Synthesized DNA is used to make artificially created cell, researchers report

LOS ANGELES — In a major step toward the creation of artificial life, researchers announced Thursday that they had inserted DNA synthesized in a laboratory into the nucleus of a living cell that had been stripped of its own DNA, obtaining a functioning semi-synthetic microorganism.

The artificially created cell — a bacterium — did not have any unusual characteristics, because the inserted DNA was a chemical copy of an existing genome. But the feat showed that synthesizing a genome and having it control a cell can be done, paving the way for the creation of microbes with specialized properties that could be of great value to industry.

Molecular biologist J. Craig Venter, the primary author of the report detailing the findings, described the converted cell as "the first self-replicating species we've had on the planet whose parent is a computer."

Other scientists were similarly enthusiastic. "This is a tour de force and a landmark paper ... that is akin to Jurassic Park or Frankenstein," said Dr. Anthony C. Forster, a molecular biologist at Vanderbilt University who is an expert in the field of artificial life forms. "I think it will probably be regarded as the dawn of synthetic genomics."

Calling the accomplishment a "benchmark," molecular geneticist Paul Keim of Northern Arizona University, added: "It points toward a future in genetic engineering where, instead of doing single gene-engineering events, we will have the ability to do very complex genetic engineering feats that will involve the combination of many genes and many complex biological functions."

Neither Forster nor Keim was involved in the new research.

Although most scientists overwhelmingly praised the achievement, reported online by the journal Science, some environmental groups warned against unforeseen consequences. Friends of the Earth called on governmental agencies to begin regulating synthetic biology experiments.

The technology watchdog Action Group on Erosion, Technology and Concentration, or ETC Group, a Canadian organization concerned about the effects of new technologies on marginalized peoples, went even further, calling for a moratorium on the work.

"The government and society in general are not ready for self-replicating artificial life forms," said ETC Executive Director Pat Mooney. "There hasn't been adequate monitoring of this while it was being developed. It's being born into this environment where there is no real regulation and no understanding of it."

The new results, reported by Venter and his colleagues at the J. Craig Venter Institute in Rockville, Md., and the San Diego community of La Jolla did not, however, surprise people who monitor developments in artificial life. Venter, best known for his work on the Human Genome Project, has been inching toward this point for years.

He and his colleagues launched this particular line of research in 1995 when they sequenced the tiny bacterium Mycoplasma genitalium, which has the smallest genome of any species. They subsequently found that they could strip out about 100 of its 500 genes and still have a functioning cell that could be used as a framework for further modifications.

In 2007, the team removed the genome from one bacterium and transplanted into a microbe of a different species. The recipient, which had been stripped of its own genome, then behaved like the donor species. Learning how to do that was the key step in the process, said microbiologist Clyde Hutchison, a co-author at the La Jolla site.

A year later, the researchers showed that they could add marker genes to the donated genome so that they could identify it accurately in daughter cells.

But combining all these steps in one experiment proved difficult, in part because M. genitalium is very slow growing, impeding the pace of their experiments.

The team thus shifted to Mycobacterium mycoides, which is nearly twice as large as M. genitalium. The researchers first sequenced its genome, then showed last year that they could modify the DNA to carry markers that would allow them to track it after it had been inserted into another bacterium, the related species, M. capricolum.

The researchers then ordered a DNA copy of the genome in 10,000-base sequences that were synthesized by a commercial manufacturer. It was necessary to order such short segments because the technology for synthesizing DNA lags well behind that for sequencing it. (Bases are the individual chemicals that form DNA.)

Working in yeast, the researchers assembled these fragments, first into groupings 100,000 bases long, then into the full 1.1 million bases of the genome. To further identify the material, they inserted sequences that, in code, contained an e-mail address for the project, the names of several participants and a selection of famous quotations. They also inserted a gene that would cause the cells to turn blue.

After much work, they succeeded in inserting the synthetic M. mycoides genome into M. capricolum from which all DNA had been removed and got the bacterium to grow. The host bacterium made proteins characteristic of M. mycoides and otherwise behaved just like it.

"This has important scientific implications and potential practical applications," Hutchison said. "From a practical aspect, this should enable building cells that have things added that will help with a variety of social needs."

The team is working, for example, to create bacteria that could gobble up oil spills like that in the Gulf of Mexico or produce artificial fuels that would limit our reliance on petroleum. Experts suspect that the first such totally synthetic bacterium is at least five years off, however. The institute has contracts with BP and Exxon, which provided some of the funding for the project, to develop biofuels.

Meanwhile, it is highly unlike that the technology could be put to use by terrorists. Because of the great cost and the amount of time required — about $40 million so far over 15 years — "It would be extremely difficult to make dangerous bacteria this way and to do it in an undetectable way," Forster said.

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