http://bmj.com/cgi/content/full/325/7356/122/b
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Deborah Josefson Nebraska
US scientists have synthesised viable polio virus from scratch, arguably synthesising life and raising questions about biological safety, ethics, and the ability of bioterrorists to replicate the procedure.
The work was conducted by researchers from the State University of New York in Stonybrook and was funded by the Pentagon in an effort to develop to counter-measures biological warfare. The Defense Advanced Research Projects Agency provided about $300 000 (£191 630m, €298 531) to fund the programme over three years.
The scientists, led by Drs Eckhard Wimmer, Aniko Paul, and Jeronimo Cello, constructed the polio virus using commercially available, mail order, nucleic acid base pairs. The nucleic acid bases can be bought as cheaply as 20 cents (12p) a piece.
They found the polio virus sequence on an internet website and reproduced its RNA sequence base by base. Since RNA is inherently unstable, the researchers converted it into DNA. The first part of the sequence was painstakingly pieced together by hand and took over a year. The researchers then hired a commercial laboratory, Integrated DNA Technologies, to synthesise the remaining two thirds of the sequence mechanically. This took an additional two months. Nineteen marker mutations were inserted into the polio virus DNA sequence to distinguish it from native strains.
Once the entire sequence was replicated, it was reconverted into RNA by enzymatic means. Viral propagation and replication were accomplished by throwing the virus into a predesigned protein soup that contained all the polymerases and other enzymatic ingredients necessary for RNA transcription and translation. The synthetic virus was able to successfully replicate itself from this mixture.
The viral copies were then injected into the brains of mice, which subsequently developed paralysis indistinguishable from polio. The paralytic symptoms developed within a week. However, the synthetic virus was weaker than wild-type virus, and 1000 to 10 000 times more virus was required for a lethal dose than with native polio.
Debate continues over whether viruses can be considered "alive" as they are incapable of reproducing without a host. By providing the machinery of replication, the Stonybrook scientists allowed the virus to reproduce itself and arguably created life from its genetic blueprints.
The experiment has shown that viruses can be produced from scratch, including lethal viruses such as smallpox and Ebola, which could be used to manufacture viruses for use in bioterrorism.
The experiment also calls into question current vaccination and viral eradication policies. If the threat of a re-emergence of smallpox and other viruses is still present owing to synthetic introduction or otherwise, then vaccinations should continue. Moreover, no microbe can ever be considered to be totally eradicated.
The creation of synthetic polio virus was met with concern by the biomedical community. Several notable scientists, including Dr Craig Venter, who started Celera Genetics, the biotechnology company that sequenced most of the human genetic code, called the work "irresponsible." Others dismissed it as a stunt. Dr Wimmer defended the research, claiming that it would not promote bioterrorism, as the terrorists already had access to the same information, and that it reinforces the need to continue vaccinations.
The research has been published online at
www.sciencemag.org
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