Genetic variation ensures that patients all respond differently to the same medicine. Can you give a practical example that shows this?
“Three months ago I received an email from a Canadian doctor. He said that his brother in his late fifties developed colon cancer, was treated with medication and then died quickly. Afterwards, a genetic test was done which showed that he had a certain DNA variant. Thanks to our research in the Netherlands, we now know that you need to adjust the drug dosage for colon cancer with this DNA variant. So his brother died from the drugs and not from the tumor. Fortunately, such a DNA test for colon cancer is already part of the treatment in the Netherlands.”
Medicines often don’t work as well as we would like. Is that the problem you are looking for a solution for?
“As a hospital pharmacist and clinical pharmacologist, I work with medicines all day long. We are very happy that they are there, but we also see that they do not always work as well as we would like. Medicines also cause side effects in a large number of people. Of course there is a positive balance between the risks and the effects, otherwise medicines would not be on the market anyway. As a clinical pharmacologist, I want the right medicine in the right dosage for every patient so that it has maximum effect without side effects. We are still a long way from that.”
Your example of the patient with colon cancer shows that medicines sometimes do not work properly due to our specific DNA. When did you get the idea to start researching this?
“During an elective course in my Pharmacy studies, I learned that genetics can influence the effect of medicines. So that theory is not new. Thanks to all the technological developments and our studies at the LUMC, it is now really possible to predict the effect of medicines based on someone’s DNA profile. In our laboratory we perform thousands of DNA tests on patients in the hospital. It is fascinating every day to see that one base pair in DNA can have an enormous effect on drug treatment and its outcome.”
In February this year you had an important publication in The Lancet. About the first study worldwide that shows that prescribing medicines based on a patient’s DNA profile works in practice.
“Our research shows that patients for whom we match the dosage of a set of 39 medicines to their DNA have a significantly lower risk of serious side effects. This is because one patient processes a drug at a different rate than another, and therefore requires a different dose to achieve the same effect. A personal approach is therefore desirable. In the study we used a DNA medicine card that links a patient’s DNA profile to medicines whose processing is influenced by the DNA. By scanning this pass, doctors and pharmacists know what the optimal dose is for the patient.”
At the same time, there is so much we don’t know yet, you say in previous interviews. This research is just ‘the tip of the iceberg’.
“In the Dutch pharmacogenetics working group, we have drawn up concrete advice for approximately 50 medicines on how treatment can be adapted to the patient’s DNA profile. This makes it possible to do a test before starting treatment to prevent side effects. But research with twins also shows that we cannot explain all hereditary differences in the processing of a medicine. To better predict the effect of DNA, we need to look at many more DNA variants in much larger groups of patients.
In addition, there are also many non-genetic factors that influence the effect of medicines. For example, if you have inflammation, this affects the breakdown of medicines. We are also investigating that.”
What do you hope to one day achieve as a professor? A DNA medicine pass for every world citizen?
“Such a DNA medicine card is certainly a step forward, but I expect that we will eventually receive the genetic code from everyone and store it electronically in a kind of digital safe. And that we can give people advice about treatment with medicines based on their DNA profile if they become ill. In this way we ensure that patients receive a medicine that works as well as possible.”
The study in The Lancet received a lot of media attention. What does that mean for your field?
“I notice that many doctors and patients now also know what pharmacogenetics is. Recently someone sent me a very nice video of a German television show where they had a question about our studies. The question was ‘How can you prevent side effects of medicines?’. The answer options were: by taking a rest of 2 hours after ingestion, by coating the pills with a fatty film, or by a DNA test. The viewers were then shown an explanatory video about pharmacogenetics. This illustrates well that pharmacogenetics is no longer a theory, but is now really finding a place in patient care.”
The inaugural lecture ‘In Search of PharmacoPerfection’ by Prof. Jesse Swen will be on Friday, November 17, 2023 from 4:00 PM to 5:00 PM in the Academy Building in Leiden. Unfortunately there are no more places available. You can follow the inaugural lecture via a live stream.
Jesse Swen has worked at the Leiden University Medical Center (LUMC) since 2004. Between 2006 and 2011 he trained as a hospital pharmacist, in combination with PhD research into the application of pharmacogenetics in primary care. After obtaining his PhD, Swen worked within the PharmGKB group at Stanford, but was soon brought back to Leiden to conduct research into pharmacogenetics at the pharmacy lab at the LUMC. Since 2016 he has been section head of the Clinical Pharmaceutical Laboratory.
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LUMC researchers: 30% fewer side effects if medication is tailored to DNA | LUMC
Jesse Swen appointed professor of clinical pharmacy | LUMC
