How to Hack a Genome

Posted by Pete Shanks July 20, 2011
Biopolitical Times
George Church

George Church and 15 co-authors last week published a paper in Science that represents a potentially important step in the direction of massively altering genomes. To use a word-processing metaphor, they did a search-and-replace in an E. Coli genome to change all 314 occurrences of TAG to TAA; since the two are essentially synonyms (they are both stop codons), swapping them does not by itself change the meaning. But it's very significant, as noted in their abstract:

Our methods treat the chromosome as both an editable and an evolvable template, permitting the exploration of vast genetic landscapes.

Having deleted TAG, as Frederick Blattner (who was not part of the team) told New Scientist, they might then be able to reprogram the cell's machinery to assign the empty space to produce whatever they wanted, perhaps an entirely new amino acid and thus entirely novel proteins:

"That's the vision, completely refactoring the genome to where it is quite substantially different from any other life forms. ... We can manipulate the fundamental aspects of life."

This is not exactly a done deal yet. What's been published is a technique, and there is no certainty that such a grandiose scheme will pan out. Which is why Gerald Joyce told the New York Times this is "a major technical breakthrough which has great promise for scientific breakthroughs to follow," adding:

"This is really macho molecular biotechnology."

In effect, this is another step along a road that Church has been describing (and publishing about) for several years. It's the technique he anticipated in 2008 when he suggested that there were plausible prospects of re-creating a wooly mammoth. (Nicholas Wade went there again in the second paragraph of last week's Times report, though Church has always seemed more interested in biofuels.) It's a different approach than that taken by Craig Venter, and might be more robust, since it involves tinkering and remodeling rather than trying to design and build from scratch.

Church clearly has few qualms about creating novel organisms, and he's not alone in that. The topic has been gradually making its way in to the discourse, for instance at the Presidential Bioethics Commission, but so far the debate seems largely to have been treated as theoretical. This should add a little more urgency to the discussion.

Previously on Biopolitical Times: