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Terror By Oligo?

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Vendors assess the threat of their wares to national security

By Aaron J. Sender

It began in July with SUNY Stony Brook virologist Eckard Wimmer’s publication in Science describing his construction of poliovirus from gene fragments and oligonucleotides ordered online. The press had a field day: “Deadly Ebola Virus ‘Kit’ for Sale over Internet,” shouted the headline in the London Sunday Times.

DARPA and the National Academies of Science each immediately arranged workshops to examine whether such work should be published. Congress, too, became alarmed: Polio may not make an ideal weapon, but if raw materials for deadly pathogens are freely and anonymously available, couldn’t Ebola or smallpox be next?

With bioterrorism a significant focus of the newly established US Department of Homeland Security, inspection of oligo sales is more than likely. But there’s still debate over whether the unfettered accessibility of oligos is truly a threat to national security, and what oligonucleotide vendors should do about it.

Integrated DNA Technologies, which supplied Wimmer’s nucleic acid, was aware of the threat before, but that somebody actually relied on its services to synthesize a virus was an eye opener. Now, “we’re going to make sure we know what the fragments are,” says CEO Joe Walder. “We’ll do a Blast search against all the known sequences.” And if the sequences seem suspicious, “we might be forced to contact the appropriate people” — who exactly that would be (the local police precinct? the FBI?) is unclear.

Still, Integrated DNA only checks orders for large gene fragments cloned into plasmids — a fraction of its business. It still delivers oligos no questions asked, in part to protect its customers’ intellectual property.

And an informal survey of several other suppliers turned up just one, GenScript, that takes any steps to prevent possible illicit intentions.

Epoch Biosciences, Proligo, and Invitrogen, for example, all consider the gravity of the threat to be overblown. “I don’t think you’re going to see Invitrogen initiating anything like that,” says spokesman Paul Goodson. “If a terrorist group set up shop in Indiana … as Molecular Biology Associates, and called us and said, ‘We want these oligos,’ hey, they would get them. I guarantee you.”

Part of the argument is that restricting oligo purchases would be as effective as confiscating Grandma’s nail file at the airport. “There are so many other things that go into making a virulent virus that legislation to prevent this on the oligo side is somewhat ridiculous,” says Epoch marketing manager Steve Harrison.

Despite 33 years of intimate experience with poliovirus, Wimmer took three years to construct the pathogen. And poliovirus is tiny, containing only 7,500 base pairs. Larger viruses such as Ebola (19,000 bp) or smallpox (160,000 bp) are currently beyond reach, Wimmer says.

The key word, though, is ‘currently,’ says Integrated DNA’s Walder. “If you look at the progress of molecular biology over the last two decades, you have to believe that within 20 years, or maybe even within 10 years, it’s going to be much easier to do,” he says. “So it’s important that we start thinking about it now.”

But regulations on oligos would be pointless, says Bruno Poddevin, Proligo VP for primers and probes. “There would be no difficulty for a terrorist to just buy a synthesizer and reagents and synthesize the sequence himself.”

Real threat or not, the oligo community had better prepare for government scrutiny. Two weeks after Wimmer’s publication, Congressman Dave Weldon of Florida drafted a resolution condemning it. And the Homeland Security Act gives the federal government broad powers to surreptitiously mine data from public, personal, and commercial records looking for trends associated with potential terrorist acts.

This may worry some, but not Walder. “Bioterrorism is an area we need to take very seriously now,” he says.

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