Prelog Lecture 2025

It is with great pleasure that the Laboratory of Organic Chemistry at ETH Zurich awards the Prelog Medal and Lectureship 2025 to Professor Sir Shankar Balasubramanian for pioneering chemical approaches that allow us to read DNA – not only its four canonical bases, but also its chemical modifications – and for translating this chemistry into technologies that have transformed the life sciences and medicine. 

Prof. Balasubramanian was born in India in 1966 and moved with his family to the UK at a very young age. He did his undergraduate degree in Natural Sciences at the University of Cambridge and carried out a PhD under the supervision of Prof. Chris Abell. After postdoctoral studies at Penn State University with Prof. Stephen Benkovic, he started his independent academic career in 1994 at the University of Cambridge and remained there ever since. Prof. Balasubramanian holds a joint appointment between the Clinical School and the Department of Chemistry. He is the Herchel Smith Professor of Medicinal Chemistry in the Yusuf Hamied Department of Chemistry at the University of Cambridge and a Senior Group leader at the Cancer Research UK Cambridge Institute.

His laboratory’s work is internationally recognised for fundamental and applied advances in understanding the chemistry, structure and function of nucleic acids. 

A central strand of his research and an achievement that reshaped modern biology is the invention, together with David Klenerman, to sequence DNA by synthesis. By devising reversible terminator nucleotides with fluorescent readout and cleavage chemistry and by implementing massively parallel arrays, his team made it practical to decode genomes with extraordinary speed and fidelity. This concept, developed in academia and advanced through the company Solexa (subsequently Illumina), moved sequencing from decade-long, single-genome projects into day-long population-scale practice. Today, high-end instruments read trillions of bases in about a day, enabling applications that range from basic discovery to clinical diagnostics. The global impact of this chemistry is reflected in the 2020 Millennium Technology Prize awarded to Balasubramanian and Klenerman for next-generation DNA sequencing. 

Prof. Balasubramanian’s group has also extended the chemistry of ‘reading’ DNA beyond genetics to epigenetics. His laboratory has devised elegant chemical methods to map and sequence DNA bases that carry epigenetic modifications such as 5-methylcytosine and 5-hydroxymethylcytosine. These innovations, culminating in ‘six-letter’ sequencing developed through the company Biomodal, allow simultaneous reading of genetic and epigenetic information at single-base resolution. Most recently, the group introduced an unnatural base-pairing concept to resolve 5-formylcytosine, further expanding the chemical alphabet that can be read in native DNA. These advances have created new opportunities to elucidate how epigenetic modifications shape gene regulation in development, aging and disease.

A third major theme in the Balasubramanian lab concerns exploration of non-canonical DNA structures, especially G-quadruplexes. Starting from computational prediction and sequencing-based mapping to antibody-based detection in human cells, his group helped establish that G-quadruplex formation is coupled to an open chromatin state and active transcription at specific gene loci. Building on this fundamental insight, they have advanced small molecule probes that stabilise these DNA structures and display synthetic-lethal interactions in defined genetic backgrounds, pointing toward a new therapeutic modality. 

The breadth and depth of Prof. Balasubramanian’s science are matched by the reach of its translation and impact. In addition to founding Solexa, Prof. Balasubramanian founded Biomodal to democratise integrated genetic-epigenetic sequencing for discovery and healthcare. His recognitions have been recognised with numerous honours, among them: Knighthood (2017), the Breakthrough Prize in Life Sciences (2022, with David Klenerman and Pascal Mayer), the Novo Nordisk Prize (2024, with David Klenerman), and the Canada Gairdner International Award (2024, with David Klenerman and Pascal Mayer). 

Since 1986, the Prelog Medal has honoured outstanding advances in chemistry and its related disciplines. Prof. Balasubramanian’s work exemplifies this spirit, combining rigorous molecular research with creativity and translation that have reshaped both science and medicine. 

The ETH Laboratory of Organic Chemistry was honoured to welcome Prof. Sir Shankar Balasubramanian for the Prelog Lecture 2025, entitled ‘Chemistry for reading your DNA’.

2025 marked the 50th anniversary of Vladimir Prelog being awarded the Nobel Prize in Chemistry (1975). The Laboratory of Organic Chemistry therefore had the honor of welcoming Andrea Bekić, the Croatian ambassador to Switzerland, as a special guest at this lecture.

All photos shown in the gallery below by Rahel Heeb | LOC