The genome pioneer J. Craig Venter has taken another step in his quest to create synthetic life by synthesizing an entire bacterial genome and using it to take over a cell.
Dr. Venter calls the result a “synthetic cell” and is presenting the research as a landmark achievement that will open the way to creating useful microbes from scratch to make products like vaccines and biofuels. At a press conference Thursday, Dr. Venter described the converted cell as “the first self-replicating species we’ve had on the planet whose parent is a computer.”
“This is an important step, we think, both scientifically and philosophically,” Dr. Venter said in an interview with the journal Science, which is publishing the research this week. “It’s certainly changed my views of definitions of life and of how life works.”
Other scientists agree that he has achieved a technical feat in synthesizing the largest piece of DNA so far — a million units in length — and in making it accurate enough to substitute for the cell’s own DNA.
But some regard this approach as unpromising because it will take years to design new organisms, and meanwhile progress toward making biofuels is already being achieved with conventional genetic engineering approaches in which existing organisms are modified a few genes at a time.
Dr. Venter’s aim is to achieve total control over a bacterium’s genome, first by synthesizing its DNA in a laboratory and then by designing a new genome stripped of many natural functions and equipped with new genes that govern production of useful chemicals.He took a first step toward this goal three years ago in showing that the natural DNA from one bacterium could be inserted into another and would take over the host cell’s operation. Last year his team synthesized a piece of DNA with 1,080,000 bases, the chemical units of which DNA is composed. In a final step, a team led by Daniel G. Gibson, Hamilton O. Smith and J. Craig Venter report in Thursday’s Science that the synthetic DNA takes over a bacterial cell just as the natural DNA did, making the cell generate the proteins specified by the new DNA’s genetic information in preference to those of its own genome.
The team ordered pieces of DNA 1,000 units in length from Blue Heron, a company that specializes in synthesizing DNA, and developed a technique for assembling the shorter lengths into a complete genome. The cost of the project was $40 million, most of it paid for by a company Dr. Venter founded called Synthetic Genomics.
But the bacterium used by the Venter group is unsuitable for biofuel production and Dr. Venter said he moved on to different organisms. Synthetic Genomics has a contract from Exxon to generate biofuels from algae. Exxon is prepared to spend up to $600 million if all its milestones are met. Dr. Venter said he will try to build “an entire algae genome so we can vary the 50 to 60 different parameters for algae growth to make superproductive organisms.”
On his yacht trips round the world, Dr. Venter has analysed the DNA of the many microbes in seawater and now has a library of some 40 million genes, mostly from algae. These genes will be a resource to make captive algae produce useful chemicals, he said.
Other scientists say that, aside from assembling a large piece of DNA, Dr. Venter has not broken new ground. “To my mind Craig has somewhat overplayed the importance of this,” said David Baltimore, a leading geneticist at Caltech. Dr. Baltimore described the result as “a technical tour de force” but not breakthrough science, but just a matter of scale.
The polio virus genome synthesized in 2002 by Eckard Wimmer was 7,500 units in length, and the bacterial genome Dr. Venter has made is more than 100 times longer. The synthetic polio genome was shown to build a live polio virus that could infect and kill mice, in the same way that the synthetic bacterial genome controls the far more complex bacterial cell.
In each case, the synthetic genome was a copy of the natural one, and although Dr. Venter said “this is a philosophical advance as much as a technical advance,” suggesting that the “synthetic cell” raised new questions about the nature of life, other scientists saw the work in a different light.
“He has not created life, only mimicked it,” Dr. Baltimore said.
Friends of the Earth, an environmental group, denounced the synthetic genome as “dangerous new technology,” saying that “Mr. Venter should stop all further research until sufficient regulations are in place.” The genome Dr. Venter synthesized is copied from a natural bacterium that infects goats. Dr. Venter said that before copying the DNA he excised 14 genes likely to be pathogenic, so the new bacterium, even if it escaped, would be unlikely to cause goats harm.
In terms of making useful products like biofuels, conventional genetic engineering approaches have a head start. Several companies, like LS9 and Amyris, are already making various fuels. Joule Unlimited, of Cambridge, Mass., is about to turn on a pilot plant that will produce ethanol from a genetically engineered microorganism.
Dr. Venter’s approach “is not necessarily on the path” to produce useful microorganisms, said George Church, a leading genome researcher at the Harvard Medical School. Leroy Hood, of the Institute for Systems Biology in Seattle, described Dr. Venter’s report as “glitzy” but said lower level genes and networks have to be understood first before it would worth trying to design whole organisms from scratch.
