The DNA Revolutionary Who Refuses to Settle

After years in academia, Dr Lawrence Lee is betting everything on a technology that could rewrite the future of genomics. And he’s learned not to care who laughs

By Mary O’Malley

DNA sequencing is the hidden machinery of modern science. It powers medical diagnoses, drug discovery, population genetics, even the food we grow. But for all its influence, much of today’s dominant sequencing technology still relies on workarounds such as amplifying DNA into dense clusters before it can be read.

Dr Lawrence Lee has spent recent years examining this limitation. Now, as co-founder and CEO of SWAN Genomics, he believes the company may have identified a way to address the problem at its root. It involves reading single molecules, with native DNA that lands on their platform being sequenced directly: A single molecule, single-read solution that Dr Lee believes will be accurate, scalable, cheap and require minimal sample preparation.

Dr Lee notes that the core concept behind SWAN Genomics’ approach has been explored before, but that turning it into a practical, working technology has proven elusive. What has changed, he says, is not the physics but our ability to harness it: recent advances in synthetic biology and biomolecular self-assembly now allow access to nanoscale optical effects that were previously inaccessible. With the theory established, the engineering may finally be ready.

‘At Swan, we are reimagining genomics for tomorrow,’ Dr Lee says. If successful,  Swan’s approach could eliminate the fundamental trade-offs that have that have constrained how widely the benefits of DNA sequencing can be realised, where gains in accuracy, read length, scalability, turnaround time or cost have typically come at the expense of others.

To understand what makes this approach distinctive, it helps to understand the constraints that shape DNA sequencing today. According to Dr Lee, different sequencing technologies are optimised for different purposes, each with its own strengths and limitations. No single platform currently delivers high accuracy, long reads, scalability, speed and low cost all at once, so users must choose technologies based on their application and resources.

When the Human Genome Project concluded in 2003, it had taken more than a decade and roughly US$3 billion using Sanger sequencing, developed by Frederick Sanger, the Cambridge scientist who won two Nobel Prizes for his contributions to molecular biology. Sanger sequencing remains a gold-standard method for accuracy and is still widely used today for targeted and clinical applications, but it lacks the scalability required for whole-genome sequencing at population scale.

Much of the industry subsequently pivoted toward next-generation short-read sequencing, now dominated by companies such as Illumina. The key innovation was scalability: the ability to process billions of DNA fragments in parallel, dramatically reducing the cost of sequencing and enabling genomics to be deployed at unprecedented scale. Today you can sequence a human genome for around $300. What took 10 years now takes days. But there’s a catch.

The human genome contains around six billion base pairs. ‘That’s roughly equivalent to the number of letters in about 2,000 copies of War and Peace,’ Dr Lee explains. Short-read DNA sequencing works by chopping the genome into fragments of around 100 to 300 bases at random, then attempting to computationally reassemble the original sequence. It’s rather like shredding Tolstoy’s novel into ten-word snippets and trying to reconstruct the book a process that works well in many places, but struggles to perfectly recover the original text, especially where passages repeat

Long-read sequencing technologies can read up to 100,000 bases at a stretch, enough to piece together a whole genome without a reference. But they’re not as scalable, workflows are complex and accuracy varies. Every user faces the same question: Which compromise today?

‘That’s the problem we’re trying to address,’ Dr Lee says.

Dr Lee is also candid about what it takes to translate a scientific idea into a commercially viable technology. During a recent presentation, he paused on a photograph of his wife, four children and grandchild. ‘There is a price to pay,’ he said. ‘And it’s not only the founder, it can also affect the people around them.’

The journey has also brought him into contact with a wide range of highly accomplished people.

At one dinner, he met Baron Michael Hintze, the Australian-British businessman and philanthropist who was born in Harbin, China, to parents of Russian descent, who has since become a noted philanthropist and life peer in the UK House of Lords among many other impressive achievements. Hintze, a pattern of self-imposed disruption that has defined his career.

Dr Lee took three lessons from that conversation. First, choose to innovate rather than settle. Second,  be ok to put yourself out there. Third, back yourself.

He used to fear asking questions at conferences, worried what people would think. Now he lives by “the laugh test”: always find the opportunity to see what you might be missing, and don’t fear the empty laughter from those who won’t put their own hand up.