Genetic Engineers Are Building a Biological Kill Switch

By Sarah Zhang on at

The fear of genetically-modified creatures escaping from the lab is the basis for a thousand sci-fi stories, but it’s also a legitimate concern. That’s why genetic engineers are inventing kill switches, or genetically-encoded suicide triggers, for GMOs they want to keep contained. Here’s how they work.

Why we need kill switches

When we talk about GMOs now, we usually mean genetically modified food: corn, soybeans, canola, extra-crisp apples. While GM crops have occasionally spread into the wild, plants are, relatively speaking, easy to contain.

But what about a GM mosquito that can fly away? Or microscopic GM bacteria oozing through the ground? Once such organisms escape, there’s really no going back. And these aren’t far-fetched scenarios. Scientists are already investigating ways to mobilise GM bacteria to clean up toxic spills. And the mosquito scenario is already happening — we’ve been using sterile GM mosquitoes to stop the spread of dengue fever. What we don’t want is an unintended ecological disaster, as GM organisms and their genes spread through the environment.

What’s to stop it? A kill switch, or a piece of genetic code that kills the GM organism when its job is done. Kill switches have already been developed to confine lab-made GMOs to the lab. But if we’re going to purposely release GMOs into the wild, we’ll need more sophisticated kill switches. And they are coming.

Get ‘em hooked on a lab chemical

A kill switch is basically a lethal piece of genetic code that be easily switched on or off. The trigger could be a change in the environment, such as heat or cell density. The most common strategy, though, is basically chemical dependence: Feed the GMO a lab chemical that it can’t get in the wild. Then make the GMO’s life dependent on it. If the GMO escapes into the outside world, it dies without its chemical.

We’re already using this kind of kill switch right now. Genetically modified Aedes aegypti mosquitoes are used to fight dengue fever. The company Oxitec has experimented with releasing these mosquitoes, which need tetracycline to survive. Tetracycline is better known as an antibiotic, but it plays very different role for these modified mosquitoes.

Oxitec has inserted in its mosquitoes a genetic sequence that includes a protein called tTa, or tetracycline transactivator. The genetic sequence is engineered in such a way that once tTa is activated, it causes the cell to keep making more and more of the protein—leading to the runway production of tTA. tTa then gunks up the cellular machinery, eventually killing the mosquito.

Tetracycline acts like an antidote to tTA. Oxitec raises male mosquitoes with the tTA and feeds them tetracycline. Once released into the wild, they die without the antibiotic—but not before mating and passing the tTa genes off to offspring that can’t live without tetracycline either. It’s pretty ingenious.

What’s still missing: The tTa system might work with mosquitoes, but it’s not a one-size-fits-all solution to GMOs. That’s especially true for GM bacteria, which might be the wiliest of them all.

For one, bacteria evolve very quickly, in part because they have the special ability to suck up DNA they encounter in the environment. A kill switch that relies on, say, a GM bacteria’s inability to metabolise a single vital nutrient might be easily foiled if it picks up that relevant gene. This also means that killing a GM bacteria might not be enough to prevent its genes from spreading. If its modified DNA sticks around, other bacteria in the environment might pick it up.

That’s why this year, scientists have suggested two new strategies. They both still involve a chemical trigger, but they add another piece to the puzzle.

Synthetic amino acids

One strategy takes synthetic nutrients one step further to synthetic amino acids, the very molecules that are the building blocks of proteins. Earlier this year, scientists announced they were able to create E. coli that take up synthetic amino acids by actually modifying translation, the process by which our cells read the genetic code of RNA to make proteins.

Translation usually works like this. Every three letters of RNA makes up a codon, which corresponds to one of the 20 amino acids that make up proteins. Codons are redundant, so that more than one codon can code for the same amino acid. There are also three stop codons (UAG, UAA, UGA) that all signal the end of a protein. Scientists took one of these stop codons (UAG) and assigned it to a 21st amino acid—a synthetic one. Then they redesigned essential proteins in the cell to include this synthetic amino acid. Take away this synthetic amino acid, and the cell can no longer survive. It also can’t as readily pass on its genes to other bacteria, since this tinkers with the very process of making proteins.

Self-destructing DNA

This week, scientists announced a new type of kill switch that kills the genetically modified organism (GMO) and erases its modified genes. It uses CRISPR, a hot new tool in molecular biology right now. The CRISPR system has an enzyme that cuts target DNA very precisely.

In a new study, scientists specially engineered E. coli with genes for CRISPR that only become active in the presence of a sugar called arabinose. Once the bacteria sense arabinose, the CRISPR machinery comes alive, chewing up DNA to kill the cell. Its CRISPR system can also be tweaked to erase manmade DNA sequences, keeping them out of the environment and also keep them secret in case of, you now, trade secrets.

In the cases of both synthetic amino acids and self-destructing DNA, the recent studies are proofs of concept, and it’ll be years before the technology is ready for primetime. But scientists are definitely thinking about how to contain genetically modified organisms. More sophisticated GMOs are coming, and we’ll need more sophisticated ways to contain them.

Top image: Sergey Nivens/shutterstock