2024 NIHF Inductee Shankar Balasubramanian: Taking an Unpredictable Path

Every year since 1973, the National Inventors Hall of Fame^® has named a new class of Inductees – inventors and innovators who have shaped industries, advanced technology and improved lives. Some of our Inductees, like Shankar Balasubramanian and David Klenerman, have given us a greater understanding of what makes us who we are: our DNA.

Keep reading to learn more about Balasubramanian, a 2024 Hall of Fame Inductee who co-invented the Next Generation DNA Sequencing method Sequencing-by-Synthesis (SBS).

Fearless Exploration

Balasubramanian was born in Madras, India, on Sept. 30, 1966. In 1967, his family moved to the U.K. Growing up in Cheshire, he spent much of his time playing soccer, and he dreamt of playing professionally for Liverpool FC. He also spent his summers as a laborer at a local farm, gaining an appreciation for the value of hard work.

Embarking on a journey toward science that “wasn’t a predictable pathway,” Balasubramanian explored many career possibilities without a fear of failing.

“For me, there’s no such word as failure,” he said in an interview with the National Inventors Hall of Fame. “This is how you learn, by trying things. Each experience changes you, nudges you in a slightly different direction.”

When Balasubramanian’s path led him to the University of Cambridge, he earned a bachelor’s degree in natural sciences in 1988 and a doctorate in enzyme chemistry in 1991. To complete his postdoctoral research, Balasubramanian came to the U.S. and attended Penn State University. In 1994, he returned to Cambridge and began his research career.

Successful Collaboration

It was at Cambridge that Balasubramanian met and began collaborating with his fellow National Inventors Hall of Fame Inductee Klenerman. Balasubramanian explained that they began to pursue a fundamental idea: “to build a piece of instrumentation and use it to watch DNA being synthesized one building block at a time by an enzyme, a DNA polymerase, using fluorescence detection.”

In 1995, the collaborators gained funding for their idea, and they recruited postdoctoral researchers to join them. Together, they began to see a way to sequence DNA with a transformative new 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.

Describing the benefits of their new method, Balasubramanian said, “The reason [SBS] is powerful is you can do it to literally billions of different DNA sequences, all arrayed on the surface of a chip by massive parallelization, [which] allows you to retrieve more information quickly, and at reduced cost.”

Ongoing Impact

To advance SBS, in 1998, Balasubramanian and Klenerman founded Solexa, which was acquired by Illumina in 2007. SBS is now used in labs worldwide.

By enabling efficient, low-cost and large-scale genome sequencing, SBS 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.

In 2000, sequencing a single genome cost over $1 billion and took more than 10 years. Now, it costs just $200 and can be done in one day. With SBS, more than 1 million human genomes are sequenced every year.

Balasubramanian, who now serves as professor of chemistry at the University of Cambridge and senior group leader at the Cancer Research UK Cambridge Institute, was knighted for his contributions to science and medicine in 2017. In 2022, he won the Breakthrough Prize in Life Sciences.

Reflecting on the ongoing impact of SBS, Balasubramanian said he could not have imagined it would become ubiquitous across life sciences research. “As a scientist, you're always driven by your curiosity. But deep down, you hope that one day you may play a part in something that makes a difference for other human beings.”

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