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The revolution began at a local pub: now, the human genome can be read in just one hour

In a serendipitous moment, two then-unknown chemists engaged in conversation at a pub and laid the foundation for a genomics revolution. Professors Sir David Klenerman and Sir Shankar Balasubramanian are now being honoured with the 2024 Novo Nordisk Prize for their pioneering work, which enables the human genome to be sequenced in just an hour. This has opened the door to personalised healthcare and enhances our understanding of human diversity and disease. Photo: Nathan Pitt, University of Cambridge.

Humans are, of course, all different. Understanding the genetic basis for what makes us all unique, including disease-related aspects, requires sequencing of not just one, but many, human genomes.

Professors Sir David Klenerman and Sir Shankar Balasubramanian at the University of Cambridge co-invented a technology that has revolutionised our fundamental understanding of life by enabling fast, accurate, large-scale genome sequencing.

In 2000, one human genome took over 10 years to sequence at a cost of more than 1 billion dollars. Their new technology means that a human genome can be sequenced in just one hour and for less than USD 1,000, meaning millions are sequenced each year. The technology, now known as Solexa-Illumina Next-Generation DNA Sequencing (NGS), transformed the understanding of cancer by enabling targeted treatments through the identification of key genetic mutations. It has also revolutionised the diagnosis of rare genetic diseases by significantly reducing the time to diagnosis, facilitating rapid, targeted interventions. NGS played a pivotal role during the COVID-19 pandemic, aiding in the tracking of the virus’s spread and the evolution of variants.

For their pioneering efforts, Sir David Klenerman and Sir Shankar Balasubramanian are receiving the 2024 Novo Nordisk Prize.

“The achievements of Sir David Klenerman and Sir Shankar Balasubramanian represent breakthrough innovations in science. Their work has enabled a new phase in personalized medicine, significantly improving our ability to diagnose and manage many diseases. Their technology for rapid and affordable genome sequencing unlocks scientific advancements critical for our future, and it exemplifies how forward-thinking research can help solve urgent global challenges. The Novo Nordisk Foundation is proud to recognize their monumental contributions, which are consistent with our commitment to supporting scientific innovation that enhances human health,” says Professor Mads Krogsgaard Thomsen, CEO of the Novo Nordisk Foundation.

Jørgen Frøkiær, Chair of the Novo Nordisk Prize Committee, adds:
“The groundbreaking technology created by Sir David, Sir Shankar and their team is set to drive major progress in disease detection and therapy in the coming decades. However, the medical community is already leveraging this innovation. Remarkably, cancer cells shed part of their DNA into the bloodstream. By collecting and analysing this free-floating DNA, we unlock a powerful method for early cancer detection, significantly improving patient survival rates and providing effective treatment.”

The prize is awarded by the Novo Nordisk Foundation and recognises active scientists who have provided outstanding international contributions to advance medical science to benefit people’s lives.

David Klenerman says: “It might sound a bit corny, but the greatest reward is seeing the technology in use and knowing that it has genuinely saved people’s lives. Receiving recognition from this award is wonderful. Shankar and I were fortunate enough to initiate the whole process, but in my mind, the Prize represents acknowledgment of a technology to which a large number of people contributed. They took an idea from a piece of paper and turned it into reality.”

It started in a pub
In 1994, when David Klenerman and Shankar Balasubramanian met, neither was contemplating DNA sequencing. Balasubramanian needed someone with laser experience to conclude a study, which is how he met Klenerman and started collaborating in a study of the genetic copy machine DNA polymerase. However, the experiments did not proceed as smoothly as they had hoped. To brainstorm solutions, they visited the Panton Arms pub with their two postdoctoral fellows.

“At the time, the Wellcome Sanger Institute nearby was determining the three billion bases of the human genome for the first time ever. The Human Genome Project underscored the need for a more rapid and cost-effective sequencing method. We realised that our work could be adapted to meet this need,” recounted Sir Shankar.

Their innovative approach revolutionised DNA by employing parallelisation. Instead of analysing one DNA molecule at a time, they fragmented the three billion bases of the human genome into millions of tiny pieces – allowing for the simultaneous sequencing of millions of fragments and speeding up the sequence determination.

“Then we could reconstruct the genome sequence by finding and connecting overlapping segments. Key to our process was the colour-coding for the four different DNA bases using fluorescent markers. Each added base emits a specific colour, allowing us to read the sequence as the DNA is being synthesised,” explains Sir David.

In November 1997, Balasubramanian and Klenerman proposed their concept to venture capitalists from Abingworth, leading to the founding of Solexa in 1998, which was acquired by Illumina for USD 650 million in 2007. They overcame significant challenges, and Solexa developed a sequencing technology that was ultimately able to detect billions of coloured spots on a chip and determine how their colour changed as DNA was synthesised step-by-step, to decode the DNA sequence.

“Today’s sequencers can process multiple trillions of bases per experiment, so we have now achieved over a million-fold improvement. In experimental science, million-fold enhancements don’t happen very often. So I believe it is a technology that has made, is making, and will continue to have an impact in the life sciences and human health,” concludes Balasubramanian.

About Sir David Klenerman

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

About Sir Shankar Balasubramanian

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

About the Novo Nordisk Prize
The 2024 Novo Nordisk Prize will be awarded at a prize ceremony in Bagsværd, Denmark on 19 April to Professors Sir David Klenerman and Sir Shankar Balasubramanian from the University of Cambridge.

The Novo Nordisk Prize recognises active scientists who have provided outstanding international contributions to advance medical science to benefit people’s lives.

The prize is awarded annually by the Novo Nordisk Foundation and is intended to further support biomedical research in Europe.

The prize is accompanied by DKK 5 million (€672,000) and comprises a DKK 4.5 million (€605,000) research grant and a personal award of DKK 0.5 million (€67,000).

The Foundation will award an additional DKK 0.5 million for hosting an international symposium within the recipient’s field(s) of research.

Further information
University of Cambridge: Sarah Collins, Communications Manager (Research), [email protected]; [email protected]

Yusuf Hamied Department of Chemistry: Diane Harris, Communications Officer, [email protected]

Novo Nordisk Foundation: Christian Mostrup, Senior Lead, Corporate Affairs, +45 3067 4805, [email protected]

See video about the prize recipients: