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Polio Virus Created in Test Tube

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TIMES STAFF WRITER

Using a genetic recipe from the Internet and mail-order DNA, scientists in New York have built an infectious polio virus from scratch, raising the grim prospect that bioterrorists could eventually create their own virulent diseases in test tubes.

The man-made concoction passed the ultimate test for a virus: It successfully infected and paralyzed laboratory mice.

The work, published today in the journal Science, was immediately criticized by some scientists and bioethicists as irresponsible and dangerous. Others called it a sobering glimpse of potential dangers.

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Virologist Eckard Wimmer of State University of New York at Stony Brook said he conducted the controversial experiment to demonstrate how easily bioterrorists could create deadly viruses for mass distribution.

“People have for the first time really come to realize that written information that is available in the public domain about viruses can be used to regenerate the real virus,” Wimmer said.

“Experts have talked about that in the past three years, but nobody took it seriously,” he said. “Now they have to take it seriously.”

The Department of Defense already does. Wimmer’s work was funded by the Defense Advanced Research Projects Agency. Last year, the Defense Department classified a paper written by Raymond Zilinskas, a chemical and biological weapon expert at the Monterey Institute of International Studies, suggesting it was possible to construct small viruses from scratch.

Zilinskas said he did not think the new report would be useful to terrorists without the necessary scientific training and facilities. But he added that a military laboratory could easily create and test viruses. “You would need very good people,” he said. “You would need some time to do it, and you would have to do pretty thorough field testing to make sure that whatever you construct actually worked.”

It took Wimmer’s team nearly three years and several thousand dollars’ worth of raw materials to string together the virus, but co-author Jeronimo Cello called the work “very easy to do.”

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While the virus contains genetic material, it is not considered a living entity, meaning the scientists did not “create life.” All they did was create a complex chemical, Wimmer said. Most scientists do not consider viruses to be life because they depend on their hosts for survival.

The scientists downloaded the genetic code for polio and ordered raw genetic material through the mail. They then undertook the painstaking process of arranging each of the fragments in the proper order to create their nearly perfect replica. They estimated that the work could now be done in a matter of months.

The creation of the man-made polio virus came just a month after the World Health Organization had declared polio eradicated from Europe and projected total eradication of the disease by 2005. Last year, only 480 cases were reported in the world.

Creating viruses from scratch now challenges the notion that any virus can be truly eliminated. As Columbia University virologist Vincent Racaniello said in Science: “Polio virus will never be gone.”

The fear is that terrorists could cobble together viruses more lethal than polio, such as smallpox, the painful, disfiguring and essentially untreatable scourge that has claimed hundreds of millions of lives over the centuries.

Smallpox was declared eradicated in 1980; the only known supplies are kept in heavily guarded refrigerators at the Centers for Disease Control and Prevention in Atlanta and the Russian Vector lab in Siberia. Iraq and North Korea are believed to hold covert supplies.

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Polio was relatively easy to re-create because its genetic code consists of just 7,741 molecular letters. Smallpox, in contrast, has nearly 200,000 letters in its code and has a complicated geometry.

“The polio virus is a pretty small genome,” Zilinskas said. “To get a larger virus, you would have to do everything correctly in a three-dimensional structure, and that becomes quite a technical feat.”

Wimmer agreed that it is unlikely terrorists would resort to sophisticated genetic techniques to create viruses since many of them are easily obtainable.

The creation of the polio virus from scratch was not seen as a huge scientific advancement and was considered inevitable by many because of other basic research that made the feat possible.

“This may be the culmination of sewing Frankenstein together, but this is not the research that led up to Frankenstein,” said C.J. Peters, the director of the Center for Biodefense at the University of Texas Medical Center at Galveston, for Associated Press.

Many scientists criticized the work and called its publication irresponsible and questionable. A spokeswoman for the American Assn. for the Advancement of Science, which publishes Science, said the group was considering adopting a formal policy on how to deal with potentially dangerous research reports. But she defended publication of the work as an important and exciting scientific advance.

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Wimmer defended the research as putting the world on notice that terrorists could create weapons without getting their hands on dangerous microbes. He said another lab would have done the work if he hadn’t. He added that the dangers of replicating polio were minimal because most of the world has been vaccinated against the crippling virus.

He said there could be therapeutic benefits to the work. The man-made virus had turned out to be less virulent than the original, suggesting that the work could lead to new ways to disarm viruses and create vaccines for other diseases.

Bioterrorism expert Zilinskas agreed, saying: “There’s undoubtedly peaceful uses that will come out of that information. The unfortunate part is that, with other powerful technologies, there may be misuse.”

Bioethicists said that in this new environment of bioterrorism concerns, the possibilities for misuse could force new restrictions on scientific journals and the sale of scientific material, both of which have been relatively unfettered.

“This is a wake-up call,” said Alexander Capron, an expert in bioethics and a professor of law and medicine at USC.

“It raises an issue that most scientists are reluctant to acknowledge: that results of great interest to scientists can be dangerous as well.”

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Times staff writers Robert Lee Hotz and Charles Ornstein contributed to this report.

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