What is the ‘exposome’?

Why you need to know about the Human Exposome Project

The Human Exposome Project does not (yet) involve multi-billion research budgets, nor will it send rockets into space - but work by a group of scientists and visionaries promises to unlock the puzzle of how to protect each one of us from the diseases which will cut short or blight our lives.

They gathered in Washington DC and on 15 May they issued a declaration of their global scientific endeavour- a ‘moonshot’- to decode how our health is shaped by environmental exposures, from the moment of conception to death.

The findings are intended to help prevent chronic diseases and extend ‘healthspan’, the number of years we live in good health. In the UK, according to the Office for National Statistics (ONS), this is currently around 61.5 years for men and 61.9 for women, but, worryingly, this has fallen from 63.2 years and 63.8 respectively since before the Covid pandemic.

The project, sponsored by Bloomberg and organised by Johns Hopkins, Columbia and other leading universities and institutions worldwide, brings together experts to build a global research infrastructure, standardise methodologies, and integrate vast datasets. I was honoured to attend, as a founding member of the Steering Committee.

The implications of this project are profound. In the UK, health spending accounts for 18.4% of all public spending while the USA spends around 18% of its GDP on healthcare- nearly twice the average of OECD countries- yet has seen declining life expectancy over the past few years. We are treating people once they are sick, rather than helping to prevent them getting sick in the first place, and this approach is reaching a breaking point.

So far, so familiar. But the exposome is not a global reboot of a public health campaign to eat our ‘Five a Day’ portions of fruit and vegetable or to undertake our NHS- recommended 150 minutes of moderate-intensity activity each week.

To understand the colossal scale of the opportunity we need to step back a quarter of a century. In 2003, the Human Genome Project decoded the full DNA sequence of individuals, laying out genetic susceptibility to disease. Job done? Not so fast.

Most diseases are not purely genetic or environmental: for example, a person may have a genetic risk of asthma, but it might only be triggered by air pollution or smoking. On the positive side, diet and exercise can switch genes on or off (through a process known as epigenetics) which influences the chance of succumbing to a disease with a genetic predisposition.

The word ‘exposome’ was coined in 2005 by Dr Christopher Wild and the concept that an individual’s health across their lifetime is influenced by their exposure to multiple environmental factors and external stresses has matured into an independent field of study.

He put it thus: ‘The routine sequencing of an individual’s complete genome was several years away as the Human Genome Project came to fruition. But the potential was staggering. Was there an equivalent for an individual’s complete exposure history, encompassing the totality of exposures in a dynamic fashion over a lifespan?’ His concept was mind-bending, encompassing both ‘internal biological processes, such as inflammation, gut microflora, body morphology, aging [sic] as well as… the built environment, socio-economics, climate, social capital etc.’

For leading causes of death globally, such as diseases of the lung, heart, and liver, the exposome explains a greater proportion of variation in incidence than genetic factors.

Also, an understanding of the exposome also shows that instead of primarily relying on treatments for established conditions, we can focus on identifying and mitigating the wide range of environmental exposures throughout life that are the root causes of these conditions.

Designing sustainable urban environments, informed, for example, by exposome testbeds that I am developing to support the Human Exposome Project, would involve tackling diverse factors such addressing air and water pollution, promoting healthy diets and physical activity, managing psychosocial stress, improving communities and living conditions, and ensuring access to green spaces.

Genetics is not destiny- the good news is that our health is in our hands, and the policy makers who shape the public realm. A large study using UK Biobank data found that the exposome was responsible for 10 times more variation in mortality risk than genetic predisposition and that the vast majority of the identified risk factors (such as smoking, low physical activity and low education level) were modifiable and hence potentially subject to intervention.

This optimistic mindset animated our Victorian forebears, who, when confronted by a population sickened in the ‘dark satanic mills’ of the world’s first industrialised society, responded by making some of the most important advances in public health in history. They dramatically reduced waterborne diseases such as cholera, typhoid and dysentery, by improving water and sanitation from the mid-19th century.

Future generations carried the torch. From the mid-20th century, Clean Air Acts reduced mortality from respiratory diseases, heart disease and lung cancer. Other public health initiatives raised both overall life expectancy and healthy life expectancy across whole populations. Improvements in maternal and infant care can be dated to the early 1900s, with gains in nutrition and food fortification from the 1920s. Antibiotics came on stream from the 1940s, with vaccination from the 1950s and measures to reduce smoking from the 1960s.

We are now ready to take the next step.