When he wrote a postcard from a farm on New Zealand’s South Island, asking to return to Gonville & Caius College for a PhD with Professor David Ellar, Geoff Smith (Natural Sciences 1985) was beginning to map out a future which could have a groundbreaking clinical impact.

Almost 40 years on, Geoff’s experience in developing DNA sequencing technology at Solexa and Illumina has helped him and his colleagues at Syndex Bio to  US$ 15million in seed financing led by ARCH Venture Partners, to develop their proprietary mcPCR (methyl-copying polymerase chain reaction) platform.

It was personal relationships forged at Caius – and on the river, more of which later – which saw Geoff pursue a PhD. And David, a Fellow for more than 50 years who died in May 2020, is cited as a major influence.

“I wrote a postcard with a picture of a sheep on, saying, ‘David, I'd like to come back and do a PhD’,” Geoff says. 

“I returned to Cambridge. He had all the forms ready and I just needed to sign them. These were different times – the effort people go through nowadays to get a PhD place is remarkable. 

“But it showed that extraordinary belief that David had in me. You have that slight arrogance of youth assuming that it's always like that. It's only looking back thinking, well actually it was David that was pretty special in doing that for me.”

The PhD was “vital” as Geoff learned first principles, learning things he is still using today. 

He adds: “It was an embryonic time for molecular biology.  PCR had just been invented and so many new things were possible. A PhD gave me complete academic freedom to explore this new molecular technology, and David’s lab was a great place to do that.”

PCR is a technique used to “amplify” small segments of DNA. Its use in modern molecular biology is almost ubiquitous, and core to many different applications from DNA fingerprinting to the diagnosis of genetic disorders. It revolutionised the study of DNA to such an extent that Kary B Mullis, its creator, was awarded the Nobel Prize for Chemistry in 1993.

Working by stealth from Melbourn, a village south of Cambridge, Geoff’s small team at Syndex Bio developed mcPCR, a method for amplifying DNA that also copies the patterns of DNA methylation, overcoming a fundamental limitation of traditional PCR. In recent years, DNA methylation has become a critical biomarker for the diagnosis of many diseases, especially in cancer.  The ability of mcPCR to amplify methylated DNA from blood and other clinical samples enables the development of highly sensitive molecular tests, and will transform early disease detection and recurrence monitoring. 

Clinical samples are due to be tested in 2026, with the future aim of working with the NHS and pharmaceutical companies for early detection of potentially life-limiting and threatening diseases.

Being based near Cambridge has allowed Syndex Bio to grow rapidly in the last year, from four people to 18. Over half the team worked previously with Geoff on the technology behind the US$1000 genome, which was developed by Solexa, a University of Cambridge spinout company, acquired by Illumina in 2007 for US$ 650 million.

“The extraordinary talent that is concentrated around Cambridge is really hard to replicate,” he says.

Geoff reflects on his undergraduate days fondly. An eight-week lecture course during the second year of his undergraduate degree on DNA cloning proved seminal. And being at Caius and at Hall alongside scientific luminaries like Professor Stephen Hawking left an impression.

“Being exposed to people of that once-in-a-generation mind seemed amazing,” adds Geoff, who made many friends through Caius Boat Club which endure.

“I loved the rowing, and the fantastic friendships you make on the river, and it makes me very happy to still have so many of my former crew as friends.” 

Once again, like with David, it comes down to people for Geoff – and sending that postcard.