Speed test: How two researchers made DNA analysis faster, cheaper, simpler
They refer to it as a “happy accident”. Chemists Shankar Balasubramanian, 54, and David Klenerman, 61, weren’t trying to change the world when they met at Cambridge’s Panton Arms pub in August 1997. They were working out a simple research problem whilst enjoying an evening in the beer garden.
Klenerman, on a flight to Germany, had worked out a straightforward formula for copying and measurably reading a single strand of DNA using colour codes for the acid’s components. As the two men discussed this, one thing became clear: the genius was not in the copying, but in the reading. They’d just discovered a new way to sequence DNA — the essence of every organism’s unique makeup.
The two set to work quickly, jointly founding the company Solexa in 1998, and building a DNA analyser using their new Next Generation Sequencing (NGS) method. By 2007, the life-science tools company Illumina had acquired the firm, boosting research. Balasubramanian and Klenerman developed a way to fragment bits of DNA on the surface of a chip and analyse millions of the bits simultaneously. They ended up with a faster, cheaper, more accurate, and more commercially viable process than had been tried before.
How fast and how cheap are we talking? In 2000, sequencing a single human genome took 10 years and cost more than $1 billion. Today, the average NGS process can do it in just a day, for $1,000. Almost 90% of the world’s genetic tests — from mouth swabs to trace your ancestry, to bone and brain samples to detect cancer — run on NGS. It has given medical research a shot in the arm, offering a faster, more reliable way to understand diseases.
Earlier this month, the duo won the Millennium Technology Prize, one of the world’s largest tech awards, with a cash purse of €1 million or $1.2 million. “This is the first time we’ve received an international prize that recognises our contribution to developing the technology,” the scientists said in a joint statement. “But it’s not just for us, it’s for the whole team that played a key role in the development of the technology and for all those that have inspired us on our journey.”
They’re in stellar company. The foundation Technology Academy Finland (TAF) instituted the prize in 2004, awarding it every two years to an innovation developed for social good. The first laureate was Tim Berners-Lee, who set up the World Wide Web. Prizes have been awarded for ethical stem-cell research, open-source operating systems, and atom-level layering tech in smartphones. Three of the nine previous winners have gone on to win a Nobel Prize.
Balasubramanian and Klenerman make it look easy, but their success was hard won. “There were many failures along the way,” Balasubramanian says, in a video put out on the Millennium Technology Prize website. “I kept telling my research group that the secret of success is to fail quickly.”
This approach explains why the NGS method was adopted so quickly too — it went from idea to large-scale use in under a decade, a rarity in the medical field. Add to that, the breathtaking potential of this technology to alter the field of medicine.
With sequencing so quick and cheap, the hope, says Klenerman in the video, is that “if you’ve been sequenced, you’ll know which diseases you’re predisposed to getting.” Therapies and medicines can then be tailored for each patient or family group; lifestyle changes can be incorporated to prevent or delay certain illnesses; lives can be saved by creating specific antibodies for diseases.
TAF selected Balasubramanian and Klenerman for the prize in February 2020, before the outbreak of Covid-19 was declared a pandemic. The NGS technology has been the backbone of all genetic research on the virus. It has been used by scientists to track and study the virus’s variants and mutations, a key step in containing its spread, and to study the human immune response to the virus, which has helped companies create safe vaccines more quickly.
The tech is also helping immunologists understand why the virus might affect some kinds of people differently within the same geographical and economic group.
Sequencing is poised to get faster still. Klenerman, in an interview on the website of the University of Cambridge (where both men are professors), says their highest capacity sequencing machine can sequence 48 human genomes in two days; that’s one genome an hour. They’re now set to incorporate their data into national healthcare systems, so doctors can cross-diagnose their patients.
It’s a world removed from the Cambridge pub. “I’d never have dreamt of some of the novel applications we’re seeing,” Balasubramanian says in the interview. “That’s what happens when you put technology into the hands of smart, creative researchers worldwide. But the impact and breadth of utility of this technology has gone way beyond my imagination, and it’s still in its infancy.”
Shankar Balasubramanian was born in Chennai in 1966. His family moved to the UK the following year.
He’s lived a life in science, completing an undergraduate degree in Natural Sciences Tripos at Fitzwilliam College, Cambridge, a PhD in chemistry at the University of Cambridge and a postdoctoral fellowship at Pennsylvania State University.
He returned to Cambridge as a fellow, was appointed professor in 2007. In 2017, he was knighted for “services to science and medicine”.
When he’s not changing the world, Balasubramanian, 54, enjoys hiking and cycling trips with his wife and two children. He’s also an endurance runner and cyclist and says he uses sport as a form of meditation, to help him think.
David Klenerman has a PhD in chemistry from the University of Cambridge.
The 61-year-old is also known for his work on nanopipette-based microscopy scanning. His research group was successful in achieving high-resolution images of live cells, in precise delivery of small molecules to cells, and in studying real-time detailed cell functioning.
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