DETAILS of a technique for making very long sequences of DNA to order were made freely available last week. To show it works, its inventors synthesised a bacteria-infecting virus, or bacteriophage, from scratch in just two weeks.
The technique could accelerate progress in any field that uses genetic engineering, from vaccine research to agricultural biotechnology. There are also dangers, as the method would make it easier for bioterrorists to recreate dangerous viruses using publicly available sequence information.
But at a press conference last week, the inventors focused on more grandiose possibilities. We might one day be able to design 鈥渟uper-microbes鈥� for cleaning up toxic waste, mopping up carbon dioxide or producing hydrogen fuel, claimed Craig Venter and his colleagues from the Institute for Biological Energy Alternatives in Rockville, Maryland, a non-profit organisation founded by Venter. The work was funded by the US Department of Energy.
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Venter thinks creating a living organism from scratch will help achieve these aims, a project he announced several years ago (快猫短视频, 30 November 2002, p 12). His team has identified 300 genes it believes are the minimum necessary to sustain life. But to make these would mean creating a DNA chain 300,000 letters long, and none of the existing methods for making DNA were up to the job.
Only short DNA sequences around a few hundred letters long can accurately be assembled base pair by base pair. These can be combined to make longer chains, but until now only two or three sequences could be joined at a time. Thanks to automation, some companies can now make chains up to 10,000 base pairs long to order, but it takes several weeks and costs around 拢30,000.
Venter鈥檚 team took far fewer steps to make their viral genome, which is 5386 base pairs long. The actual synthesis took just eight days. The team鈥檚 technique, dubbed polymerase cycle assembly, is a modification of a related one called PCR. The key is to start with short chains whose sequence overlaps, so they self-assemble into long chains in just a few hours (see Graphic).
The end product is not perfect, tending to have one mutation every 2000 base pairs. Venter says existing techniques can easily correct any faults. Despite the occasional mutation, when viral DNA was put into bacterial cells, the cells made complete viruses capable of infecting bacteria.
This is not the first time a virus has been made from scratch. In 2002, Eckard Wimmer at Stony Brook University in New York state created a poliovirus by stitching together hundreds of small DNA chains obtained by mail order. It took him three years to complete the poliovirus, which is a similar size to the bacteriophage. Wimmer says he could now do it in several months, still not as fast as Venter鈥檚 team. 鈥淚f I had to do it again I鈥檇 use their method,鈥� he says.
Wimmer鈥檚 work was highly controversial. The critics included Venter. 鈥淚 think it鈥檚 inflammatory without scientific justification,鈥� he said at the time. 鈥淭o purposely make a synthetic human pathogen is irresponsible.鈥�
Venter says his latest work underwent 鈥渢he highest level of scrutiny鈥� by the government and the journal that published it, Proceedings of the National Academy of Science (DOI: 10.1073/pnas.2237126100). 鈥淏asic science at every level can鈥檛 contemplate people doing evil things,鈥� Venter told 快猫短视频. 鈥淭hat would stop fundamental advances that have tremendous positive potential.鈥� The method is not being patented, so anyone who wants to use it can learn how by reading the paper, he says.
At the press conference, Nobel laureate Hamilton Smith, the scientific director of the Rockville institute, answered one question by describing the simple steps that might make it possible to recreate the smallpox virus, which is far larger and more complex than the bacteriophage. Then he paused. 鈥淚 shouldn鈥檛 have said that, I guess.鈥�