The EU is making important progress in researching the links between environment and disease, but the field needs more collaboration from the rest of the world, according to its pioneering researcher Dr Chris Wild, director of the World Health Organization’s International Agency for Research on Cancer.
In 2004 you first came up with the concept of the exposome which has changed the way we look at disease. Can you explain it?
‘Ten years ago, there was tremendous excitement as we completed the sequence of the human genome. I was excited too. It was a historic scientific achievement. In anticipation, we started to build vast databanks that collect biological samples from hundreds of thousands of people and follow them over decades to see how their health evolved.
‘The promise was that these studies would unravel the complex causes of chronic diseases like cancer and Alzheimer’s. But I realised that if we didn’t put some effort into improving measurements of all the non-genetic factors impinging on our health, we were not going to be able to fulfil those promises. I proposed the exposome as the mirror image of the genome. We needed to put the two pieces of this puzzle together in order to understand the causes of disease.’
Was the idea well received?
‘No, not at all. Several journals rejected the original paper and, even after publication, it drew almost no reaction. Ironically, just as I moved to the World Health Organization in 2009 to focus on cancer, the topic took off. I think that, as the field of genomics matured from basic research to applications, scientists were forced to return to face questions about the major causes of diseases. In the last five years, interest has grown internationally and become particularly strong in Europe. One of the outcomes which I find most exciting has been the emergence of the EU Exposome Initiative and the three research projects that it funds.’
How do you know that diseases are caused by our exposome?
‘We know that the environment and lifestyle are important from how fast the patterns of certain diseases change over time and vary geographically. Look at how lung cancer has come down since people smoke less and how children from migrant communities tend to share the disease patterns of their neighbours rather than their parents. In some parts of the world, the incidence of colon cancer and obesity are changing over a few decades. This is too fast to be caused by a change in the human genome. The challenge is to identify what aspects of those environments are causing these disease patterns.’
Do you follow ongoing research into the exposome?
‘I am familiar with the work of HELIX and HEALS and am involved directly in the EXPOsOMICS project. What I like in particular about the European projects is that they take account of the importance of our life course. There appear to be critical times in our life when we are particularly susceptible to certain exposures. HELIX focuses on the early life exposome and HEALS covers many age groups. EXPOsOMICS is slightly different in that it aims to tease out the underlying risk factors from a whole mix of air and water contaminants. Finding the root of a disease from a lot of intertwined factors is a real challenge for epidemiology in general.’
Is this how you envisioned exposome research ten years ago?
‘In some ways, yes. I hoped we would study environmental risk factors in entire populations by applying the latest advances in technology. EXPOsOMICS, HEALS and HELIX all use omics techniques (which look at the links between biological molecules and organisms in fields such as genomics or proteomics), smartphones and environmental measurements in a very intelligent way.
‘In that sense, I am delighted, but I was hoping, perhaps naively, for more international collaboration. The EU is conducting commendable international research, but the Human Genome Project also benefited from coordination with Australia, Japan and North America. Scientists from all over the world recognised that they could do this better together. They met, they discussed what needed to be done and they divided up the task. I think there is still room for that kind of strategic outlook in the emerging field of exposome research.’
‘Most chronic diseases originate from elements in our exposome.’
Dr Chris Wild, director of the World Health Organization’s International Agency for Research on Cancer
Which diseases might be prevented with a better understanding of the exposome?
‘Most chronic diseases originate from elements in our exposome. They include cancer, cardiovascular disease and, in principle, asthma and some neurodegenerative diseases like Parkinson’s or Alzheimer’s. One area we are just beginning to grapple with is the impact of very early life exposures on gene expression which may affect disease risk. A few years ago, the EU-funded NewGeneris project showed that in-utero (in the womb) exposure to acrylamide (a chemical used in some dyes and in papermaking) could cause biological changes in children shortly after birth. This alertness to longer-term health implications of present exposures is integral to the three ongoing EU projects and I look forward to seeing their results.’
What would we do if we found a factor in our exposome that caused a particular disease?
‘We would intervene. Finland had very high cholesterol levels and high heart disease rates in the 1970s. On the advice of scientists and health services, the government launched the North Karelia Project to reduce public exposure to fatty foods. This brought heart disease mortality rates down by 70 % in just twenty five years. It is a good example that if you identify the right risk factor and take the right action, the disease rate drops.
‘Action means educating individuals but also formulating policies on a national and a European level. This may be beneficial for air pollution and exposures that are outside public control, but regulation could also reduce the health impact of alcohol and certain aspects of nutrition in a similar way as it has done with tobacco.’
How can you keep track of all the factors included in the exposome?
‘When I proposed the idea, I suggested that you could understand a lot about diseases even by improving measurements for a single suspicious factor in the exposome. Some people favour all-encompassing studies instead where, a little like we did with the genome, you study as many aspects as possible. You compare the results with disease incidence and see what pops up. This so-called agnostic approach is perfectly valid, but then researchers and funding institutions have to be brave enough to validate the findings with further epidemiological and experimental studies. Repeat studies are often difficult to fund but I think single studies would provide too little evidence to base conclusions.’
What is the next step in exposome research?
‘We need to make sure that we bring all the different measurement tools at our disposal to bear on the important questions. We then have to integrate our understanding of exposure into the existing large-cohort studies I mentioned earlier – the ones that collect biological samples and follow people over long periods of time to study the impact on their health.
‘That is a challenge that requires interdisciplinary research. In addition, as the global health community develops a better understanding of how best to approach the exposome, we would certainly benefit from identifying which exposures need to be better understood. We should then pool our efforts to investigate these parts of the exposome through international collaboration to avoid duplicating work or missing important areas. There is a temptation also to get distracted by all the different things that we can measure. We should remain driven by the questions, not the technology.’
Do you foresee ethical obstacles to research on the exposome due to issues of data privacy?
‘In contrast to genomic studies, I believe the exposome will offer very little insight into health risks on an individual level. It only reveals a glimpse of a very dynamic process in an individual, but allows us to build valuable statistics over vast populations. Scientists shouldn’t be tempted to make too many claims about the predictive value of this information for individuals and European efforts have wisely focused public health goals at a national scale. Still, if research on the exposome is to be successful, it has to take account of people’s sensitivity with respect to their personal data. We have to communicate clearly what it is that we are trying to do and what the findings can be used for.’
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