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WHO Puts Off Destruction of U.S., Russian Caches

Science
25 Jan 2002
Vol 295, Issue 5555
pp. 598-599
GENEVA— Humankind's worst public health enemy, on death row for more than 2 decades, has won another reprieve. Last week the World Health Organization's (WHO's) governing board agreed to delay destruction of the last known samples of smallpox, now kept on ice at two high-security facilities in Russia and the United States. The decision is a “victory for common sense,” says Lev Sandakhchiev, director-general of the State Research Center of Virology and Biotechnology, which houses Russia's smallpox facility.
The decision reflects a new consensus that the stocks may be needed to defend humanity against the possible use of smallpox as a bioweapon, fears heightened in the wake of last fall's World Trade Center attack and anthrax-tainted letter campaign. “We regard the potential release of smallpox as a critical national and international security issue,” says Kenneth Bernard, special adviser for national security, intelligence, and defense at the U.S. Department of Health and Human Services.
In staying an execution scheduled for this December, WHO's board has handed a dramatic victory to researchers hoping to develop drugs and a better vaccine. “There's been a sea change in thinking—and that's very good news,” says virologist Peter Jahrling of the U.S. Army Medical Research Institute of Infectious Diseases in Fort Detrick, Maryland, whose team is developing a potential monkey model for the disease. The board acted on a recommendation from WHO Director-General Gro Harlem Brundtland, who based her decision on a report last month from a scientific advisory committee.
One sticking point, however, is whether WHO should set a new date to destroy the stocks. The two countries holding all the publicly acknowledged smallpox cards—the United States and Russia—favor an open-ended research program. Setting a deadline “would make it impossible to carry out some research,” insists Yuri Fedorov, chief of the Russian health ministry's emerging disease unit. However, China, Cuba, and several other nations are expected to lobby hard for a deadline out of fear that an open-ended program increases the risk that terrorists could steal the virus or that the virus could escape in a lab accident. Observers speculate that the World Health Assembly (WHA) could set a deadline of 2005 or 2006 to destroy the stocks when it meets in May.
Not terminated.
WHO's board has approved Gro Harlem Brundtland's recommendation to continue research on the known smallpox stocks.
CREDITS: (TOP TO BOTTOM) GELDERBLOM/OLIVER MECKES/PHOTO RESEARCHERS; DONALD STAMPFLI/AP
Smallpox is thought to have claimed hundreds of millions of lives in a reign of terror that began with the first human settlements. But Variola major, which kills nearly one in three people it infects, has an Achilles' heel: Humans are its only hosts. That weakness allowed WHO to mount a successful global immunization campaign that led to its eradication in 1980. All nations with declared stocks of live smallpox complied with a WHO request to incinerate these samples, with the Soviet Union and the United States permitted to hold on to live smallpox for research.
These stocks were slated for destruction in 1993, but two developments helped persuade WHA to delay that order. A well-placed defector revealed that the Soviet Union amassed tons of weaponized smallpox virus after the country had lobbied hard for the disease's eradication and had signed a 1972 treaty outlawing bioweapons development. And after the Gulf War, an Iraqi researcher admitted to United Nations inspectors that he had done research on camelpox, a close cousin of smallpox that does not harm humans. Analysts suggested that the work was a surrogate for smallpox research, says Jonathan Tucker of the Monterey Institute of International Studies in Washington, D.C., who described these concerns in Scourge: The Once and Future Threat of Smallpox (Atlantic Monthly Press). The allegation heightened concerns about clandestine smallpox stocks in other countries as well.
In 1999, WHO's variola advisory committee proposed a research program to extract as much information from the virus as possible before putting it to death at the end of 2002. Working at the U.S. repository, the Centers for Disease Control and Prevention (CDC) in Atlanta, researchers have sequenced 10 strains. The sequences are highly conserved, particularly in regions coding for proteins essential for replication. Such proteins would be good targets for potential drugs.
One intriguing development is a potential animal model for smallpox, which could be important for testing drugs and vaccines. “The grand old gentlemen of smallpox eradication have been claiming for years that it was impossible to create smallpoxlike disease in primates, and thus there was little reason to keep the virus around,” says Jahrling. And indeed, he says, “our initial attempt to infect primates at CDC was a dismal failure.” But in a presentation last month to WHO's variola panel, Jahrling described how his team succeeded at infecting cynomolgus macaques after switching to a strain very similar to one that the Soviet Union had weaponized. Nearly all the animals died within a week from a condition that included skin pustules and other hallmarks of smallpox.
The model still has several shortcomings, however. Jahrling's group injected the macaques with large amounts of smallpox, whereas humans would normally contract the disease through the air. The disease was also more deadly than what's observed in humans. Although critics say this suggests that the animal model would be a poor surrogate, Jahrling says that he expects to refine the model by testing lower doses and alternate infection routes. The Russian repository has won funding to ramp up its smallpox effort this year, and it too hopes to vet the monkey model.
Some countries are troubled by an open-ended research effort. “A final date for destruction should be determined, and no excuses should be given for further delay,” says Sha Zukang, China's Permanent Representative to the United Nations in Geneva. But China, which is not on the governing board, is unlikely to find many allies to press that point. An Indian representative, for example, sat quietly throughout the discussion at the WHO board meeting, although his country had until recently advocated swift destruction of the stocks.
The heightened concern about bioterrorism has led some health experts to question the central tenet that stocks of any microbial killer should be destroyed once it is eradicated in the wild. But proponents of eradication say that steps are also being taken to address a bioterror threat. With respect to polio, “efforts have been under way for some time to inventory laboratory stocks and to develop a framework for specimen storage and future research,” says James Hughes, director of the CDC's National Center for Infectious Diseases. The fact that the debate is taking place at all, however, represents another example of the expanding legacy of last fall's tragic events.

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Science
Volume 295 | Issue 5555
25 January 2002

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Published in print: 25 January 2002

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