2024 NIHF Inductee David Klenerman: Pushing Scientific Boundaries

To inspire the next generation of creators and innovators, the National Inventors Hall of Fame^® is dedicated to sharing the lessons and stories of our Inductees – inventors whose work has made our lives easier, safer, healthier and more fulfilling.

As we prepare to welcome our 2024 Inductee class, we are proud to share the stories of impactful inventors like David Klenerman, who together with fellow Inductee Shankar Balasubramanian co-invented Sequencing-by-Synthesis (SBS). This Next Generation DNA Sequencing method has enabled applications in genomics, medicine and biology, enhancing our understanding of life.

Read on to learn more of Klenerman’s story.

Finding Empowerment in Education

Born Sept. 9, 1959, Klenerman grew up in London. In addition to participating in sports including swimming, water polo, rugby, tennis and squash, Klenerman recalls his parents introducing him to the arts from a young age.

His father, a surgeon and professor, and his mother, a biological researcher, also placed an emphasis on education. “The value of education is definitely quite ingrained in my family, and certainly how important that is and how empowering that is,” Klenerman stated.

At school, Klenerman enjoyed studying mathematics and physics, and he was especially interested in chemistry. As his interest in the subject grew, he chose to study chemistry at the University of Cambridge, where he earned a bachelor’s degree in 1982 and a doctorate in 1986. Klenerman then came to the U.S. to complete his postdoctoral research at Stanford University as a Fulbright Scholar in 1987. He described his time at Stanford as “a great cultural and scientific experience.”

Tackling Complex Problems

Upon returning to the U.K., in 1987 Klenerman took a position with BP Research applying state-of-the-art laser spectroscopy to oil industry problems. He said this experience was his “first exposure to assembling a team of people to tackle a complex problem.”

Klenerman joined the faculty at the University of Cambridge in 1994, and he continues to serve as a professor of biophysical chemistry there today. It was at Cambridge that he met his co-inventor and 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.”

Klenerman and Balasubramanian’s goal was to create an instrument they could use to watch DNA being synthesized one building block at a time by an enzyme, a DNA polymerase, using fluorescence detection. In 1995, they gained funding for their idea and recruited postdoctoral researchers to join them. As they worked, they began to see a way to sequence DNA with a revolutionary new method.

With SBS, scientists could fragment DNA, decode each fragment, base by base, and color code them with fluorescent nucleotides added by an enzyme. By repeating this cycle many times, they could determine the DNA sequence of every fragment.

Enabling New Possibilities

To develop and commercialize their technology, Klenerman and Balasubramanian founded Solexa in 1998, and it was acquired by Illumina in 2007.

SBS has made possible efficient, low-cost and large-scale genome sequencing. 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. With SBS deployed in labs across the world, more than 1 million human genomes are sequenced each year.

“It went impressively fast, from an idea on a piece of paper to something being used all over the world within just under around 10 years or so, having impact well beyond what we imagined when we came up with the original idea,” Klenerman said.

SBS has been applied to identify disease genes, advance our understanding of cancers, perform noninvasive prenatal testing and further COVID-19 research. Describing just one application 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. In 2022 he won the Breakthrough Prize in Life Sciences.

“I am very motivated by seeing what's possible, just pushing the boundaries of what's possible with science in our area,” said Klenerman. “I think it's really exciting to see what science can do and what is actually possible if you try.”

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