Researchers Create Polio Virus From Scratch

Rick Weiss (Washington Post) (The Signal Online

Researchers in New York have created infectious polio viruses from ordinary, inert chemicals they obtained from a scientific mail-order house, marking the first time a functional virus has been made from scratch and raising a host of new scientific and ethical concerns.

The laboratory-synthesized viruses are virtually identical to the naturally occurring viruses that cause polio, a paralyzing neurological disease. The new viruses proliferated in test tubes and caused polio when injected into mice, according to a report published Thursday.

A massive vaccination program sponsored by the World Health Organization aims to rid the world of polio by 2005 and has already eliminated the disease from all but a handful of countries. But the new work indicates that polio and perhaps other viral ailments–including some with bioterror potential such as smallpox–can be manufactured from raw materials and so may never be eliminated with total assurance.

“What they’ve done is demonstrate a potential that’s very alarming,” said Scott Peterson, a molecular biologist with the Institute for Genomic Research in Rockville, Md. “It really challenges the notion of what ‘extinct’ means.”

Others went further, suggesting that the work should not have been done or that the results, which some called a blueprint for making a biological weapon, might best have been left unpublished.

“Everyone wants free inquiry and exchange of ideas, but putting the formula up for making dangerous microbes and viruses is a questionable thing to be doing in this day and age,” said Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania. Caplan was a member of an expert panel that two years ago studied the ethics of creating new life forms from scratch, which concluded that such work, while not inherently unethical, posed profound questions of scientific responsibility.

Eckard Wimmer, the scientist who led the poliovirus effort at the State University of New York at Stony Brook, said Thursday he did the experiment to verify that the decades-old published version of the virus’ genetic code was correct, and to offer graphic proof that bioterror agents can be made without a terrorist ever having access to dangerous microbes themselves.

“Our argument is that we have to put the society on notice that this is possible,” he said.

Wimmer said that if his team had not done the work, another group would have. And he maintained that the danger was minimal because most of the world has been vaccinated against polio.

Wimmer also took issue with those who might accuse him of “playing God” by creating life. For one thing, he said, many scientists–including himself–do not consider viruses to be alive, since viruses are so dependent on host organisms for their survival.

“We shy away from using the word ‘create,'” Wimmer said in an interview. “We want to make a distinction between us and the Creator. I want to avoid getting letters.”

Scientists generally reserve the term “alive” for entities that can respire, reproduce and grow on their own. The first conglomeration of chemicals into free-living, microscopic membrane-bound packets worthy of being called living cells occurred about 3.5 billion years ago. Viruses, which appeared later, are chemical entities that can make copies of themselves only by hijacking the molecular machinery inside cells.

In their report, published in the online journal Science Express, Wimmer and co-workers Jeronimo Cello and Aniko Paul call poliovirus “a chemical with a life cycle.”

More precisely, a poliovirus is a microscopic protein shell containing ribonucleic acid, or RNA, a chemical cousin of DNA, the genetic material found in human cells. The Stony Brook team started with nothing more than a written copy of the virus’ RNA code, a string of 7,741 molecular “letters” that tell the virus how to live its parasitic non-life.

The first task was to construct a strand of RNA that reflected that written blueprint. But since RNA is relatively unstable in the laboratory, the team first made a DNA version of the virus’ code by ordering customized pieces of DNA from an Iowa-based company that sells made-to-order snippets of genetic material. The team assembled the molecules into a DNA equivalent of the full-length polio genome, then used an enzyme that turns DNA into RNA to make a working copy of the poliovirus’ natural RNA core.

When placed in a tube filled with appropriate chemicals and enzymes, those pieces of RNA did what they do in nature: They made duplicates of themselves and they also started producing proteins, including protein shells into which newly made pieces of RNA got spontaneously packaged.

The result was countless functional polioviruses, which caused paralytic disease when injected into mice.

“This shows it’s now possible to go from data printed on a piece of paper or stored in a computer and, without the organism itself … reconstruct a life form,” said John La Montagne, deputy director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Craig Venter, president of the Center for the Advancement of Genomics in Rockville, was one of several scientists Thursday who downplayed the scientific achievement as a minor advance over previous work while criticizing it as posing unjustifiable risks.

“I’d go so far as to say I see it as irresponsible science,” Venter said. “They could have demonstrated their prowess with a (harmless) bacterial virus, but making a human pathogen deliberately and giving the instructions of how to do it, I see no valid reason for doing it.”

Other experts said that although the task is complicated, it is within the skill range of many molecular biologists today and could be done with perhaps as little as $10,000 worth of equipment and reagents.

That doesn’t necessarily mean that rogue scientists could build larger and more deadly viruses from scratch. Scientists said it would be far more difficult to make a more complicated virus such as smallpox, which has 200,000 molecular letters in its code. But several said they’d no longer say it’s impossible.

Even for polio alone, La Montagne said, the advance has enormous implications for public health policy, including “whether we can ever stop using polio vaccine.” The WHO has said it plans to halt global vaccinations once polio is eradicated.

Katrina Kelner, deputy managing editor for biological sciences at the American Association for the Advancement of Science, which publishes Science Express, said the organization is now deciding whether it needs a formal policy on how to deal with potentially dangerous reports, but defended the decision to post the polio research.

“We take the problem of providing sensitive information in our pages very seriously,” Kelner said. “But we felt it was astonishing that this can even be done–that starting with only a (genetic) sequence you can make an infectious particle. We felt it was an important proof of principle and we thought it was one exciting enough to publish.”

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