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Genome Synthesis Synthetic Biology -- Is Cheaper and Easier Always Better?


Over the winter holidays in Nature, Harvard molecular biologist George Church and University of Houston chemist Xiaolian Gao described a new technique for fabricating long strands of nucleotides using microchips that promises to make genome synthesis even more efficient and accurate. For researchers hoping to design functional proteins, pathways, or engineered cells that don’t otherwise exist in nature, this is good news. But for scientists worried about easy access to technology that could be used to create new and super-virulent organisms, such advances come with a hint of fear.

First off, what are the possible uses of synthetic biology? Some of these applications, Church says, could include: (1) making many novel “designed proteins” which have no homolog in nature; (2) re-engineering biotech workhorse E. coli to have new genetic codes for safety and accommodate new amino acids; (3) testing vast numbers of vaccine polypeptides; (4) creating and optimizing new bio-pathways to drugs like Artemesin (a top anti-malarial drug); (5) shuffling protein segments to optimize desirable properties; and (6) changing codons for expression in new species. However, he adds: “It’s easier to design new applications for synthetic DNA, but harder — and more expensive — to determine which of these new creations actually work.”

One problem is determining when synthesizing genomes of super-virulent organisms becomes so cheap and efficient that any old ne’er-do-well can whip out a weapon of mass destruction. With current technology, it costs about $1.45 per assembled base, and Church estimates that the technique he describes in Nature could be between 1,000 and 5,000 times cheaper. Of course, it’s not clear that cost is the main factor that will decide whether scientists should be concerned about who has access to the know-how.

Claire Fraser, president and director of The Institute for Genomic Research, writes in an e-mail that, to some extent, the genie is already out of the bottle. “I think that it’s difficult, if not impossible, to determine at which point the speed or cost of such an approach reaches a threshold for concern,” she says. “We should have already been concerned based on published work because if somebody was absolutely set on creating a new super-pathogen it is possible that it might be done, given enough time and money.”

Tian, J.; Gong, H.; Sheng, N.; et. al. "Accurate multiplex gene synthesis from programmable DNA microchips" Nature 2004, 432, 1050 – 1054.

— John S. MacNeil


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