Scientists create cell based on man-made genetic instructions

By David Brown
Friday, May 21, 2010; A03

Scientists reported Thursday that they have created a cell controlled entirely by man-made genetic instructions -- the latest step toward creating life from scratch. The achievement is a landmark in the emerging field of "synthetic biology," which aims to control the behavior of organisms by manipulating their genes.

Although the ultimate goal of creating artificial organisms is still far off, the experiment points to a future in which microbes could be manufactured with novel functions, such as the ability to digest pollutants or produce fuels. Some ethicists fear that the strategy could also be used to produce biological weapons and other dangerous life forms.

In a paper published online by the journal Science, researchers from the J. Craig Venter Institute described using off-the-shelf chemicals and the DNA sequence of Mycoplasma mycoides's genes to make an artificial copy of the bacterium's genome. The scientists then transplanted that genome into the cell of a different (but closely related) microbe.

The donor genome reprogrammed the recipient cell, which went on to replicate and divide. The result was new colonies of Mycoplasma mycoides.

"We think these are the first synthetic cells that are self-replicating and whose genetic heritage started in the computer. That changes conceptually how I think about life," said J. Craig Venter, 63, who gained fame a decade ago as the co-sequencer of the human genome. His institute has laboratories and offices in Rockville and San Diego.

Other scientists characterize the experiment in less revolutionary terms. They say that only the genome was synthetic; the recipient cell was equipped by nature and billions of years of evolution to make sense of the genes it received and turn them on. Still, they praised Venter's 24-member team for showing that such a transplant was feasible.

"From a technical standpoint, this is clearly a very important advance," said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

"It is a milestone in synthetic biology," said Gregory Stephanopoulos, a professor of chemical and engineering and biotechnology at MIT. "Over the long term, it will have an impact, although over the short term, not so much."

The Venter team stopped short of creating new cells with new functions. Instead, it manufactured a Mycoplasma mycoides genome that was virtually identical to the natural one and used it to make cells that were also nearly indistinguishable from the natural cells.

In that sense, the experiment's success is more symbolic than practical. It is unlikely to have any immediate effect on the biotech world, which for more than two decades has used various methods of recombinant DNA technology to manipulate to manufacture drugs, produce pest-resistant crops and enhance the nutritional value of food.

The development nonetheless engaged the attention of President Obama, who on Thursday asked the Presidential Commission for the Study of Bioethical Issues to "undertake, as its first order of business, a study of the implications of this scientific milestone, as well as other advances that may lie ahead in this field of research."

The early consensus is that Venter's achievement poses no hazards beyond those that exist with current modes of moving or tweaking genes.

"It does not represent an additional threat for biological weapons," said Paul S. Keim, a molecular biologist at Northern Arizona University who chairs the National Science Advisory Board for Biosecurity, a 17-member committee of academic scientists and federal officials that advises the government on "dual use" technologies that can be employed for both good and harmful purposes. Keim said that Venter has been transparent about the direction of his research and had provided the board with a copy of the new paper before it was published.

Under current methods of gene manipulation, scientists harvest a gene from one cell through a process called "cloning" and put it into a transfer vehicle. That vehicle (often a subcellular structure called a plasmid) is then inserted into a different cell, which activates the gene, leading to the production of a scientifically or commercially useful protein.

Venter's project was more ambitious. The scientists knew the order of the 1,089,202 DNA letters ("nucleotides") of Mycoplasma mycoides's genome. They built it in pieces, nucleotide-by-nucleotide. Then they stitched the pieces together.

The result was a man-made copy of the genome that Mycoplasma mycoides produces naturally. However, it was not an exact duplicate. Fourteen of the bacterium's 850 genes were altered or deleted during the experiment -- 12 intentionally, two accidentally. None of those was essential for the bacterium's survival.

Parts of the process remain mysterious even to the scientists. For example, the cells receiving the synthetic genome also contained a natural genome, and the two genomes were sent into different "daughter" cells when the bacterium divided.

"We don't know exactly what happens during the genome transplantation experiment," said Daniel Gibson, 33, a molecular biologist at the Venter Institute who did much of the work.

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