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A step to artificial life: Manmade DNA powers cell

Lauran Neergaard, Ap Medical Writer 05/21/10

WASHINGTON – Scientists announced a bold step Thursday in the enduring quest to create artificial life. They've produced a living cell powered by manmade DNA.

While such work can evoke images of Frankenstein-like scientific tinkering, it also is exciting hopes that it could eventually lead to new fuels, better ways to clean polluted water, faster vaccine production and more.

Is it really an artificial life form?

The inventors call it the world's first synthetic cell, although this initial step is more a re-creation of existing life — changing one simple type of bacterium into another — than a built-from-scratch kind.

But Maryland genome-mapping pioneer J. Craig Venter said his team's project paves the way for the ultimate, much harder goal: designing organisms that work differently from the way nature intended for a wide range of uses. Already he's working with ExxonMobil in hopes of turning algae into fuel.

"This is the first self-replicating species we've had on the planet whose parent is a computer," Venter told reporters.

And the report, being published Friday in the journal Science, is triggering excitement in this growing field of synthetic biology.

"It's been a long time coming, and it was worth the wait," said Dr. George Church, a Harvard Medical School genetics professor. "It's a milestone that has potential practical applications."

Following the announcement, President Barack Obama directed the Presidential Commission for the Study of Bioethical Issues he established last fall to make its first order of business a study of the milestone.

"The commission should consider the potential medical, environmental, security and other benefits of this field of research, as well as any potential health, security or other risks," Obama wrote in a letter to the commission's chairwoman, Amy Gutmann, the president of the University of Pennsylvania.

Obama also asked that the commission develop recommendations about any actions the government should take "to ensure that America reaps the benefits of this developing field of science while identifying appropriate ethical boundaries and minimizing identified risks."

Scientists for years have moved single genes and even large chunks of DNA from one species to another. At his J. Craig Venter Institute in Rockville, Md., and San Diego, Venter's team aimed to go further. A few years ago, the researchers transplanted an entire natural genome — the genetic code — of one bacterium into another and watched it take over, turning a goat germ into a cattle germ.

Next, the researchers built from scratch another, smaller bacterium's genome, using off-the-shelf laboratory-made DNA fragments.

Friday's report combines those two achievements to test a big question: Could synthetic DNA really take over and drive a living cell? Somehow, it did.

"This is transforming life totally from one species into another by changing the software," said Venter, using a computer analogy to explain the DNA's role.

The researchers picked two species of a simple germ named Mycoplasma. First, they chemically synthesized the genome of M. mycoides, that goat germ, which with 1.1 million "letters" of DNA was twice as large as the germ genome they'd previously built.

Then they transplanted it into a living cell from a different Mycoplasma species, albeit a fairly close cousin.

At first, nothing happened. The team scrambled to find out why, creating a genetic version of a computer proofreading program to spell-check the DNA fragments they'd pieced together. They found that a typo in the genetic code was rendering the manmade DNA inactive, delaying the project three months to find and restore that bit.

"It shows you how accurate it has to be, one letter out of a million," Venter said.

That fixed, the transplant worked. The recipient cell started out with synthetic DNA and its original cytoplasm, but the new genome "booted up" that cell to start producing only proteins that normally would be found in the copied goat germ. The researchers had tagged the synthetic DNA to be able to tell it apart, and checked as the modified cell reproduced to confirm that new cells really looked and behaved like M. mycoides.

"All elements in the cells after some amount of time can be traced to this initial artificial DNA. That's a great accomplishment," said biological engineer Ron Weiss of the Massachusetts Institute of Technology.

Even while praising the accomplishment — "biomolecular engineering of the highest order," declared David Deamer of the University of California, Santa Cruz — many specialists say the work hasn't yet crossed the line of truly creating new life from scratch.

It's partially synthetic, some said, because Venter's team had to stick the manmade genetic code inside a living cell from a related species. That cell was more than just a container; it also contained its own cytoplasm — the liquid part.

In other words, the synthetic part was "running on the 'hardware' of the modern cell," University of Southern Denmark physics professor Steen Rasmussen wrote in the journal Nature, which on Thursday released essays of both praise and caution from eight leaders in the field.

The environmental group Friends of the Earth said the new work took "genetic engineering to an extreme new level" and urged that Venter stop until government regulations are put in place to protect against these kind of engineered microbes escaping into the environment.

Venter said he removed 14 genes thought to make the germ dangerous to goats before doing the work, and had briefed government officials about the work over the course of several years — acknowledging that someone potentially could use this emerging field for harm instead of good.

But MIT's Weiss said it would be far easier to use existing technologies to make bioweapons: "There's a big gap between science fiction and what your imagination can do and the reality in research labs."

Venter founded Synthetic Genomics Inc., a privately held company that funded the work, and his research institute has filed patents on it.

http://news.yahoo.com/s/ap/20100521/ap_on_sc/us_sci_synthetic_cell



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Synthetic Life May Reveal Origins of Natural Life

Stuart Fox, LiveScience Staff Writer

After he announced the creation of the first organism with a fully synthetic genome last Thursday, Craig Venter, founder of the genomics research institute that bears his name, went on to talk about how this breakthrough will benefit industries like pharmaceuticals, energy and materials.

In his explanation of the methods used to create the synthetic bacterium, Venter highlighted an important use for synthetic organisms: research. Like living test tubes, bacteria created by scientists could serve as controlled platforms for experiments by reducing the complexity that obscures the workings of many biological systems.

This work could lead to staggering findings in two major ways.

First, cells with synthetic genomes could allow scientists to essentially snip out the complexities of living cells leaving only the simpler parts. This would give researchers a better way to untangle the enormously complicated interactions that occur in natural cells, and could help unravel the secrets of baffling diseases like cancer.

Second, while cells with synthetic genomes couldn't be used to recreate extinct creatures, they could be used to create organisms that have the genes of extinct organisms, possibly even those of Earth's earliest life forms. This could lead to a better understanding of the very nature of life and how life began, scientists say.

"People are really pretty much stuck about what actually happened on our planet to make new life forms," said David Fitch, an associate professor of biology at New York University. "There have been lots of experiments that propose different ways new living systems could have arisen, and maybe some of these issues could be addressed by synthesizing new genomes with very simple kinds of pathway structures."

Designing more elegant experiments

In natural cells, a vast array of chemical reactions constantly takes place. Many of these reactions happen in series, and scientists refer to these as chemical pathways. But the pathways intersect with each other, making each one difficult to study.

In a cell with a synthetic genome, scientists could eliminate some of these intersections. For instance, scientists studying how the interactions between two pathways cause a disease could design a bacterium that generates only those pathways, said T. Martin Embley, a professor of evolutionary molecular biology at Newcastle University in England. By using a simplified synthetic organism instead of a vastly more complex natural bacterium, researchers could design more elegant experiments with clearer results, Embley told LiveScience.

"It can be useful as a research tool, because you can reconstruct entire pathways and the interaction between pathways. You know exactly what's going into the cell, because you made it," Embley said.

Some pathways determine how the cells in multicellular organisms naturally develop from unspecified cells into those with specific functions. Cells with synthetic genomes could shed light on those processes too, Fitch said. When multicellular organisms mature, waves of signaling molecules ebb back and forth across the developing embryo, and the interaction of those signals tell cells whether to become hairs, nerves, shells, flippers or wings.

A bacterium with a synthetic genome could be designed to produce only a single signal, allowing scientists to understand how this mechanism for differentiation first evolved, Fitch said in a telephone interview.

Breathing life into fossils

Alternatively, rather than creating never before seen cells, scientists could create organisms that went extinct millions of years ago by mathematically deriving the genome of the extinct creature from the genomes of its living descendants, said Martin Kreitman, a professor of molecular biology at the University of Chicago. Animating an extinct creature through synthetic biology would allow scientists to measure cell properties not immediately apparent from the genome itself, such as growth rates and temperature resistance.

Researchers have already done similar experiments on a small scale, Embley said. In those older experiments, scientists replicated an older form of an enzyme to test whether or not it performed the same function earlier in its evolution, Embley said. But with the methods announced by Venter, researchers could go beyond just an enzyme.

"One of the ways [synthetic biology] might be interesting is the ability to reconstruct evolutionary intermediates," Kreitman said. "You're essentially bringing a fossil back to life."

Scientists could reconstruct the genome of extinct creatures by looking at the DNA of living descendents, and then assembling the extinct creature's genome and inserting it into an "emptied" cell using the same technique as the Venter Institute team. These synthetic organisms could provide scientists with valuable data about the environment they lived in, Kreitman told LiveScience. For example, probing the temperature and pH tolerance of an extinct bacterium could teach scientists about the chemistry of an ancient ocean, Kreitman said.

"People have taken particular enzymes involved in the stomach, created an ancestral enzyme, and looked to see if it still worked," Embley said. "[Synthetic biology] allows you to do this on a larger scale, with many genes. Using parsimony argument, you can reconstruct the genomes of common ancestors."

First life on Earth

Going even further into the past, scientists could create a bacterium with the minimum number of genes needed to live, Embley said. This pared-down bacterium would effectively simulate the first cell on Earth, allowing scientists to test hypotheses about how inert chemicals made the jump to self-perpetuating life, Fitch said.

Venter addressed this issue on Thursday, noting that he and researchers at his institute had themselves debated how this technology would allow scientists to test the minimum level of biological material needed to spark life.

"I think it'll be interesting as the people working on origins of life, people trying to understand these minimal early possible precursors to life as those programs proceed in one direction, and we proceed from the other, building on top of the evolution of an information system, we might be able to meet somewhere in the middle and have some exciting new tools," Venter said.

By understanding how life on Earth evolved from non-living matter, synthetic biology could also bridge the gap between in vitro and in vivo experiments, Fitch said.

In biology, in vitro experiments are those done in a test tubes, while in vivo experiments are done in living organisms. Often, reactions that work well during in vitro experiments progress differently during in vivo experiments, thanks to the influence of other chemicals in an organism. This can frustrate the process of scientific discovery. For example, a drug that treats diseased cells in a test tube might not actually work to cure a person who has that disease.

But with synthetic bacteria acting as living test tubes designed specifically for an experiment, scientists could iron out some of that discrepancy, Fitch said, initiating an era where designing an experiment becomes synonymous with creating a new species.

"In vitro systems that allow you to test hypotheses can be very complex now. At some point, the complexity becomes life," Fitch said.

http://news.yahoo.com/s/livescience/20100525/sc_livescience/syntheticlifemayrevealoriginsofnaturallife



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Italian bishops concerned by synthetic life cell

ROME (AFP) – Senior Italian Roman Catholic bishops expressed concern Friday at the creation of the first synthetic living cell which they said could be a "devastating" move.

Scientists in the United States say they developed the cell, by constructing a bacterium's "genetic software" and then transplanting it into a host cell.

"In the wrong hands, today's novelty could lead to a devastating step into the unknown tomorrow," said Bishop Domenico Mogavero, head of the legal affairs commission for the Italian Episcopal Conference, in an interview with La Stampa daily.

"Man comes to God, but he is not God: he remains human and he has the possibility to give life through procreation, not through constructing it artificially," he added.

Lead US researcher Craig Venter said when announcing the development on Thursday that the method could be used to design bacteria specifically to help produce biofuels or to clean up environmental hazards.

"We call it synthetic because the cell is totally derived from a synthetic chromosome, made with four bottles of chemicals on a chemical synthesizer, starting with information in a computer," he said.

Catholic religious leaders have expressed fears however that scientists are "playing God".

"It is human nature which gives its dignity to the human genome, not the inverse. The nightmare to be fought is the manipulation of life," said Mogavero.

Bruno Forte, archbishop of Chieti-Vasto in central Italy and a theologian, said: "The worry can be resumed in one question -- is what is scientifically possible also just from an ethical point of view?"

He added in comments to Corriere della Sera that he admired modern research and that the Church was not "fundamentally" opposed to it but was carefully monitoring.

Vatican spokesman Federico Lombardi told the ANSA news agency late Thursday that more detail on the discovery was needed. "There have already been similar announcements which after a while have been changed."

http://news.yahoo.com/s/afp/20100521/sc_afp/scienceusgenomeresearchreligionitaly

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