New method accelerates prospect of designer microbes.
Scientists have built a virus from scratch in only two weeks. Their new technique paves the way for synthetic viruses and bacteria, but stirs concerns over biological weapons and the environment.
The virus was created by genome sequencing pioneer Craig Venter and his team at the Institute for Biological Energy Alternatives in Rockville, Maryland, and revealed at a press conference yesterday.
It is the second virus to be synthesized from commercially available ingredients. The first - a poliovirus completed by Eckard Wimmer and his colleagues in 2002 - took three years to make. "If we had to do it over, I would use [Venter's] method," says Wimmer, who works at the State University of New York at Stony Brook.
Venter's team cobbled together the virus, called phi-X174, following its published genetic sequence. They stitched up its DNA from ready-made overlapping fragments called oligonucleotides, each built from 40 chemical building-blocks, or bases.
The smart part, according to Wimmer, involved steps that eliminated genetic errors. For example, the team filtered out common oligonucleotides that harbour genetic mutations.
The team used enzymes to glue the oligonucleotides together accurately into the complete 5,386-base genetic strand, and to copy it many times. When the synthetic viral genome was injected into bacteria, the bacterial cell's machinery read the instructions and created fully fledged viruses.
Genetically, one of the resulting virus strains was 100% identical to the natural virus, says Venter. By contrast, Wimmer's polioviruses, which were some 7,500 bases long, had to be laboriously checked for mistakes as each genetic piece was added.
Mix and match
The new method is a step towards a bigger goal, claim Venter and members of the US Department of Energy, which is funding the work - namely, building designer bacteria that can pump out hydrogen fuel or gobble up greenhouse gases.
They want to mix and match genes from various organisms to make cellular genomes at least 300,000 bases long. The technique will need some refining first. For example, a cell might be unable to turn more complicated DNA into a working organism without the addition of key proteins.
“It reminds us that we'll continue to confront these issues Stephen Morse , Columbia University”
The study may revive concerns that such techniques could one day be hijacked to make pathogens such as polio or even smallpox for bioweapons. This was widely discussed following the publication of Wimmer's work. The prospect of synthetic viruses or bacteria also raises fears about their possible environmental impact.
"It reminds us that we'll continue to confront these issues in an accelerating way," says public-health expert Stephen Morse of Columbia University, New York City. Now, as then, Morse and others argue that the benefits of the new technique outweigh the risks and that the method should be made public.
The details of the manufacture of virus phi-X174 will be published online in the Proceedings of the National Academy of Sciences in three weeks1.
Smith, H. O., Hutchison, C. A., Pfannkoch, C. & Venter, J. C. Generating a synthetic genome by whole genome assembly: PhiX174 bacteriophage from synthetic oligonucleotides. Proceedings of the National Academy of Sciences, in the press, (2003).