Environmental Factor – March 2021: Paradigm shift needed in environmental health


The Human Genome Project sparked a paradigm shift in genetics that I believe holds important insights for environmental health scientists. February marked the 20th anniversary of the first draft sequence and analysis of our genetic blueprint, and much has changed in the intervening years.

Instead of analyzing just one gene at a time, many scientists now study an individual’s complete set of DNA. Their work helps to show how we respond to environmental exposures, promising to reveal the molecular changes involved in toxicity. Meanwhile, knowledge has expanded in complementary fields such as metabolomics, proteomics, and transcriptomics. Those fields involve large-scale analyses of metabolites, proteins, and RNA, respectively.

Similarly, many environmental health scientists now realize the benefits of moving beyond studying only one agent in isolation. These researchers embrace an approach for analyzing the multitude of exposures people experience during their lives, which is called the exposome.

Rick Woychik, Ph.D., NIEHS Director's Corner Both innovation and collaboration, which I stressed in my first Director’s Corner column, are critical to expanding exposome research. (Photo courtesy of NIEHS)

That concept is the focus of my recent conversation with Gary Miller, Ph.D., from Columbia University. He has written two groundbreaking books on the exposome, in addition to studying how different chemicals can influence neurodegeneration. I spoke with Miller, an NIEHS grant recipient, about these and other topics, including his career inspiration (see first sidebar).

The sum of our exposures

Rick Woychik: What exactly is the exposome, and why should scientists and the public care about it?

Gary Miller, Ph.D. Before joining Columbia University, Miller served as founding director of the NIEHS-funded HERCULES Exposome Research Center at Emory University. (Photo courtesy of Gary Miller)

Gary Miller: Learning as much as we can about the external factors that affect human health is at the heart of exposome research. This involves analyzing more than just chemicals. Outside stressors of any sort, whether related to socioeconomic issues, mental health, or lack of green space, for example, are also part of the equation.

The key thing to remember is that if these external forces are going to affect our health, they have to be converted into biochemical signals. In other words, there must be corresponding biological changes, such as epigenetic alterations, which are chemical modifications to DNA that affect gene expression but not the underlying genetic code. So, studying the exposome is about both capturing as many exposures as possible and figuring out how the body responds to them.

Such research is more complicated than analyzing the genome, which is far more static. The exposome changes day to day, month to month, throughout a person’s life. Whatever your body is doing right now is a reflection of this summation of exposures that have occurred, built upon your genome. The idea is to collect as much of that information as we can.

Ultimately, the goal is to design more comprehensive experiments that merge datasets from genomic, exposomic, and proteomic studies, for example. That way, we can build a fuller understanding of how external and internal environmental factors may affect us. In my view, the exposome is not a trendy buzzword but rather an essential aspect of biological sciences.

Paradigm shift

RW: Last year, you published “The Exposome: A New Paradigm for the Environment and Health,” which is an update to your 2013 primer on this concept. You refer to a term coined by the philosopher Thomas Kuhn and suggest that a paradigm shift is needed in the biomedical and environmental health science communities. What would such a shift look like?

GM: Perhaps I can start by explaining how the shift happened in my own thinking. Early in my career, when I studied environmental contributors to Parkinson’s disease, I…

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