MICHAEL SNYDER wears four watches, two on each wrist. A , California, he isn’t obsessed with time – only with buying us all a little more of it. The watches track his movements and vital signs such as heart rate and body temperature. He also carries round a walkie-talkie-sized device to sample everything airborne he comes into contact with, from chemicals to viruses.
Snyder is trying to help answer an age-old conundrum: how does our environment affect our health? Every time we breathe, eat, drink, wash, exercise, get dressed, go to work or climb into bed, we expose ourselves to potentially harmful substances – air pollution, synthetic chemicals, contaminated food and water, radiation, pharmaceuticals, alcohol, noise and microorganisms, to name but a few.
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Every year, between 9 and 12 million people die prematurely through the cumulative effect of such exposures, mainly air and water pollution, heavy metals, synthetic chemicals and workplace carcinogens and particulates. Yet our ignorance about what exactly is going on is breathtaking. “For most exposures, probably the things you’re breathing right now, we’re not really sure what they’re doing,” says Snyder.
Now he and others are attempting to spearhead a revolution in understanding how our environments make us sick. “It might sound similar to what has been done in the past, but now we’ve got this big concept,” says . Its name is exposomics, and big it certainly is – it aims to measure everything we are exposed to throughout our lives and link this with effects on our health. Can that ever succeed?
The notion that the environment can be bad for our health is nothing new. Cholera and the black death were once blamed on noxious gases emanating from rotting matter, and malaria literally means “bad air”. We now know that these are infectious diseases caused by microorganisms. But in the past century or so, it has become abundantly clear that exposure to things such as dust, smog, chemicals and radiation are a different, insidious, long-term health hazard.
This was the birth of the discipline of toxicology. For most of its existence, it consisted of studies of short-term exposures to individual toxic substances. Around the turn of this century, however, it became clear that this approach was lagging behind other areas of health science. In particular, moved genomics on from sequencing genes to looking at the complex interplays between many of them. The project was declared complete in 2003, but in 2005 Christopher Wild at the University of Leeds, UK, who later became head of the International Agency for Research on Cancer, pointed out that despite this success, we were still largely in the dark about the causes of chronic illnesses.
For most of these – cancer, diabetes, asthma, dementia, cardiovascular disease and so on – genetic susceptibility was turning out to be only a fraction of the explanation. By process of elimination, things that happened during our lives – environmental exposures – were an overwhelmingly more influential factor in mortality risk. But exposure to what, exactly?
To fill in this huge gap, Wild proposed complementing the Human Genome Project with an even more ambitious enterprise, one that would ideally measure lifetime exposures to everything in our environment and link those to disease risks. Exposomics was born.
Wild admitted that the goal was “extremely challenging”. He wasn’t wrong. “The human exposome is vast, it’s highly dynamic”, says Snyder. “It’s a big ambition,” says , Germany, “but I think it’s the right one.”
“For most diseases, exposure to environmental pollution plays a far greater part in mortality risk than genetics”
The alternative is that millions of people continue to die preventable deaths. The upper figure of 12 million deaths each year from the cumulative effect of potentially harmful environmental exposures, or “insults”, represents around 20 per cent of all deaths worldwide, and a third of premature deaths, .
Most of those deaths are down to exposure to substances we ourselves are allowing to leak into the environment. That increases the moral imperative to prevent them, says Vicente Franco at the European Commission’s Directorate General for Environment, which is responsible for setting the European Union’s environmental policy. “If you take the global perspective, pollution is the main killer worldwide,” he says. “It has been for decades – it kills more than infectious diseases, more than violence, more than war, more than tobacco – so we need to address it, there’s just no excuse. It’s almost accepted, but I find it absolutely mind-boggling.”
A general pledge to tackle the problem at source, as the EU made in its , published in May 2021, is one way forward. But we need far better information about what is already out there. Since 1950, hundreds of thousands of new chemicals and pesticides have been synthesised, for example. For most, we have no knowledge of their health effects. “We need to measure more, we need to monitor more, because what doesn’t get measured doesn’t get addressed,” says Franco.
“One of the big keys for this field is to move away from trying to understand individual elements in isolation to really understand them as lifetime exposure,” says Bennett. That means finding out far more about the effects on us of the chemicals found in the products and the building materials that we use, the industrial pollutants in the air that we breathe, the pesticides and other agricultural chemicals that may find their way into our water and our food, and the cosmetics and the sunscreens that we put on our skin – as well as the influence of lifestyle factors such as diet, smoking, vaping and stress.
A joined-up view
Since Wild issued his call to arms in 2005, we have made significant progress towards a more comprehensive view of what we are exposed to. According to , an exposome scientist at Utrecht University in the Netherlands and chair of the Exposome Network (EHEN), we already know the identity of roughly 50 per cent of the environmental risks we face. In other words, the glass is now half full, and filling fast. In the next 10 years, we should be able to get that number to 90 per cent, says Snyder. “It’s a big data problem, but it’s doable.”
“We need to get to grips with an enormous variation in our ability to deal with toxic substances in our environment”
One factor that fuels such confidence is a battery of new techniques designed to allow researchers to move beyond studies of short-term exposures to get a more joined-up view of an individual’s lifetime exposure. The US National Institute of Environmental Health Sciences (NIEHS), for example, recently developed prototype methods for , urine, saliva, water and household dust. “It is a brand new world,” says Snyder. “The way we measure things is way beyond what we could do 15 years ago.”
Meanwhile, other projects are looking in a concerted way at how the things we are exposed to affect our health. Many studies focus on “barrier organs”, such as the skin, lungs and gut, which are well-adapted to deal with environmental assaults. Others concern internal organs and systems, such as the lungs, liver and gut and the cardiovascular, immune and metabolic systems. These studies confirm what has long been suspected: the barrier organs are routinely breached, and our bodies flooded full of chemicals. “Even though some exposures may only be detected at the barrier organ, the impact goes far beyond, say changing our metabolic function,” says Peters.
As just one example of many, at a , Doug Walker at the Icahn School of Medicine at Mount Sinai in New York reported how his team has linked various chemical exposures to a liver disease called primary sclerosing cholangitis, which was previously of unknown origin. The research also confirmed a long-standing hypothesis that exposure to benzene – an intermediate in the manufacture of many industrial chemicals and a by-product of burning fossil fuels – can cause leukaemia.
And if we want to truly understand the impact of the environment on our health as individuals, we need to get to grips with the enormous variation in our ability to deal with toxic substances. These differences are mostly down to the genes we inherit from our parents, but can also be epigenetic, caused by changes to our genetic make-up as a result of events through our lives. Experiments in mice suggest that the speed with which benzene is cleared from the bloodstream varies between individuals by as much as a factor of 10. “This is probably true for most toxicities,” says Rick Woychik, the director of NIEHS. “An exposure that may be dangerous and detrimental to one individual may not apply to someone else.”
On top of that, people in the same place may not receive the same insults. “Two people in the same room can have very different exposures depending on where they are sitting,” says Snyder.
Woychik worries that such complexities could be the undoing of exposomics, a fatal flaw that prevents it becoming environmental health science’s answer to the Human Genome Project. At the moment, it risks becoming “everything about everything about everything”, says Woychik. “I believe we need to do a better job of defining precisely what it [exposomics] is.” To be truly worthy of becoming a new -omics, it needs to follow the footsteps of genomics and produce a joined-up understanding of all of the environmental exposures that are out there and how they influence our biology, says Gary Miller at Columbia University in New York, the editor of a new scientific journal called Exposome.
These are serious challenges, but researchers are increasingly confident of rising to them. Last year, Peters and her colleagues Andrea Baccarelli at Columbia University and Tim Nawrot at Hasselt University in Belgium published what they hope will become a landmark paper. Its title, , is a knowing nod to two earlier ones that have had a transformative impact. (2000) and (2013) both took big, seemingly intractable biological problems and boiled them down to underlying principles. The ageing paper, for example, takes the fuzzy idea that ageing is a general breakdown of biological function and re-conceptualises it as the accumulation of , many of which are now targets for medical intervention. It has been cited more than 7000 times.
In the new paper, Peters and her co-authors break down the ways in which environmental insults affect the human body, from oxidative stress and inflammation to impaired nervous system function (see “Eight ways the environment affects our bodies“,). The hope is that doing this could help develop and focus prevention strategies and treatments. “Every day we learn more about how exposure to pollutants in air, water, soil and food is harmful to human health,” says Baccarelli. “Less understood, however, are the specific biological pathways through which these chemicals inflict damage on our bodies.”
It also begins to explain why some types of exposure are so damaging. For example, persistent exposure to air pollution, which has been identified as the direct cause of about 4 million preventable deaths worldwide every year, hits all eight hallmarks. Observational studies show that fine particulates smaller than 2.5 micrometres across are particularly problematic for our health.
Another insight is the overlap between the hallmarks of exposure and those of ageing. Four of the eight – genomic alterations and mutations, epigenetic alterations, mitochondrial dysfunction and altered intracellular communication – are hallmarks of ageing. Another, oxidative stress and inflammation, is a known cause of diseases that hit us more as we grow older: things like dementia, cancer, diabetes, heart and respiratory conditions, Parkinson’s disease and osteoarthritis. Exposure to environmental insults is literally causing us to age more rapidly, says Peters. “As our bodies age, we accumulate changes at various sites. For environmental exposures, it’s the same thing.”
The primary focus of exposomics is improving human health, but it could have a positive effect on planetary health generally, too. Plants and non-human animals respond to environmental insults in a similar way to humans, says Peters. “So this underlying framework can be a major contribution to overcoming the challenge we currently have with pollution,” she says.
Not only that, but as , many of the things we can do to minimise our exposure to harmful pollutants – reduce air pollution, switch to healthier diets and choose active transportation such as walking and cycling – intersect with actions that can help the climate.
For many of us, minimising our exposure to environmental pollutants is easier said than done – and we aren’t far enough down the line of teasing out the interplays between exposure and genetics to make recommendations beyond that. “It would be hard to say that, based on this risk factor, you shouldn’t do this,” says Snyder. But signs of actionable results are starting to emerge, he adds: we now know, for example, that certain combinations of genes increase the risk of pesticide exposure leading to Parkinson’s.
Even with the hallmarks framework in place, there are still knowledge gaps. Peters and her co-authors considered adding stem cell dysfunction to their list, but didn’t have quite enough evidence to do so. Other hallmarks may well emerge, says Peters. Snyder also points out that the relentless focus on harmful exposures risks ignoring a healthier side of the exposome. “What are we missing? The good stuff,” he says. “We always think of exposures as bad, but there are probably a lot of good health compounds out there. That’s a whole blank area.” He speculates, for example, that chemicals given out by natural environments, for example by trees in forests, might account for some of the health benefits we seem to accrue by being in such environments.
Working out longer-term exposure effects is something else that needs work and time. “Long-term effects is one of the hardest problems out there,” says Snyder. “But that is no reason not to start now. We should start studies now that will give us data 30 years from now, 50 years from now, so that at least our grandkids will get some benefit out of that.”
If we want to halt the pandemic of chronic disease and premature ageing, then we can’t start soon enough. “There is so much health to gain and well-being to gain,” says Vrijheid. “If we are serious, this will change our lives.”
Eight ways the environment affects our bodies
In the paper published last year, researchers set out eight distinct ways in which the things we are exposed to in our environments can have effects on our health.
1. Oxidative stress and inflammation
Many environmental pollutants contain extremely aggressive chemicals called reactive oxygen species. These can overwhelm our natural antioxidant defences and cause inflammation, cell death and organ damage.
2. Genomic alterations and mutations
Mutagens in pollutants damage DNA and trigger cancer and other chronic diseases.
3. Epigenetic alterations
Air pollution, pesticides and heavy metals have been shown to induce harmful changes in gene expression during our lifetimes through effects such as DNA methylation and histone modification, which are known to be linked to the process of ageing.
4. Mitochondrial dysfunction
Mutagens and reactive oxygen species can also damage the genome and epigenome of mitochondria, our cells’ power packs. Such damage seems to increase the risk of conditions such as type 2 diabetes and breast cancer.
5. Endocrine disruption
Many chemicals found in the environment, food and consumer products disrupt the regulation of hormones, something that might be associated with type 2 diabetes and age-related thyroid dysfunction.
6. Altered cell communication
Some pollutants directly interfere with cell-to-cell communication, and prematurely aged cells can become dysfunctional communicators. The result can be “inflammaging”, or system-wide chronic inflammation that is a hallmark of ageing.
7. Altered microbiome communities
Toxic environmental substances reaching the gut can alter its microbial communities, increasing susceptibility to allergies and infections.
8. Impaired nervous system function
Noise pollution can disrupt the autonomic nervous system, leading to hikes in blood pressure and cardiovascular disease. Microscopic particles in air pollution reach the brain through the olfactory nerve and interfere with cognition.
