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January 28, 2022

Harvard discovers new method of biocontainment

By TONY WU | January 29, 2015

Genetically modified organisms (GMOs) spark numerous debates regarding human safety and the efficient use of resources. Some advocate GMOs as a way through which humans can battle hunger and disease. The flood of cheap and beautiful genetically modified crops in supermarkets and the success of genetically modified mosquitoes in wiping out their disease-carrying counterparts seem to support this view. However, opponents of GMOs cite the potential dangers to human health if genetically modified foods are consumed and the possibility of mutations in genetically modified organisms. Recently a research team at Harvard has discovered a method of biocontainment, built-in mechanisms that prevent GMOs from surviving in unintended places.

Numerous methods of biocontainment have been tested in the past. One approach involves modifying the E. coli genome so that the bacteria becomes an auxotroph. Normal E. coli can create nutrients needed for growth, while auxotrophic E. coli lack these nutrients. As a result, scientists can control the bacteria by withdrawing these nutrients and turning E. coli into auxotrophs. Another method involves a kill switch encoded in the E. coli genome. The kill switch increases the vulnerability of the bacteria to toxins, simplifying cleanups after bacteria spills. However, bacteria such as E. coli may overcome these biocontainment methods. Auxotrophic bacteria may find nutrients outside of their intended environment, or they may develop mutations that allow the synthesis of nutrients. E. coli with kill switches can also mutate to turn off the switch, increasing their resistance to toxins.

George Church, a professor at Harvard Medical School, led the research team in constructing the first GMO with built-in biocontainment centered around amino acids, the building blocks of proteins. The team selected a strand of E. coli and heavily modified its genome. With the modified genome, bacteria created by the team would be unable to survive without a constant supply of synthetic amino acids. This is due to the fact that many genes within the genome encode proteins that require these artificial amino acids for the proteins to fold properly. Without the synthesized amino acids, proteins created by the cell will not fold properly and cannot carry out their functions.

As a result, E. coli with modified genomes can be regulated by scientists since the synthetic amino acids are not present naturally. In addition to being an effective control, the method of biocontainment developed by the Harvard team also presents an advancement in genome engineering. To make E. coli dependent on synthetic amino acids, the team designed an artificial amino acid that the modified genome requires.

The experiments conducted by the researchers yielded two strains of modified E. coli and three artificial proteins. Both strains of E. coli depend on the three artificial proteins, minimizing their chances of survival outside of controlled surroundings. To test the effectiveness of this biocontainment method, the team cultured one trillion bacteria. None escaped, even after two weeks.

The method of utilizing amino acids as biocontainment differs from other approaches because it is difficult for the bacteria to overcome their dependence through mutation. The genetic changes introduced by Church’s team involve 49 mutations. Chances are slim that the bacteria can successfully revert the mutations. The placements of these mutations are carefully calculated so that the resulting proteins will play a vital role in the ability of the E. coli to survive. Since the proteins are essential to the normal functions of the bacteria, deprivation of the amino acids will result in death rather than an incapacitated E. coli. Lastly, the modified E. colidepend on synthetic amino acids that are not found in nature, reducing the probability that it can survive outside of laboratory environments.

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