“Kill switches” shut down engineered bacteria

Researchers have developed safeguards in the form of two “kill switches,” which can cause the synthetic bacteria to die without the presence of certain chemicals

Many research teams are developing genetically modified bacteria that could one day travel around parts of the human body, diagnosing and even treating infection according to MIT.

However, before such bacteria can be safely let loose, scientists will need to find a way to prevent them from escaping into the wider environment, where they might grow and cause harm.

In a paper published this week in the journal Nature Chemical Biology, researchers at MIT, the Broad Institute of MIT and Harvard, and the Wyss Institute at Harvard University described their two kill switches, which they call “Deadman” and “Passcode.”

There have been a number of attempts to develop kill switches over the past year, according to James Collins, from MIT’s Department of Biological Engineering and Institute for Medical Engineering and Science (IMES), who led the research.

These include efforts to reprogram the entire genome of the organism to ensure that it requires the presence of certain amino acids or other chemicals in order to survive, divide, and grow.

However, this approach can be both labor- and resource-intensive, and could introduce changes that might make the organism less useful as a monitoring or diagnostic tool, Collins says.

Collins said: “In our case, we are introducing standalone circuits that can be popped in to any number of different organisms, without needing to rewire or change much of the genome in order for it to accommodate the switch,” he says.

The Deadman switch, for example, is part of a bacterial strain that needs an external chemical to prevent a continuously expressed toxin from killing the cell.

The switch was motivated by the so-called deadman brakes on old trains, which required a conductor to be in constant contact with the handle or pedal in order for the vehicle to move forwards, Collins says.

The system, which builds on previous work in Collin’s lab, consists of a genetic “toggle” switch made up of two transcription factor genes.

The switch can flip between two states, in which either one of the two transcription factor genes is turned on. The researchers altered the expression of these two transcription factors, leading to strong expression for one gene and weak expression for the other.

The presence of a small molecule keeps the switch in its weak state, but as soon as this is removed, the switch will flip to its strong state. The switch is programmed to express various toxins as soon as this strong state is turned on, Collins says.

Collins said: “If the system does get flipped, by removing the small molecule, it would express toxins at a very high level that could then quite rapidly and readily kill off the bug.”