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For the first time, scientists create a virus using only its genome sequence


Driven by "strong curiosity" as much as by "an urgent need to understand, prevent and cure viral disease," a team of scientists has built a virus using entirely artificial means. As reported in Science, the virus is virtually identical to the one that causes the childhood disease poliomyelitis. This project, financed by the US Department of Defense as part of a biowarfare response program, has attracted both praise and criticism. It marks the first time a genome has been synthesized without the help of a natural template.

Illustration of polio virus.

Some members of the scientific community have objected to the creation of a human pathogen. J. Craig Venter, president of The Center for the Advancement of Genomics (TCAG) in Rockville, Maryland, has called the work "irresponsible" and "inflammatory without scientific justification." Others maintain that the project, which represents only a minor scientific innovation, is unnecessary considering the risk involved.

The scientists themselves, however, say the social or political value of their work lies in the message it sends about bioterrorism. Arguing that ubiquitous immunity has made poliovirus relatively harmless, they insist that the project will alert authorities to the relative ease of producing viruses.

The team of three virologists at the State University of New York, Stony Brook, used genomic data available on the Internet and materials from a mail-order chemical supply company. "The reason we did it was to prove that it can be done and it is now a reality," said researcher Eckard Wimmer.

Poliomyelitis, or infantile paralysis, affects only humans. Attacking the central nervous system of infected patients, the disease can cause paralysis and death. Poliovirus is highly contagious, transmitting readily through the air.

To create the virus, the researchers first assembled single nucleotide bases into DNA based on the virus' known genetic sequence. An enzyme then transcribed the DNA into the single-stranded RNA genome. The virus could then replicate itself naturally.

A variety of experiments on cell cultures and in mice confirmed that the artificial virus was almost identical to the natural one. It invaded cells and reproduced the same way, and it was inhibited by the same antibody. These results confirm that the data describing the chemical structure and genetic sequence of the natural virus, published more than two decades ago, were accurate.

Viruses are unusual because they have characteristics of living and nonliving entities. Poliovirus, which the researchers call a "chemical with a life cycle," has a mere 7,500 nucleotide bases in its entire genome. (A typical bacterial genome has millions.) The virus invades cells, where its RNA genome is translated into various proteins. Simultaneously, it replicates the genome thousands of times. The new RNA can be combined with proteins inside a viral coat and then released for invasion of other cells.

Though there is no cure for poliomyelitis, the 1955 introduction of the Salk vaccine drastically reduced its incidence. The last documented case in the United States occurred in 1979. Despite an aggressive World Health Organization campaign, however, this devastating disease has yet to be fully eradicated worldwide. The researchers hope their work will discourage officials from ever relaxing programs of immunization.

See related GNN article
»Scientists shut down genes in poliovirus and HIV in cell cultures

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Cello, J. et al. Chemical synthesis of poliovirus cDNA: Generation of infectious virus in the absence of natural template. Science Express. Published online July 11, 2002.

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