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Pimp My Genome


By Kevin Davies

Aug 15, 2005 | The first five albums by the British rock group Queen included a defiant footnote on the back cover, to wit: “No synthesizers were used in the making of this record.” It wasn’t until the ’80s that the band finally experimented with, or perhaps succumbed to, the inevitable march of technology.

DNA synthesizers, pioneered by Bio-IT World’s 2005 President Award winner Leroy Hood (see “Hood Hails ‘Century of Biology,’” page 19), have enjoyed a niche role in biotechnology at best for manufacturing DNA strands for microarray platforms and other applications. But as costs plummet, the ability to rapidly synthesize and customize longer, more intricate fragments of genomic DNA opens up a plethora of applications in basic and applied biology.

DNA synthesizersThe term “synthetic biology” was originally coined in 1980, but since 2003, its usage has become analogous to synthetic chemistry and covers the application of engineering and computer science to genomic circuits to construct small biological devices. As noted in a recent review*, these include “diagnostic tools that improve the care of patients with infectious diseases, as well as devices that oscillate, creep, and play tic-tac-toe.”

If there is a distinction, “synthetic genomics” is less about tinkering with genetic circuitry and more about customizing microbial vehicles “for groundbreaking scientific advances, including the development of alternative energy sources, and the production of new vaccines and pharmaceuticals,” says J. Craig Venter. “Synthetic genomics has the potential to enable significant societal, environmental, and medical benefits.”

This summer, two companies have established the beginning of a commercial synthetic biology industry. Codon Devices, founded by a quartet of molecular biologists from MIT, Harvard, and UC Berkeley, raised $13 million in venture capital (see “Synthetic Biologists Assemble Codon Devices Company,” July 2005 Bio-IT World, page 1). It will initially focus on developing customized genetic toolkits for biosensors and engineered cells for chemical and protein manufacture.

Meanwhile, Venter is stepping back into the boardroom (for the first time since leaving Celera Genomics in 2002) by founding Synthetic Genomics. Eschewing venture capital, the company has secured $30 million in private financing, about half from Mexican agrotechnology billionaire Alfonso Romo Garza. “We’re moving from reading the genetic code to writing it,” Venter told the Wall Street Journal, which broke the news of Venter’s new company. Having cracked the genome, evidently it’s time to start stitching it up again.

As if on cue, the J. Craig Venter Institute announced it will participate with MIT in a Sloan Foundation-funded project to examine the societal implications of synthetic genomics, particularly the potential risks and necessary safeguards to prevent bioterror abuses.

Minimal Genome
The significance of Venter’s arrival on the synthetic biology scene should not be underestimated, given his remarkable sixth sense for developing and exploiting key technologies. Venter’s first foray into synthetic genomics came six years ago with a landmark paper on the “minimal genome.” Although Japan’s Mitsuhiro Itaya first coined the term in 1995, Venter and colleagues published a landmark paper in Science in 1999 suggesting that a mere 300 genes might be necessary and sufficient to encode life. Progress was suspended while Venter tackled the human genome, but last year, his group took another important step with the “resynthesis” of a viral genome — an important proof-of-principle for synthetic genomics, which will require pimping much larger genomes.

The new Synthetic Genomics Web site says it all: “Imagine a future where clean, environmentally friendly microorganisms produce the bulk of industrial materials that are today made from petrochemicals...where specifically tailored organisms harness the sun to create clean energy...when researchers can use a modular, software-like product to design new microbial genomes which are manufactured on an industrial-like scale.”

This may sound a tad fanciful, but the tantalizing prospect of harnessing microbes to synthesize drugs and other biomaterials will not be lost on our readers. As for abundant clean energy, have you checked the price of oil lately?

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* Benner, S.A. and Sismour, A.M. “Synthetic biology.” Nat Rev Genet 6, 533-43; 2005.

Contact Kevin Davies at: kevin_davies@bio-itworld.com.

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