The Nobel-winning research by Kenso Soai and Henri B Kagan advances the understanding of mirror-image molecules, offering new possibilities for developing safer medicines. Their work on asymmetric chemical reactions could also help explain why life favours one molecular form over another
Kenso Soai, Japanese, and Henri B Kagan, French, both Chemistry professors, have built on a discovery by 19th-century French chemist Louis Pasteur and solved a long-standing riddle of asymmetric mirror-image molecules. This discovery, which is hugely important for pharmaceutical manufacturing, earned them the 2026 Nobel Prize in Chemistry. While Soai is 76 years old, Kagan is 95 years of age, making him the third-oldest person to be awarded a Nobel Prize.
Henri Kagan, who is at the University of Paris-Sud, first discovered a new way of manipulating chemical reactions in 1986. This allowed him to create a greater excess of one of the mirror images than had previously been thought possible. He had already missed out on the Nobel Prize in Chemistry in 2001, as he was fourth on the list and, at most, three chemists can share the award in a year. Kenso Soai, from the Tokyo University of Science, took the next step in 1995. He published a scientific paper in the journal Nature, describing the first-ever chemical reaction that had the potential to produce one of the mirror-image molecules desired for pharmaceuticals. Soai ultimately achieved success in 2003.
The Nobel Committee recalled that, in the 1950s, the drug thalidomide was prescribed for pregnant women to sedate them and help them overcome morning sickness. Thousands of children were affected by birth defects caused by the sedative. Thalidomide is a chiral molecule; the right-handed version provides an effective treatment, while the left-handed version is toxic. Researchers found that it was the active substance’s mirror image, i.e. the left-handed version, that caused the harm. It was always a challenge to create the right form of a chiral substance, and Kagan and Soai succeeded in creating an excess of one form through asymmetric reactions.
Several molecules essential to life exist in ‘left-handed’ and ‘right-handed’ forms, which are mirror images of each other. For example, amino acid molecules, the building blocks of proteins, exist in two forms, both of which are mirror images of each other, yet only one is found in the proteins of our cells. Another example is the sugar molecule, a constituent of DNA in living organisms. Amino acids are all left-handed, and sugars are all right-handed in living organisms. When products are manufactured in a laboratory, both left-handed and right-handed versions normally mix and are similar and difficult to distinguish, as quite a few properties, such as weight, boiling point and solubility, are identical. Living organisms depend upon only one version, and this phenomenon of one-handedness in organic chemistry is known as ‘homochirality’. Chemical reactions in a laboratory usually create a 50-50 mix of both left- and right-handed molecules. Between the two, one might have disease-fighting properties, while the other can be ineffective or can even harm the body.
Think of a handshake. A right hand fits neatly into another right hand, but if a handshake is offered to a left hand, the grip goes wrong. The body works in a similar way. Its cells are full of structures that can treat the two mirror-image forms very differently. One form of the molecule may do the job it was meant for, while the other version may do little or cause unwanted effects.
Similarly, the left-handed version of a drug can have one effect, while the right-handed version can have another. The laureates provided important and powerful tools to selectively prepare drugs in either of the two versions. The discovery has made it possible to understand how chemical reactions can be driven to favour a single molecular mirror image. In 1986, the Frenchman Kagan cracked the problem with non-linear effects, using catalysts to make products in which the two versions would not maintain proportionality in their left- and right-handed mix. Thus, the non-linear effect occurs when the product can come out purer than the catalyst would suggest.
Cancer survivor Soai, in 1995, with asymmetric autocatalysis, a reaction that can copy itself and become purer at every stage, like compound interest, boosted the hope of making pure medicines with compounds of the desired version. Asymmetric organic synthesis means building carbon-based molecules so that one mirror-image form is made in preference to the other. It is a non-linear effect when the product can come out purer than the catalyst would suggest. When the reaction’s product also acts as a helper, speeding up its own production, it is autocatalysis.
In 1996, Soai started with 51% left-handed and 49% right-handed ingredients and succeeded in achieving 87% of the former in the product. In 2003, he succeeded in achieving 99% of the left-handed molecule of the medicine. He began with ingredients that had no handedness at all. Both forms appeared at first; chance gave one a slight lead, and that lead was enough. In one version, a head start of 0.00005%, roughly one extra molecule of the favoured form in every two million, grew to more than 99.5% in three runs. That is an amplification of 630,000 times, according to the Nobel Committee’s scientific background.
To understand how catalysts really work, they are built from metal atoms that hold on to two helper molecules, giving three pairs: right with right, left with left, and mismatched right with left. Kagan found that only matching pairs do the job, while mismatched pairs are ineffective. The Nobel Committee gave a simple example: if 75% is right-handed and 25% is left-handed, most matching pairs in the product would be right-right, and the left-left pair would be rare. The reaction behaves as 90% right-handed and 10% left-handed. This showed how tiny molecular imbalances can be magnified and offered a new way of making pure medicines. Indian chemists find this work extremely useful, as it helps save the costs of medicines and provides direction for young researchers to proceed further.
French chemist Louis Pasteur had looked at tartaric acid, which was important in wine production, and had found that bacteria fermented only one form, which was naturally found in grapes, of the two forms of tartaric acid. There was no fermentation possible with the other form, which proved that some substances occur in two forms with different properties, one of which can have a damaging effect on health. A few years before the Nobel Prize awards started in 1901, Louis Pasteur had died.
Advances in chiral technology and synthesis are driving innovations and opening up new possibilities in pharmaceuticals, material sciences and the manufacture of agrochemicals useful for agriculture and beyond. It is not just pharmaceuticals; chemists are now learning to build that preference into materials, too. Current research and promising developments highlight the transformative potential of chiral science; future directions offer exciting opportunities for continued progress.
Life on Earth was created four billion years ago, and how and when a mirror image is created is the most fundamental question in life, but now, for the first time, it is mimicked in the laboratory. Experts in the biology of chirality are of the opinion that Nobel-winning chemistry could help reveal how and why life favours one-handedness. Professor Robert Mokaya, President of the UK’s Royal Society of Chemistry, said, “Powerful example of how fundamental Chemistry can underpin solutions to some of the biggest challenges facing society. Different isomers (or versions of molecules) can have completely different biological and physical effects, so they are crucial in finding effective medicines to treat all sorts of illnesses.”
Life on Earth was created four billion years ago, and how and when a mirror image is created is the most fundamental question in life, but now, for the first time, it is mimicked in the laboratory. Experts in the biology of chirality are of the opinion that Nobel-winning chemistry could help reveal how and why life favours one-handedness
B K Singh is the retired Head of Forest Force, Karnataka; Views presented are personal.