A category of synthetic organisms known as “mirror life,” with molecules that are mirror images of natural counterparts, may present unprecedented risks to human life and ecosystems, according to a perspective article by leading experts, including Nobel Prize winners. The article, which was published in Science on December 12, is accompanied by a detailed report outlining their concerns.
Mirror life pertains to the common phenomenon in nature where a molecule or object cannot be superimposed on another. For instance, your left hand cannot simply match your right hand. This asymmetry is prevalent in the natural world.
Molecules of the same type often exhibit the same asymmetry. DNA nucleotides are typically right-handed, while proteins are made up of left-handed amino acids.
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Chirality, also known as handedness, plays a crucial role in biology as interactions between biomolecules depend on their specific structure. For example, if the handedness of a protein is reversed, it cannot bind with other molecules, such as cell receptors. “It’s like hands in gloves,” explains Katarzyna Adamala, a synthetic biologist at the University of Minnesota and co-author of the article and accompanying technical report, which spans nearly 300 pages. “My left glove doesn’t fit my right hand.”
The authors raise concerns about mirror bacteria, the simplest form of life to which their worries apply. Although the ability to create mirror bacteria is not yet a reality and may be “at least a decade away,” progress is being made. Scientists can already synthesize mirror biomolecules like DNA and proteins. Simultaneously, advancements have been made in constructing synthetic cells from non-mirrored components. In 2010, researchers at the J. Craig Venter Institute (JCVI) in California integrated synthetic DNA into a cell to develop the first cell with a completely synthetic genome.
Additional breakthroughs would be necessary to create mirror life, but they are feasible with significant investment and effort. “We don’t rely on speculative scientific advancements that may never materialize. I can outline the necessary steps to create a mirror cell,” asserts Adamala. “It’s no longer science fiction.” Adamala previously worked towards generating mirror cells, but now fears that if mirror bacteria are produced, it could lead to irreversible ecological harm and loss of life. The article’s authors, consisting of experts in immunology, synthetic biology, plant pathology, evolutionary biology, ecology, and two Nobel laureates, urge researchers, policymakers, regulators, and society at large to initiate discussions on understanding and mitigating the identified risks. Unless evidence emerges that mirror life would not pose extraordinary hazards, they recommend refraining from conducting research aimed at creating mirror bacteria.
The initial excitement about creating mirror versions of bacteria began with simpler concepts. Scientists contemplated handling mirror versions of proteins and other molecules that constitute such an organism. For instance, drugs that degrade due to biological processes may need to be frequently administered. Mirror molecules would not interact with these processes, so a drug built with mirror molecules could have longer-lasting effects. .
Numerous immune system mechanisms also hinge on handedness. T cells, responsible for identifying foreign invaders, might struggle to bind to entities with incorrect handedness. Consequently, such therapies could prevent provoking immune responses in patients. “A mirror peptide will resist degradation, making it potentially effective as a therapeutic,” says co-author John Glass, a synthetic biologist at JCVI. “We see no reason to prohibit this.”
One possible application of mirror bacteria might be bioreactors, biological facilities utilizing cells or microorganisms to produce various compounds, like antibiotics and pharmaceuticals. Bacteriophages (viruses that infect bacteria) can eliminate bacteria-based bioreactors, incurring substantial time and financial costs, but they are unlikely to infect mirror bacteria since they would not recognize their molecules. Likewise, natural predators such as amoebae, which feed on typical bacteria, would not identify mirror bacteria as prey.
It is these purportedly advantageous characteristics that have sparked the scientists’ concerns. “All the practical uses that intrigued us about this field are the reasons why we are apprehensive now,” notes Adamala. The ability to evade immune responses could enable bacteria to cause lethal infections as they reproduce unchecked. Unlike viruses, bacteria do not require specific molecules to infect an organism, and mirror bacteria could infect a broad range of hosts, including humans, animals, and plants. Furthermore, the absence of predators could facilitate the widespread dissemination of mirror bacteria within ecosystems.
Initially, many authors believed mirror bacteria would not survive outside a lab due to the absence of mirror nutrients, Glass states, but the report affirms that adequate nutrients exist to sustain mirror bacteria. The researchers discuss potential biosafety measures, like developing mirror phages viruses to infect and eliminate mirror bacteria, but acknowledge that these measures may not be sufficient. “None of the [authors] has identified a countermeasure we believe would be effective enough to protect the biosphere from these organisms,” says Glass.
Not everyone agrees that mirror bacteria entail significant risks. “I argue that a mirror-image bacteria would face significant competitive disadvantages and would not thrive well,” asserts Andrew Ellington, a molecular biologist at the University of Texas at Austin specializing in synthetic organisms. He is skeptical of sounding an alarm so far ahead of any threat or even before the existence of technology that could be used to create it. “It’s like banning the transistor out of concern about cybercrime 30 years down the road,” Ellington remarks. He also expresses concerns that governments and regulators may not respond as expected by the authors, potentially stifling beneficial research. “I’m not overly concerned about a mostly unknown threat 30 years from now compared to the good that can be achieved today,” he adds.
While the exact risks may be uncertain, it is certain that any threat remains distant. “The technology is not available yet, so it is challenging to assess the risk scenarios, but this paper can initiate those discussions,” states Sarah Carter, a science policy biosafety consultant and former JCVI policy analyst based in California who focuses on biosecurity and policy implications of emerging biotechnologies. “Hence, I commend this group for looking ahead and drawing attention to this matter.
