Li Ka Shing Institute of Health Sciences
Professor of Medicine & Chemical Pathology
Chinese University of Hong Kong
AsianScientist (May 11, 2016) – Professor Dennis Lo is living proof that hard work—and unfailing dedication to your cause—pays off. In 1997, Lo and colleagues discovered the presence of fetal DNA circulating freely in maternal blood plasma, which challenged the previously-held belief that DNA could only be found in cells. Based on this initial groundbreaking discovery, Lo’s group sought to explore its full potential, succeeding at detailing a genome-wide genetic map of the fetus through analysis of these small amounts of fragmented DNA in the blood of the pregnant mother.
It subsequently took Lo sixteen years to develop non-invasive prenatal blood tests that can not only uncover the sex of the baby, but also detect chromosomal abnormalities such as Down’s, Edwards and Patau syndromes. Today, mothers-to-be the world over benefit from the fruits of his labor.
Trained at Cambridge and Oxford, Lo has been the recipient of several awards for his noteworthy research, and he was elected as a Fellow of the Royal Society in the UK in 2011 and a Foreign Associate of the US National Academy of Sciences in 2013. Most recently, he was the first Chinese scholar to be awarded the prestigious 2015 Wallace H. Coulter Lectureship Award from the American Association for Clinical Chemistry.
Here, Lo tells Asian Scientist Magazine about his journey, which was not without its challenges; “Eureka!” moments during his illustrious career; and the importance of first-hand research experience.
- Instead of going down the typical medical specialist route, what attracted you to the field of chemical pathology?
A chemical pathologist is also a doctor. Actually, we can say that a chemical pathologist advises other doctors on the use and interpretation of laboratory tests, so he or she is a doctor for other doctors!
I like to develop new technologies for molecular diagnostics. Chemical pathology is a discipline that provides me with the laboratory to do this, as well as a clinical base to evaluate the new tests that have been developed.
- You had an “Eureka!” moment when you first thought of looking for fetal cells in the mother’s blood plasma. Could you tell us more about your thought process at the time?
Actually my Eureka moment was when I was looking for cell-free fetal DNA in the mother’s blood plasma, rather than fetal cells. This is the essence of the discovery. Prior to my work at the end of 1996, researchers working on non-invasive prenatal testing were looking for fetal cells in the mother’s blood. However, such cells are extremely rare and so progress in this area had been very slow.
I read a couple of papers that talked about the detecting of cell-free tumor DNA in the plasma and serum of cancer patients. I thought that there were some similarities between a fetus developing inside a pregnant mother and a tumor growing in a cancer patient. Hence, if a cancer could release enough DNA for us to see in the plasma/serum, then may be a similar phenomenon would be present in pregnancy.
Such thought prompted me to look for cell-free fetal DNA in the mother’s plasma/serum using the detection of Y chromosomal sequences from male fetuses in the pregnant mothers’ plasma/serum as a model system. Indeed, excitingly, such fetal signals were indeed found in pregnant mothers carrying male fetuses.
- It took sixteen years of painstaking work before the full implication of your 1997 discovery—of the presence of fetal DNA in the mother’s bloodstream—presented itself. What kept you motivated throughout this period?
The main challenge in this field is that while fetal DNA is present in the mother’s plasma, most of the DNA in maternal plasma is still derived from the mother’s own cells. In other words, fetal and maternal DNA molecules are mixed together. This had presented a number of challenges for the development of robust tests for Down’s syndrome using this approach.
Even though the final test took many years to achieve, we were making progress one step at a time during the progress. Such small steps served as small motivations along the way. Also, I enjoyed the process of solving the problem.
- How have the blood tests that you developed transformed the way we screen for genetic diseases in fetuses? What sort of diseases or disorders can today’s blood tests detect?
Since the launch of non-invasive prenatal testing (NIPT) for Down’s syndrome and other chromosomal abnormalities in 2011, the test is now available in over 90 countries; millions of pregnant women have benefited from this technology. This technology basically makes prenatal testing safer than conventional invasive techniques such as amniocentesis (amniotic fluid test) and much more accurate than conventional non-invasive techniques, like maternal serum screening for biochemical markers.
- 92 percent of pregnant women who receive a diagnosis of Down’s syndrome end up terminating their pregnancies. What, in your opinion, are some of the ethical implications of prenatal genetic screening?
I am very aware of the ethical, social and legal implications of a powerful new technology such as NIPT. One important reason for our efforts in developing NIPT is that we wish to save the babies who are exposed to the risk of conventional invasive testing, which has been quoted as some 0.5 percent.
Most of such babies are healthy, but the pregnancies concerned have been flagged as potentially abnormal due to the relatively high false-positive rate of conventional prenatal screening approaches prior to the advent of NIPT. Because of the much higher specificity of NIPT, the number of invasive procedures has been reduced significantly in many centers worldwide.
As regard to your statement that many pregnant women who receive a diagnosis of fetal Down’s syndrome end up terminating their pregnancies, this decision should be one that is made after appropriate counselling so that the pregnant woman concerned has all necessary information to make this important choice.
- What developments do you expect to see in the field of prenatal genetic testing and diagnostics in the next 20 years?
Currently, most centers use NIPT in the context of fetal chromosomal abnormalities. There are a number of publications and even commercial products for detecting such conditions. Such applications are more challenging as many of such subchromosomal aberrations have very low incidence; hence the test would need to have a higher specificity than even for Down’s syndrome screening for it to have a major clinical impact.
Another important application of NIPT that has thus far been somewhat utilized is its use for the testing of monogenic diseases [which result from errors in a single gene occurring in all cells of the body]. We reported the core concept of such testing in our 2010 paper in Science Translational Medicine.
I expect to see an increasing amount of interest in both of these areas in the coming years.
- What is one piece of advice that you would give to aspiring doctors and medical students?
Research can be seen as a journey that would take us to places never explored before. However, this journey is often long so it would be good to start early. Hence, it would be a good idea for medical students and doctors in training to take part in research projects to have first-hand experience about research as early as possible.
This article is from a monthly series called Asia’s Scientific Trailblazers. Click here to read other articles in the series.
Copyright: Asian Scientist Magazine; Photo: Dennis Lo.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.