.”

If ST-246 gets approved, Hruby expects it to be sold in bulk to the military and the federal government for storage in the CDC’s Strategic National Stockpile. Some may also be sold to hospitals or large private employers for use in case of an emergency. He envisions the capsules packaged in vivid blister packs…

 

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