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Poliovirus Baked From Scratch

11 July 2002 (All day)
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According to plan. Poliovirus reconstructed from its genetic sequence is indistinguishable from the original, shown here.

With mail-order DNA and more than 2 years of painstaking work, researchers for the first time have assembled a virus from scratch. The lab-built poliovirus killed mice and was almost indistinguishable from the original. It's as yet unclear how difficult it would be to construct far bulkier viruses such as smallpox to create bioweapons.

A genomic runt at just 7741 bases, poliovirus, the cause of polio, is composed of a single strand of RNA and ranks among the most thoroughly dissected viruses of all time. When it infects a cell, the RNA translates itself into a large protein, which is then cleaved to produce a cluster of smaller ones that attack the central nervous system. Once the trigger of panicky epidemics, polio is now nearing global eradication, although poliovirus samples are stored in labs around the world.

Virologists Jeronimo Cello, Aniko Paul, and Eckard Wimmer of the State University of New York, Stony Brook, built an almost perfect replica of the virus by reading the publicly available recipe of letters that make up its chemical code. Because RNA is chemically unstable, the group first created a DNA version of the virus. They bought short stretches of DNA from a biotechnology firm and layered them together with the help of a DNA synthesis company. The team inserted 19 markers to distinguish the synthetic virus from natural strains, then used enzymes to convert the construct back to RNA. Mice injected with the synthesized virus became paralyzed after about a week, as did animals infected with normal poliovirus, the team reports online in the 12 June Science Express. However, between 1000 and 10,000 times more synthetic virus was needed to kill an animal. The team suspects that one or more of the markers hobbled the virus.

Scientists hail the research as a technical achievement, but some were troubled by its implications. "It is a little sobering to see that folks in the chemistry lab can basically create a virus from scratch," says James LeDuc, director of the Division of Viral and Rickettsial Diseases at the Centers for Disease Control and Prevention in Atlanta. However, LeDuc doesn't believe that rebuilding a virus such as smallpox--far more massive than polio at 185,000 bases--is imminently doable. The researchers say that scientists they consulted encouraged them to publish the paper. As Cello points out, "By releasing this, you alert the authorities ... [to] what bioterrorists could do."

Others say the finding means that wiping scourges from the planet may no longer be possible if the agent can simply be recreated. "It erodes the underpinning of the whole eradication concept," says Peter Jahrling, a smallpox researcher at the U.S. Army Medical Research Institute of Infectious Diseases in Fort Detrick, Maryland.

Related sites
Eckard Wimmer's home page
The World Health Organization polio eradication initiative
Polio information center

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