What makes us ill?
Genes predict whether you have a propensity for an illness but environmental factors often have the last word: nutrition, air pollution, lifestyle, stress. The exposome as both culprit and chance. Large-scale research is being carried out into this at Leiden. Thomas Hankemeier, Professor of Analytical Bioscience, talks about the clinical chemistry of the future.
This interview previously appeared in the October number of alumni magazine Leidraad.
Our DNA has already been quite efficiently mapped but as far as environmental factors are concerned, there’s still a lot to be done. How do they affect our health? Leiden biochemist Hankemeier immediately indicates a dot on the horizon: in roughly ten years, every Dutch citizen will be able to map their personal chemical characteristics for less than 50 euros, using a home test. You provide blood and urine and a digital dashboard will show you what your physiological parameters indicate. If the result is negative, it’s time to take action. That will allow you to prevent or slow down diseases. ‘The clinical chemistry of the future’, as Hankemeier calls it. ‘At present, people only go to the doctor when they have symptoms and then it’s often already too late.’
So the dot on the horizon is prevention. Prevention is the magic word these days. However, Hankemeier feels we should be looking much more at the individual. ‘Why does one person develop Alzheimer’s disease and another doesn’t? Which biochemical processes are behind that? In short: what makes us ill?’
To answer that question, large-scale exposome research is needed. This has led to the construction of the Exposome Scan laboratory. The lab gives researchers from all over the country the opportunity of carrying out research at Leiden into environment and health. It's no coincidence that Hankemeier has been asked to collaborate. ‘I’ve been working at Leiden for some time on measuring the metabolism to gain understanding of how we can stay healthy for longer. Together with Amy Harms, by the way.’
Thomas Hankemeier is a busy man. But if you get the chance to talk to him, you’re talking to the future. He is co-founder of MIMETAS, the company that developed organ-on-a-chip in 2013 and made it available to researchers and industry. This is a chip on which organs are simulated making it possible to study disease processes and the effect of medicines. At the end of last year, he was asked by the clinicians and with government support, to research coronavirus. Why does it affect one person and not another? Hankemeier summarises the answer: ‘It’s all about immune fitness. Your immune system has to be perfectly in balance.’ Again, it’s no coincidence that he was asked. He has been analysing metabolism products (metabolomics) for years, with big data: important in the development of medicines.
Exposome Scan is the next step for Hankemeier. ‘We want to understand which circumstances knock the biological system out of balance; how diseases are affected by environment and lifestyle; in which combinations environmental factors are harmful and whether we are extra vulnerable in certain phases of our lives.’
‘We’ being researchers from all over the country. Environment epidemiologist Roel Vermeulen, for example, a professor at Utrecht, is responsible for the analysis of the environmental data. Hankemeier is involved in building the Exposome Scan, and he is also in close contact with doctors such as Hanno Pijl, for example, who is working on lifestyle medicine within LUMC. ‘He wants to use the data supplied by Exposome Scan for his patients.’
Environmental factors play a major role in seven out of ten chronic diseases. Diabetes Type 2, for example, and some heart conditions. ‘With these, we know that lifestyle and environmental factors are the major causes’, says Hankemeier. ‘We just don’t know exactly how yet. Take Parkinson’s disease, for example. It has been connected with the use of pesticides for years. There are studies that show the people living near fields where flower bulbs are grown develop Parkinson’s disease more often than people who live further away. That’s already proof, in principle, but what we want to do is confirm it with readings. Do we see actual mitochondrial damage in people who have been exposed to pesticides?’
We come in contact with millions of invisible molecules throughout our lives, which can make us ill: air pollution, toxic substances in food, bacteria, UV light or those which affect us, such as food. How can we keep any environmental factors that are bad for us at bay? Hankemeier: ‘I never touch doorknobs. The government’s current advice to wash your hands is something that, as a biochemist, I’ve been doing my whole life. I’d rather not get ill. And it seems to me that that applies to everyone. That’s my motivation: making sure we all stay healthy for longer. Unfortunately, keeping an adverse exposome at bay is a bit more complex than simply washing your hands.’
Better get used to it: thanks to the research by Hankemeier and his colleagues, the fit eighty-something will no longer be the exception in the future. However, he doesn’t believe in immortality. ‘At some point, something will go wrong biochemically, and you will die. Not only that, but it’s impossible to completely avoid exposure to adverse exposomes. But you can monitor the effect of exposomes, allowing you to prevent or postpone diseases by modifying your lifestyle, eating differently, maybe even moving house. I can hear you thinking: surely we’ve all known for some time now what’s healthy and what’s not? That’s true, but the notions about health are general and not adjusted to the individual. And they’re not always true, because people who have eaten healthily their whole lives can also develop depression. The immune system is too active in one person and too passive in another. Put differently: people with a certain type of gene are at greater risk of developing Alzheimer’s disease. If those same people do not get Alzheimer’s disease, they must have been able, at some point in their lives, to compensate for the risk. That’s interesting: how is it possible that people with a high genetic risk profile don't actually get ill?’
On a large scale
Research into environmental factors is not new, Hankemeier concedes: ‘As long as two thousand years ago, Chinese physicians were getting ants to smell urine. European doctors were drinking urine for the same reason: if it tasted sweet, it contained glucose, which is an indicator of diabetes.’ He laughs. ‘Luckily, we’ve advanced since then. We can now just measure everything. On a large scale. And that’s something that is new: large-scale measuring of the thousands of chemical substances out of the environment, including foodstuffs, in addition to substances we create ourselves, in our blood and urine. What we’re aiming to set up in Leiden, for large-scale measuring, is not being done anywhere else in the world yet. That makes Exposome Scan unique, and important. The huge amount of data it provides us with will bring us closer to the answer to what may well be the most important question in life: what makes us ill? Put more positively: how can we stay healthy for longer?’
Thomas Hankemeier (1966) obtained his doctorate in analytical chemistry from the VU in Amsterdam. He then spent some time as a lead researcher at TNO. Since 2004, he has been Professor of Analytical Bioscience at Leiden and Rotterdam. In 2008, he founded the Netherlands Metabolomics Centre as scientific director. He is a member of the Academy of Technology and Innovation (AcTI) and co-founder of MIMETAS, a biotechnology company that develops human organ-on-a-chip tissue models and products for the development of medicines.
At cell level
Cell biologist and assistant professor at Leiden University, Sylvia Le Dévédec, manages the research that takes place at the Leiden Cell Observatory. She zooms in on living cells with the aid of advanced microscopes and studies the effect of chemical substances (the exposome) on mini livers and kidneys. She also follow metabolic changes live at cell level.
Bob van de Water, Professor of Medicine Safety at Leiden, measures biological disturbances at cell level. To do so, he uses fluorescent substances. The aim is to chart, at cell level, the activities of a great number of chemical substances to which people are exposed. ‘This allows us to finally reach a conclusion about the possible harmful health effects of individual chemical substances’, Van de Water says.
Exposome Scan is building on the knowledge acquired in the BiomedicalMetabolomics Facility Leiden, led by Amy Harms. Together with Thomas Hankemeier, she supervises the measuring of products of the metabolism (metabolites) with the help of mass spectrometry. ‘My successes in the last ten years are also her successes.’ Harms makes sure that analytical methods developed by PhD students can also be deployed routinely for measurements in blood and urine, which is crucial for measuring large numbers of samples for the exposome research.
The Metabolomics Facility at Leiden University is a collaboration between two research groups from the faculties of Mathematics and Natural Sciences, both well-known for their expertise in two different fields. They are the Biomedical Metabolomics Facility Leiden, experts in clinical metabolomics and the Natural Products Laboratory, pioneers in metabolomic research into plant and herbal medicine.
Text: Nicolline van der Spek
Photo above article: Monique Shaw