Many of the molecules that are the building blocks of life on earth have a curious property: they are asymmetrical and can exist in one of two possible mirror-image forms. DNA and RNA, for example, are built from “right-handed nucleotides,” while proteins contain “left-handed” amino acids. This property is known as chirality, and it’s pervasive throughout the entire tree of life.
Some synthetic biologists are exploring how to build reversed versions of biological molecules. Because the body takes longer to break down these synthetic molecules, the goal of this research is to one day use them to create long-acting drugs.
But there is also interest in using reversed molecules to—one day—create “mirror bacteria.” Now, researchers are sounding the alarm that such bacteria could have devastating consequences for humanity if they were successfully created.
Although the invention of mirror bacteria is still at least a decade away, and possibly several decades, a team of 38 scientists from around the world have come together to call for a global discussion about the unprecedented risks that mirror bacteria could pose. Among them is Ruslan Medzhitov, PhD, Sterling Professor of Immunobiology at Yale School of Medicine. We spoke with Medzhitov to learn more about this emerging threat:
Tell me about yourself and your research interests.
I’m a professor in the immunobiology department at the medical school. My research focuses on immunology, the biology of inflammation, as well as on allergies and other inflammatory diseases.
You’re a part of a team that recently published a report in Science on the unprecedented risks of “mirror bacteria” to humans and the environment. What are mirror bacteria, and why are scientists trying to create them?
Most molecules that make up our cells can exist as mirror images, or isomers. For example, all amino acids are one particular type of isomer. Sugars also exist as a particular isomer, as well as nucleic acids and so forth. Now, let’s say we have a protein made of amino acids that are one type of isomer. Some researchers are asking, what if we use amino acids of the other type of isomer and create the mirror image of this protein?
Synthetic biology is a field of biology that focuses on the creation of novel molecules, signaling modules, parts of cells, et cetera from scratch or existing modules. This branch of biology is also focused on using different versions of biomolecules, and in some cases, specifically chiral isomers—meaning the mirror images of these biomolecules.
Mirror bacteria are not something that exist today—and they likely won’t for at least a decade, or even several. But technology develops very quickly, and there have been some advances in synthetic biology that indicate that the development of these bacteria is within reach. On the default trajectory of technological progress, we think it will happen at some point if such research continues.
Experts who study biosafety are concerned about this, and they wanted to assemble a team of people from different walks of science, including ecology, plant science, and immunology. That’s how I got involved in this work. The idea of our publication is: if these advances continue and mirror images of bacterial cells are created, what would be the consequences? And we think that they wouldn’t be good.
The creation of live mirror bacteria is years away. What progress has been made that has drawn concern from your team?
Scientists are still very far from creating mirror bacteria. But there have been advancements in chemistry, biochemistry, and molecular biology that have been making it easier and easier to build things from scratch. There have been advances in synthesizing, for example, mirror nucleic acids that are the reverse chirality versions of the nucleic acids that make up our own cells, as well as other more intricate biomolecular complexes made up of mirror molecules. Again, researchers are far from putting this all together and building a living cell—nobody has yet built an entire normal chirality cell from scratch. But our thinking is that, if such research continues, eventually this will be in reach—perhaps in a decade or so.
What makes mirror bacteria so dangerous?
There are a couple of reasons. One is the fact that if such bacteria are created, they will not be controlled by normal ecological factors. One major factor that controls bacterial population sizes is competition with other bacteria for resources. Another is bacteriophages [which literally means, “bacteria-eater”], which are viruses that infect bacteria and play a critical role in regulating the populations of bacteria in the biosphere.
Mirror bacteria would likely not be susceptible to bacteriophages due to incompatibility of molecular interactions. This, in turn, could lead to explosive, exponential growth of mirror bacteria that could lead to them becoming invasive in a range of environments, which could have cascading impacts on the populations of species further up the food chains and so forth. This would also have an enormous impact on ecology that could affect agriculture and so forth.
Furthermore, animals and plants would not be able to use their normal immune defenses to protect themselves from mirror bacteria. As with bacteriophages, due to the incompatibility of molecular interactions, their immune systems would likely not be able to detect and destroy microbes. The mirror bacteria would essentially be invisible. This could lead to catastrophic consequences to animals and plants. It would be similar to the situation in humans with severe immunodeficiencies—they are highly vulnerable to microbial infections.
And then, there are things we cannot even predict. Once mirror bacteria are created, they can replicate, which means they can evolve. I think this is the bigger issue here—that we cannot predict how mirror bacteria might evolve if they got into the wild.
Are there any steps that can be taken to develop mirror bacteria in a safe way?
One can take all kinds of measures to reduce risks, but again, it’s fundamentally impossible to avoid all of the consequences once bacteria are able to replicate and mutate. No mirror bacterium could be made provably safe — accidents happen at research laboratories and pathogens escape and can cause problems of different scales. As I’ve heard one of my fellow authors put it, the only safe mirror bacterium is one that doesn’t exist.
Based on this report, what are your team’s recommendations?
Our main goal was to draw attention to the risks of research on mirror bacteria and the potential negative consequences of such research well before it becomes feasible to build mirror bacteria and the risk becomes more acute. Secondly, it’s a call for a broader discussion about this research—about the capabilities currently available or that could be available at some point, and what they can create that could potentially be dangerous.
Our goal is not to tell everyone what to do, but rather to offer an invitation for a thoughtful and careful discussion. We also suggest that research laboratories and funding agencies take the risks of mirror bacteria into account and perhaps make a collective decision on whether it’s a good idea to pursue such research. This is an issue that’s not just for one country or research entity to decide. There needs to be agreement from everyone as it could be devastating for the entire world if mirror bacteria are created and unintentionally generate something that quickly gets out of our control.
Some of the co-authors of our paper are organizing dialogue events next year to bring together the wide set of stakeholders whose perspectives we need to tackle the best path forward here. These are at the National University of Singapore, the Institut Pasteur in France, and the University of Manchester in the U.K. I hope these discussions, and others like them, help elucidate some of the path forward.
More broadly, what research do you have underway that you are excited about?
My research is about the very basic biology related to immunity, inflammation, and various inflammatory diseases. I’m especially excited about the research we’re doing to better understand allergies, as well as our research on how the immune system communicates with the nervous system and can affect behaviors in some cases. And we’re also interested in understanding some of the basic mechanisms of diseases—what makes the human body vulnerable to particular types of diseases and what are the underlying features of our physiology that lead to certain diseases. We’re interested in these types of questions, which are part of the branch of evolutionary medicine that aims to understand the ultimate causes of diseases.
Have you had any significant findings emerge recently?
Yes, we had one recent publication in Nature on the interaction between the immune system and behavior in the context of allergies. Allergies are a condition in which our immune system reacts in a certain way to non-microbial substances in the environment, including food antigens—or molecules coming from food. The evolutionary reason why such reactions exist, we believe, has to do with defense against toxic substances in the environment, and the best way to protect ourselves from toxic substances is to avoid coming into contact with them. For example, if there is something toxic in food, the best defense would be to not eat it. This is called avoidance behavior.
We found that these avoidance behaviors toward allergens are mediated by immune recognition through antibodies. Then, the antibodies communicate with the nervous system—particular centers in the brain—and tell them, “Avoid.” This is something that we found very recently. It’s a very exciting demonstration showing that inputs detected by the immune system can be translated into a language that the brain can understand, and then the brain, in turn, controls these protective behaviors.