Deep Science Ventures Harry Macpherson explains why there is a pressing need to measure the chemical exposome.
My country, the UK, is one of a handful in which increases in life expectancy have stalled while the number of healthy years we live has fallen. Increasing prevalence of chronic illnesses at younger ages is worsening our quality of life, with 7% of the workforce unemployed due to long-term illness. Globally, some important health metrics are just as concerning. Since the 1990s, childhood obesity has increased by 300% and cancer in the under 50s has increased by 79%. Average sperm counts have decreased by 52% since the 1970s, and Parkinson’s disease is up by 160% since 1993. If living standards are increasing, smoking is less popular, and medicine continues to advance, what is causing these trends?
The best place to look for answers is the exposome: influences from our environment such as diet, exercise, smoking, relationships, and chemical exposures. Data from the UK Biobank, recently showed the exposome to be significantly better at explaining differences in mortality than genes.
Our genes are not changing fast enough to cause these health trends, but the exposome is. Chemical production has increased fifty-fold since the 1950s and plastic production has increased two-hundred fold, with over 40,000 synthetic chemicals produced industrially.
Today, even rainwater in many parts of the world is contaminated with PFAS, also known as forever chemicals, and most people have PFAS, bisphenols and phthalates present in their urine or blood. Toxic chemicals have also been found to contaminate breast milk and foetuses, which is important because exposures during key developmental stages can affect lifelong health.
Chemical exposures have largely been a blindspot in our understanding of health and longevity, and large gains in healthspan could potentially be achieved by shining a light on them. This could be done by discovering and quantifying synthetic chemicals in the biological samples which have been so generously donated to long term population studies.
Long term population studies track the lives and health of often hundreds of thousands of participants, and many have associated biobanks: enormous freezers with millions of samples such as blood, urine, saliva, and breast milk. These samples are very valuable, and are commonly used to sequence the participants’ DNA, proteins and metabolites. These studies help us understand development, aging, and diseases, and also help us to invent new therapeutics. Importantly, they track their participants over several decades or even generations, but are very underutilised for studying chemical exposures.
For many chemicals there is good evidence that exposures cause disease, and we already know enough to take action. Studies have found that environmental factors, rather than genes, are the dominant causes of Parkinson’s disease and pesticides, and dry cleaning chemicals, heavy metals and air pollution all contribute. Men with high blood PFAS levels have been found to have half the normal sperm count of those with low levels. Children with the highest exposure to PCBs in the womb were found to be three times more likely to have low IQ scores. Finally, people with the highest PBDE levels were found to have an approximately 300% increased risk of cancer mortality compared with those with the lowest.
Reducing the public’s exposure to hazardous chemicals would likely bring significant health and economic benefits, in line with historical precedents like the phaseout of leaded petrol (gasoline) which is estimated to have increased average IQ by between two and five points and halved the incidence of intellectual disability.
While there is a lot we do know, we surprisingly have very limited understanding of the toxicology of the vast majority of chemicals. 87% of chemicals known to contact food lack hazard data required for safety prioritization, and of food additives allowed in the US, 80% lack the data required to estimate safe intakes.
If we are to phase out hazardous chemicals and replace them with truly safer alternatives, we need to better understand which chemicals the public is exposed to and why, which chemicals influence disease and which do not, and what the mechanisms are. My colleagues and I at Deep Science Ventures, alongside our university partners, believe mapping the chemical exposome of long term population studies could be the key to these questions.
Biomonitoring programmes such as the National Exposure Report in NHANES are fantastic sources of insight, but analyze a limited list of target chemicals, and measure only a few thousand participants who are not followed longitudinally. We could unlock so much more understanding by combining non-targeted techniques, which can discover chemicals, with targeted techniques, which can precisely quantify them. This would be especially powerful if we apply these techniques to long term population studies. Long term population studies have the benefits of much larger cohorts for increased statistical power, and have longitudinal data and samples so that cumulative effects can be understood, as well as petabytes of other relevant data.
For example, they commonly have information on employment, location, and diet, which we could use to understand how people are exposed and which lifestyle changes can reduce exposure. Some have even conducted repeated imaging studies on their participants, which could be used to understand how chemical exposures affect organ and brain aging.
Some of the largest long term population studies are: the UK Biobank, Our Future Health, All of Us, and the China Kadoorie Biobank. There are many more around the world, but to my knowledge, comprehensive mapping of the chemical exposome has not yet been done in any large long term population studies. With so much valuable information already recorded, and the samples in the freezers ready to be tested, the chemical exposome is the missing piece.
We have developed the tools in mass spectrometry, exposome methodology and AI needed to unravel the chemical exposome’s effects. National exposomics infrastructures have been set up in Europe and the United States interconnected by coordinating bodies such as NEXUS and EIRENE. What we urgently need now is investment in our large genotyped population cohorts to provide measurements of chemical exposures at scale. If we act now, a healthier future awaits us.
About Harry Macpherson
Harry Macpherson is a Senior Associate at Deep Science Ventures. After graduating from Oxford University with an MEng in Materials Science he developed electrochemical processes for the recycling of lithium-ion batteries and the transformation of CO2 to chemicals at Johnson Matthey. In 2023 he co-founded Yama which is developing an electrochemical technology for CO2 capture from dilute point sources and air. At Deep Science Ventures he helps founders to build companies tackling outcomes from the decarbonisation of ironmaking to the miniaturisation of wastewater treatment. He has a particular interest in detoxifying the economy by creating safer chemicals and materials, mapping the chemical exposome and improving methods of toxicology screening and prediction.
