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Quest to create artificial life ends

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Scientists announced a bold step on 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.



The Pioneer > Online Edition : >> Quest to create artificial life ends


David Ropeik: Scientists Bring Back Artificial Life -- and Our Fear of Frankenstein
 
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Scientists Create First Self-Replicating Synthetic Life

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In a feat that is the culmination of two and a half years of tests and adjustments, researchers at the J. Craig Venter Institute inserted artificial genetic material — chemically printed, synthesized and assembled — into cells that were then able to grow naturally.

“We all had a very good feeling that it was going to work this time,” said Venter Institute synthetic biologist Daniel Gibson, co-author of the study published May 20 in Science. “But we were cautiously optimistic because we had so many letdowns following the previous experiments.”

On a Friday in March, scientists inserted over 1 million base pairs of synthetic DNA into Mycoplasma capricolum cells before leaving for the weekend. When they returned on Monday, their cells had bloomed into colonies.


“When we look at life forms, we see fixed entities,” said J. Craig Venter, president of the Institute, in a recent podcast. “But this shows in fact how dynamic they are. They change from second to second. And that life is basically the result of an information process. Our genetic code is our software.”

Coaxing the software to power a cell proved harder than expected.

After the Venter Institute announced in early 2008 that it had assembled a synthetic Mycoplasma genitalium genome, the assumption was that it would be running cells in no time. But this particular cell type, despite its minimal size, was not an ideal research partner. One problem was speed.

“We had to deal with the fact that M. genitalium had an extremely slow growth rate,” Gibson said. “For every experiment that was done, it took more than a month to get results.”

Moreover, transplanting the code into recipient cells was failing. So researchers cut their losses and called in a substitute, opting for the larger, speedier and less finicky Mycoplasma mycoides. The choice was a good one.

“Over the last five years the field has seen a 100-fold increase in the length of genetic material wholly constructed from raw chemicals,” said synthetic biologist Drew Endy of Stanford University. “This is over six doublings in the max length of a genome that can be constructed.”

Plunging costs of synthesis allowed a leap past the 1 million base-pair mark, from code to assembly. “Imagine doubling the diameter of a silicon wafer that can be manufactured that much, going from 1 cm to 1 meter [fabrications] in just five years,” Endy said. “That would have been an incredible achievement.”

“They rebuilt a natural sequence and they put in some poetry,” said University of California at San Francisco synthetic biologist Chris Voigt. “They recreated some quotes in the genome sequence as watermarks.”

It’s an impressive trick, no doubt, but replicating a natural genome with a little panache is also the limit of our present design capabilities.

Researchers, for instance, figure yeast can handle the assembly of 2 million base pairs, but they’re not sure about more. And an energy-producing cyanobacteria that sequesters carbon, Gibson says, is still several years off.

The ultimate goal, of course, is a brand-new genome from the ground up. Now, Voigt said, “what do you do with all that design capacity?”

Scientists Create First Self-Replicating Synthetic Life | Wired Science | Wired.com
 
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