GENET archive


SCIENCE & GENES: Replacing a genome boosts race to develop designer bugs: study

                                  PART 1

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SOURCE: France24, France

AUTHOR: Agence France Press, France


DATE:   28.06.2007

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Researchers transformed one bacterial species into another by swapping their genomes, a move that will accelerate the race to develop custom-built synthetic bugs, a pioneer on genetics said Thursday.

Craig Venter, who had a hand in mapping the human genome, said a team of his researchers had transplanted the entire genetic code of one bacterial organism into another closely related species.

The experiment marks the most ambitious attempt yet to re-engineer a living cell with a view to one day developing microorganisms that could be used for biofuels, cleaning up toxic waste, sequestering carbon or other applications.

It ”is a landmark in biological engineering taking us from moving one gene or a set of genes to the ability to move an intact genome,” said Barbara Jasny, deputy editor of the journal Science, which first reported the experiment in this week’s issue.

For decades, molecular biologists have genetically modified microbes and other kinds of cells by adding short DNA sequences, whole genes and even large pieces of chromosomes in their quest to fashion synthetic bugs that can make anti-malaria drugs or novel biofuels.

But this is the first time that researchers have transplanted an entire genome into a living organism and shown that the cell can express the foreign DNA.

”This is very simple in concept, very complex in delivery,” Venter said. It has taken the team ”several years to go from simple concept to making it work.”

With this experiment, the scientists at the J. Craig Venter Institute in Rockville, Maryland, have shown that it is possible to transplant a genome into a host cell, even though in this case, the genome they used was naturally-occurring rather than chemically synthesized.

”It’s a key enabling step,” said Venter. ”Synthetic biology still remains to be proven, but now we are much closer to knowing it’s absolutely theoretically possible.”

In the experiment reported in Science, the researchers took the genome of a simple, one-celled organism called Mycoplasma mycoides and transplanted it into a close relative, M. capricolum.

Both of these bacteria, which are innocuous goat pathogens, lack an outer membrane, facilitating genome transfer.

Before transplantation, the researchers modified the DNA of the donor bacteria, adding two genes that would provide proof if the transfer had worked. One gene conferred antibiotic resistance, the other caused bacteria expressing it to turn blue.

The enhanced Mycoplasma mycoides genome was added to a test-tube of M. capricolum, and the contents of the tube were exposed to an antibiotic.

Within four days blue colonies appeared, indicating that the host organisms had taken up the foreign DNA.

When the team analyzed the blue bacteria for DNA sequences specific to either mycoplasma, it found no evidence of the host bacteria’s genetic material.

Many questions still remain. The researchers acknowledged that they were not sure how the one genome displaced the other.

”We don’t know for certain how the donor genome takes over,” Hamilton Smith, a lead author on the paper, told a teleconference.

The process is also ”extremely inefficient” with a success rate of one in 150,000, said John Glass, a lead author on the paper.

Still, Venter said this proof of concept is likely to speed research in this emerging discipline, yielding new developments in months, instead of years as was previously the case.

                                  PART 2

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AUTHOR: The Associated Press, by Lauran Neergaard


DATE:   28.06.2007

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Talk about identity theft: Scientists changed one species of bacteria into another by performing a complete gene swap.

It’s a step in the quest to one day create artificial organisms, part of a bigger project to custom-design microbes that could produce cleaner fuels. But the way it was performed, dubbed a ”genome transplant,” has genetics specialists buzzing.

”This is equivalent to changing a Macintosh computer to a PC by inserting a new piece of software,” declared genome-mapping pioneer J. Craig Venter, senior author of the new research published Thursday by the journal Science.

For years, scientists have moved single genes and even large chunks of DNA from one species to another. But Venter’s team transplanted an entire genome, all of an organism’s genes, from one bacterium into another in one fell swoop.

These weren’t complex bacteria, but cousins from a family of small, simple microbes known as Mycoplasma. Nor do the researchers know exactly how the transplant took hold. But somehow the new genes cleanly replaced the old and started working correctly - not very often, but in just enough cells to prove the concept.

The experiment ”is a landmark in biological engineering,” said Dr. Barbara Jasny, a deputy editor of Science.

Beyond pushing scientific boundaries, why would switching a goat germ into a cattle germ be useful?

That’s not the real aim. It’s part of a broader field called ”synthetic biology” or ”synthetic genomics” that aims to build new organisms that work in ways totally different than nature intended - and scientists are divided about whether the Venter approach will really play a big role.

”There are people doing some important synthetic engineering efforts with other approaches,” cautioned Dr. David Relman, a microbiologist and infectious disease specialist at Stanford University. ”This is a different one that is a little more daring, and perhaps dramatic.”

”One could wonder whether this method will be used for more than a tiny research community,” added Dr. George Church, a genetics professor at Harvard Medical School. ”Most people find it easier to work with pieces” of DNA.

Church points to the most popular synthetic biology method under study, genetically modifying existing organisms, such as E. coli bacteria, to make them do such things as churn out medications.

In contrast, Venter’s self-named institute in Rockville, Md., is trying to create an artificial chromosome - the structure that carries DNA - that contains industrially useful genes such as ones that could help produce alternative fuels.

That work is far from complete, but to make it work, they’d have to put the artificial chromosome into a living cell and it would have to jump-start that host. Thursday’s experiment was designed just to prove an entire-genome switch is possible, with regular bacteria DNA.

The Venter team picked two Mycoplasma species, simple germs that contain a single chromosome and lack the cell walls that form barriers in other bacteria. First, they added genes to turn the donor bacteria an easy-to-spot bright blue, and to make it resist an antibiotic used to kill off any host germ that retained its own genes.

Then they stripped off the donor chromosome’s proteins, to see if naked DNA alone could ”reboot” a foreign cell. Blue germs appeared within days of dropping the genome into lab dishes containing the second bacteria. Not many - only about one in every 150,000 cells took up the donor genome and grew, but they bore no evidence of the original DNA.

”That’s extremely inefficient,” acknowledged lead scientist John Glass, a Venter Institute microbiologist. ”We think we can steadily improve this.”

”Synthetic genomics still remains to be proven, but now we are much closer to knowing it’s actually theoretically possible,” added Venter.

It’s not clear that the method would work on larger, more complicated bacteria, other specialists cautioned. Nor does the work automatically mean an artificial chromosome alone could activate a living cell.

”It’s going to be much more complicated to do with synthetic organisms,” said Dr. Jonathan Eisen, an evolutionary biologist at the University of California, Davis. Still, ”it’s a great first step.”

                                  PART 3

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SOURCE: ETC Group, Canada/USA

AUTHOR: Press Release


DATE:   28.06.2007

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Synthia – the ”Original Syn” artificial microbe – may have jumped a hurdle that Dolly – the cloned sheep – never could

Synthia, the (theoretical) human-made synthetic microbe – still barely a twinkle in J. Craig Venter’s eye – may be in search of a surrogate micro-mom sometime very soon. According to a research report released today in Science magazine, Synthia (the subject of a patent application discovered by ETC Group a few weeks ago -see ”Goodbye Dolly -- Hello Synthia!”) may have overcome her last hurdle. The report, authored by Craig Venter and his colleagues at Synthetic Genomics Inc., claims to have inserted a foreign bacterial genome into the cell of another bacterial species. Nobel laureate Hamilton Smith who is one of Venter’s co-authors in the research article told a meeting of synthetic biologists in Zürich on Monday that this represents a significant step en route to building a whole new life form. As the article itself concludes, ”…we have discovered a form of bacterial DNA transfer that permits … recipient cells to be platforms for the production of new species using modified natural genomes or manmade genomes…”

”In the case of Dolly the cloned sheep,” says Jim Thomas of ETC Group, ”the job was to insert a single parent’s DNA into an embryonic cell for replication. Venter’s group replaces the host cell’s natural DNA with another species.” ”The peas in this pod would not look alike at all,” adds ETC’s Executive Director, Pat Mooney, ”it’s like pod-outcasting.”

The team of synthetic Genomics scientists inserted the whole genome of Mycoplasma capricolum – a bacterium that often infects goats – into another bacterium showing that it is possible to ”boot up” a new species through the cells of another species. ”Synthia – the artificial goat bug – may, if it works, surpass Dolly – the lamb clone – with the scientific breakthrough,” says Pat Mooney.

The patent application disclosed at the end of April showed that – at the time of application – no one had created artificial life. But, at the same time, the patent claims that the method it disclosed could make artificial life possible. Today’s article, by some of the same inventors, seems to suggest that the patent may need updating. Presumably, Synthetic Genomics Inc. is submitting a new application for this new approach. ”For at least two years now, Craig Venter has been promising the world artificial life in a matter of months,” Thomas notes, ”The promises keep coming and the months keep rolling by. Now the research team may have just overcome one of the last hurdles to synthetic life.” Pat Mooney adds, ”However, the real hurdle that Synthia and Craig Venter have to overcome is society. Synthetic biology is a form of extreme genetic engineering that has enormous implications for everyone who lives on this planet.”

Despite the delays and the changes, no one attending the Synthetic Biology 3.0 gathering in Zürich this week really doubts the ability of the technology to build unique life forms. ”Perhaps the most shocking thing about all this,” concludes Jim Thomas, ”is that scientists now treat the construction of artificial life as a ’given’. Everyone seems to feel it is just a matter of time.” During the Zürich conference earlier this week, Jim Thomas of ETC Group called for scientists to join with civil society and governments in a broad societal discussion over the socio-economic, environmental, health, and ethical implications of the new technology. (For further information about the Zürich meeting, see

ETC Group will be discussing the implications of Synthetic Biology and the potential development of artificial life forms when the UN Convention on Biological Diversity’s scientific subcommittee meets next week in Paris (July 2 – 6). Climate change is on the UN body’s agenda and Craig Venter is claiming that Synthia could be used to improve agricultural crops as agri-fuels. As the intergovernmental agency responsible for the Cartagena Protocol (the treaty on the transboundary movement of genetically-modified organisms), ETC Group believes that the Convention should study whether entirely artificial life forms (unnatural biodiversity) come under the remit of the protocol and (whether they do or not) what the impact might be on natural biodiversity.

                                  PART 4

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SOURCE: Business Week, USA

AUTHOR: John Carey


DATE:   25.06.2007

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Craig Venter says success is near, but critics blast efforts to patent synthetic organisms

First he succeeded in reading humanity’s genetic code. Now gene pioneer J. Craig Venter believes he is within weeks or months of creating the world’s first free-living artificial organism in his laboratory. It won’t be much to look at—a tiny bacterium with only a few hundred genes. But if it’s truly feasible, he says, ”it will be one of the bright milestones in human history, changing our conceptual view of life.”

It also could be lucrative. Venter’s company, Synthetic Genomics Inc., has already filed controversial patents on synthetic bugs, which could make fuels such as ethanol or hydrogen. And on June 13 it announced a deal with energy giant BPPLC to find and modify naturally occurring microbes that can turn coal or oil below the earth’s surface into cleaner fuel. Microorganisms ”have the potential to provide all the transportation fuel we need in the U.S.,” says Venter. ”I joke that I’m going from the gene king to the oil king.”



In this emerging field of synthetic biology, though, Venter has plenty of competitors. Amyris Biotechnologies adds suites of genes to yeast or bacteria to make an antimalaria drug and novel biofuels. Dozens of so-called gene foundries, including a Massachusetts Institute of Technology spin-off called Codon Devices Inc. in Cambridge, Mass., have sprung up to sell synthetic strands of DNA and other products. One company, EraGen Biosciences in Madison, Wis., even makes DNA from basic building blocks not found in nature, opening the door wider to new types of life. And many academics are trying to fashion free-living organisms from scratch. So far, they have synthesized such simpler microbes as the polio virus and the 1918 flu virus.

The benefits of such research could be enormous: not just drugs and fuels but also bugs that clean up pollution or flash when they detect explosives, plus a far deeper understanding of the basic mechanisms of biology. Venter imagines creating organisms worth billions or trillions of dollars.

But the pitfalls could be huge as well. What’s to stop terrorists from buying pieces of DNA and fitting them together into a vicious pathogen, frets David C. Magnus, director of Stanford University’s Center for Biomedical Ethics. ”There are plenty of people lying awake worrying about this,” he says.

Magnus and others have been working with DNA foundries, suggesting measures to reduce the chances of dangerous organisms being unleashed, purposely or inadvertently. One idea: use software to spot purchases of DNA sequences that could be used as weapons. Another is to have ”biosafety” officials oversee research to ensure that pathogens created in labs are kept under control. Such measures are still voluntary. ”We’ve essentially made a gamble that the science will keep us one step ahead of any nefarious uses,” Magnus says.

Even if synthetic biology can be kept out of the hands of terrorists, some scientists and activists worry that it could be locked up for commercial gain. In early June, the ETC Group, a watchdog organization based in Canada, launched a campaign against Venter’s patent application. His synthetic organism will be a much bigger deal than Dolly, the cloned sheep, predicts ETC’s Jim Thomas. He charges that Venter’s company aims to be the ”Microbesoft” of synthetic biology.



Venter is not surprised by the attacks on his work. ”Patents are a hot word,” he says, ”and people are afraid of synthetic organisms.” He has won kudos for convening panels of bioethicists, religious leaders, and biowarfare experts to study the issues. They’ve concluded the research shouldn’t be stopped—though synthetic organisms must be controlled and contained. Environmental groups should be ”ecstatic about what we are doing, since we provide one of the clear alternatives to burning oil and coal,” Venter says.

Within weeks, his team expects to publish a paper showing how they have leapt many of the technical hurdles to creating synthetic life. But overcoming objections may not be as easy. While creating new life may not be playing God, says Arthur L. Caplan, director of the Center for Bioethics at the University of Pennsylvania, ”it has revolutionary implications for how we see ourselves. When we can synthesize life, it makes the notion of a living being less special.” And there’s a perception that synthetic biologists may be ”manipulating nature without knowing where they are going,” he says. ”There are arrogant scientists, and our friend Venter may be one of them.”



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