Homochirality and the Origin of Life

From Issue: R&R – Issue 43 #11

[EDITOR’S NOTE: The following article was written by A.P. auxiliary staff scientist Dr. Deweese who holds a Ph.D. in Biochemistry from Vanderbilt University and serves as Professor of Biochemisty and Director of Undergraduate Research at Freed-Hardeman University.]

What would it take to make a living organism from a mixture of chemicals? Researchers interested in pursuing a naturalistic origin of life (i.e., origin of life without supernatural intervention) have been exploring this question for decades. Most school students learn about Miller-Urey experiments and the mixtures of molecules formed under presumed conditions upon the early Earth.1

The general story of these experiments is that the researchers start with purified chemical components and mix them together combined with various forms of energy (e.g., sparks or light), and the chemicals are allowed to react for a time before being isolated and examined. What is the result? Yes, some molecules relevant to life can be formed, like amino acids, carbohydrates, and nucleotide bases.2 But that is not the whole story because these building blocks alone are only one piece of the puzzle.

In their book, Stairway of Life, Change Tan and Rob Stadler identify a series of 12 steps that would be required to go from non-living chemicals to a living organism.3 The steps are illustrated as a progressively complex staircase that is not simply traversed by time and chance. After the initial step of forming the building blocks of life, they point out the issue of homochirality and the challenge that it presents to the formation of complex biological molecules needed for living systems. What is homochirality and why does it matter?

To understand homochirality, one must take a quick detour into the chemistry of organic molecules. In science, organic molecules are carbon-based molecules involved in living organisms including amino acids, nucleotides,4 lipids, and carbohydrates. Organic molecules utilize carbon as the backbone element. Carbon has some very interesting properties such as the ability to bind to four different atoms at the same time in a tetrahedral structure (Figure 1A).

One of the consequences of being able to bind to four different atoms is that there can be molecules that have the same atoms but different arrangements of those atoms in 3D space (Figure 1B). This is the concept of chirality (kai-RAL-it-ee). When carbon is bound to four different atoms or groups, the carbon is known as a stereocenter, and there are rules for how these molecules are named to distinguish between “stereoisomers” or versions of the molecule that differ based upon the connections in 3D space. For instance, there are “left-handed” and “right-handed” versions of molecules like amino acids, sugars, and nucleotides. One convention for naming uses “L” and “D” to denote the two forms. The left-handed are denoted with an “L” (from levo, from the Latin laevus for left) before the name while the right-handed are denoted with a “D” (for dextro from the Latin dexter for right). For those familiar with medicine, dextrose is a common sugar solution given in IVs and is made of D-glucose (also called dextrose).

Why does this matter? L-amino acids are what are built and used by living organisms. D-ribose and D-deoxyribose (Figure 2)5 are the forms of sugar found in nucleotides (RNA and DNA, respectively) in living organisms. Thus, homochirality (i.e., the abundance of a single form like D- or L- for a given molecule) appears to be a rule for these fundamental biochemical molecules. The issue here is that in a pre-biotic system (one where life does not yet exist) there is no clear mechanism for preferentially causing the formation of one chiral form over another. This means there is no homochirality. Instead, when chemicals react in experimental systems, researchers tend to get mixtures of L- and D- forms of molecules. These mixtures are called racemic (rah-SEE-mick).

Recent work by origin of life researchers has suggested that L- and D- forms of chiral molecules have distinct magnetic properties.6 Could magnetism in the planet or in specific material deposits on the surface influence the formation of specific forms of chiral molecules? The researchers found that under intense magnetic conditions, they did see some preference in formation of crystals of a molecule in either the L- or D-form. Of course, this seems to support the possibility that magnetism can influence the formation of either L- or D-form chiral molecules. But is that the whole story?

The scenario the researchers propose for their experiment is one of a shallow lake with magnetic deposits where these RAO crystals could form being in a state where the lake could alternately dry up and refill along with deposits of minerals, sediments, and other molecules combined with the influence of magnetic fields and solar radiation.7 What the researchers did in their study was to take ribo-aminooxazoline (RAO), which can be used as a precursor of pyrimidine nucleotides, and allow it to form crystals under intense magnetic field (Figure 2). Interestingly, their approach found that even though the RAO was a mixture of L- and D- forms, they could use magnetism and get a solution where 80% (or more with certain enrichment steps) of the molecules that crystallized were of one chiral form.8

There are a few things that need to be considered here. First, the researchers start with completely pure chemicals formed under specific laboratory conditions that did not exist in any presumed pre-biotic Earth. Additionally, they used purified chemicals and a tightly-controlled reaction to form the starting materials. In this case, they formed a racemic mixture of L- and D-RAO.

Second, most of what they demonstrated was a preferential crystallization under magnetic conditions. While not a perfect solution, it does get to an 80%/20% mixture. This is a 60% enantiomeric excess (ee) where ee is calculated by subtracting the minor form from the major form (80%-20% = 60% ee). They found they could further enrich this form and get the percentage to 100%, but this required carefully designed steps, which they claim could have resulted from a series of drying and refilling events of the hypothesized lake combined with other events.9

Third, the reactions are tightly controlled laboratory reactions that do not account for variables of a presumed early Earth. For a detailed discussion of the problems, see Tan and Stadler.10 One issue that needs to be pointed out is that the authors claim RAO is a key precursor in the formation of RNA nucleotides.11 While it is true that RAO can be used to form nucleotides in a laboratory setting, RNA nucleotides are not formed like this in nature.

Fourth, the magnetic field used in these experiments was ~6,000 times the magnetic field found on the Earth. The authors recognize this but suggest the key here is not the field strength but the effects of the surface used in the study, which they claim is prebiotically feasible.12

Fifth, note that no nucleosides were formed—just a crystal of a potential nucleoside precursor. Nucleosides are bases attached to the sugar ribose without a phosphate group (Figure 2). The nucleosides under consideration are the “simpler” of the nucleosides, uridine and cytidine—called pyrimidines (Figure 2). Adenosine and guanosine are known as purines, and these would likely require another synthetic pathway.13 Nucleosides that have a phosphate group attached to the sugar are called nucleotides. In living organisms, nucleotides are connected in long chains with a phosphate between each ribose for RNA or deoxyribose for DNA.

The intention here isn’t to disparage the work—it is, in fact, very relevant and interesting to explore the magnetic properties of chiral molecules. Magnetic properties of molecules have been known for a long time and serve as the basis for analytical chemistry methods like nuclear magnetic resonance (NMR) and medical applications like magnetic resonance imaging (MRI). Thus, the more we understand magnetic properties in molecules, the more potential there is to impact human health and understand the creation.

Taken together, the authors of a recent study examine a compound called RAO that can form two of the RNA nucleosides and found that with magnetism they could influence which stereoisomer of RAO formed a crystal.14 This is interesting but still does not solve the problem of homochirality or of the origin of biomolecules in living systems. Homochirality represents one among several significant chemistry challenges in the “stairway to life.”

Figure Legends:

Figure 1: Carbon Atoms and Stereochemistry. A: Ball and stick model for a molecule of methane (CH4) is shown. Carbon is in grey with hydrogen in white. There is a fixed angle between all four hydrogen atoms giving this molecule a tetrahedral structure. B: Carbon is attached to four different atoms (white, green, purple, and maroon). With four different groups, the carbon atom is chiral and can form stereoisomers or non-superimposeable mirror images. These molecules have the same components, but a different arrangement of atoms in 3D space.

Figure 2: Structures of Relevant Molecules. Structures for RAO, ribose, and some nucleosides are shown with symbols indicating stereochemistry. The solid black wedges represent groups that point toward the viewer (out of the page) while hashed wedges are groups that point away from the viewer (into the page). Red circles are meant to draw attention to an example of where molecules differ.


1 S. L. Miller (1953), “A Production of Amino Acids under Possible Primitive Earth Conditions,” Science, 117[3046]:528-529; S. L. Miller and H. C. Urey (1959), “Organic Compound Synthesis on the Primitive Earth,” Science, 130[3370]:245-251.

2 Norio Kitadai and Shigenori Maruyama (2018), “Origins of Building Blocks of Life: A Review,” Geoscience Frontiers, 9[4]:1117-1153, ISSN 1674-9871,

3 C.L.  Tan and R. Stadler (2020), The Stairway to Life (Minneapolis, MN: EvoRevo Books).

4 S.F. Ozturk and D.D. Sasselov (2022), “On the Origins of Life’s Homochirality: Inducing Enantiomeric Excess with Spin-Polarized Electrons,” Proceedings of the National Academy of Sciences of the United States of America, 119[28]:e2204765119.

5 S.F. Ozturk, Z. Liu, J.D. Sutherland, and D.D. Sasselov (2023), “Origin of Biological Homochirality by Crystallization of an RNA Precursor on a Magnetic Surface,” Science Advances, 9[23], DOI: 10.1126/sciadv.adg8274.

6 C. Anastasi, M.A. Crowe, M.W. Powner, and J.D. Sutherland (2006), “Direct Assembly of Nucleoside Precursors from Two- and Three-Carbon Units,” Angewandte International Edition Chemie, 45[37]:6176-6179; M.W. Powner, B. Gerland, and J.D. Sutherland (2009), “Synthesis of Activated Pyrimidine Ribonucleotides in Prebiotically Plausible Conditions,” Nature, 459[7244]:239-242.

7 Ozturk, et al.

8 Ibid.

9 Ibid.

10 Tan and Stadler.

11 Ozturk, et al.; Anastasi, et al.; Powner, et al.

12 Ozturk, et al.

13 J. Xu, N.J. Green, D.A. Russell, Z. Liu, and J.D. Sutherland (2021), “Prebiotic Photochemical Coproduction of Purine Ribo- and Deoxyribonucleosides,” Journal of the American Chemical Society, 143[36]:14482-14486.

14 Ozturk, et al.


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