Klenerman (left) and Balasubramanian in front of the pub where it all happened.
Professors Sir David Klenerman and Sir Shankar Balasubramanian have been awarded the 2024 Novo Nordisk prize for their co-invention of Next Generation DNA Sequencing, which has transformed medicine and science.
In 2000, one human genome took over ten years to sequence, at a cost of more than one billion dollars. Now, as a result of their invention, it takes just one hour and costs less than one thousand dollars, meaning millions of genomes are sequenced each year.
The technology, also known as Solexa-Illumina Next-Generation DNA Sequencing (NGS), transformed cancer understanding 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.
“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,” said Klenerman.
“Today's sequencers can process multiple trillions of bases per experiment, so we've 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 make an impact in the life sciences and human health,” added Balasubramanian.
It started in a bar
In 1994, when David Klenerman and Shankar Balasubramanian met, neither was contemplating DNA sequencing. Balasubramanian needed someone with laser experience to conclude a study, whichis 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.”
Their innovative approach revolutionised DNA by employing parallelisation. Instead of analyzing 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 – 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 in real-time as the DNA is being synthesised.”
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 $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.
The Novo Nordisk Prize
The Novo Nordisk prize recognises active scientists who have provided outstanding international contributions to advance medical science to benefit people's lives.
It will be awarded at a ceremony in Bagsværd, Denmark on 19 April. The prize is awarded annually by the Novo Nordisk Foundation and is intended to further support biomedical research in Europe.
“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,” said Jørgen Frøkiær, Chair of the Novo Nordisk Prize Committee.
"The achievements of Sir David Klenerman and Sir Shankar Balasubramanian represent breakthrough innovations in science. Their work has enabled a new phase in personalised 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,” said Professor Mads Krogsgaard Thomsen, CEO of the Novo Nordisk Foundation.