Scientists have engineered a new way to genetically modify organisms so they’re less likely to spread uncontrollably in the wild and wreak havoc. By creating bacteria that require molecules not found in nature to survive, the scientists have set the stage for a safer way to use genetically modified bacteria to make medicines, fuels and other useful chemicals.
Two teams of researchers separately used E. coli as a test case, engineering the bacterium to depend on human-made versions of amino acids, the researchers report online January 21 in Nature. Bacteria use amino acids to make proteins.
The new method drastically cuts the likelihood of genetically engineered bacteria escaping into the environment, says Floyd Romesberg, a synthetic biologist at Scripps Research Institute in La Jolla, Calif. The dependence on human-made amino acids “really creates a firewall between the cell’s life and its natural environment.”
One group of researchers, led by Farren Isaacs of Yale University, engineered bacteria to build proteins necessary for survival only when exposed to a human-made amino acid. “It would be like if I took the tires off your car,” explains Christopher Voigt, a bioengineer at MIT.
The proteins within the bacteria engineered by the other group, led by George Church of Harvard University, cannot fold into their proper shape without the human-made amino acid holding them together. It’s like taking the tires off your car and replacing them with tank treads, Voigt says. “In both cases, it’s the same idea: The car can’t run. But in one case, you fundamentally change what it’s running on.”
Both groups tested their doctored E. coli in cultures that lacked the human-made amino acid, observing them over time to make sure the bacterial colonies could not grow. In neither case did the researchers find detectable amounts of bacteria that could survive without the human-made amino acid.
Isaacs’ group went a step further and placed their E. coli in soil and blood, which the microbes might encounter if used outside the lab. Again, the bacteria failed to thrive.
Church’s group also exposed their E. coli to wild E. coli to make sure the genetically modified bacteria could not steal DNA that would break their dependence on human-made amino acids.
Previous attempts to keep genetically engineered bacteria in check include “kill switches” that wipe out the bacteria when researchers are finished with them. But even with kill switches, altered bacteria have the potential to spread beyond the lab by mutating or swapping DNA with wild bacteria. Engineering bacteria to rely on human-made compounds “significantly reduces the threat of them ever causing trouble,” says Romesberg.
The technique also may boost genetically modified bacteria’s usefulness. “Bacteria have been engineered to produce pharmaceuticals, materials and fuels,” says Karmella Haynes, a biomedical engineer at Arizona State University in Tempe. “Now that bacteria can be designed to stay put in an industrial environment, these new bioproduction technologies can be scaled up.”
The new research also lays a foundation for broader uses of genetically engineered bacteria, Isaacs said in a press briefing. They could be used away from controlled industrial environments to boost food production, fight disease or clean up oil spills and landfills.