Science and Technology

Pioneers in Genomics: The Duo Transforming Personalized Healthcare

COPENHAGEN, Denmark, March 15, 2024 — In what can only be described as a paradigm-shifting stroke of luck, two then-obscure chemists happened upon an encounter that would alter the course of genomics forever. The efforts of Professors Sir David Klenerman and Sir Shankar Balasubramanian have been rightly acknowledged as they are awarded the prestigious 2024 Novo Nordisk Prize for their groundbreaking work. This innovative development has drastically reduced the time required to sequence the human genome to just one hour, paving the way for customized healthcare and enriching our comprehension of human diversity and maladies.

All humans are unique, and the genetic intricacies that make us distinct, including those that pertain to disease, necessitate the sequencing of many human genomes. What once took over a decade and cost a colossal sum now takes no more than sixty minutes and under one thousand US dollars. The trailblazing work of Klenerman and Balasubramanian at the University of Cambridge has catapulted our foundational understanding of life by making vast-scale genomics less of a mountainous undertaking.

The significance of their co-invented technology, Solexa-Illumina Next-Generation DNA Sequencing (NGS), cannot be overstated. It has revolutionized cancer research by pinpointing genetic mutations, allowing for bespoke therapies, and it has reconstructed the approach to diagnosing rare genetic conditions by drastically curtailing the diagnostic timeline. This facilitates swift, precise interventions. During the harrowing period of the COVID-19 pandemic, NGS was instrumental in surveilling the viral spread and mutation, demonstrating its far-reaching impact.

In recognition of their pioneering endeavors, the 2024 Novo Nordisk Prize serves as a testament to the duo's contribution to the medical field. "The achievements of Sir David Klenerman and Sir Shankar Balasubramanian signify monumental innovations in scientific discovery,” asserts Professor Mads Krogsgaard Thomsen, CEO of the Novo Nordisk Foundation. “Their invention has sparked a new era in personalized medicine, substantially enhancing disease diagnosis and management. This rapid, affordable genome sequencing facilitates pivotal advances essential to our future. It embodies the epitome of proactive research that addresses pressing global health concerns. We at the Novo Nordisk Foundation are elated to honor their significant contributions, which align with our dedication to endorsing scientific advancements that improve human welfare."

Jørgen Frøkiær, Chair of the Novo Nordisk Prize Committee, attests to the profound implications of their creation, "The extraordinary technology fostered by Sir David, Sir Shankar, and their team is poised to propel significant advancements in detecting and treating diseases for years to come. Meanwhile, the medical community is already harnessing this innovation. A remarkable aspect of cancer is that malignant cells release fragments of their DNA into the bloodstream. By isolating and examining this circulating DNA, we access a potent approach for early cancer detection, markedly improving the likelihood of recovery and administering efficacious treatment."

This revered prize, conferred by the Novo Nordisk Foundation, salutes active scientists whose work has made a resounding international impact, furthering medical science and enhancing the quality of life for everyone.

David Klenerman spoke on the significance of their work, saying, "It might sound somewhat trite, but the true gratification comes from witnessing the practical use of our technology and realizing that it has indeed saved lives. Being acknowledged with this award is a splendid honor. Shankar and I were merely the initiators of this entire process, but to me, the Prize represents the collective accomplishment of a vast team who transformed an idea sketched on paper into tangible reality."

A Discovery Birthed in Casual Conversation

It all began casually in a pub back in 1994. David Klenerman and Shankar Balasubramanian weren't particularly focused on DNA sequencing at the time. Balasubramanian needed a collaborator with laser expertise for completing a study, leading him to Klenerman. Their joint research centered on analyzing the genetic copying instrument, DNA polymerase. Yet, their initial experiments faced hurdles. To find a solution, the scientists and their two postdoctoral fellows headed to the Panton Arms pub to deliberate.

"At that time, the Wellcome Sanger Institute was embarking on a pioneering endeavor to map out the human genome's three billion bases for the very first time through the Human Genome Project," Sir Shankar recollects. "It became clear that there was a gaping need for a sequencing technique that was both rapid and economically viable. We understood that our own efforts could rise to meet this significant need."

Their novel approach was a game-changer. By conducting parallel analyses of the genome, they fragmented the vast three billion bases into millions of smaller segments. This allowed for the concurrent sequencing of countless fragments, thereby accelerating the process. Once they created a system to identify and piece together the overlapping portions of these segments, the larger genome picture started to take shape. One crucial aspect of their invention was the introduction of fluorescent markers, color-coding each of the four DNA bases. This enabled them to "read" the DNA as it was assembled, with each added base emitting a distinguishable color.

In November 1997, Balasubramanian and Klenerman pitched their idea to Abingworth venture capitalists, which culminated in the foundation of Solexa in 1998. Despite considerable difficulties, Solexa-developed sequencing technology could eventually detect billions of color changes on a chip as DNA was synthesized step by step, essentially unlocking the DNA sequence. Illumina acquired Solexa for a massive USD 650 million in 2007.

"Today's sequencers are capable of processing trillions of bases in a single experiment. To envision a million-fold improvement in experimental science is something quite rare. This technology has marked, continues to mark, and will further mark significant strides in the life sciences and human health," Balasubramanian concludes with conviction.

The awarding of the Prize is slated to take place at a distinguished ceremony in Bagsværd, Denmark, on April 19.

Celebrating the Trailblazers Behind the Technology

Sir David Klenerman:

• Bachelor of Arts, Natural Sciences, University of Cambridge, 1979
• Ph.D., University of Cambridge, 1982
• Postdoctoral fellow, Stanford University, 1985
• Research Scientist at BP Research, 1987–1994
• Lecturer and Reader, University of Cambridge, 1994–2007
• Professor of Biophysical Chemistry, University of Cambridge, 2007
• Fellow of the Royal Society, 2012
• Fellow of the Academy of Medical Science, 2015
• Royal Society Glaxo Wellcome Professor of Molecular Medicine, 2016
• Group leader, UK Dementia Research Institute, Cambridge, 2018
• Foreign Member of the National Academy of Sciences (USA), 2023

Sir Shankar Balasubramanian:

• Bachelor of Arts (Hons), Natural Sciences, University of Cambridge, 1988
• Ph.D., University of Cambridge, 1991
• SERC/NATO Research Fellow, Pennsylvania State University, 1991–1993
• Royal Society University Research Fellow, 1994–1998
• Lecturer, Reader, and then Professor of Chemistry, University of Cambridge, 1998–2008
• Herchel Smith Professor of Medicinal Chemistry, University of Cambridge, 2008
• Senior Group Leader, Cancer Research UK, Cambridge Institute, 2010
• Fellow of the Academy of Medical Science, 2011
• Fellow of the Royal Society, 2012
• Foreign Member of the National Academy of Sciences (USA), 2023

About the Novo Nordisk Prize

The Novo Nordisk Prize is not merely an accolade but an impetus for scientists actively contributing to the advancement of medical science for the betterment of life. The annual award of the Novo Nordisk Foundation is designed to further catalyze biomedical research across Europe.

The honor is accompanied by a DKK 5 million prize (approximately €672,000), which is split into a DKK 4.5 million research grant (€605,000) and a personal award of DKK 0.5 million (€67,000). Additionally, the Foundation grants DKK 0.5 million to facilitate an international symposium within the recipient's research domain.

The innovation and dedication demonstrated by Sir Klenerman and Sir Balasubramanian serve as a beacon of inspiration for the global scientific community. Through their tireless work and the widespread adoption of their technologic discoveries, we stand on the precipice of a new era in healthcare—one that is more tailored, precise, and humane.

SOURCE: Novo Nordisk Foundation