The creation of genetically² modified and entirely³ synthetic⁴ organisms continues to generate excitement as well as worry. Such organisms are already churning out insulin and other drug ingredients, helping⁵ produce biofuels, teaching scientists about human disease and improving fishing and agriculture. While the risks can be exaggerated to frightening effect, modified organisms do have the potential to upset natural ecosystems⁶ if they were to escape.

 

Physical containment⁷ isn't enough. Lab dishes and industrial vats⁸ can break; workers can go home with inadvertently contaminated clothes. And some organisms are meant for use in open environments, such as mosquitoes that can't spread malaria⁹.

 

So attention turns to biocontainment: building in biological safeguards to prevent modified organisms from surviving where they're not meant to. To do so, geneticists and synthetic biologists find themselves taking a cue from safety engineers.

 

"If you make a chemical that's potentially explosive, you put stabilizers in it. If you build a car, you put in seat belts and airbags," said George Church, Robert Winthrop Professor of Genetics at Harvard Medical School and core faculty¹⁰ member at the Wyss Institute.

 

And if you've created the world's first genomically recoded organism, a strain of Escherichia coli with a radically¹¹ changed genome, as Church's group announced in 2013, you make its life dependent on something only you can supply.

 

Church and colleagues report Jan. 21 in Nature that they further modified their 2013 E. coli to incorporate a synthetic amino acid in many places throughout their genomes. Without this amino acid, the bacteria can't perform the vital job of translating their RNA into properly folded proteins.

 

The E. coli can't make this unnatural¹² amino acid themselves or find it anywhere in the wild; they have to eat it in specially¹³ cooked-up lab cultures.

 

A separate team reports in Nature that it was able to engineer the same strain of E. coli to become dependent on a synthetic amino acid using different methods. That group was led by a longtime collaborator¹⁴ of Church's, Farren Isaacs of Yale University.

 

The two studies are the first to use synthetic nutrient¹⁵ dependency as a biocontainment strategy, and suggest that it might be useful for making genetically modified organisms safer in an open environment.

 

In addition, "We now have the first example of genome-scale engineering rather than gene¹ editing or genome copying," said Church. "This is the most radically altered genome to date in terms of genome function. We have not only a new code, but also a new amino acid, and the organism is totally dependent on it."

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