First lab-created organism raises ethical questions

For the first time, scientists have assembled a full genetic code from laboratory chemicals and used it to create a living organism.

They did it by transplanting their synthetic DNA into the empty husk of a microbe and watching it come to life.

Some say the achievement could advance the development of new vaccines and drugs and lead to novel organisms designed to break down pollutants, eat carbon dioxide, or pump out biofuel.

Others see this as Frankenstein's monster in a petri dish - a profound new entity that will change our understanding of the boundary between life and nonlife.

While genetic engineering and cloning have allowed biologists to copy and rearrange the pieces of existing living things, this comes closer to the wholesale manufacture of life, said ethicist Art Caplan, who headed a University of Pennsylvania team charged with reviewing the ethical implications of the project.

"This is creating whole new living things from inanimate parts," he said. "I think we're going to see a metaphysical earthquake."

The organism they created is a replica of an existing type of bacterium called M. mycoides - with a few extra pieces of DNA added as "watermarks" to show that the synthetic DNA was running the cells.

Some biologists are quibbling over whether the result can really be considered the creation of life from nonlife - since it involved parts of existing life. But they agree it's a major advance.

The team making the announcement, from the J. Craig Venter Institute near Washington, said its creation has multiplied to about a billion cells. They are currently being stored in a freezer to halt their growth.

The researchers say that before they created their synthetic organism, they held long consultations with other scientists and sought clearance from the highest levels of government. They anticipated a strong reaction if they actually pulled it off.

Mary Shelley explored the concept of man creating life in Frankenstein, though in her 19th-century novel, the person to suffer the most from the enterprise was the monster.

Scientists have tried since the 1950s to coax life from inanimate matter, at first hoping to spark the process by which living things first arose on early Earth. That quest has proved elusive, though some scientists hope the making of a synthetic organism will lend insight into the origin of life.

The quest to synthesize this organism started 15 years ago, when geneticist J. Craig Venter and other prominent biologists envisioned making life another way - writing out the genetic code on a computer, synthesizing DNA, and transplanting it into a bacterium.

Venter gained prominence in the 1990s for pioneering new ways to decode human DNA and nearly beating the $3 billion government-run Human Genome Project to its goal.

In 2002, a rival group at SUNY Stony Brook announced they had used DNA synthesis to create an artificial version of the polio virus. Since viruses are not technically considered alive, this was seen as an intermediate step.

That work triggered a firestorm of criticism over its potential dangers, though the group's leader, Eckard Wimmer, says that his goal is to make attenuated viruses for vaccines and that he's making fast progress.

In 2007, Venter's group succeeded in transplanting the genetic code of one organism into another - leading to what Venter calls one of the group's most "philosophically important" papers, since it showed how flexible life could be.

In 2008, Venter's group announced they'd built the entire genetic code of an organism using laboratory chemicals. They re-created the DNA of a bacterium called M. genitalium (so named because it tends to colonize people's reproductive organs). They chose it because it had the shortest known bacterial genetic code.

The next step was to get the DNA to "boot up" inside a cell emptied of its own DNA. That proved difficult with M. genitalium so they switched to a M. mycoides, which carries a much longer genetic code - more than a million of the chemical coding characters known as base pairs.

The feat still required the use of existing life. The group started with small stretches of synthetic DNA, which they inserted into yeast cells. The yeast contains enzymes that act as a DNA repair mechanism and that automatically stitch these foreign pieces together.

The next step was to get the synthetic DNA out of the yeast and transplant it into an emptied-out bacterial cell. After many false starts, they got their first colony in late March. The group added several small changes to the original genetic code of the organism, including a gene that lends the bacteria a telltale blue color.

They also added DNA that could be decoded into lines of alphabet, spelling out the researchers' names and several quotes, including "What I cannot build, I cannot understand," from physicist Richard Feynman.

In other labs around the country, biologists have forged ahead with the use of synthetic DNA, splicing pieces of it into the DNA of existing organisms rather than making the whole genetic code from scratch.

The group at Stony Brook is working on a new influenza vaccine as well as one for HIV. At the University of the Sciences in Philadelphia, geneticist Jennifer Anthony is adding synthetic DNA to E. coli to make a cheaper version of vitamin A.

And in Berkeley, Calif., the company Amyris Biotechnologies has used synthetic DNA to make a once-rare malaria medicine, expected on the market this year.

Despite such promising avenues of research, some see darker possibilities.

Within minutes of the announcement, the environmental group Friends of the Earth and the ETC group, a watchdog for new technologies, shot off warnings and calls for a moratorium on research in synthetic biology.

Penn's Caplan, who headed the original ethical review, said that, like any new technology, synthetic biology could be used for good or evil. It could also have unintended consequences when used with good intentions, especially if new organisms are let loose.

"Think of kudzu, or Japanese beetles or rabbits that went nuts" reproducing in Australia, he said. "Or killer bees," referring to various ways that manipulating the living world has backfired.

For him and other ethicists and philosophers, this finding knocks down the still-prevalent belief that life is animated by some sort of vital force.

"I sometimes describe this as Darwin's second shoe dropping," said Mark Bedau, a philosopher at Reed College in Portland, Ore. "This profoundly changes our view of our place in the universe, where we come from, and what we're made of."

Bedau foresees an even bigger impact when scientists create some new forms of life that nature never made or perhaps never could have made.

"Potentially, anything under the sun is now possible."