For four days in February 2019, some 30 synthetic biologists and ethicists hunkered down at a conference center in Northern Virginia to brainstorm high-risk, cutting-edge, irresistibly exciting ideas that the National Science Foundation should fund. By the end of the meeting, they’d landed on a compelling contender: making “mirror” bacteria. Should they come to be, the lab-created microbes would be structured and organized like ordinary bacteria, with one important exception: Key biological molecules like proteins, sugars, and lipids would be the mirror images of those found in nature. DNA, RNA, and many other components of living cells are chiral, which means they have a built-in rotational structure. Their mirrors would twist in the opposite direction.
Researchers thrilled at the prospect. “Everybody—everybody—thought this was cool,” says John Glass, a synthetic biologist at the J. Craig Venter Institute in La Jolla, California, who attended the 2019 workshop and is a pioneer in developing synthetic cells. It was “an incredibly difficult project that would tell us potentially new things about how to design and build cells, or about the origin of life on Earth.” The group saw enormous potential for medicine, too. Mirror microbes might be engineered as biological factories, producing mirror molecules that could form the basis for new kinds of drugs. In theory, such therapeutics could perform the same functions as their natural counterparts, but without triggering unwelcome immune responses.
After the meeting, the biologists recommended NSF funding for a handful of research groups to develop tools and carry out preliminary experiments, the beginnings of a path through the looking glass. The excitement was global. The National Natural Science Foundation of China funded major projects in mirror biology, as did the German Federal Ministry of Research, Technology, and Space.
By five years later, in 2024, many researchers involved in that NSF meeting had reversed course. They’d become convinced that in the worst of all possible futures, mirror organisms could trigger a catastrophic event threatening every form of life on Earth; they’d proliferate without predators and evade the immune defenses of people, plants, and animals.
“I wish that one sunny afternoon we were having coffee and we realized the world’s about to end, but that’s not what happened.”
Kate Adamala, synthetic biologist, University of Minnesota
Over the past two years, they’ve been ringing alarm bells. They published an article in Science in December 2024, accompanied by a 299-page technical report addressing feasibility and risks. They’ve written essays and convened panels and cofounded the Mirror Biology Dialogues Fund (MBDF), a broadly funded nonprofit charged with supporting work on understanding and addressing the risk. The issue has received a blaze of media attention and ignited dialogues among not only chemists and synthetic biologists but also bioethicists and policymakers.
What’s received less attention, however, is how we got here and what uncertainties still remain about any potential threat. Creating a mirror-life organism would be tremendously complicated and expensive. And although the scientific community is taking the alarm seriously, some scientists doubt whether it’s even possible to create a mirror organism anytime soon. “The hypothetical creation of mirror-image organisms lies far beyond the reach of present-day science,” says Ting Zhu, a molecular biologist at Westlake University, in China, whose lab focuses on synthesizing mirror-image peptides and other molecules. He and others have urged colleagues not to let speculation and anxiety guide decision-making and argued that it’s premature to call for a broad moratorium on early-stage research, which they say could have medical benefits.
But the researchers who are raising flags describe a pathway, even multiple pathways, to bringing mirror life into existence—and they say we urgently need guardrails to figure out what kinds of mirror-biology research might still be safe. That means they’re facing a question that others have encountered before, multiple times over the last several decades and with mixed results—one that doesn’t have a neat home in the scientific method. What should scientists do when they see the shadow of the end of the world in their own research?
Looking-glass life
The French chemist and microbiologist Louis Pasteur was the first to recognize that biological molecules had built-in handedness. In the late 19th century, he described all living species as “functions of cosmic asymmetry.” What would happen, he mused, if one could replace these chiral components with their mirror opposites?
Scientists now recognize that chirality is central to life itself, though no one knows why. In humans, 19 of the 20 so-called “standard” amino acids that make up proteins are chiral, and all in the same way. (The outlier, glycine, is symmetrical.) The functions of proteins are intricately tied to their shapes, and they mostly interact with other molecules through chiral structures. Almost all receptors on the surface of a cell are chiral. During an infection, the immune system’s sentinels use chirality to detect and bind to antigens—substances that trigger an immune response—and to start the process of building antibodies.
By the late 20th century, researchers had begun to explore the idea of reversing chirality. In 1992, one team reported having synthesized the first mirror-image protein. That, in turn, set off the first clarion call about the risk: In response to the discovery, chemists at Purdue University pointed out, briefly, that mirror-life organisms, if they escaped from a lab, would be immune to any attack by “normal” life. A 2010 story in Wired highlighting early findings in the area noted that if a such a microbe developed the ability to photosynthesize, it could obliterate life as we know it.
The synthetic biology community didn’t seriously weigh those threats then, says David Relman, a specialist who bridges infectious disease and microbiology at Stanford University and a trailblazer in studying the gut and oral microbiomes. The idea of a mirror microbe seemed too far beyond the actual progress on proteins. “This was almost a solely theoretical argument 20 years ago,” he says.
Now the research landscape has changed.
Scientists are quickly making progress on mirror images of the machinery cells use to make proteins and to self-replicate. Those components include DNA, which encodes the recipes for proteins; DNA polymerases, which help copy genetic material; and RNA, which carries recipes to ribosomes, the cell’s protein factories. If researchers could make self-replicating mirror ribosomes, then they would have an efficient way to produce mirror proteins. That could be used as a biological manufacturing method for therapeutics. But embedded in a self-replicating, metabolizing synthetic cell, all these pieces could give rise to a mirror microbe.
When synthetic biologists convened in Northern Virginia in 2019, they didn’t recognize how quickly the technology was advancing, and if they saw a threat at all, it may have been obscured by the blinding appeal of pushing the science forward. What’s become apparent now, says Glass, is that scientists in different disciplines, all related to mirror life, were largely unaware of what other scientists had been doing. Chemists didn’t know that synthetic biologists had made so much progress on creating mirror cells with natural chirality from scratch. Biologists didn’t appreciate that chemists were building ever-larger mirror macromolecules. “We tend to be siloed,” Glass says. And nobody, he says, had thought to seriously examine the immune system concerns that had already been raised in response to earlier work. “There was not an immunologist or an infectious disease person in the room,” Glass says, reflecting on the 2019 meeting. “I may have come closest, given that I work with pathogenic bacteria and viruses,” he adds, but his work doesn’t address how they cause infections in their hosts.
These scientists also didn’t know that around the same time as their meeting, another conversation about mirror life was happening—a darker dialogue that was as focused on danger as it was on discovery. Starting around 2016, researchers with a nonprofit called Open Philanthropy had begun compiling research files on catastrophic biological risks. The organization, which rebranded as Coefficient Giving in 2025, funds projects across a range of focus areas; it adheres to a divisive philanthropic philosophy called effective altruism, which advocates giving money to projects with the highest potential benefit to the most people. While that might not sound objectionable, critics point out that the metrics devotees use to gauge “effectiveness” can prioritize long-term solutions while neglecting social injustices or systemic problems.
Someone in Open Philanthropy’s biosecurity group had suggested looking into the risks posed by mirror life. In 2019 the organization began funding research by Kevin Esvelt, who leads the Sculpting Evolution group at the MIT Media Lab, on biosecurity issues, including mirror life. He began reading up to see whether mirror life was something to worry about.
Esvelt made waves in 2013 for pioneering the use of CRISPR to develop a gene drive, a technology that could spread genetic changes introduced into a living organism through a whole population. Researchers are exploring its use, for example, to make mosquitoes hostile to the parasite that causes malaria—and, as a result, lower their chance of spreading it to humans. But almost immediately after he developed the tool, Esvelt argued against using it for profit, at least until proper safeguards could be set and its use in fighting malaria had been established. “Do you really have the right to run an experiment where if you screw up, it affects the whole world?” he asked, in this magazine, in 2016. At the Media Lab, Esvelt leads efforts to safely develop gene drives that can be deployed locally but prevented from spreading globally.
Esvelt says he’s often thinking about the security risks posed by self-sustaining genetically engineered technologies, and research led him to suspect that the threat of mirror organisms hadn’t been seriously interrogated. The more he learned about microbial growth rates, predator-prey and microbe-microbe interactions, and immunology, the more he began to worry that mirror organisms, if impervious to the innate defenses of natural ones, could cause unstoppable infections in the event that they escaped the lab.
Even if the first experimental iteration of such a germ were too fragile to survive in the environment or a human body, Esvelt says, it would be a light lift to genetically engineer new, more resilient versions with existing technology. Even worse, he says, the results could be weaponized. The possible path from 2019 to global annihilation seemed almost too direct, he found.
But he wasn’t an expert in all the scientific fields involved in research on mirror life, so he started making calls. He first described his concerns to Relman one night in February 2022, at a restaurant outside Washington, DC. Esvelt hoped Relman would tell him he was wrong, that he’d missed something over the years of gathering data. Instead, he was troubled.
The concern spreads
When Relman returned to California, he read more about the technology, the risks, and the role of chirality in the immune system and the environment. And he consulted experts he knew well—ecologists, other microbiologists, immunologists, all of them leaders in their fields—in an attempt to assuage his concerns. “I was hoping that they’d be able to say, I’ve thought about this, and I see a problem with your logic. I see that it’s really not so bad,” he says. “At every turn, that did not happen. Something about it was new to every person.”
The concern spread. Relman worked with Jack Szostak, a professor of chemistry at the University of Chicago, and a group of researchers to see if it was possible to make an argument that mirror life wasn’t going to wipe out humanity. Included in that group was Kate Adamala, a synthetic biologist at the University of Minnesota. She was a natural choice: Adamala had shared the initial grant from the NSF, in 2019, to explore mirror-life technologies.
She also became convinced the risk was real—and was dumbfounded that she hadn’t seen it earlier. “I wish that one sunny afternoon we were having coffee and we realized the world’s about to end, but that’s not what happened,” she says. “I’m embarrassed to admit that I wasn’t even the one that brought up the risks first.” Through late 2023 and early 2024, the endeavor began to take on the form of a rigorous scientific investigation. Experts were presented with a hypothesis—namely, that if mirror cells were built, they would pose an existential threat—and asked to challenge it. The goal was to falsify the hypothesis. “It would be great if we were wrong,” says Vaughn Cooper, a microbiologist at the University of Pittsburgh and president-elect of the American Society for Microbiology.
Relman says that as the chemists and biologists learned more about one another’s work and began to understand what immunologists know about how living things defend themselves, they started to connect the dots and see an emerging picture of an unstoppable synthetic threat.
Some scientists have pushed back against the doomsday scenario, suggesting that the case against mirror life offers an “inflated view of the danger.”
Timothy Hand, an immunologist at the University of Pittsburgh who hadn’t participated in the 2019 NSF meeting, wasn’t initially worried when he heard about mirror life, in 2024. “The mammalian immune system has this incredible capability to make antibodies against any shape,” he says. “Who cares if it’s a mirror?” But when he took a closer look at that process, he could see a cascade of potential problems far upstream of antibody production. Start with detection: Macrophages, which are cells the immune system uses to identify and dispatch invaders, use chiral sensing receptors on their surfaces. The proteins they use to grab on to those invaders, too, are chiral. That suggests the possibility that an organism could be infected with a mirror organism but not be able to detect it or defend against it. “The lack of innate immune sensing is an incredibly dangerous circumstance for the host,” Hand says.
By early 2024, Glass had become concerned as well. Relman and James Wagstaff, a structural biologist from Open Philanthropy, visited him at the Venter Institute to talk about the possibility of using synthetic cell technology—Glass’s specialty—to build mirror life. “At first I thought, This can’t be real,” Glass says. They walked through arguments and counterarguments. “The more this went on, the more I started feeling ill,” he says. “It made me realize that work I had been doing for much of the last 20 years could be setting the world up for this incredible catastrophe.”
In the second half of 2024, the growing group of scientists assembled the report and wrote the policy forum for Science. Relman briefed policymakers at the White House, members of the defense community, and the National Security Agency. Researchers met with the National Institutes of Health and the National Science Foundation. “We briefed the United Nations, the UK government, the government of Singapore, scientific funding organizations from Brazil,” says Glass. “We’ve talked to the Chinese government indirectly. We were trying to not blindside anybody.”
A year and a half on, the push has had an impact. UNESCO has recommended a precautionary global moratorium on creating mirror-life cells, and major philanthropic organizations that fund science, including the Alfred P. Sloan Foundation, have announced they will not finance research leading to a mirror microorganism. The Bulletin of the Atomic Scientists highlighted considerations about mirror life in its most recent report on the Doomsday Clock. In March, the United Nations Secretary-General’s Scientific Advisory Board issued a brief highlighting the risks—noting, for example, that recent progress on building mirror molecules could reduce the cost of creating a mirror microbe.
“I think no one really believes at this stage that we should make mirror life, based on the evidence that’s available,” says James Smith, the scientist who leads the MBDF, the nonprofit focused on assessing the risks of mirror life, which is funded by Coefficient Giving, the Sloan Foundation, and other organizations. The challenge now, Smith says, is for scientists to work with policymakers and bioethicists to figure out how much research on mirror life should be permitted—and who will enforce the rules.
Drawing the line
Not everyone is convinced that mirror organisms pose an existential threat. It’s difficult to verify predictions about how mirror microbes would fare in the immune system—or the larger world—without running experiments on them. Some scientists have pushed back against the doomsday scenario, suggesting that the case against mirror life offers an “inflated view of the danger.” Others have noted that carbohydrates called glycans already exist in both left- and right-handed forms—even in pathogens—and the immune system can recognize both of them. Experiments focused on interactions between the immune system and mirror molecules, they say, could help clarify the risks of mirror organisms and reduce uncertainty.
Even among those convinced that the worst-case scenario is possible, researchers still disagree over where to draw the line. What inquiries should be allowed and what should be prohibited?
Andy Ellington, a biotechnologist and synthetic biologist at the University of Texas at Austin, doesn’t think mirror organisms will come to fruition anytime soon. Even if they do, he isn’t sure they will pose a threat. “If there is going to be harm done to the human race, this is about position 382 on my list,” he says. But at the same time, he says it’s a complicated issue worth studying more, and he wants to see the conversations continue: “We’re operating in a space where there’s so much unknown that it’s very difficult for us to do risk assessment.”
Even among those convinced that the worst-case scenario is possible, researchers still disagree over where to draw the line. What inquiries should be allowed and what should be prohibited?
Adamala, of the University of Minnesota, and others see a natural line at ribosomes, the cellular factories that transform chains of amino acids into proteins. These would be a critical ingredient in creating a self-replicating organism, and Adamala says the path to getting there once mirror ribosomes are in place would be pretty straightforward. But Zhu, at Westlake, and others counter that it’s worth developing mirror ribosomes because they could possibly produce medically useful peptides and proteins more efficiently than traditional chemical methods. He sees a clear distinction, and a foundational gap, between that kind of technology and the creation of a living synthetic organism. “It is crucial to distinguish mirror-image molecular biology from mirror-image life,” he says. That said, he points out that many synthetic molecules and organisms containing unnatural components, including but not limited to the mirror-image subset, might pose health risks. Researchers, he says, should focus on developing holistic guidelines to cover such risks—not just those from mirror molecules.
Even if the exact risk remains uncertain, Esvelt remains more convinced than ever that the work should be paused, perhaps indefinitely. No one has taken a meaningful swing at the hypothesis that mirror life could wipe out everything, he says. The primary uncertainties aren’t around whether mirror life is dangerous, he points out; they have more to do with identifying which bacterium—including what genes it encodes, what it eats, how it evades the immune system’s sentinels—could lead to the most serious consequences. “The risk of losing everything, like the entire future of humanity integrated over time, is not worth any small fraction of the economy. You just don’t muck around with existential risk like that,” he says.
In some ways, scientists have been here before, working out rules and limits for research. Two years after the start of the covid-19 pandemic, for example, the World Health Organization published guidelines for managing risks in biological research. But the history is much deeper: Horrific episodes of human experimentation led to the establishment of institutional review boards to provide ethical oversight. In the early 1970s, in response to concerns over lab-acquired infections and growing use of biological warfare, the US Centers for Disease Control and Prevention established biohazard safety levels (BSLs), which govern work on potentially dangerous biological experiments.
And in 1975—at the dawn of recombinant DNA research, which allows researchers to put genetic material from one organism into another—geneticists met at the Asilomar conference center in Pacific Grove, California, to hammer out rules governing the work. There were concerns over what would happen if some virus or bacterium, genetically engineered to have traits that would make it particularly dangerous for people, escaped from a lab. Scientists agreed to self-imposed restrictions, like a moratorium on research until new safety guidelines were in place. As a result of the meeting, in June 1976 the NIH issued rules that, among other things, categorized the risks associated with rDNA experiments and aligned them with the newly adopted BSL system.
Asilomar is often hailed as a successful model for scientific self-governance. But that perception reflects a tendency to recall the meeting through a nostalgic haze. “In fact, it was incredibly messy and human,” says Luis Campos, a historian of science at Rice University. Equally brilliant Nobelists argued on either side of the question of whether to rein in rDNA research. Technical discussions dominated; talks about who would be affected by the technology were missing. The meeting didn’t start establishing guidelines, says Campos, until the lawyers mentioned liability and lab leaks.
For now it’s unclear whether these examples of self-governance, which arose from the demonstrated risks of existing technologies, hold useful lessons for the mirror-life community. Three competing images of the future are coming into focus: Mirror life might not be possible, it might be possible but not threatening, or it might be possible and capable of obliterating all life on Earth.
Scientists may be censoring themselves out of fear and speculation. To some, shutting down the work seems necessary and urgent; to others, it is unnecessarily limiting. What’s clear is that the question of what to do about mirror life has been both illuminating and disorienting, pushing scientists to interrogate not only their current research but where it might lead. This is uncharted territory.
Stephen Ornes is a science writer based in Nashville, Tennessee.
from MIT Technology Review https://ift.tt/ndRo9Ku
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