Shankar Balasubramanian

Sir Shankar Balasubramanian is the Herchel Smith Professor of Medicinal Chemistry at the University of Cambridge and senior group leader at Cancer Research UK’s Cambridge Institute. He works on the chemistry, structure and function of nucleic acids.

He is a co-inventor (with Sir David Klenerman) of the leading next generation DNA sequencing methodology, Solexa sequencing (now Illumina) that has made routine, accurate, low-cost sequencing of human genomes a reality and has revolutionised biology. He has invented chemistry to decode several modified (epigenetic) DNA bases and DNA secondary structures (G-quadruplexes) in the genome and has made seminal contributions towards the understanding of their dynamics and function. His work on small molecule recognition of nucleic acids has revealed molecular mechanisms that can be exploited to modulate the biology of cancer. His collective contributions span fundamental chemistry and its application to the biological and medical sciences.

Sir Shankar was knighted in the Queen’s New Year’s Honours in 2017 for his services to science and medicine and awarded the Royal Society’s Royal Medal in 2018. In 2021, he was awarded the 2020 Millennium Technology Prize jointly with Sir David Klenerman and the 2022 Breakthrough Prize for Life Sciences jointly with Sir David Klenerman and Pascal Mayer for their work on sequencing technologies. In 2023, he was elected as an international member of the National Academy of Sciences.

The Work:

Balasubramanian, Klenerman and Mayer are recognized for developing the underlying methodologies that led to Solexa-Illumina Next Generation DNA Sequencing (NGS), a technology that has enhanced our basic understanding of life, converting biosciences into ‘big science’ by enabling fast, accurate, low-cost and large-scale genome sequencing – the process of determining the complete DNA sequence of an organism.

Balasubramanian and Klenerman’s original work involved methods to observe a single molecule of DNA polymerase incorporating fluorescently labelled DNA monomers onto a growing strand of DNA hybridised to an immobilised template. They had the vision to see how this science could be extended and applied to sequencing a vast array of immobilised DNA molecules in a way that would bring huge benefits of scale, speed and cost. They co-founded the company Solexa, later acquired by Illumina, to make the technology available to the world. Mayer conceived and performed the initial development of 'DNA colony-based massively parallel sequencing by synthesis', initially at Glaxo-Wellcome’s and Serono’s research institutes in Geneva, and finally at a spin-off company, Manteia Predictive Medicine, where he was Chief Scientific Officer. This cluster technology is a key component of the Solexa-Illumina massively parallel sequencing technology. Manteia and its intellectual property were acquired in 2004 by Solexa. NGS has had – and continues to have – a transformative impact in the fields of genomics, biology and medicine. It has allowed a million-fold improvement in speed and cost when compared to the first sequencing of the human genome. In 2000, sequencing of one human genome took over 10 years and cost more than a billion dollars; today, the entire genome of multiple humans can be sequenced in a single day at a cost of less than $1,000. More than a million human genomes have been sequenced, and continue to be sequenced at scale each year, as well as genomes of animals, plants, bacteria and viruses, providing unprecedented insights into genome variation across the planet.

The Impact:

NGS has had an enormous impact on life sciences. Many aspects of the basic research into mechanisms in living systems now routinely involve high-throughput sequencing of DNA or RNA as the primary readout. Clinical research is undergoing a revolution via the application of genome sequencing, and genomic applications more generally, to discover the underlying causes and markers of diseases, along with substantial new knowledge on the genetic causes and signatures of cancers. There is a wave of new clinical diagnostics emerging for cancers, rare genetic diseases and infectious diseases enabled by NGS of patient samples that now includes minimally invasive blood sampling. During the COVID-19 pandemic, NGS was essential to the rapid understanding of the viral cause of the disease, and then in identifying and monitoring the spread of new variants. Without this technique, progress towards developing vaccines and other interventions would have been slow. It is difficult to overstate the importance and impact of NGS. It has initiated a revolution in biology, enabling the revelation of unsuspected genetic diversity in humans and their pathogens, with major implications, from cell and microbiome biology to ecology, forensics and personalized medicine.