August 20, 2009

Gene Pioneer Venter Takes Another Step Toward Synthetic Life

By Rob Waters

Aug. 20 (Bloomberg) -- A team led by J. Craig Venter, the scientist who headed a private effort to map the human genome in the 1990s, succeeded in morphing one kind of bacteria into another, edging closer to the creation of artificial life.

Venter and his colleagues outwitted the bacterial immune system that had stymied their previous efforts and produced a new form of bacteria “that had not previously existed,” the team reported in the journal Science. They used an ordinary yeast cell as a holding tank to alter the bacteria’s genetics.

The technology may help scientists radically modify the DNA of other existing organisms to create environmentally friendly biofuels or remove carbon from the atmosphere. Exxon Mobil Corp., the biggest U.S. oil company, said July 14 it would invest more than $600 million to make fuels from algae with Synthetic Genomics Inc., a closely held San Diego-based company founded by Venter.

“These are new variations of existing life forms and they can be very, very useful,” Eckard Wimmer, a professor of molecular genetics at Stony Brook University on Long Island, New York, said in an Aug. 18 telephone interview. “It’s a step closer to the manufacture of bacteria that could be used in biotechnology for the benefit of humankind.”

Wimmer, who created the first synthetic virus in 2002, was not involved in Venter’s experiments.

Failure to Boot

In 2008, Venter and his team reported that they had pieced together the longest segment of bacterial DNA ever replicated and inserted it into the shell of another bacterium whose own DNA had been removed. That well-publicized effort failed in one key respect, Venter said in a telephone interview yesterday: the new bacteria didn’t “boot up” and come to life.

The effort was frustrated by an important attribute of bacteria discovered by Hamilton Smith, a scientist with Venter’s nonprofit group, the J. Craig Venter Institute based in Rockville, Maryland. Smith earned the 1978 Nobel Prize for showing that bacteria have proteins called restriction enzymes that protect against invading organisms by chopping up their DNA.

“It’s like the immune system of bacteria,” Venter said in a telephone interview yesterday. “When foreign DNA comes in, they chew it up.”

When the transplanted bacteria in their previous effort failed to function, Venter’s team realized that the restriction enzymes might be interfering. By transplanting the DNA of the first bacteria, Mycoplasma mycoides, into yeast, whose genetics are easier to manipulate, they were able to modify the bacterial chromosomes in two important ways.

Brought to Life

First they changed its properties in ways that could be beneficial for creating new products. Second, they converted pieces of the bacterial DNA to keep them from being recognized and attacked by the restriction enzymes. This allowed them to transplant the modified bacterial DNA into a second bacterium and bring the new form to life.

“As soon as we put the bacterial chromosomes in yeast, they behave totally like a yeast chromosome,” allowing the team “to make numerous and rapid modifications of the bacterial chromosomes,” Venter said. “We created a new type of bacteria and it’s completely functional.”

Venter’s work in creating new life forms that never previously existed have raised concerns among some ethicists and environmental activists, who fear that new organisms could damage plant, animal or human life in ways that can’t be foreseen.

Ethics Debate Needed

“It is an untested technology, and there needs to be extensive debate about the ethics and environmental consequences of generating these new organisms,” said Alison Smith, a professor of plant sciences at the University of Cambridge in England.

Scientists haven’t yet figured out how to cultivate algae to produce a commercially viable energy source and Venter’s new findings “won’t have a direct contribution to the manipulation of algae for biofuel production,” Smith said yesterday in an e- mail. “But the technologies being developed will undoubtedly establish some generic principles that may then be employable in manipulation” of more complex organisms, including algae.

Re-engineered microorganisms may take on all sorts of jobs. For now, gene researchers are particularly excited about using energy-producing microbes as single-celled refineries for ethanol, biodiesel or other petroleum substitutes without using food crops such as corn.

Venter’s work on synthetic biology builds on the more than three decades of genetic engineering behind trailblazing biotechnology companies such as Amgen Inc., based in Thousand Oaks, California, and Roche Holding AG’s Genentech Inc. unit based in South San Francisco, California.

To contact the reporter on this story: Rob Waters in San Francisco at rwaters5@bloomberg.net.

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