The "exposome" revolution arrives

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Imagine about one thousand people equipped with smartphones which, in addition to the standard functions, serve to reveal using special sensors, pollutants, and which, thanks to GPS, correlate the findings whilst on the move. Now imagine that these same persons are monitored as part of an experiment where their blood and other bodily liquids are taken, dosing them with the main metabolites; the medical sphere monitors them and conducts surveys relying on questionnaires on primary lifestyle habits.

This is the shape the first Exposomics assessment takes, probably the most ambitious project governing environmental epidemiology, financed, for four years, by the European Commission, for the sum of 8.7 million euros. The consortium, which includes 12 partners and which is led by the Imperial College of London (in addition to IARC in Lyon and CREAL in Barcelona) will launch a revolution in the sphere of calculating environmental exposure and linking them up to results on health.

Up until the present day,environmental epidemiology has been based upon indirect measures, often, simply the distance of subjects from the polluting sources (the emissions of which are recreated using dispersion models): this is simply not enough to establish solid links between exposure and illnesses. Such is the case – as Paolo Vineis from the Imperial College of London states (the project leader) “it is impossible to apprehend, for example, the genuine connection between PCB and non-Hodgkin's lymphoma based solely on exposure measures and traditionally used questionnaires”.
Something new is needed, and primarily something which aligns with the molecular revolution which has been of interest to biology and medicine for decades now.

This revolution has a name: exposome, a concept first proposed by Christopher Wild, Director of the IARC in Lyon, in an article which featured in CEBP in 2005 (“Complementing the Genome with an Exposome: the Outstanding Challenge of Environmental Exposure Measurement in Molecular Epidemiology”) (also refer to the article of S. Rappaport). Exposome represents complete exposure of a subject for an entire lifetime, in other terms, from the uterus in the womb. This therefore includes all personal interaction with the environment: not just chemical and physical agents present in the air and water, but also everything incorporated as part of lifestyle (food, alcohol, physical exercise, smoking, stress, etc.) which leaves its own mark on organism molecules. And now for the second fundamental point of the project: omics. A setting which necessitates the Genome Wide Association Studies, the new approach resolves to sieve through all that which can be found in bodily liquids examined using advanced spectroscopy techniques, which will be fused with genetic mutations (of DNA and RNA), epigentic, metabolic and proteomic in nature. A top-down setting - which does not begin with hypothesis which has already been associated to an agent-illness relationship, but from “blind” scanning results of the substances present in the organism placed statistically in relation with the variations identified in the various omics of individuals examined. This can be used to shine light on unexpected associations, between bioindicators and the primary chronic illnesses; for some time now, it has been suspected that environmental exposure represents a major source. Not just “poisonous” chemicals but, – for example – the pressure of psycho-social stress, which can be seen on an organic level with the shortening of telomeres and via other biological responses, such as the “allostatic load” subsequent to neuroendocrine activity, or specific genic expressions. A new scientific frontier which will be eventually able to associate more fleeting realities, such as mental health and the status syndrome behind organic illnesses.

“The sequencing of the human genome has provided us with a significant amount of information on the genetic susceptibility involved in the arise of illnesses. However, by now, it is clear that the most common illnesses (from diabetes to cancer, from neurodegenerative to coronary illnesses) are caused by many different elements and are not just based on the genetic component continues Vineis. In this context, we can therefore say that the environment (ranging from the intrauterine development to the physical-psychological-social environment in which we live – lifestyle included) plays a significant part in the development of our health status. However, it remains an unexplored ocean, which will be scanned using new molecular instruments, those pertaining to biomonitoring and genomics.

Research of this type has already been carried out for a couple of years now, and which can additionally benefit from the accounts of of healthy and ill persons, for example, the Millennium Cohort Study of the United States Department of Defense (approximately 150,000 individuals were screened) or the wide-scale surveys of the American National cancer Institute (for example Prostate, Lung, Colorectal and Ovarian cancer screening Trial). The ability to access the databases with this biological material of accounts would enable the generation of new hypothesis governing the association between exposure (even multiple) and illnesses.

These collaborations have already began to provide the first significant results, such as the “trascrittomic analysis” (RNA molecule produced by the genome) of benzene, the different micro-RNA profile in smokers and non-smokers, or the studies overseeing the association between exposome and metabolome with Parkinson's (see The Exposome: A powerful Approach for Evaluating Environmental Exposures and Their Influences on Human Diseases, The National Academies, USA).

With this new unified pathogenesis theory - which has a similar objective than the Grand Unified Theory in physics – medicine re-assumes an holistic (whilst scientific) view of health, and can only be developed by means of large international projects such as Exposomics (see  Nature to find out what it has to say too). The association of illnesses, genetic polymorphism and the bioindicators for thousands of individuals constantly developing, my very soon, leave the scientific community facing an immense challenge in terms of information, much greater than that tackled with the sequencing of the human genome.

Over the next four years, Exposomics will monitor the accounts of 13 different individuals which fall in different age ranges (from babies to the elderly) in order to secure a wide-ranging and dynamic vision of the environmental exposure (outdoor and indoor pollution, pesticides, cosmetics and other chemical products, diet, living habits, levels of activity, etc.). The project has three main objectives: generate new hypothesis on the environmental etiology of illnesses; more accurately identify the most significant contaminates to public health, in order to be able to draw up new legislations and regulations to reduce emissions. Finally, shape a new personalized medicine able to act upon individuals based upon their profile relative to environmental and genetic susceptibility. (A fascinating objective, but which remains a long way off).

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