Genetically modified bacteria are widely used in the biotech industry to make products as diverse as yogurt and fine chemicals. But before these genetically modified organisms can be put to work outside the laboratory or factory—for example, in the human gut as probiotics—researchers need to develop reliable ways to keep them on a leash and kill them once their job is done.

A team led by Massachusetts Institute of Technology’s James J. Collins now reports two new biocontainment strategies, called kill switches, that prevent GMOs from running amuck in the environment. These new gene circuits, which are easier to use and modify than prior GMO kill switches, make it impossible for a genetically modified bacterium to survive unless it receives a specific chemical or combination of chemicals provided externally (Nature Chem. Biol. 2015, DOI: 10.1038/nchembio.1979).

To make the first circuit, dubbed Deadman, Collins and his team engineered Escherichia coli and Pseudomonas putida to have genes that code for a deadly toxin. They also engineered the bacteria so that the presence of a specific chemical, such as anhydrotetracycline, blocks expression of the toxin-producing genes. Take away the external chemical—which ideally is so unusual that the bacteria cannot scavenge it from the environment—and the GMO makes the toxin and dies.

To make the second circuit, nicknamed Passcode, the team programmed bacteria to rely on the presence or absence of a cocktail of three chemicals for survival. If the bacteria receive the right combination of chemicals—the correct “passcode”—then they do not activate their kill switch. The team demonstrated the concept by engineering E. coli so that if the bacteria are exposed to isopropyl β- D -1-thiogalactopyranoside, and at the same time, they don’t have access to cellobiose or galactose, then they die.

Sign up for C&EN's must-read weekly newsletter Email Address * Subscribe » Contact us to opt out anytime

“These synthetic gene circuits efficiently kill E. coli and can be readily reprogrammed to change their environmental inputs, regulatory architecture and killing mechanisms,” the team notes. The Passcode biocontainment circuit could also be used for intellectual property protection, the researchers suggest, because nobody but the GMO’s engineer would know the combination of chemicals that allow it to grow.