And we thought artificial life was in the distant future… J. Craig Venter and his institute has successfully manufactured the first synthetic yeast organism, in one step!

The key? "Co-transformation of 25 different pieces at once" writes lead author Daniel Gibson, a JCVI scientist, in the advance issue of Proceedings of the National Academy of Science.

“Thus, large DNA molecules can be assembled much more rapidly from synthetic or naturally occurring sub-fragments than with any other system described previously.”

J. Craig Venter Institute has dedicated its efforts to creating a synthetic organism, and this new finding is one step closer to that goal. Synthetic Genomics, founded by Venter, is reportedly using the new method to come up with biofuels and other biochemicals using synthetic biology.

Geneticist Craig Venter has announced that he is creating a life form that feeds on climate-ruining carbon dioxide to produce fuel.  He disclosed his potentially world-changing “fourth-generation fuel” project at an elite Technology, Entertainment and Design conference in California. Among the audience were Al Gore and Google co-founder Larry Page.

Biofuel alternatives to oil are third-generation. The next step, Venter says, is to re-engineer existing life forms that feed on CO2 and give off fuel such as methane gas as waste.  Simple organisms can be genetically re-engineered to produce vaccines or octane-based fuels as waste.

Venter’s team is using synthetic chromosomes to modify organisms that already exist, not making new life.  The limiting part of the equation isn’t designing an organism, it’s the difficulty of extracting high concentrations of CO2 from the air to feed the organisms.  Scientists put “suicide genes” into their living creations so that if they escape the lab, they can be triggered to kill themselves.

“We have 20 million genes which I call the design components of the future,”Venter said. “We are limited here only by our imagination.”

“If they could produce things on the scale we need, this would be a methane planet,”Venter said. “The scale is what is critical; which is why we need to genetically design them.”

Venter anticipates having his fourth generation fuels available within 18 months with CO2 as the fuel stock.

Elaine Warburton  www.geneticsandhealth.com

Micrograph images of synthetic Mycoplasma genitalium 

J Craig Venter and his team at the J Craig Venter Institute Rockville, Md. Venter continue to expand our horizons of what constitutes life.  They have built, from scratch, a synthetic chromosome containing all the genetic material needed to produce a primitive bacterium - this is considered a giant step toward the creation of artificial life.

The feat is described in an online edition of the journal Science.  A team led by Dr. Hamilton Smith, director of the Venter Institute’s Synthetic Biology Group, has manufactured from laboratory chemicals a ring of DNA containing all the genes of Mycoplasma genitalium - the tiniest bacteria ever found. That means the team is incredibly close to creating an artificial form of life that could replicate itself using these machine-made genes.

The plan is to slip the synthetic chromosome inside the microscopic skin of one of the Mycoplasma bacterium, replacing its natural genome with the machine-made one and sparking the creature into a life form that can reproduce itself.

Venter says ”If we’d done that already, we’d be letting people know. That’s not the kind of secret you keep … But I am virtually certain it will happen this year … It puts a lot of power in the hands of humans”.

Venter insists that his Institute’s work is not merely a demonstration of laboratory finesse,  but a step toward development of technologies that could grow fuel in bacterial vats and speed cures for diseases. 

The resulting M genitalium ”creature” might pass for artificial life, it would not be entirely synthetic because only the genes would be machine made. In addition, scientists who work with much smaller viruses can now, almost routinely in elite laboratories, produce living viruses using laboratory-designed genes. What is different here is that the bacterial genome Venter’s lab has fabricated is about 20 times larger than the longest viral genome ever made by machines. Consisting of sequences of paired chemicals represented by the letters A, C, T and G, a computer printout of the Mycoplasma chromosome fills 147 single-spaced pages of paper. The secret to the success of the project was finding ways to assemble the 100 pieces into subgroups, then joining the subgroups into successive larger pieces, until the entire genome could be spliced together from four lengthy chains. Inside Smith’s lab, the heavy lifting was performed by yeast bacteria, which were genetically engineered to manufacture the largest sequences of DNA.

This photo issued by the J. Craig Venter Institute shows the synthetic Mycoplasma genitalium bacteria, single molecule from SMgTARBAC37 preparation isolated from yeast observed over a period of 0.6 seconds.

The actual synthetic chromosome, Venter said, is “the largest molecule ever built by humans, by a large margin.” And unlike human-made viruses, a synthetic bacterium would be able to make copies of itself by cell division. Viruses must hijack the machinery of living cells to replicate, a reason many biologists consider them infectious agents rather than living things. Once the laboratory produces living, replicating bacteria using this artificial chromosome, Venter scientists plan to strip away genes systematically, to find how few are truly necessary to sustain life. It is largely an academic exercise, but in the process the scientists hope to refine the tools for building living organisms from this fundamental base, and custom-design them to perform certain tasks - such as manufacturing fuel.

“We are sparking an industrial revolution,” said Venter, whose own genome has been decoded. 

Jim Thomas, a Montreal researcher for ETC, a Canadian environmental and social justice advocacy group, said the “synthetic biology” work pursued by Venter’s group is potentially dangerous and ought to be subject to government oversight. “There are real concerns about biosafety for synthetic organisms, and this takes us a step closer to them,” he said. “Because of the push toward rapid commercialization, an environmental release of a synthetic organism is inevitable. This is an ecological disaster waiting to happen.” The push to develop synthetic fuels using these bugs, he suggested, will place more stress on farmland to produce energy crops. “We are already seeing fuel versus food conflicts because of the drive to produce ethanol,” he said.

With support from the Alfred P. Sloan Foundation, the Venter Institute, MIT, and the Center for Strategic and International Studies in Washington, D.C., published in October an analysis of the risks and benefits of synthetic biology. Not surprisingly, the group concluded that the benefits outweighed the risks. However, the group also acknowledged that public concern was not groundless, arguing instead that measures can be taken to minimize any misuse of the technology. “We found no ‘magic bullets’ for assuring that synthetic genomics is use only for constructive, positive applications,” the authors wrote. Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania, has been following the implications of this technology since 1998. He received a grant from Venter to report on the ethics of the work, which was published in the journal Science in 1999. “Is it right for anyone to try to create synthetic life? The answer is yes,” said Caplan. “There is nothing that violates religious restrictions, or God’s will, and it is not too full of hubris to go down that road.” However, Caplan said that the safety concerns, and fears that a synthetic life form could escape, are justified. “Right now, there is not adequate oversight,” he said.

Elaine Warburton