In an experiment with implications for bioterrorism and the worldwide campaign to eradicate polio, scientists have used poliovirus’ widely known genetic sequence to synthesize that virus from the building blocks of DNA and a broth of other chemicals.
“It’s the first time someone has started with a sequence on paper and put together the necessary ingredients chemically to create the virus specified,” says Eckard Wimmer of the State University of New York at Stony Brook, who led the work. “We don’t need any nature-formed template anymore. We just need the Internet to tell us the sequence of a virus. You can make pretty much any virus this way.”
“Scientifically, the results are not surprising or astounding in any way,” says virologist Vincent Racaniello of Columbia University. “The point here, of course, is that the DNA can be synthesized from the [genetic] sequence, and this could be done by any third-rate terrorist.”
Wimmer has worked on the genetics and replication of poliovirus for more than 3 decades. The virus stores genetic information in a long strand of ribonucleic acid (RNA) rather than DNA. In the new work, described in an upcoming Science, Wimmer and his colleagues used common laboratory machines to synthesize DNA strands harboring the same protein-encoding instructions that a typical poliovirus carries.
Currently, scientists can more easily create long strands of DNA than of RNA.
Wimmer and his team then mixed the lab-made DNA with an enzyme that converts DNA into RNA. Next, they added the resulting strands to a mixture of chemicals similar to that in the cells that poliovirus typically invades. This brew generated whole polioviruses that subsequent tests in cells and animals confirmed as infectious.
To distinguish any synthesized viruses from lab contaminants, the investigators introduced subtle changes into the virus’ genetic code that didn’t alter the proteins it encodes. Unexpectedly, however, the newly created viruses turned out to be much less potent than the typical lab strain. Higher doses of the synthetic poliovirus were needed to kill mice, for example.
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Wimmer, Racaniello, and other scientists suggest that the new findings could make it pointless to destroy the last few stockpiles of viruses such as smallpox. “The sequence [of the smallpox virus] has been published and is available. It’s a difficult virus to recreate, but it will be possible,” says Wimmer.
Similar concerns about poliovirus may occur if the worldwide campaign to eliminate polio succeeds. Scientists are already debating whether to then destroy all poliovirus samples and stop polio vaccinations. Racaniello, who calls for continued vaccination after eradication, notes that Wimmer’s success makes it clear that poliovirus will never truly be gone.
“In the posteradication era, we must always have plans for what to do in the event that the virus reappears, whether by accident or by evil intent,” Racaniello says. “Unfortunately, and frighteningly, there are no such plans at hand.”