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Last Updated

03 Jan 2003

Source: Wall Street Journal, June 26, 2002.

In Strictest Security, Scientists Infect Monkeys With Smallpox


ATLANTA -- In an experiment unfolding under tight security, six rust and silver monkeys this past week grew listless, refused to eat, and broke out in blisters. Four have become sick, and two have died. The cause: smallpox.

On June 18, microbiologist Peter Jahrling and a team of spacesuited scientists passed through steel doors with key cards, and entered an air-locked laboratory -- the "Hot Suite" -- at the Centers for Disease Control and Prevention. Their mission: to infect animals with an extinct disease that is now the world's most feared bioterror pathogen.

Historically, smallpox killed millions of people and left millions more scarred or blind. But by 1980, the World Health Organization had eradicated it. Now, just two sanctioned repositories of frozen virus exist, the one here and one in Russia. But the Sept. 11 attacks on the World Trade Center and Pentagon, and the anthrax letters that followed, have raised fears of terrorists' procuring the virus and unleashing it.

The point of the experiment here is to create an animal model of human smallpox. Never before achieved, it is critical to creating 21st-century drugs and vaccines in case of an epidemic. Animal models are systems for testing treatments without endangering human volunteers. Currently, no drugs exist to treat smallpox. And the vaccine to immunize against it, while effective, causes side effects, including death in about three out of every million people vaccinated.

Doctors stopped giving smallpox shots in 1972, so most people under 30 aren't vaccinated. Even among the vaccinated, immunity has eroded with time, leaving most people vulnerable. Scientists hope the monkey model might help them develop both safer vaccines and an effective treatment.

Now government health officials have made smallpox drugs a priority of biodefense research, setting off a rancorous debate. Alfred Sommer, dean of the public health school at Johns Hopkins University in Baltimore, calls the animal work "an abhorrent experiment by government idiots." He warns that it could spark a bioweapons arms race with countries such as Iraq and North Korea. The way to fight smallpox isn't by injecting monkeys, he says, but by destroying the stockpiles of virus. Dr. Sommer says 18 of the nation's 29 public-health school deans signed his petition calling for destruction of the stockpiles. This past spring, the WHO and the Bush Administration agreed to preserve the virus until new drugs were developed.

D.A. Henderson, the leader of the WHO's successful smallpox campaign, also thinks the Jahrling project is misguided. He doubts doctors will ever find a drug to treat the disease once its lesions appear, and thinks the government should be spending its time and money finding a drug to treat reactions to the vaccine. Dr. Henderson is currently senior scientific adviser on public-health preparedness to Health and Human Services Secretary Tommy Thompson.

"We're very proud of the research agenda that's under way," says James LeDuc, the CDC's director of viral diseases and its point man on smallpox, defending Dr. Jahrling's work. "There's been a lot of hysteria." But now, he adds, "It's yielding positive results. We're happy to share the good news."

After the Sept. 11 attacks occurred, Dr. Jahrling, a senior research scientist at the U.S. Army Medical Research Institute of Infectious Diseases at Fort Detrick, Md., was impatient to follow up work he began a summer ago with an initial experiment on monkeys. For months the 56-year-old researcher waited his turn at the CDC's only smallpox lab. Finally, he got the green light and hoped to infect monkeys on June 13.

On June 3, an advance team thawed vials of virus from the CDC's freezer. Mixed into flasks containing a culture of monkey kidney cells, the virus grew more slowly than expected, delaying the test five days. "An experiment of this complexity is like a space launch," Dr. Jahrling says. "Everything must be perfect."

At 10 a.m. on June 18, members of the team were dressed in green surgical scrubs and zipped into biohazard suits with attached hoods, booties and gloves. They taped on outer gloves and boots for extra security. Onto this protective skin, they hooked coiled orange hoses of filtered air. The air inflated their suits, making them look like the Michelin man. Then, the bulky figures entered Biosafety Level 4 Laboratory, one of two top-level containment facilities for deadly viruses here at the CDC. Its twin lab houses hemorrhagic fever viruses, such as Ebola.

Dr. Jahrling has courted controversy by giving monkeys as many as one million times the dose that is infectious to humans, and by exposing them in a different way. People contracted smallpox by inhaling the virus. But macaques, the monkeys used in this experiment, don't get smallpox in nature. Previous aerosol exposures produced only a mild nonlethal rash.

To try to infect monkeys with lethal smallpox last year, Dr. Jahrling double-dosed them with aerosol and intravenous virus, using a super-virulent strain -- India I -- the strain of choice of former Soviet germ warriors. If anything, it worked too well.

"By day four, they checked out," says Dr. Jahrling. Death came so swiftly that the blisters barely budded, leading critics to charge that the monkeys died, not from smallpox, but from blood poisoning. So this time, Dr. Jahrling employed a less-hot virus called the Harper strain. Forgoing "that hellacious fog," he used only an IV infusion. His aim: to slow the disease down to something resembling the 10- to 14-day course of human smallpox.

To maintain virulence, he still set the dosage at between 100 million and one billion infectious units of the virus, an amount almost certain to be lethal. He grants that that exceeds the 30% human death rate that would be expected from an actual outbreak of the disease. But, an experiment designed to mimic the expected real-world mortality rate would require 60 monkeys, far more than the 12 animals he can handle at a time. At 100% lethality, he reasons, future drug and vaccine tests can show statistically significant results using fewer animals.

The monkeys, weighing from six to 28 pounds, were anesthetized -- both for their comfort and workers' safety. "You don't want a monkey who can bite, scratch or get off the table and swing from the water pipes," he says, "when you're holding one billion infectious virus particles."

The sedated animals didn't so much as twitch as five team members oversaw the infusion: Dr. Jahrling, Army drug researcher John Huggins, a veterinary pathologist, an animal technician and an animal caretaker. After securing the animals under protective tents, the five underwent an eight-minute chemical decontamination of their suits, then took soap and water showers.

Now the team is monitoring the disease's downward spiral. "We're not interested in killing monkeys capriciously," Dr. Jahrling says. "Sometimes I sit bolt upright in the middle of the night. Then I remember why I'm doing this. I do have a conscience."