The concept of what is called the ‘exposome’ is the study of all exposures to which an individual is subjected throughout their life, and beginning before birth, such as from the environment, through diet, and from their social and economic lifestyle, and the consequences these non-genetic factors have on health, and notably the development and progress of chronic diseases.
It involves the measurement of exposure to chemicals in the air, water and soil, and social factors – what are called the ‘external exposome’ – and also the internal effects on the human body, on molecular changes, which is called the ‘internal exposome’.
This multi-disciplinary field of research was first developed ten years ago, since when it has been adopted by several countries in their public health policies, including in France where it is a focus of research in the 2021 national plan on health and the environment.
Late last year, the French public agency for food, environmental and occupational health and Safety, ANSES, together with the country’s national agency for health and medical research, INSERM, organised a scientific conference in Paris dedicated to exposome research, called exposomics.
One of the speakers was Italian epidemiologist professor Paolo Vineis, Chair of Environmental Epidemiology at Imperial College, London, a leading European expert in exposomics whose research includes two projects funded by the European Commission. In this interview with Mediapart’s Jade Lindgaard, he details the very complex interactions of exposures that affect human health, the methods used to measure them, and how the concept of the exposome was born.
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Mediapart: You are a specialist in environmental epidemiology, and the head of a European Union research project into the exposome. What does the notion entail, and what does it bring to the understanding of pollution on living organisms?
Paolo Vineis: The concept was coined about 12 or 15 years ago by Christopher Wild, who was director of the International Agency for Research on Cancer. It includes two ideas. The first is that we know environmental exposures are crucial for human diseases and after much early research on genomes we know that inherited genomic alterations do not explain a large number of diseases – probably five to ten percent of all diseases. The rest is due to the environment.
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However, despite knowing that environmental exposure was so important, the methodology for investigating environmental exposure, including air exposure, was less developed than the methodology used in genomics. So, Chris Wild said we’ve put a lot of resources into genome research and now we need something about the ‘exposome’, and he coined this word. It became rather successful both in Europe and the Unites States. I have to say that the first investments [for research] were in Europe, through the European Commission which almost immediately embraced the idea. There were several calls for grants and I received one of the first which was for [the project called] ‘EXPOsOMICS’ .
The idea of the exposome is to improve the assessments of exposure to the environment. With sensors, for example, we have used silicone wristbands which capture chemicals in the environment and you can analyse them with mass spectrometry. Without going into details, with this you can measure chemicals in the environment better than we could in the past.
One very interesting approach is now used by my colleague Leon Barron of Imperial College [London] who measures chemicals in water using, again, mass spectrometry on the samples collected. Mass spectrometry is very sensitive so you can identify for example antibiotics, or chemotherapeutic agents, pesticides, chemicals coming from factories, whatever. So you have a picture of what is in that river – and its difference with what is in another river – and which goes in very small levels into drinking water. The whole thing was initiated after Leon Barron was involved in measuring illicit drugs – you may have heard of this, when they found cocaine in water coming from the toilets of the UK Parliament! Anyway, all this is one side of the improvement of exposure assessment using different methods, called external exposome.
Another side is to investigate what happens within the body, called internal exposome. We can use the same methods, like mass spectrometry of the blood or urine, which is called metabolomics, to look at metabolites. Or we can use other methods, like looking for proteins, [which is] proteomics. In general, we look for changes in body molecules to see what is the effect of body exposure. Then we look for links between these changes and the outcome of diseases, like cardiovascular disease, asthma, cancer and so on.
Mediapart: Several scientific fields are brought together in this research, including biology, chemistry and medicine. During the recent conference in Paris, you presented the notion of the ‘social exposome’. What does this add to what you have just described?
P.V.: Well, this comes from the observation that people belonging to low social-economic strata of society firstly have an increased risk of disease, and their mortality is greater in comparison to people in higher strata. Depending on how you cut up the population groups, you may have as many as eight or nine years of difference in life expectancy between extremes, and basically in all societies.
The question secondly is why do people belonging to low social-economic strata have higher mortality rates and a higher risk of disease and so on. Part of that is explained by behaviours; it is true that they smoke more and drink more, but this is not the only explanation. Some people like [British epidemiologist and public health policy specialist] Michael Marmot believe it is due to psycho-social stress, also defined as weathering, which means that people are exposed to stressful conditions that are related to their job, to their existential problems like low pay and now the gig economy – unstable jobs – and this is essentially unexplored. We do not know why social-economic status and also stressful living and work conditions increase the risk of disease and mortality, and it has been a kind of black spot in epidemiological research. Not much has been invested in it.
So, using a second grant I received for a project called Lifepath I involved social scientists to see whether we might work together and help fill the gap between social sciences and biological sciences. Because I noticed several times that there is a sort of reciprocal prejudice. Social scientists are not interested in biology because they say it is about DNA and all these ‘strange’ things. They often believe – and I think they are right to – that biologists or medical researchers tend to simplify things, that they are reductionists, that they reduce everything to molecules. On the other side, bio-medical researchers have a prejudice about social sciences because they think they are up in the clouds, nothing really material, or concrete; and this really doesn’t help research.
We were inspired by the work of [social epidemiologist] Nancy Krieger, a researcher in the United States, who coined the word ‘embodiment’, which became the motto for Lifepath – we also say ‘social to biological transition’. We wanted to understand how psycho-social stress, or existential problems, the social-economic position, influenced biological changes via the internal exposome. So in Lifepath we investigated a number of things, and I would say that the main goal was to look at epigenetics and what we call ‘the epigenetic clock’, which is a measure of age acceleration. This is a way to investigate the intermediate section between psycho-social stress or other exposures and health outcome, with biological age acceleration based on DNA.
Mediapart: What is the impact of atmospheric pollution on human health?
P.V.: We very often hear estimates of the numbers of deaths in the world that are attributable to air pollution, but we have to be careful because there is a huge difference between low-income and high-income countries. Air pollution has decreased a lot in high-income countries over the last, say, 50 years, and it continues to decrease, thanks to several reasons like improvements in engines, more controls and regulations. This does not mean it is enough – and air pollution also contributes to climate change, by the way – but air pollution has decreased. It has changed its composition depending upon the types of engines and so on. But the situation is much more dramatic in low-income countries where the most of the burden of diseases related to pollution lies. When we say millions of deaths occur every year due to pollution in the world, that refers mainly to low-income countries.
Having said that, we have also with exposome investigated pollution with biomarkers and we have found clear evidence of an effect. What we have found are mainly inflammatory changes relating to air pollution and these in turn are related to diseases like asthma, cardiovascular disease or lung cancer. So it is likely that inflammatory and immunological changes mediate the effect of air pollution on the outcome.
Mediapart: Official environmental air pollution regulations place limits on the amounts of toxic substances present in the atmosphere, below which the volumes of pollutants in the atmosphere are not deemed to be dangerous. But this is contested by a number of people, who believe the pollutants can be dangerous even if their volume is below the threshold. What does exposome research show about this?
P.V.: Yes, it is probably the most difficult question in environmental issues […] There are several ways to answer your question. First of all, the usual threshold used in for example occupational settings are usually based on animal experiments, when animals are treated with chemicals, and certain outcomes are observed and a safety factor is applied. For example, the level at which no effect is observed is then multiplied by one thousand, to be on the safe side. So, this is the empirical way to define threshold values for many chemicals.
Then there is an epidemiological observation. What happens when you look at low levels of exposure to carcinogens, for example, is that in most cases the relationship is linear; the risk goes down to zero in a linear manner, meaning that there is no threshold. The problem is that you need very large numbers of people to observe a small effect, because if your population is small you will observe just a few cases of cancer at a low level of exposure and you cannot establish a dose-response relationship which is accurate and credible.
With [tobacco] smoking, with the investigations of millions of people, including [those affected by] passive smoking, the relationship was linear. It seems that at [even] low or very low levels you have an increased risk. Why? For several reasons; there may be a genetic susceptibility in some people, what is called a polygenic risk where you have several variants in genes involved in metabolism or the repair of DNA, so you may be more susceptible because of several inherited variants of genes. Or you may have had other exposures. For example, if you are a smoker you have a kind of chronic inflammation of the lungs so if you are exposed to something else you might have an increased risk. There are examples of multiplicative interactions, like smoking and [inhalation of] asbestos.
These are the reasons that explain why you may find a risk at low or very low levels of exposure where those people who catch a disease may have had other exposures or have a higher genetic susceptibility.
But we are in the infancy of the exposome, we have different expectations to the contribution of the exposome, for example on the question of multiple exposures.
Mediapart: As you said earlier, air pollution in high-income countries is decreasing, but we are exposed to increasing numbers of chemical substances in the environment. What is your view on that, and can the exposome research help to understand more about that process?
P.V.: Researchers in the past have been focussing on a limited number of chemicals. In the United States they call them ‘legacy’ chemicals because they have been regulated for many years by the EPA, the Environmental Protection Agency. These include all the well-known chemicals like PCBs [polychlorinated biphenyls], asbestos and more recently PFAS [per- and polyfluoroalkyl substances]. But, as I said before, the methodology was limited; the ability to measure them in the environment, and even more so in the body, was limited.
This is probably one of the main goals of the exposome, because we know that there are probably many tens of thousands of chemicals in the environment – maybe hundreds of thousands. Where do they come from? Well, there is the issue of trans-national movement of chemicals, they cross borders, in the air. For example, coal energy plants in Poland pollute the rest of Europe, this is well-known. Also, there is the suspicion that many new chemicals come from China, distributed through the air and in other ways, for example through the goods we buy.
So how can we detect these chemicals? With the new improvements of the exposome, like the sensors and the internal measurements, and so on. [But] for most of these chemicals we know very little in terms of toxicology.
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- A video of the presentation by Paolo Vineis (in English) at the November 30th Paris conference organised by ANSAS and INSERM is available here.
A French translation of the above interview, which was conducted in English, can be found here.