David Klenerman and Shankar Balasubramanian co-invented Sequencing-by-Synthesis (SBS). This Next Generation DNA Sequencing (NGS) method made possible efficient, low-cost and large-scale genome sequencing, and enabled significant advances in genomics, medicine and biology.
Born in 1959, Klenerman grew up in London. While he engaged in many sports throughout his childhood, his father, a surgeon and professor, and his mother, a biological researcher, also placed an emphasis on education and the arts. In an interview with the National Inventors Hall of Fame®, Klenerman said, “The value of education is ingrained in my family, and certainly how empowering that is. We also took advantage of being in London, regularly going to the theater.”
Klenerman’s lifelong affinity for science led him to study chemistry at the University of Cambridge, where he earned his bachelor’s degree in 1982 and his doctorate in 1986. He completed his postdoctoral research at Stanford University as a Fulbright Scholar in 1987.
Following his time at Stanford, which he describes as “a great cultural and scientific experience,” Klenerman returned to the U.K. and took a position in 1987 with BP Research applying state-of-the-art laser spectroscopy to oil industry problems. “It was my first exposure to assembling a team of people to tackle a complex problem,” he said.
In 1994, Klenerman joined the University of Cambridge, where he continues today as a professor of biophysical chemistry. Here, he met fellow National Inventors Hall of Fame Inductee Balasubramanian. “At the time, there was this revolution in physical science where chemists began to see single molecules, and it was very exciting because typically we studied billions of them at a time,” Klenerman said. “I met Shankar, we wrote a grant to try and study single molecules and we chose DNA polymerase, the enzyme that inserts nucleotides into DNA.”
Together with a team of postdoctoral researchers, Klenerman and Balasubramanian developed a transformative method. SBS involves fragmenting DNA into many small pieces that are immobilized on the surface of a chip, decoding each fragment and color coding them with fluorescent nucleotides. As scientists detected the color-coded nucleotides and repeated this cycle hundreds of times, they could determine the DNA sequence of every fragment.
“Within 10 years, we went from this idea written on a piece of paper to a functioning instrument,” Klenerman said. To advance SBS, in 1998, Klenerman and Balasubramanian founded Solexa, which was acquired by Illumina in 2007. SBS is now used in labs worldwide and continues to make a significant impact across applications, from identifying disease genes and performing noninvasive prenatal testing to furthering COVID-19 research and advancing our understanding of cancers. While in 2000 sequencing a single genome cost over $1 billion and took more than 10 years, now it costs $200 and takes just one day. Thanks to SBS, more than 1 million human genomes are sequenced each year.
Describing just one use of SBS, Klenerman explained, “You take a piece of a biopsy of someone's cancerous lung and their normal lung, and you sequence them and see the differences. In a lot of cases, you can find out what's gone wrong and design a treatment.”
Klenerman was knighted in 2019 for his service to science and for the development of high-speed DNA sequencing. He holds nine U.S. patents and his many awards include the 2022 Breakthrough Prize in Life Sciences.