Dennis Lo has received in Madrid the Commemorative Lecture Award from the Conchita Rábago de Jiménez Díaz Foundation
Most do not know his name, but millions of women owe Dennis Lo (Hong Kong, 60 years old) something as valuable as having had a safer and calmer pregnancy. The scientist is the father of non-invasive prenatal diagnosis, a test that allows us to rule out chromosomal alterations in the fetus, avoiding the risks associated with amniocentesis. His discovery that circulating DNA could be detected in plasma has also made him a pioneer of the so-called liquid biopsy, whose purpose is the early detection and monitoring of cancer. For all his contributions to Medicine, he has received awards such as the prestigious Lasker Award for Clinical Medical Research in 2022 or the Jiménez Díaz Commemorative Lecture Award, awarded by the Conchita Rábago Foundation and which he recently collected in Madrid. But theirs is not a story of easy and dazzling success. If there is one word that describes his career, it is perseverance. Because, before finding the key to his investigation, he spent years “looking in the wrong place.” There were “a lot of problems to solve along the way, but I always believed in the idea,” he recalls.
- Do you remember what it was like the first time you saw fetal DNA floating in maternal plasma?
- I had been working for a long time to try to identify it and looking in the wrong place. Until I thought I could try to find DNA from male fetuses in plasma by taking a sample and heating it for five minutes. And we saw a very clear sign. The first time I couldn’t believe my eyes. Anyway, that was just a step along the way. We quickly realized that it could be very useful for prenatal diagnosis, but it took another 10 years of work to be able to demonstrate that it could be used to detect Down syndrome, in which the fetus has an extra chromosome on the 21st pair. It wasn’t easy to get it.
- During that period, the first company to which he offered to license the technique rejected the proposal. Did he think about throwing in the towel?
- We made the first discovery in 1997 and, as I mentioned, until 2007 or 2008 we were not able to demonstrate its clinical usefulness for cases of Down syndrome. The rejection of this company was around the year 2000, very early on. I was also very young, no more than 36 or 37 years old, so it wasn’t something that worried me too much. I thought that if they didn’t want it, someone else would. I was convinced that it was a good idea and that we had to continue investigating it. Looking at it over time, I think it was fortunate that they returned the proposal to us because it was not the right company.
- I have read that this was not the only obstacle they had to overcome and that the investigation got stuck on more than one occasion. Is it true that on one of those times when the project was not moving forward, you found inspiration to solve the problem by watching a movie from the Harry Potter saga?
- Yes, exactly. After achieving the goal of Down syndrome, we wanted to continue exploring the technology and try to sequence the baby’s complete genome. We thought about how to develop an algorithm, a formula that would allow us to find that information, but we couldn’t. We couldn’t find the key. At that time the movie Harry Potter and the Half-Blood Prince was being released and I went to see it at the cinema. I don’t know if you remember, but the first few minutes of that movie are in 3D. I was at the cinema, with my 3D glasses, and when I saw the Harry Potter symbol on the screen, specifically the H in the name, I thought that the two legs of that letter were like two chromosomes. And there, in that moment, I thought that all of us, in each of the chromosomes, have a pair inherited from our father and another from our mother and that we were not going to need a single algorithm to be able to sequence the entire genome, but two. It was a eureka moment. I still have the email I sent to my colleagues when leaving the cinema to tell them the idea and what we should do. It worked.
When he remembers the anecdote, Lo can’t help but smile. “It’s not the only time ideas have occurred to me in unexpected places,” she says. And, immediately afterwards, she searches on her phone for an image of a painting that shows railway tracks, flanked by various barriers, signs, and level crossings. «Recently, when I saw that painting, I realized that in the research we are carrying out in my laboratory we were not asking the right questions, that the perspective had to change. “Sometimes you have to look at things differently, from different directions to find solutions,” she emphasizes. “And inspiration can be anywhere.”
The researcher is now immersed in a recent area of study, fragmentomics, which aims to advance one step further in cancer research. Despite the complexity of the process, Lo explains what he is doing right now in the laboratory in plain language, stopping to choose the words and with the enthusiasm of someone beginning to explore a new field full of potential: “DNA when it is found inside a cell it is a very long sequence. However, the DNA circulating in the blood is fragmented, cut into many pieces. We have been studying how these fragmentations occur, whether they are random or not. And we have discovered not only that they are not random, but that by the way each of these fragments is cut we could know if the patient has cancer or not,” he points out.
The scientist is convinced that the technology that allows us to peer into what happens in the plasma that circulates through our vessels still has much more to contribute to Medicine, that we are only at the beginning of an era.
- Do you think liquid biopsy will change the way tumors are detected and followed?
- Cancer is a very important disease. Today, approximately 50% of people will probably develop cancer during their lifetime and 35% will die from it. I believe that liquid biopsy can help detect tumors early, which is key for premature treatment and reducing mortality. In 2017, my team did a study on nasopharyngeal cancer in 20,000 people in Hong Kong, where this type of tumor is very common. We showed that liquid biopsy allowed it to be detected very early and that, in fact, doing so reduced mortality by 10 times.
- Could the same be done to detect any type of cancer?
- It’s complicated. We have developed a test that analyzes epigenetic changes and aims to target 50 types of cancer. Its goal is to tell where the tumor is. The technology has been licensed to a company that has already published some preliminary data indicating that when the test is positive, the chances of that individual having cancer at that precise moment are 75%. On the other hand, if the result is negative, the probability is 2.5%. In addition, it also indicates with an accuracy of 85% where the tumor is located. A trial is currently being carried out in the United Kingdom with 140,000 people to evaluate its effectiveness. I think that in a couple of years we will be able to know more.
- What other health questions could we find out by looking at circulating DNA?
- I think many. For example, you can know how a transplant is going. You can see the early signs of organ rejection. It can also be used in Cardiology or Neurology. I believe that in the coming years its use will increase in different areas of Medicine.
Son of a psychiatrist and a music teacher, Lo remembers a happy childhood and “relaxed” early school years, where they let us explore our interests and hobbies. Photography, he assures, was one of his first passions. «It wasn’t like now, there was no Photoshop, so I spent hours taking photos and then developing them in the darkroom. Many times I have thought that this was like a first introduction to what it means to do a scientific experiment, because you had to follow a protocol, and take into account many parameters, such as the concentration of the solutions or temperature control,” he recalls. . He says that, although he was always interested in science, he was not a brilliant student from the beginning, but rather his grades progressively improved to the point where, after finishing high school, he could choose between studying Medicine at Cambridge or Engineering at Stanford, where he also They had accepted him. «I had helped my father many times to prepare the slides for his medical conferences, because at that time we didn’t have PowerPoint either and I suppose that had an influence. But I also remember that in my Biology book there was a photo of Watson and Crick in front of King’s College Chapel in Cambridge and I had always found it a fascinating place. So decide to go there. If I had chosen the other path, perhaps today I would be a technology entrepreneur in California but I am quite happy with the result. Today I feel very honored to be in Madrid to receive this award for which I am very grateful.
- What advice would you give to young scientists?
- I think that in terms of technology, humanity today is probably at its peak, at its best, ever. When I started, the Human Genome Project did not exist, DNA had not been sequenced, artificial intelligence as we know it now did not exist. Nowadays, young scientists have all this at their disposal. That is why I am convinced that new generations can make discoveries far superior to those that have been made in the last 50 years. I would encourage anyone who is interested in science to sign up without hesitation and get to work.