What is "mirror life"? Why did 38 Nobel Prize winners scare them so much that they jointly banned its artificial synthesis?

On December 11, 2024, Science magazine published a 299-page report titled “Confronting risks of mirror life.” The report was co-authored by 38 Nobel Prize winners and industry experts from nine countries, calling for a global ban on research on mirror life [1].

Image source: www.science.org

This may sound like the beginning of a science fiction novel, but it is a real scientific discussion.

What is "mirror life"? Why does it scare scientists so much? We must first start with the strange phenomenon of "mirror life".

01. Life’s preference : protein to the left, DNA to the right

When we stand in front of a mirror, the image reflected in the mirror is still ourselves, but all the features are reversed.

This phenomenon can also be seen in the microscopic world at the molecular level. Some molecules, like the left and right hands of a person, can exist in the form of their own mirror images, that is, they are symmetrical but cannot overlap . Molecules with mirror images of each other are called "chiral molecules", "enantiomers" or "optical isomers".

Amino acid compounds that are mirror images of each other. They have the same chemical composition and connection method, but different spatial arrangements. Source: cn.chem-station.com

Most of the organic molecules that make up life are chiral molecules. Chiral molecules are divided into two forms: left-handed (left-handed) and right-handed (right-handed). Usually L- represents left-handed and D- represents right-handed . When scientists synthesize organic compounds in the laboratory, the left-handed and right-handed molecules obtained usually account for half each.

But strangely, in nature, living organisms often prefer one of the two. Except for glycine, which has no chirality, the remaining amino acids that make up proteins are almost all left-handed (L-type), while the ribose in ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) is right-handed (D-type ) [2].

Why nature prefers a particular chirality remains a mystery, but this choice has profound effects on how living molecules interact. For example, the left-handedness of a carvone molecule determines whether it smells like spearmint or caraway. Left-handed and right-handed glucose, which are synthesized in the laboratory, taste the same, but only right-handed glucose can be metabolized by the human body for energy because the enzymes in our bodies can only process right-handed glucose[3].

Want to lose weight with L-glucose? Forget it—not only is it expensive, it can also cause diarrhea, though it can be used as a laxative.[4]

02. The dual nature of chiral drugs

Chiral characteristics are common in drug molecules. According to incomplete statistics from the 2010 edition of the Chinese Pharmacopoeia, among the 1,018 drugs with different structures, 43.22% contain chiral centers. Among them, 31.34% of the drugs have strict requirements for their chiral configuration.

For example, levofloxacin is more effective than ofloxacin, dexibuprofen is more effective, and levoesciprofloxacin requires a smaller dose and has fewer side effects...

However, chiral drugs have also caused disasters. In the 1950s, the famous anti-pregnancy drug thalidomide (commonly known as thalidomide) had a dextrorotatory compound that could inhibit pregnancy reactions and provide sedative effects, but its levorotatory compound could cause fetal malformations[5].

A British "seal deformity baby" and her father｜Source: dailymail.co.uk

However, the scientific community at the time did not know that the effects of mirror-image compounds in the human body would differ so greatly, and due to the lack of detection methods, it was impossible to distinguish their chirality during preparation[6].

Today, it has become a consensus in the industry to treat different configurations of chiral drugs as different compounds, and regulatory agencies have changed the requirements for pharmacological testing and safety evaluation.

As medicine develops, drugs and treatments are also evolving. We will use more biological molecules (such as a small piece of protein) to make cancer-targeted drugs. They are very effective, but they are also easily broken down by enzymes in the human body, limiting their efficacy.

Therefore, researchers try to use mirror-inverted amino acid molecules to synthesize target proteins, perhaps they are not so easily broken down by enzymes in the human body. To imagine this, you can assume that the enzyme is a left-handed baseball glove. When the protein we put into the body is in the right-handed form, the baseball glove cannot "put on" to capture it.

03. Risks of Mirror Life

Today, scientists have successfully synthesized some mirror-image biological molecules, such as left-handed DNA and fully functional "mirror enzymes". So with the development of synthetic biology, scientists are looking forward to the question: Can we create mirror-image life, such as mirror-image bacteria?

Mirror-image DNA molecule | Image credit: theconversation.com; Mark Lorch Mark Lorch

In fact, some research groups are already doing this. They synthesize biomolecules and try to assemble them into functional cells that can reproduce. However, many people are aware of the risks in advance.

The most common concern is that once these mirror-image bacteria are created and then leaked from the laboratory and escaped into the natural environment, their unique structure may make them invincible in the ecological environment and form an epidemic that is difficult to control, whether the invaders are other bacteria, plants, animals or humans.

Remember the baseball glove analogy above? There are also many mechanisms in the biological immune system that are mediated by chiral molecules. Faced with mirror-image bacteria, the immune system is likely to be helpless, and similarly, they are likely to escape the predation of natural chiral phages ; conventional drugs will also face similar problems.

Mirror bacteria may escape recognition by the immune system and fail to activate the corresponding immune cells to eliminate them, eventually entering the blood and multiplying uncontrollably. Image source: Reference [1]

With current technological advances, scientists predict that it will take at least 10 years to create true mirror-image bacteria. However, this process is far more than simply packing left-handed DNA into the shell of right-handed proteins. Once out of control, its impact may be difficult to predict and may even cause an ecological disaster[7]. Therefore, many scientists believe that a cautious attitude should be adopted.

Some scientists also hold opposing views. For example, Andrew Ellington, a synthetic biologist at the University of Texas at Austin, believes that "this is like banning the use of transistors now because we are worried about the emergence of cybercrime 30 years from now."

However, as can be seen from the attitude of the joint report, scientists still believe that such risks are not worth taking. They recommend a complete ban on the research of mirror bacteria and call on institutions to stop funding such projects. Because even if the mirror bacteria are not as vigorous as their natural compatriots, once they can escape the natural immune mechanism, they may bring uncontrollable biosafety threats, which will be devastating to the entire world.

References

[1] Adamala et al. Technical Report on Mirror Bacteria: Feasibility and Risks. December 2024. https://doi.org/10.25740/cv716pj4036

[2] Wang Wenqing. Symmetry breaking in the origin of life[J]. Journal of Peking University (Natural Science), 1997, 33 (2): 265-272.

[3] Yue Kuiyuan. Chirality, a strange phenomenon in life [OL]. Chengdu Branch of the Chinese Academy of Sciences http://www.cdb.cas.cn/kyzc/kysb/201406/t20140625_4143907.html

[4] Michael Caswell, Edward Delaney, Mohammed Rahman. L-sugar colon cleanser and its application [P]. 2012, CN 102448976 A

[5] Zhang Weiguang, Zhang Shilin, Guo Dong, Zhao Ling, Yu Lajia, Zhang Hui, He Yujian. Focus on chiral drugs: starting from the "thalidomide incident". University Chemistry[J], 2019, 34(9): 1-12 doi:10.3866/PKU.DXHX201904021

[6]Hoffmann, R. The Same and Not the Same; Columbia University Press: New York, 1995.

[7]Bob Service, Leading scientists warn against developing 'mirror-image' bacteria, doi: 10.1126/science.zmatxfw

Author: Wan San

Planning & Editing: Little Dandelion

Acknowledgements: Dr. Hu Zhiguo from the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, provided scientific guidance for this article

Cover image source: National Institute for Allergy and Infectious Diseases