The advent of recombinant DNA technologies in the 1970s brought about many genetic cloning methods, ushering in the field of biotechnology (1). These advances in biotechnology have made it possible to create genetically modified organisms (GMOs). Over the decades, scientists have discovered numerous applications for GMOs in biomedical research, allowing better research on human disease (1,2). Scientists have also created GMOs that can synthesize novel chemicals for biofuels and pharmaceuticals (1,2). Such advances have improved different industries such as fishing and agriculture. (2).
E. Coli cells under a microscope.
Image courtesy of Rocky Mountain Laboratories, NIAD, NIH
However, although progress with synthetic organisms has created much excitement among scientists, it has also caused much worry. GMOs have the potential to disrupt ecosystems if they were to escape into the environment. Although there are guidelines for physical containment and safe use of GMOs, physical containment is simply not sufficient, especially for GMOs created for applications in the open environment (1). Therefore, to protect our ecosystems, it is necessary to develop biocontainment methods that prevent GMOs from thriving outside of the laboratory (3).
Until recently, one common strategy for biocontainment was to modify organisms to be auxotrophic (3). Auxotrophic organisms cannot synthesize every chemical they need to survive. Humans are auxotrophic: we cannot synthesize all the vitamins we need to live healthily. However, making organisms auxotrophic does not always work. Some organisms, such as E. coli, can scavenge essential nutrients from their environments (2). E. coli can also evolve a way of synthesizing essential nutrients or acquire the ability by exchanging bits of DNA with other E. coli, thus reverting the modification (2).
George Church, Robert Winthrop Professor of Genetics at Harvard, has worked to improve methods of biocontainment. On January 21 of this year, Church and his colleagues claimed to engineer a “synthetic auxotroph” that drastically improves biocontainment (2). They genetically modified E. coli to make it dependent on a certain synthetic amino acid (2). This synthetic amino acid is not available in nature, and without it, the E. coli cannot synthesize properly folded proteins and replicate.
Church’s group used computational tools to design proteins that ensured the E. coli’s “irreversible, inescapable dependency” and tested them on normal E. coli cells (2,3). This along with the 49 alterations made to E. coli genome made the chances of E. coli evolving around the mutation very slim (2). Church claimed, “This is the most radically altered genome to date in terms of genome function. We not only have a new code, but also a new amino acid, and the organism is totally dependent on it” (2).
Weaknesses in Church’s biocontainment strategy have yet to be seen. He and his colleagues hope to one day “develop something that eventually will be so biologically contained that we don’t need physical containment anymore” (2). In the meantime, however, Church says that we will still use physical containment to debug his biocontainment method and make sure that it actually works (2).
Sources:
1. Rovner AJ, et al. (21 Jan 2015). Recoded organisms engineered to depend on synthetic amino acids. Nature. Retrieved January 25, 2015 from http://www.nature.com/nature/journal/vaop/ncurrent/full/nature14095.html
2. Harvard Medical School (21 Jan 2015). Biological safety lock for genetically modified organisms. ScienceDaily. Retrieved January 25, 2015 from www.sciencedaily.com/releases/2015/01/150121135619.htm
3. Mandell DJ, et al. (21 Jan 2015). Biocontainment of genetically modified organisms by synthetic protein design. Nature. Retrieved January 25, 2015 from http://www.nature.com/nature/journal/vaop/ncurrent/pdf/nature14121.pdf