Dr Dennis Lo has won some of science's highest honours. In just the past three years, he has been granted The Breakthrough Prize, the Royal Medal and the Lasker-DeBakey award—an honour often seen as a precursor to winning a Nobel prize. There is a good reason for this: Lo is the inventor of a genetic testing technology that has revolutionised prenatal care for millions of women around the world. It has also been found to have promising applications in the detection of cancer.

If that wasn't enough, he's also a delightful storyteller. As he shares highlights from a remarkable career, he can recall the smallest of details: The name of a biology textbook from childhood. The knot in his stomach, over 30 years ago, as he waited to meet with famed Oxford physician and scientist Sir David Weatherall: “You knew he was in that office just by the way the pipe smoke crept through the slit in the door,” he says. 

Lo’s narrative abilities may come from his natural gift for treasuring what the rest of us miss. In 1989, he became one of the first researchers in the world to discover the presence of an unborn child’s DNA in its mother’s bloodstream. Like bits of radio chatter, these random snippets of genetic code had gone undetected for years. In 1997, Lo had another game-changing idea by looking for foetal DNA in the mother’s plasma, the amber-coloured liquid in which blood cells are absent: “Frankly, the last place you would expect to discover any DNA,” he says.

Lo spent the next decade reassembling these fragments back into a complete genetic picture of the unborn child. In the process, he co-parented a revolution in medical diagnostics: non-invasive prenatal testing (NIPT). Today, doctors use his patented DNA testing technology to learn a baby’s sex and test for chromosomal abnormalities such as Down Syndrome, all with a simple blood test.

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As he tells it, the story of NIPT began at Oxford University in 1986, when as a 22-year old medical student he attended a lecture given by the geneticist Sir John Bell. The topic that day was an exciting new technique called PCR, which Lo had learned could “amplify” sections of DNA, vastly increasing the power of genetic analysis. “Nowadays, everyone knows PCR because we’ve all taken Covid-PCR tests, but back then it was a very new technology,” Lo says. “Sir John told us on that day that PCR had the power to change the world, and I was a believer,” he says.

After the lecture, Lo approached Bell and requested that he teach him the radical new technique—no small act of valour, as Lo says he was still gaining confidence with speaking English. To his delight, the veteran scientist agreed, and invited Lo into his lab. “Suddenly, it was like I had this powerful technique at my disposal,” Lo says. “PCR had become like this wonderful new toy.”

Because he was training to qualify as both a doctor and a scientist, Lo was eager in those early days to find uses for PCR that could directly help his patients. He found that opportunity on his obstetrics training rotation. There, he witnessed the only method available in the 1980s for prenatal DNA testing, called amniocentesis, which involves extracting the DNA through a large-gauge needle placed in the mother’s uterus.

“I looked at that and saw that it carries risk and discomfort for the mother. So that got me thinking, could I possibly use PCR to search for foetal cells instead?” Inspiration struck him at a dinner one evening with two colleagues. The topic at the table had turned to having children, and whether they would prefer caring for a male or female newborn. “That was the moment that it suddenly clicked in my head: could I use PCR to detect the Y chromosome of a baby boy inside his mother’s womb?” After a very simple experiment that involved boiling a small sample of blood—“I was short on grant funds in those days”—Lo found that he was absolutely correct: foetal DNA was detectable in a mother’s blood.

Lo would continue perfecting his techniques for detecting foetal DNA while earning his PhD and medical degrees at Oxford in the 1990’s. By this time, he had married Alice Siu—whom he had met at Oxford where she was completing her DPhil in physics—and had begun considering his future: “My wife and I decided we wanted to come back to Hong Kong because it’s our home. Our parents and our families are here, so we always wanted to come back; it was just about finding the right opportunity.” In 1997, Lo accepted a position as a senior lecturer in the department of chemical pathology at the Chinese University of Hong Kong (CUHK)

His work on the foetal genome was abruptly paused in March 2003 when Prince of Wales Hospital, the teaching institution attached to the CUHK faculty of medicine, admitted its first patient suffering from the Sars-CoV-1 respiratory virus. Lo and his team were approached by Hong Kong’s public health officials and asked to commit to studying this novel virus. “I remember the dean asked me into his office. He told me that a very serious new disease was being reported worldwide, that doctors were getting sick. He asked if I was willing to do some research on it.”

“Because Sars is very serious and potentially deadly, I had to ask my team to volunteer. I said, I'm going to work on this; who amongst you are willing? We had to find a special lab, and we devoted the next six months of our lives to the project.” Lo’s research group became one of the first to sequence the full Sars-CoV-1 viral genome, as well as to discover the existence of multiple viral subtypes.

After the Sars epidemic, Lo continued his work on NIPT, thanks in large part to more radical advances in gene sequencing tech. “In 2003, I could sequence 16 samples in one go. Today’s next-generation sequencing technology can actually sequence 10 billion molecules in one go, which is just staggering,” he says.

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These technologies also allowed Lo to begin expanding his prenatal DNA testing technology to a surprising new area: cancer. “In some biological aspects, a developing foetus shares characteristics with an uncontrolled cell growth, which is how we first thought to apply this technology to testing for cancer… Cancer is basically a genomic disease, so we have been able to apply the same basic principles that are behind our prenatal tests… namely, detecting DNA from the tumour itself, circulating in the patient’s blood plasma.

While he has been honoured by the global scientific community many times throughout his career, he says nothing makes him feel prouder than when he can meet people who have benefited from his discoveries and inventions. “I’m so pleased that our work has been able to help patients, to help pregnant women.”

Yet for all its profound impact on clinical medicine, NIPT almost didn’t make it to market at all. For several years, his patent languished under an unproductive commercial deal. “Back in 1997, it wasn’t common for professors in Hong Kong to have their own companies, and our university was not well experienced in this area yet. The default thinking was that you had to license out your technology, which we did—to essentially a technology wholesaler, which gathers technologies from universities and packages them together—and they just simply didn’t realise the significance of our work.

“They sat on it for maybe three years before deciding it was rubbish and actually giving it back to the university,” he adds with a chuckle. “It’s a little unbelievable, given how valuable the technology has become.”

In 2014, Lo co-founded two biotechnology companies with his former graduate students Dr Rossa Chiu and Dr Allen Chan. Xcelom, founded through investments by mainland biotech Berry Genomics, has commercialised Lo’s non-invasive prenatal testing research and is the exclusive licensor to this region. His second venture, Cirina, expands his DNA testing technology for the detection of cancer. In late 2021, it was purchased by life science giant Illumina as part of a US$7.1 billion acquisition of its parent company, Grail.

Lo is the current Director of the Li Ka Shing Institute of Health Sciences, a position that allows him to lead valuable medical research while remaining an influential voice in Hong Kong’s R&D ecosystem. “I can’t imagine a better job,” he says.

As he looks to the future, Lo says he expects researchers in Asia to continue increasing their role in the world of science and technology. “Asia has 60 per cent of the world’s population, so I think we do have responsibility to push forward science for the world,” he says. He points to the fact that China now publishes the highest number of scientific papers in the world—nearly one in four— according to a 2021 report by Japan’s National Institute of Science and Technology Policy. When it comes to the most-cited research (ie the top one per cent of all papers), China contributes over 27 per cent of the total scientific research.

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“I’ve been back to the region for 26 years now, and I will say that the level of attention and importance the government and general public are placing on science and innovation is without comparison,” he says. When Lo opened his first lab in Hong Kong in 1997, he had a research grant for HK$600,000. “That’s peanuts today,” he says, explaining that grants have climbed into the tens of millions of Hong Kong dollars in the decades since Sars—his current facilities at CUHK are funded by a HK$470 million grant from the InnoHK public scheme.

But he also believes policymakers have much to do in order to help the regional R&D ecosystem thrive, and particularly in the area of increasing cooperation with mainland Chinese institutions. “In genomics, access to DNA and data is crucial. But if I want to collaborate with a mainland hospital today, it’s very difficult to even get samples across the border. We also need policies that can streamline intellectual property. If you have a patent granted in mainland China, you can register it in Hong Kong, but not vice versa. We need to make sure we are advancing as one scientific community.”

Overall, Lo finds it difficult to overstate Asia’s contribution to global scientific progress. “We have seen the speed of DNA sequencing increase by a factor of roughly a million over the past 20 years. That includes work done by scientists in Asia. And when you consider recent achievements in areas such as AI—things that were unimaginable just a few years ago—we really are living in a golden age for science right now.

“The importance our policymakers have placed on science is unprecedented. The technology we have available to us is also unprecedented. To the next generation considering careers in science, I say jump in and join us. The next three decades will amaze you.”

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