March 2, 2015

Microbes given a new lease on shelf life

Critics of genetic engineering have long worried about the risk of modified organisms escaping into the environment. A biological-containment strategy described this week in Nature has the potential to put some of those fears to rest and to pave the way for greater use of engineered organisms in areas such as agriculture, medicine and environmental clean-up.

The new approach gives GMOs an Achilles heel. The researchers who have produced the organism have built in vital dependency on an artificial nutrient. If the nutrient is withdrawn, or the organism spreads to where it is no longer available, then the organism cannot survive.

The research marks an elegant step forward for the growing field of synthetic biology. In the first paper, Farren Isaacs and his colleagues at Yale University in New Haven, Connecticut, describe how they have produced various GMOs whose growth is restricted by the expression of multiple essential genes that depend on synthetic amino acids (A. J. Rovner et al. Nature; 2015). In the second, separate study, George Church at Harvard Medical School in Boston, Massachusetts, and his colleagues redesigned essential enzymes in a GMO to make it metabolically dependent on synthetic amino acids (D. J. Mandell et al. Nature; 2015). The modifications are made throughout the genome to make it harder for the altered sequences to be ejected.

The new technique originated in the laboratory of George Church. Two years ago, Church and his team (which included Isaacs) reported the synthesis of a strain of Escherichia coli that had a reprogrammed genetic code3. Instead of recognizing a particular DNA triplet known as the amber stop codon as an order to terminate protein synthesis, the recoded bacterium read the same instruction as a directive to incorporate a new kind of amino acid into its proteins.

Church and Isaacs have independently made this engineered microbe reliant on unnatural amino acids. The Isaacs team used genomic sequencing to identify sites in essential bacterial proteins where the microbes could incorporate synthetic amino acids without affecting overall function, whereas Church’s group started with the protein structures and added elements to help integrate and accommodate the artificial amino acids. “This is really the culmination of a decade of work,” says Church.

These organisms are also more resistant to viruses than their natural counter­parts because of the mismatch between the genetic code of the virus and that of its host3. Looking ahead, Church and his team are working to co-opt seven different codons, instead of just one.

The research in both papers is with bacteria, but there seems no reason why the techniques they describe could not be used to engineer more-complex, multicellular organisms — including crops — in the same way.

So what is the downside? Much of the controversy over genetic modification relates to early, clumsy, attempts by big business to commercialize crops, and to gain control over where, when and how they were grown to maximize profit. A crop that needs constant nourishment with a bespoke foodstuff — unavailable elsewhere and with manufacture protected under probable patents — could be presented as a way of tying vulnerable farmers still closer to largely unloved seed companies.

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