Our hands are mirror images of each other. Unless you flip one hand around, they’ll never look the same.
Scientists call this chirality, and the mirror-like property is fundamental to all life on Earth. DNA and RNA—life’s genetic molecules, from viruses to humans—are made of components that exist in their right-handed form. Amino acids, the building blocks of proteins, are left-handed. Switching the handedness usually causes cells to break down.
That is, it did until synthetic biology came along.
For the past decade, scientists have been engineering “mirror life” by changing the chirality of life’s building blocks. Flipping evolution’s design, they’ve made right-handed amino acids and left-handed sugars to build genetic material.
So far, this flipped biological universe only exists in individual molecules. But they could one day—potentially, in just a decade—be used to build mirror bacteria.
This month, dozens of scientists penned a warning against making mirror bacteria in Science. Among them are J. Craig Venter, a long-time enthusiast for rewriting life’s code. If released, mirror bacteria could evade the immune system, potentially causing lethal infections in people, animals, and plants. With utterly “alien” genomes, they are also likely to dodge antibiotics and other treatments, allowing them to rapidly spread like an uncontrollable invasive species.
“We are passionate defenders of allowing scientists to conduct their research with as few limits on intellectual curiosity as possible, and calling for a ban is not something that we do often or lightly,” wrote John Glass and Katarzyna Adamala at the J. Craig Venter Institute and the University of Minnesota, respectively, in an essay in The Scientist. Both contributed to the new paper.
“However, every rule has exceptions, and this is one of them,” they wrote.
Pushing Boundaries
Synthetic biology taps into the building blocks of life to expand upon nature’s design.
The field’s made leaps over the past decade. Storing data in DNA is old news. Recent studies have created DNA-based computer circuits that can play chess and living bacteria that thrive even with most of their genes removed—running instructions written on a fully synthetic chromosome designed in a computer and synthesized in a lab.
These advances could impact our daily lives.
Synthetic circuits that allow bacteria to pump out drugs, for example, could aid the fight against diabetes and malaria. Bacteria modified to chomp plastic or make strong but biodegradable materials, such as artificial silk, could protect the environment. Constructing synthetic components that mesh—or clash—with living organisms helps us better understand our own biology. As Richard Feynman famously said, “What I cannot create, I do not understand.”
While all this might already sound like science fiction, these studies still play out under evolution’s rules of chirality.
Mirror life breaks them.
There’s reason to explore these “flipped” molecules. For one, they could make longer-lasting medication. Proteins grab onto drugs to break them down. But like a right hand trying to fit into a left handprint, hypothetically, mirror molecules specifically designed to interact with a single protein target wouldn’t engage with other natural components in the cell—potentially making them more stable with fewer side effects.
Scientists have already made DNA and proteins from flipped building blocks. Some are now considering the next step: Using these components to build a mirror life form. The technology doesn’t yet exist. But “with the right components and nutrients,” flipped DNA or proteins could “boot up” a bacteria completely alien to all life on Earth, wrote Glass and Adamala.
“While both of us were initially excited about the prospect of developing mirror life, when we learned that mirror bacteria might have an incredibly deadly impact if they were ever introduced into the wild, we changed our minds,” they wrote.
Why So Dangerous?
Glass and Adamala are among dozens of experts in the field who penned a warning against making mirror life forms.
To be clear, they are not advocating a ban on research into individual therapeutic mirror molecules, which could benefit medicine. Rather, their focus is on mirror bacteria with the potential to reproduce.
Once bacteria or other living creatures can be entirely developed using synthetic DNA, synthetic proteins, and synthetic lipids, a living mirror bacteria could be constructed in the same way, wrote the authors.
Although the technology remains at least a decade away, now is the time to consider risks.
In isolation—say, in a petri dish—mirror bacteria would likely live like normal cells if given mirror-image nutrients and be as feeble or strong as their natural peers. The problem? Many “normal” bacteria can also survive on nutrients without chirality, suggesting that mirror bacteria could also take advantage of those nutrients.
It could be a problem, then, if mirror bacteria break loose. Although lab breaches are rare, they do happen. Mirror bacteria’s “flipped” genetic makeup would make them completely immune to phages—viruses that prey on bacteria in the wild. Because of their flipped chirality, they’re completely hidden from predators.
This resilience could allow mirror bacteria to spread across ecosystems. Through evolution, they could also optimize their mirror genes to survive, in their perspective, in a “flipped” world.
“An unstoppable replicating mirror bacteria free in the environment could cause consequences that are disastrous,” wrote Glass and Adamala.
More worrisome is perhaps their danger to human health. Our immune systems rely on proteins that latch onto invading pathogens. But they can only recognize proteins with the same chirality. If we were infected with mirror bacteria—and that’s still a big if—they could evade our immune systems, essentially making us immunocompromised.
Early signs already show that mirror proteins can withstand being broken down in cells. Because they’re “hidden” from the immune system, these bacteria could enter the body—through the skin, gut, or lungs like normal pathogens—without triggering antibodies or other immune defenses. Current antibiotics, engineered to tackle bacteria with natural chirality, likely wouldn’t work on mirrored ones. So, they could, in theory, cause devastating outbreaks.
What to Do?
There are ways to reduce risk that balance research into the benefits of “flipped” life molecules. Scientists could intentionally hobble mirror bacteria with a synthetic kill-switch that doesn’t harm other living creatures. But once created, it would be relatively easy for others to free so-called “bio-contained” bacteria of safeguards, argued the authors.
“We therefore recommend that research with the goal of creating mirror bacteria not be permitted, and that funders make clear that they will not support such work,” they wrote.
The opinion doesn’t include mirror DNA or proteins for therapeutic uses. In addition to their Science paper, which summarizes results, the team released a full report and welcome scientists, policymakers, industry, and the general public to jump into the debate.
“Once a mirror cell is made, it’s going to be incredibly difficult to try to put that genie back in the bottle,” said Michael Kay at the University of Utah, who contributed to the new article. “That’s a big motivation for why we’re thinking about prevention and regulation well ahead of any potential actual risk.”
Image Credit: Adapted from NIAID on Unsplash