Dennis Lo, molecular biologist: “Genetic information is exchanged between the child and the mother” | Health and wellness

“Conventional thinking is that mother and baby have separate circulations and that metabolism is limited by the nutrients the mother gives to the baby,” recalls Dennis Lo (Hong Kong, 60). The researcher explains that his findings showed that the exchange is much more intimate. “There is an exchange of genetic information between the child and the mother,” he notes.

Since the late 1997s, Lo has been looking for fetal DNA in a pregnant woman’s blood and has developed methods to analyze it and detect diseases before birth. Their work led to the development of a non-invasive test to detect Down syndrome, a disorder that until then could only be detected through methods that could endanger the life of the fetus. The technology was launched in 2011 and has changed prenatal diagnostic practices by reducing the need for invasive testing.

Law visited Madrid this week to receive a memorial lecture award from the Conchita Rabago de Jiménez Díaz Foundation in recognition of his research work. The Chinese University of Hong Kong professor is also one of the world leaders in the development of liquid biopsy, a method that can diagnose tumors using a blood test.

Ask. In addition to detecting chromosomal changes such as Down syndrome, prenatal diagnostic techniques provide DNA to sequence the baby’s entire genome. Could this be useful in preventing disease?

Reply. There is work showing that it is possible to obtain a complete genome, but people use this method for more selective purposes. If you have a number of genetic diseases that you want to test for, you can use this technology. The UK National Health System has such a service. But if we talk about the whole genome, there are some things that we have to discuss and debate. Personally, I think that a woman already has a lot to worry about during pregnancy, so she shouldn’t be burdened with information she doesn’t need. You need information to know if the baby may be suffering from any serious life-threatening illness at this time, during pregnancy or immediately after.

If we talk about completely sequencing a child’s genome, then we can learn something about his health in the distant future. I don’t think a mother needs to know that her child has a high chance of developing diabetes at age 40. Moreover, our knowledge of the consequences of this information is not complete. You can see the whole genome and not know what it means, and that will also worry the mother. So I think for now it’s best to limit this information to looking for important and early diseases.

TO. Would it be interesting to combine the information offered by prenatal diagnostics to identify genetic disorders with gene editing techniques to correct them?

R. Currently, ethical and legal guidelines state that you cannot change a child in such a way that the change will be inherited. You’ve probably read about the case of a Chinese scientist who modified the genome of infants to make them resistant to HIV. The case was condemned around the world, and the question remains whether these changes that confer resistance to HIV will have other consequences later in these children’s lives, making them, for example, more susceptible to other viral infections. However, when this scientist performed gene editing, he used non-invasive prenatal diagnosis (NPD) to test whether his editing worked.

TO. However, there are still tumors, for example of the lungs or pancreas, which are often detected too late. Is it possible that liquid biopsy will change this situation?

R. There are tests for one type of cancer, and there are tests for several types. For a specific type of cancer, I developed one for head and neck cancer. It’s easier to conduct clinical trials for one tumor type because you only have one cancer and one risk group. In this case, the results can be impressive. In Hong Kong, I focused on nasopharyngeal cancer, which is very common in southern China. A Cantonese like me has a one in 39 risk of getting this type of cancer. We used liquid biopsy for this type of cancer and saw that if you don’t test, about 75% of cases are detected at stage three or four (very late stage), but if you do the test, 70% They are detected in the first or second phase and are treated earlier. Survival rate has increased tenfold, so that’s a big improvement. We published an article in 2017 in the journal New England Journal of Medicine

and we are now introducing this technology in Hong Kong.

To analyze many types of cancer, since each cancer has different genomic changes, it is difficult to perform the test for all tumor types that have their own mutations. We have developed a test that looks at epigenetic changes. Epigenetics is when the DNA sequence does not change, but the formatting of the sequence does. The interesting thing is that different organs of the body have different formatting, so (through formatting) you can find out where the cancer is located. We developed this technology several years ago, which has now been licensed to Grail, a company that I co-founded scientifically. The Grail now has a test for 50 types of cancer. According to the latest data they published, if the test is positive, the probability that that person has cancer at that time is 75%. If it is negative, the probability is 2.5%. And they can tell where the cancer is with 86% accuracy. The current weakness of this test is that for stage 1 cancer the sensitivity is 25% and for stage 2 cancer it is about 57%. Therefore, we need to improve.

TO. Can’t so much information be stressful, make us feel like we’re always preventative patients waiting to find cancer?

R. I think health education and the ability of health systems to monitor people and treat them appropriately is important in eliminating stress. If you have technology that indicates a risk but you can’t treat it, it’s not helpful, but we can see what happens with blood clots and cholesterol control. Many people, especially over a certain age, take medications to control the problem and do not worry too much. They take statins and monitor themselves regularly. It would be something similar with cancer.

TO. Can liquid biopsy be used to better monitor disease treatment?

R. The idea behind a liquid biopsy is that the blood absorbs DNA from different parts of the body and contains a mixture that provides insight into what is happening in the body at that moment. And this allows us to look at multiple clones of a tumor at the same time, see how it develops, and tailor treatments. In lung cancer, the EGFR (epidermal growth factor receptor) gene is present, and if you have an EGFR mutation, you can treat the tumor with drugs called tyrosine kinase inhibitors. Subsequently, the tumor can develop, develop resistance and metastasize, and then you will also see more DNA circulating in the blood.

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