Home > Focus HK
Wednesday, January 6, 2016, 08:59

Chuck the needle

By Wang Yuke

Dennis Lo is tirelessly working at evolving a non-invasive procedure to gather prenatal genetic information in the early stages of pregnancy. Wang Yuke reports.

Professor Dennis Lo Yuk-ming, a pioneering DNA research scientist, has devoted almost his entire career making prenatal examinations safer and much less of an ordeal for expectant mothers. The world-renowned specialist in chemical pathology spends his days trying to solve scientific conundrums in his lab at the Chinese University of Hong Kong.

His primary goal is “to provide pregnant women and their doctors the most important prenatal, genetic information possible, in the most accurate and safest way possible”.

Nearly two decades ago, Lo rocked the world of science when his pioneering research led to the discovery that fetal DNA may be found in the blood plasma of pregnant women.

It was an important breakthrough that led to a non-invasive prenatal test (NIPT). NIPT could determine genetic abnormalities in the fetus, eliminating much of the need for painful amniocentesis, which entails inserting a needle into the mother’s womb.

Now NIPT could detect abnormalities in earlier stage into pregnancy than amniocentesis, today he continues to develop that research and hopes NIPT could also aid early treatment of certain genetic diseases and abnormalities.

Chuck the needle

The NIPT procedure, he says, is “not perfect” yet. He wants to find the remedies.

By going through NIPT expectant mothers are spared the pain of amniocentesis, but the procedure is not good enough to pinpoint whether abnormal DNA stems from the mother or the fetus. “That is to say if the result of the blood test is positive, the mother has to undergo amniocentesis, to rule out the possibility that the problem is her own,” Lo said.

He also wants to develop non-invasive tests to a state where it would be possible to identify the presence of a healthy fetus despite abnormalities in the DNA, because such cases do happen.

Lo is considered a quietly obsessive man, determined to solve any puzzle that confronts him. He loves watching Harry Potter movies, saying the magic frees his mind and allows his imagination to soar. “I thought about the method to sequence the entire fetal genome from maternal blood while watching Harry Potter movies!” he quipped.

“I consider research a hobby, so I enjoy the process, instead of just focusing on the end results,” he said.

Lo seems somewhat fastidious, stepping aside to fix his hair and make sure his suit is immaculate before taking an interview. He’s a perfectionist.

His colleague in fetal cell research, Professor Rossa Chiu Wai-kwun, recalls, “Once he wanted to complete an experiment as soon as possible, but a certain reagent needed for it wasn’t available in Hong Kong.” Lo arranged for his collaborators in the UK to buy the item, directed a student to fly to London to pick it up and return on the next available flight.”

Chuck the needle
Dennis Lo Yuk-ming is good at interpreting complicated scientific theories in simple terms. (Photo by Frentee Ji / China Daily)

Leading the pack

Lo received the Pioneer Award at the 2015 Personalized Medicine World Conference, in recognition of his contribution to the battle against genetic diseases. He is a foreign associate of the US National Academy of Sciences and was made a fellow of the World Academy of Sciences. His ground-breaking work also earned him the King Faisal International Prize for Medicine in 2014.

Lo’s search for fetal cells in the mother’s plasma began in the 1980s when he obtained his undergraduate degree in preclinical medical training at the University of Cambridge. He spent the next three years studying towards Doctor of Medicine and Doctor of Philosophy at Oxford.

The presence of fetal DNA in the mother’s plasma had long been suspected but never proven. The breakthrough for Lo and his team came in 1997. Lo, who was just back home in Hong Kong, read in a scientific journal that tumor cells release DNA into the plasma and blood serum of cancer patients. It struck him that the same was probably true of a fetus in the mother’s womb.

Scientists had assumed that fetal DNA would be present only inside the cells of the fetus. So to detect fetal DNA, fetal cells must be identified first.

“I would say, from the 1980s to 1997, we were looking in the wrong direction,” Lo said.

Lo calls the change of direction in 1997 a “conceptual leap”. He decided to shift research focus from DNA inside fetal cells to DNA coming out of fetal cells and circulating in the mother’s blood plasma.

Lo’s hypothesis proved correct. Fetal DNA was detected in blood plasma samples taken from the mother. It amounted to roughly 10 percent of the total amount of DNA in the plasma. Non-invasive screening for genetic diseases in the fetus is possible for the presence of fetal DNA, exiting outside the cellular structure.

Chuck the needle
Blood samples would be packed and bound for the US for genetic testing, which costs more than in Hong Kong. (Photo by Frentee Ji / China Daily)

Patience pays

After his major breakthrough, Lo continued his research, looking for a technique to distinguish the faulty DNA responsible for Down syndrome. Down syndrome is one of the most common genetic abnormalities all around the world. Lo thought a study of the condition suited his research interests.

People showing Down syndrome have three copies of chromosome 21 in their DNA, instead of the regular two. In theory, the number of chromosome 21 under a microscope can be counted through blood analysis. If extra copies of the chromosome were found, it would imply the fetus was at high risk of developing Down syndrome, explained Lo.

In practice, however, microscopic examination proved challenging. “The chromosomes (or DNA) are floating and swimming in the water (amniotic fluid). We need to catch them, detect them, and count them,” he said. “That’s why it took 10 years to conceive of a technique with 99 percent accuracy.”

The journey to discovery was long and difficult. “In attempting to invent a non-invasive prenatal test for Down syndrome, we had to try many approaches simultaneously. We didn’t want to leave any stones unturned,” said Lo.

Chuck the needle
Lo mentors lab researchers in processing DNA in mother’s blood plasma. (Photo by Frentee Ji / China Daily)

No wonder he repeats the phrases, “stay patient” and “never expect overnight solutions” like a mantra. “Something worth doing is typically difficult, otherwise other people would have done it,” he says.

Even when irregular DNA is detected in baby, there is a possibility that the baby is actually healthy. Lo explained, in a small number of cases, the genetic makeup of the placenta where the fetal DNA is derived may have nuanced differences with the genetics in other parts of the baby’s body.

NIPT requires only a blood sample from the mother. It’s much safer than amniocentesis, which can be painful and puts mothers at risk for miscarriage. Lo referred to statistical evidence that one in 200 women undergoing amniocentesis has a miscarriage.

Only a handful of clinics and laboratories in Hong Kong are equipped with the technology and trained personnel to perform NIPT. The procedure costs between HK$ 6,000 and HK$8,000. Most blood samples are sent to the US for testing, jacking up the costs. Lo expects more local public hospitals to receive more government funds so that they may offer the facility at affordable rates soon.

Lo takes a relaxed attitude to his research. “One thing to bear in mind is that even though the final solution may be slow in coming, we are making small progress, bit by bit.” He is convinced that it is such small steps that provide him with the encouragement to carry on.

Latest News