Mirror Bacteria Research Poses Significant Risks, Dozens of Scientists Warn todayheadline

As synthetic biologists, we have spent the last few decades in awe of the breakthroughs in the field. In the last fifteen years, synthetic biologists have stored books, images, and even videos in DNA, developed the ability to modify and engineer genes with remarkable accuracy, and even created an organism with chromosome designed using a computer and synthesized in the lab.^1-5

These advances have allowed us to develop effective drugs against diseases like malaria, innovate lightweight, biodegradable, and high-strength materials such as artificial spider silk, and bolster our understanding of how life forms.^6-8 In many cases, these breakthroughs were unforeseen and would not have happened if scientists could not conduct their research freely.

However, we recently joined a number of other scientists in calling for a certain line of research to not be pursued: work that could result in the creation of “mirror bacteria.”⁹ These are bacteria made of all components that natural cells possess, but with every biopolymer being of opposite stereochemistry. 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. However, every rule has exceptions, and this is one of them. Unless compelling evidence emerges showing that mirror bacteria do not pose unacceptable risks, we believe research to develop mirror life should not continue. 

The Allure of Mirror Life

Life is deeply complex and fascinatingly mysterious. What drew us toward synthetic biology is precisely how much we can learn about life—and all the important ways we can employ life—by attempting to rebuild it from scratch. It is for this reason that both of us have dedicated much of our careers toward the creation of synthetic cells. 

Cells are the basic building blocks of life. The creation of synthetic cells by using synthesized molecules to reproduce cell functions, or by assembling natural molecules into synthetic systems, can be used to do everything from developing bacteria-based self-healing concrete to creating a minimal cell that allows us to investigate the first principles of cellular life.^10,11 

Minimal cells are especially valuable because normal cells contain many different components that can react with many other molecules and cells in complex ways, making them difficult to use for research or drug development. Because minimal cells were created by eliminating genes not required for growth in laboratory culture, they are incapable of surviving outside of our laboratories. The extreme simplicity of these minimal cells makes them ideal platforms for research to understand the basics of life and to understand how drugs might affect basic cell biology.

For these reasons, in 2018, we, along with others, launched the “Build-a-Cell” community—a network of researchers that aims to develop synthetic living cells.¹² It was around this time that we also started working on the development of a “mirror cell.”   

Many molecules are chiral, which means they exist in a left-handed and right-handed form. When you put a chiral molecule in front of a mirror, their mirror image has a different three-dimensional orientation. Mirror images of a ball or wine glass can look identical, but the mirror image of a right hand will look like a left hand. Nature tends to prefer one of these forms. For example, amino acids—the building blocks of proteins—tend to exist in a “left-handed” form. Sugars—the building blocks of carbohydrates—tend to exist in a right-handed form. The term “mirror molecules” refers to molecules with the opposite chirality from the form most commonly found in nature. Unnatural mirror molecules such as right-handed amino acids or left-handed sugars have been made in labs.^13,14

Many of the undesirable reactions that mirror cells avoid depend on sensing and reacting with chiral molecules. Therefore, cells made up of mirror molecules would simply not interact with most normal molecules and cells in the first place. Mirror cells could offer a promising approach for studying life forms with much less contamination, or for producing mirror drugs that would not be broken down or removed by cellular processes in the human body. We began work on mirror cells to achieve these benefits and more, all of us were looking forward to seeing this area of research succeed in the coming decades. 

With the right components and nutrients, normal cells could soon be booted to form living life forms, such as bacteria. Similarly, with the right components and nutrients, mirror cells could be booted to form mirror bacteria. This technology is further away, and were it to happen, it would be an incredibly impressive feat of engineering. 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. 

Why Are Mirror Bacteria Dangerous?

It is often the case that artificial or modified organisms struggle harder for survival compared to their natural counterparts. Microorganisms developed in laboratory settings are typically grown in highly specific conditions and with very particular nutrients whose composition and concentrations do not reflect the complex and diverse conditions found in nature. As a result, while laboratory breaches unfortunately do happen—with hundreds of  “possible release” events per year leading to at least one or two detected infection events per year—most of those involving artificial or modified organisms do not result in an outbreak, as they are too ‘fragile’ to thrive in the adverse environment of the outside world, making them easy prey to natural predators such as viruses that target bacteria (bacteriophages).¹⁵

However, many interactions between organisms and cells depend on being able to sense and react with chiral molecules in the first place. Their incompatibility with natural biological reactions would leave mirror bacteria with no natural predators in the wild, as they could not be sensed, killed, or digested by bacteriophages or other organisms. Crucially, many of the immune responses in humans, other animals, and plants also work by sensing and reacting with chiral bacterial molecules.  If a human were to be infected with mirror bacteria, it could be as if they were immunocompromised, as their immune systems would face great difficulty in detecting or killing the mirror cells. As a result, mirror bacteria could hypothetically replicate to extremely high levels in the human body, causing conditions similar to septic shock.

The downside of having a biology that renders mirror bacteria ‘invisible’ to natural enemies is that they would not be able to consume many of the chiral nutrients found in nature. However, several nutrients, such as glycerol, are achiral (they do not have mirrored forms), and thus could be consumed by mirror bacteria. Well-intentioned scientists could also engineer mirror bacteria that can consume naturally occurring chiral molecules such as sugars and amino acids.  

In turn, mirror bacteria could spread throughout the environment without natural predators, infect organisms without triggering much of their immune response, and possibly cause fatal infections. An unstoppable replicating mirror bacteria free in the environment could cause consequences that are disastrous.¹⁶

The Exception, Not the Rule

We are deeply passionate about all synthetic biology has to offer. We share concerns about the dangers of restricting science because it goes against political interests, because it is seen as unhelpful, or because it is simply misunderstood. Free science is usually better for the world. 

However, there are important exceptions. We restrict research involving live smallpox virus, dangerous human psychological experiments, and nuclear explosive testing in the environment because it is too dangerous. We think that the creation of mirror life falls into the same class of research that is simply too risky to conduct.^17-19

However, we believe that regulations on mirror biology should not affect the vast majority of synthetic biology research in medicine or the pharmaceutical industry. Very few laboratories are interested in the creation of mirror life, and it is not clear to us that the development of mirror life offers unique benefits we cannot achieve any other way. For example, we noted that mirror molecules offer promise for pharmaceuticals because they can avoid detection by the body. But many of these mirror proteins, mirror carbohydrates, and other small mirror molecules are already made in a safe manner, and with no applications towards the creation of mirror life.^20,21 While there should be measures in place to ensure large mirror molecules (such as mirror genomes) are not created to develop mirror life, research into small mirror molecules should continue freely.

Ultimately, the best way to ensure synthetic biologists continue developing breakthroughs is to ensure we do not jeopardize global safety, damage public trust, or cause science to result in tremendous amounts of harm. Curiosity is not a good enough reason to create something that could be so dangerous. For the good of mankind—and science itself—we must avoid the creation of mirror life.