The new boundaries of environment and health research

Paolo Vineis, 27 September 2023

What we know about the effects of environmental exposures (broadly defined) on human health depends largely on epidemiological research; however, important contributions also come from other scientific disciplines. During the past century, the foundations for understanding the causes of disease were laid, for example, through the study of migrant populations that unequivocally demonstrated that diseases have primarily environmental and not genetic (hereditary) causes: for example, the Japanese who migrated to the United States had at the second generation an incidence of cancer much closer to that of Americans than to that of the Japanese who remained at home, ruling out a primarily hereditary origin. In addition, the large epidemiological studies of the last century showed that tobacco smoking and a range of occupational exposures (aromatic amines, asbestos, heavy metals ..) caused cancer. Refinement of investigation techniques and the availability of large populations to investigate have also made it possible to highlight the harmful effects of air pollution.

The large epidemiological studies of the past-and even their use for regulatory purposes-now show some important limitations: (a) they generally focused on a single or few exposures, but as Persson of the Potsdam Center has shown [1], there are too many chemicals in circulation to be studied with such an analytical approach. In addition (b), chemical exposures generally occur as mixtures, and may therefore give rise to nonlinear interactions in the human body. (c) Epidemiological investigations are time-consuming and complex, and therefore impact assessment and regulatory agencies make use of other types of tests, such as animal or in vitro assays (see, for example, the excellent Monographs of the International Agency for Research on Cancer)[2].

To overcome the limitations of epidemiology, a branch of research called the “exposome” was developed. The term was coined as complementary to the “genome,” and the purpose was to enhance research into environmental causes of disease with resources at least equal to those used for hereditary causes. The exposome makes use of entirely new technologies, often based on developments in mass spectrometry, that allow the measurement of thousands if not hundreds of thousands of molecules in the human body (metabolomics, proteomics, transcriptomics, epigenetics, etc.)[3]. To give an example, many researches have suggested that industrial-derived ultra-processed foods (UPFs) increase the risk of obesity, cancer, and cardiovascular disease in adults, while evidence was insufficient for childhood obesity. An exposomics approach identified intermediate molecular events (mainly metabolomics-based) that linked children’s consumption of UPFs to increased obesity [4]. This type of research supports the plausibility of causal links beyond simple statistical associations.

The contribution of new analytical technologies is indeed revolutionizing epidemiology, as also evidenced by the explosion of research on epigenetics. Epigenetics refers to the influence of environmental exposures on gene expression [3]. One of the major recent successes of epigenetics has been to demonstrate that there is an acceleration of biological age, which can deviate from chronological age due to the effect of external exposures; a person exposed to risk factors, including environmental ones, can in fact have a biological (epigenetic) age several years older than the chronological age[5].

Today, the challenges posed by the environment are even greater because they originate from planetary changes whose effects are as yet little explored, ranging from mortality due to heat waves (62,000 more deaths in 2022 in Europe), to the spread of infectious diseases due to climate change, to changes in gut microflora due to loss of biodiversity. Identifying these health effects requires a much more complex interplay between disciplines [6]. Knowledge about heat wave deaths would not exist if there were no regular and widespread measurement of temperatures and continuous and accurate recording of causes of death. But identifying the spread of infectious diseases such as malaria, dengue, chikungunya and others also requires sophisticated monitoring systems and investigations into the interactions between animal species, their migrations, the effects of temperature and biodiversity loss on vectors, etc.

What should be clear to everyone (e.g., those who deny the value and importance of science) is that what we can do to avoid the negative impact of environmental changes on our health depends entirely on conducting robust, independent scientific investigations. These investigations can only be on large populations: observation of individuals or sporadic events, in fact, is generally of no scientific or practical value.

The “great acceleration” of environmental transformations, which are increasingly rapid and increasingly severe, presents us with enormous challenges: scientific research must proceed at a pace at least as rapid as that of environmental change, and equally rapid must be the development of new solutions, both technological and social. It is precisely the social component-that is, the ability to disseminate knowledge, gain consensus, reduce inequalities, and make shared decisions-that has probably been left behind if not neglected. A major driver of change in Europe, which also includes the social component, is the Green Deal whose historical importance cannot be underestimated [7].

1. Persson L. et al. Outside the Safe Operating Space of the Planetary Boundary for Novel Entities. Environ. Sci. Technol. 2022, 56, 3, 1510–1521

2. IARC Preamble:

3. Vineis P, Robinson O, Chadeau-Hyam M, Dehghan A, Mudway I, Dagnino S. What is new in the exposome? Environ Int. 2020 Oct;143:105887. 

4. Vineis et al. The contribution to policies of an exposome-based approach to childhood obesity. Exposome, Volume 3, Issue 1, 2023

3. Vineis P, Robinson O, Chadeau-Hyam M, Dehghan A, Mudway I, Dagnino S. What is new in the exposome? Environ Int. 2020 Oct;143:105887. 

5. Robinson O, Chadeau Hyam M, Karaman I, Climaco Pinto R, Ala-Korpela M, Handakas E, Fiorito G, Gao H, Heard A, Jarvelin MR, Lewis M, Pazoki R, Polidoro S, Tzoulaki I, Wielscher M, Elliott P, Vineis P. Determinants of acceleratedmetabolomic and epigenetic aging in a UK cohort. Aging Cell. 2020 Jun;19(6):e13149.

6. De Donato F et al. The importance of public health in defining climate change policies. Epidemiol Prev. 2023 May-Jun;47(3):3-4.

7. Marieni A, Vineis P: Il Green Deal. Volume “Europa”, Enciclopedia Treccani, 2023 (in stampa)