“…the missing everything else.”

DNA may be extraordinary, but it is not destiny. The blueprints used to design a building can lead to the construction of the building, but its ultimate utility is dependent upon the tenants, the commerce, and multiple other factors. These externalities play a greater role in determining the ultimate outcome of the edifice than the blueprints outlined during the design phase. Human life is similar. Our genomes provide the blueprints, but it is our environment writ large that determines what we become. Living conditions, diet quality, pollution, workplace stress, relationships, socioeconomic status, exposure to infectious agents, climatic conditions, and other factors play a greater role in the final outcome of most complex diseases. Yet, we tend to operate under a genome-centric model to study human disease.

Since its introduction in 2005 by Dr. Christopher Wild to provide a complement to the human genome (Wild, 2005), the exposome has evolved to represent the systematic and comprehensive analysis of the non-genetic factors influencing our health, which is essential if we want to understand the basis of complex disease (Vermeulen et al., 2020).

In most developed countries we focus on the treatment of disease after it has been diagnosed. We also look for genetic causes or risk factors and design drugs or therapies to target the genetic pathways. We don’t spend sufficient effort or resources on the environmental contributors to Alzheimer’s disease, mental health, autoimmune disorders, or cancer. We do not focus on identifying the preventable root causes of disease. It is the non-genetic factors that provide the greatest opportunity for prevention and intervention to keep people healthy. These non-genetic factors represent the essence of the exposome.

You can read Chapter 1 The exposome: purpose, definitions, and scope from the new edition of The Exposome for limited time on ScienceDirect.

Fortunately, exposome-based approaches are catching on and dozens of universities in North America, Europe and Asia have begun exposome research centers, institutes, or projects. The European Commission recently awarded over 100,000,000 euros for the European Human Exposome Network, a collection of 11 different projects that examine the complex environmental exposures involved in a host of diseases, from immune-mediated disorders to cardiovascular disease (www.humanexposome.eu/). This book discusses how the exposome can be integrated into existing research programs that examine the development, progression, and treatment of nearly all human diseases. For example, there is compelling evidence that the severity of COVID-19 is worse in ethnic minorities and studies clearly indicate that these disparities are not due to genetic factors. The answer is obvious—the exposome. Air pollution, poor nutrition, or low socioeconomic status result in a change in biology and contribute to the development and exacerbation of disease.

At the Launch of the European Commission Human Exposome Network program in Brussels, Belgium I had the distinct honor of speaking after Dr. Wild and emphasized the importance of global collaboration for exposome research. I also stated that geneticists look for missing heritability, while exposome researchers look for the “missing everything else.” Dr. Wild sent out a tweet endorsing the challenge to the field to identify the “missing everything else.” With the current genome-centric scientific worldview, we need the exposome more than ever. Hopefully, this book helps promote this critical topic to the current and future generations.

The Exposome: A New Paradigm for the Environment and Health, is available now on ScienceDirect. Want your own copy? Order via the Elsevier store and enter code STC320 at the checkout to save up to 30%

About the author

Gary W. Miller, PhD is the Vice Dean for Research Strategy and Innovation and Professor of Environmental Health Sciences at the Columbia University Mailman School of Public Health. He was founding director of the HERCULES Exposome Research Center at Emory University, the first exposome-based center in the U.S. In addition to his work on the exposome, his research interests include the role of environmental factors in neurodegenerative disorders, such as Parkinson’s disease and Alzheimer’s disease, and the regulation of dopamine signaling in the brain. He served as Editor-in-Chief of Toxicological Sciences, the official journal of the Society of Toxicology, from 2013-2019.
To learn more about the Human Exposome Project, follow @exposome on Twitter or visit the website.