An international group of researchers has recently warned the broader scientific community and the public of the risks of mirror life—specifically, the creation of mirror microbes by scientists in the laboratory. But what are mirror microbes?
Mirror microbes are a synthetic form of bacteria that could be created by scientists in which all molecules would be the reverse or ‘mirror’ form of what is seen in nature. In this article, we delve into the world of mirror microbes: once a science-fiction fantasy, now a not-too-distant threat to life on Earth.
“It's not only that it could be done if somebody tried, but also the default path of technological progress will take us further and further there,” said Sebastian Oehm, a synthetic biologist and biosecurity expert at the J. Craig Venter Institute and founder of synthetic biology company SynX Therapeutics. “There's a lot of enabling that's needed, and a lot of it is not developed to make mirror life, it's developed for other reasons. But as we develop it, we'll get closer and closer to this ability to make mirror life.”
Mirror Microbes: The Basics
To understand what are mirror microbes, we must first explore the concept of chirality. Let’s investigate what chirality is, how it affects chemical and biological molecules, and how these discoveries led to the concept of mirror life.
What is chirality?
Most biological molecules are chiral, meaning that they cannot be superimposed on their mirror image.1 Take human hands, for example: Our left and right hands are mirror images of each other, yet it is impossible to fit a right hand into a left-handed glove, or to shake someone’s left hand with your right hand.
Alanine is an example of a molecule with chiral enantiomers: L-alanine cannot be superimposed on its mirror image, D-alanine.
Erin Lemieux
A chiral molecule and its corresponding mirror image molecule are together known as enantiomers.1 Standard chemical reactions produce equal proportions of these left- and right-handed molecules, resulting in what is referred to as a racemic mixture. Despite having the same chemical structure, enantiomers can rotate light in different directions and have markedly different effects on biology.2
Some chemical enantiomers smell different despite binding to the same olfactory receptor; (4R)-(−)carvone smells like mint, while its enantiomer (4S)-(+)-carvone smells like the herb caraway.3 One of the best-known examples of enantiomers having different effects on biological systems is the notorious drug thalidomide, which was approved for the treatment of morning sickness in pregnant women. The drug was quickly recalled after scientists discovered that while one enantiomer had a sedative effect, the other was a teratogen and caused significant birth defects.4
Nucleic acids, amino acids, and sugars are all chiral molecules; DNA and RNA are right-handed molecules, while amino acids are left-handed. They do not have naturally occurring enantiomers. Because these molecules are the building blocks for larger structures—such as proteins and cells—those larger structures are also chiral.
“An amazing feature of nature is that all life on Earth, from the smallest bacterium, to plants, to animals, to humans, we're all made of the same building blocks,” said Oehm. . “And these building blocks that we're made of, and they could, in principle, exist in two mirror forms, but life only uses one mirror form.”
Since the discovery of chiral molecules by Louis Pasteur in 1848,5 and the subsequent realization that life on Earth exists in only one mirror form, scientists have frequently wondered: What if we could create not only mirror molecules, but also mirror life?
What are mirror microbes?
Sebastian Oehm, a synthetic biologist and biosecurity expert, contributed to a recent report warning about the dangers of mirror microbes.
Sebastian Oehm
Mirror microbes are a hypothetical, synthetic form of life in which all of the components of the bacterial cell would have reversed chirality. For example, they would have left-handed DNA and right-handed proteins—the opposite of what is seen in a natural bacterial cell. They are just one potential form of mirror life, and the most feasible for scientists to create; they are significantly less complex than human cells, and do not need host cells to replicate like viruses do.
“They're a form of bacteria that do not exist. They could never emerge by evolution,” Oehm explained. However, some synthetic biologists have shown interest in generating mirror microbes, and recent years have seen technological advances that would make it possible to create these organisms in the laboratory. Oehm was part of an international group of scientists who recently released a technical report on the feasibility and risks of mirror microbes.
“For such a long time, this has been science fiction…that scientists could create life in a test tube,” said Oehm. But in recent years, scientists have realized that creating mirror microbes is no longer just an abstract fantasy. While it’s still years away from reality, Oehm said that it could be achieved with significant inputs of money and expertise.
Mirror Life Microbe Research: How and Why?
Mirror life microbe research is still very much hypothetical. So how would scientists go about creating mirror microbes, and why would they want to do so?
How would scientists create mirror microbes?
There are two ways that scientists could theoretically create mirror microbes. The first would be to create a mirror microbe from scratch, otherwise known as the bottom-up approach: Scientists could create synthetic mirror components of a bacterial cell and put them together to create a mirror microbe. The other pathway is a top-down approach, in which scientists would start with a living bacterial cell and convert each of its components to mirror molecules.
While Oehm said that the bottom-up approach is the more likely scenario in the short term, there are still massive obstacles. For example, to create a mirror microbe cell, scientists would need to synthesize large amounts of mirror DNA—an expensive and time-consuming endeavour. Chemistry advances have made it possible to create small mirror proteins, but creating large, complex proteins is currently out of reach.
One of the key limiting factors to creating mirror microbes would be to create a mirror ribosome, one of the most complex and important cell organelles. “[The ribosome] consists of three big RNAs and then over 50 proteins, and they all have to assemble and be put together in exactly the right way to make a high-efficiency ribosome that can then be used to kick start life,” Oehm said.
Even if scientists could create all the individual components of a mirror microbe cell, Oehm said, there remains a key question: Can those non-living mirror pieces be put in a test tube to create a living mirror organism? “Scientists so far have never been able to make life, but we're getting there,” he added.
Why study mirror microbes?
Scientists have been interested in creating synthetic mirror microbes for several reasons. Firstly, mirror biomolecules are highly desirable in therapeutics owing to their ability to avoid detection by the human immune system and resist degradation through normal biological processes. Because mirror microbes would naturally produce biomolecules with reversed chirality to normal cells, they could be used to produce these mirror biomolecules at scale in more cost-effective manner than can be achieved using chemical synthesis.
In addition, the mirror microbes grown in large bioreactors to create mirror biomolecules would themselves be immune to the microbial infections that often plague these large-scale protein production systems. However, despite the allure of synthetic mirror microbes, Oehm said it isn’t worth the risk.
Why Are Mirror Microbes Dangerous?
In their technical report and a corresponding publication in Science,6 Oehm and his colleagues discuss the risks of mirror microbes to human health. “We thought a lot about this early on, when we studied the immune response, and what it would actually do in the human body,” Oehm said. “Unfortunately, the answer isn't positive.”
Mirror microbes would not be invisible to the human immune system, but their recognition and processing would be severely reduced. “What we think would be the disease progression of the mirror bacterium is very different from the way that disease will work for natural chirality pathogens,” Oehm said.
According to Oehm, if mirror microbes came into contact with a human through the skin or gut, they would eventually reach the bloodstream through minor barrier leaks between cells. Once in the blood, where there are enough achiral nutrients in the blood for mirror microbes to feed and grow, they could grow unchecked, as it is unknown if the immune system could eliminate the mirror microbes as it does for natural bacteria.
“This could lead to a sepsis-like response, where it's basically like blood poisoning, and eventually you get cumulative damage, and then an immune shock, and you can die from that. It could be that [the mirror microbes] deplete nutrients, and suddenly all the cells are out of oxygen or sugar,” said Oehm.
The mirror microbes could spread unchecked around the world and infiltrate natural ecosystems as well as infect humans. “[Mirror microbes] could potentially kill a lot of people around the world. It could cause a lot of ecological harm and catastrophe. It could invade ecosystems that have never seen mirror life before, it could spread there and persist there,” Oehm remarked. “This is even worse than many other ecological catastrophes, in that it's so broad-hitting—it hits humans, and it hits the environment.”
Should Creating Synthetic Mirror Microbes Be Banned?
Oehm and his colleagues have called for a global ban on efforts to create mirror microbes because the significant risks of harm to humans, animals, and entire ecosystems far outweigh the limited potential benefits. Through the lens of biosecurity, Oehm said that it would not be possible to adequately contain synthetic mirror microbes; whether through human error or deliberate misuse, there would be potential for the bacteria to escape. “Even if you made it safe, can you make it secure?” he added.
Mirror life microbe research is still at least a decade away from becoming reality, and conservative estimates suggest this timeline is closer to 30 years. As far as Oehm and his colleagues are aware, no scientists are currently attempting to create mirror microbes, and several research groups who were on the path to mirror life have turned from it after realizing the risks.
Oehm said that this field of research should be strongly regulated, and any technologies that would enable the creation of mirror microbes should be banned. To avoid restricting scientific innovation and discovery, their focus will be on identifying key bottlenecks on the way to mirror life that can be prevented without incurring significant costs to the broader scientific field—for example, the mirror ribosome. “I'm not so convinced that mirror ribosomes would have a lot of a lot of beneficial uses that we couldn't just get through chemical methods,” Oehm stated.
Most scientists have been supportive of the group’s suggestions, and ongoing discussions about how the technology will be regulated have brought together researchers from around the world. “You have limited benefits versus unprecedented risk, potential for unprecedented harm,” said Oehm. “The balance is very, very clear in my eyes.”
- Inaki M, et al. Cell chirality: its origin and roles in left–right asymmetric development. Philos Trans R Soc B Biol Sci. 2016;371(1710):20150403.
- Nguyen LA, et al. Chiral drugs: An overview. Int J Biomed Sci IJBS. 2006;2(2):85-100.
- Brookes JC, et al. Odour character differences for enantiomers correlate with molecular flexibility. J R Soc Interface. 2009;6(30):75-86.
- Tokunaga E, et al. Understanding the thalidomide chirality in biological processes by the self-disproportionation of enantiomers. Sci Rep. 2018;8(1):17131.
- Vantomme G, Crassous J. Pasteur and chirality: A story of how serendipity favors the prepared minds. Chirality. 2021;33(10):597-601.
- Adamala KP, et al. Confronting risks of mirror life. Science. 2024;386(6728):1351-1353.
