‘DNA sequencing could help cancer treatment’

By Amit Roy

SIR Shankar Balasubramanian, a Cam­bridge University professor of chemis­try, has spoken to Eastern Eye about the 2020 Millennium Technology Prize that he and a colleague, Professor Sir David Klenerman, have been awarded for their “development of revolutionary DNA se­quencing techniques”.

They hope their work will make it pos­sible for cancers to be detected early and also help with personalised treatment targeted at individual patients.

Both professors were in Helsinki last week to accept “one of the world’s most prestigious science and technology priz­es”, awarded by Technology Academy Fin­land. It was handed over by Finland’s presi­dent, Sauli Niinistö. Worth one million eu­ros (£863,000), the prize is given every two years for “ground-breaking technological innovations that benefit millions of people around the world”.

“The duo’s Next Generation Sequencing (NGS) technology means DNA can now be read in super-fast times,” said a statement.

“This means huge benefits to society, from helping the fight against killer diseas­es such as Covid-19 or cancer, to better un­derstanding crop diseases and enhancing food production.”

The technology prize was launched in 2004, when it was awarded to Sir Tim Bern­ers-Lee for the World Wide Web.

Speaking after returning home from Hel­sinki to Cambridge, Balasubramanian re­counted the collaboration on DNA se­quencing that he began with Klenerman in the mid-1990s. In 1998, they started a com­pany, Solexa, whose technology was ac­quired by the American firm Illumina in 2007. “I stayed involved with Illumina until 2017,” said Balasubramanian.

Explaining the complex science behind DNA sequencing, he said: “DNA is the fun­damental information that defines cells and organisms. DNA is composed of a string of four letters – G, C, T and A – and arranged in a particular sequence. One copy of the DNA sequence in the human genome is a very long code – 3.2 billion letters. The technology that we created reads that code in a way that is more than a million times faster and lower in cost than the technology for sequencing back in 1997 when we were just starting this project.”

The first human genome project “took 10 years and involved very many people across the world. And the cost was of the order of billions of dollars. The lat­est systems using our tech­nology will sequence one human genome per hour on one instrument. And the cost is below $1,000 for one genome, which is very ac­curately sequenced.”

On how all this is relevant for cancer, he said: “Cancer is caused by changes to DNA. That’s at the root cause of cancer. And all cancers are not the same.”

Cancer genome sequenc­ing research “is leading to a better understanding of how to deploy therapeutics against cancer. Some peo­ple call this personalised medicine, where a particular cancer with a particular pattern of genetic changes may be more responsive to a certain therapy. So the information can be used for therapy selec­tion. I would stress that we are in the early phases of this. And as more and more work is done to sequence tumours, over the next 10 to 20 years, we’ll find out the full extent to which genomic information can be used.

“If you can detect cancer early, the ability to treat it successfully and have a better pa­tient survival outcome is much higher. Any­thing that can help patient outcomes can­not come soon enough. I think with cancer, we’ve come a long way. And clearly there’s a long way yet to go. Certainly, we are opti­mistic that over the next 10-20 years, there will be more transformative change that will translate into patient care.

“One is predisposition. Certain muta­tions and particular genes can predispose to cancer. So it’s an early warning. The hope is that there may be a new modality for de­tecting cancer earlier. And prevention is certainly better than cure.”

With Covid, “the pathogens have a ge­nome. And by sequencing the genome of the pathogen, you can also see if the patho­gen is changing. And this sort of informa­tion allows us to detect variants, and also track the spread of variants.”

It has become apparent Covid affects some much more seri­ously than others. “There are projects ongo­ing to try and understand how a patient’s genome might help us predict and under­stand the difference in response to infection.”

Asked for his views on the pattern of the pandemic in India, Balasubramanian re­plied: “I think the evidence so far, certainly from countries like the UK, is that rolling out the vaccines quickly clearly made a very positive impact on the population, particu­larly in terms of reducing the cases of se­vere illness. The vaccine programme as a whole across all vaccines looks at this stage to be very helpful. So I think in countries like India, and indeed other countries, rolling out the vaccination programme throughout the population quickly and efficiently is one of the important things to focus on.”

Balasubramanian and Klen­erman are both based at the chemistry department at Lens­field Road, Cambridge. Last year, the department was renamed after Yusuf Hamied, the head of the Indian pharma giant, Cipla, who had himself once studied chemistry at the same venue.

Hamied, who arrived in London on Monday (24), rated Balasubramani­an as “very bril­liant. Among the leading chemists of the world, he’s one of the best. His work on DNA is outstanding.”

Their prize citation read: “Professors Balasu­bramanian and Klener­man co-invented the Solexa-Illumina Next Generation DNA Se­quencing (NGS), tech­nology that has en­hanced our basic understanding of life, converting biosciences into ‘big science’ by enabling fast, accurate, low-cost and large-scale genome sequencing – the process of determining the complete DNA sequence of an organism’s make-up. They co-found­ed the company Solexa to develop the tech­nology into a commercial system that was made more broadly available to the world.”

Balasubramanian told Eastern Eye about his family background. “I was born in Ma­dras (Chennai) in 1966,” he said. “I was nine months old when my parents migrated to the UK. I don’t come from a family of scien­tists. My father – he’s retired now – is an ar­chitect. Both my grandfathers were engineers. My mother worked in the civil service.”

He grew up in a rural area just outside Runcorn in Cheshire and was educated at Daresbury (primary) and Appleton Hall High School (secondary). “I was fortunate in getting a place at Fitzwilliam College, Cambridge. I studied natural sciences and ended up specialising in chemistry, par­ticularly organic chemistry. And then I did a PhD in Cambridge.”

After that, he went to Pennsylvania State University as a postdoctoral fellow. “I was tempted to stay in the US because it was certainly an exciting place to do science. One of the senior professors in Cambridge, Sir Alan Fersht, who was a kind of a mentor to me, persuaded me to come back to the UK. And so I came back in 1994 to the chemistry department in Cambridge, and have absolutely no regrets whatsoever. It has been a splendid place to learn to be­come a professional scientist.

“When I came back as an academic, I was made a fellow at Trinity College. Of course, Venki (Nobel Laureate Venkatraman Ram­akrishnan) is at Trinity as well. Amartya Sen (also a Nobel Prize winner) is also a Fellow. (The Indian mathematical genius, Sriniva­sa) Ramanujan was at Trinity (from 1914- 1919). Being in Cambridge and being in Trinity, you have a lot to live up to if you’re an Indian because there have been many great Indian scholars.”