The exposome and health: Where chemistry meets biology

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Science  24 Jan 2020:
Vol. 367, Issue 6476, pp. 392-396
DOI: 10.1126/science.aay3164

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  • RE: Measuring the Exposome: The social and epidemiological survey complements the challenges and interpretation
    • Fengyu Zhang, Director and Investigator, Global Clinical and Translational Research Institute
    • Other Contributors:
      • Donald R Mattison, Vice President, Risk Sciences International

    The concept of exposome has received increasing interests and discussions in recent years including the National Academy of Sciences workshop and meeting on exposome (1-3). In the recent Special Issue-Chemistry for Tomorrow's Earth, investigators (4) discussed the feasibility of using high-resolution mass spectrometry (HRMS) to identify and measure the chemicals and metabolites (or small molecules) in the body, which include those produced by both exogenous and endogenous exposure to known or unknown chemicals. If implemented with rigorous study design, the high-throughput approaches would advance environmental health and understanding of the underlying mechanisms. Here we provide a comment and additional discussions.
    Further discussions of the exposome may help to turn this concept into practice in research and to maximize the benefits of the new technologies. First, the measurement of the exposome may not be comparable with that of the genome. We have known that a limited number of polymorphisms are in the human genome, which can be measured with microarray or the next-generation sequencing technologies. The common genetic variants can be largely regarded as fixed attributes, i.e., little variation in the genetic variants within an individual over time. In contrast, the measurement of the exposome is highly variable and dynamic, which might limit the progress of advancing this type of approach if used a...

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    Competing Interests: None declared.
  • RE: The exposome and health: Where chemistry meets biology
    • Ronald Neil Kostoff, Biomedical Researcher, Research Affiliate, School of Public Policy, Georgia Institute of Technology

    Letter to the Editor,

    Nongenetic factors have been shown to play an increasingly dominant role in their contribution to disease. A recent article in Science [1] proposed a massive increase in efforts to characterize the exposome in order to understand this role better. While such an effort will add to our understanding of myriad contributing factors to disease, there is much we can do now to reduce disease with knowledge already generated, but woefully underutilized.

    A 2015 study [2] examined hundreds of thousands of Medline records, and identified ~8,000 contributing factors (of which ~800 were termed ‘pervasive’) to a broad spectrum of ~4,000 diseases. Later development of protocols to prevent and reverse chronic diseases expanded the numbers of contributing factors to be eliminated [e.g., 3]. A 2018 study [4] showed that (based on sampling) OSHA’s legally enforceable Permissible Exposure Limits are from one-to-four orders of magnitude higher than exposures shown in the biomedical literature to cause damage.

    A two-pronged approach is required to eliminate the incidence and prevalence of chronic diseases: 1) action now, and 2) research now, as a prelude to future action! Action now has two main components: information and regulation. Communicate the information currently available to the public about toxic stimuli to be avoided, where possible. Strengthen the exposure limits on toxic stimuli such that they match exposures shown in the biomedica...

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    Competing Interests: None declared.
  • RE: Anthropology for the Exposome
    • Richard Marcantonio, Graduate Student, Kroc Institute for International Peace Studies and Anthropology Department, University of Notre Dame
    • Other Contributors:
      • Agustin Fuentes, Professor and Departmental Chair, Department of Anthropology, University of Notre Dame

    Vermeulen et al (2020) thrust the exposome framework into full view again in Science.
    First proposed by Wild (2005), the exposome framework highlights the critical interaction between the human genome and environmental exposures. Genetic expressions are strongly mediated by the environmental contexts within which biological materials manifest and operate. What perfuses the environment can thus shape and become biology. Sequentially stated, environmental contexts and possibilities are ex ante, whereas biological uptakes and outcomes are ex post, though in reality these processes are mutually mutable and dynamically interconnected. And many environmental contexts are human-produced.
    Vermeulen et al. note that in the time since Wild proposed the exposome framework an array of research better understands the effects of metabolites within the body. Landrigan et al. (2018), for example, have measured health outcomes resulting from industrial pollutants and other human-produced chemical compounds that were largely untested but have become ubiquitous, generating 9 million deaths annually. The bulk of this research has been conducted in epidemiology, genomics, biology, and other biophysical fields of science.
    Because of the complex of practices humans employ in everyday life, and the day-to-day variations in these practices, close ethnographic study can identify critical exposure vectors that other more materially focused but less granular methods might overlook...

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    Competing Interests: None declared.
  • RE: bodily integrity and a climate system capable of sustaining human life

    Former director of the Centers for Disease Control and Prevention National Center for Environmental Health, Richard J. Jackson, stated "environmental health in the United States is vested in many agencies, not just those titled Environment or Health, but also Transportation, Education, Housing, Energy, Agriculture, and Defense. Each has its critical primary mandate, but each influences essential elements of the requirement to protect health and the environment. The complex challenges of the 21st century cannot be met by a set of stovepipes as disconnected as these" (

    Jackson goes on to offer a solution by way of example: "The Food Quality Protection Act of 1996 required that children's health be the benchmark for decisions on allowable levels of pesticide residues in food, the tenet being that protecting the most exposed and sensitive in the population protects everyone. [By 2006], one-third of pesticide tolerances have been revoked. Recognizing the improvements that a children's health initiative could bring about, President Clinton ordered that all agencies develop strategies to improve the health of children, and mandated twice-yearly cabinet-level meetings to make it happen. After a cautious and questioning start, each agency recognized that it had large impacts on children's well-being, for example, Transporta...

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    Competing Interests: None declared.

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