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From the moment of conception onward, genes control our development and health. But they don’t do it alone. The exposome — all the internal and external chemical exposures we experience during the course our lives — influences, for better or worse, the genes and proteins they code for. A better understanding of the exposome, a concept still in its infancy, will help identify how nongenetic factors influence biological reactions and possibly the development of chronic diseases.

There’s a canonical equation in genetics: P = G + E. In English, it means that an individual’s Phenotype (observable health and physical traits) is the sum of his or her Genetics and Environment.

I think the E should stand for exposome, a term coined in 2005 by Christopher Wild, now the director of the International Agency for Research on Cancer. It encompasses the food we eat and the drugs we take; pollutants in water and air; ionizing radiation from sunlight and other sources; the biosynthetic activity of the bacteria living in and on us; even noise pollution.


Noise pollution? Indeed! The human body is a chemical manufacturing machine. Everything we hear, see, smell, touch, or taste is communicated to the brain in the form of chemicals. In addition, loud or sustained noise can increase stress, which in turn increases blood levels of known stress-related chemicals such as cortisol. Prolonged exposure to cortisol and other stress hormones can be harmful to human health.

Yet little is known about how these exposures affect humans or potentially influence the onset of cardiovascular disease, diabetes, asthma, Alzheimer’s, many cancers, and other chronic diseases.


The human genome and disease research

I believe that the greatest scientific achievement in the past 30 years has been sequencing the human genome. Since then, the primary focus of disease research has been identifying statistical associations between single nucleotide polymorphisms — the most common type of genetic variation — and disease in very large studies commonly referred to as genome-wide association studies.

Although these studies have shed great light on many factors that cause disease, it is becoming increasingly evident that genetic factors alone may not be the main cause of disease. Overall, genetics accounts for less than 20 percent of disease, ranging from about 3 percent for leukemia to nearly 50 percent for asthma. The genetic heritability of disease at the population level averages around 50 percent.

If many chronic diseases do not have a purely genetic origin, something we have known for decades, it doesn’t make sense to me that we have invested so much time and money in genome-wide association studies without a concomitant investment in exposome-wide association studies.

That’s changing. Governments around the world have recognized this disparity and begun funding large-scale exposome research.

Measuring the exposome to better understand chronic disease

Over the past five decades, the focus of these studies has been on identifying and measuring pollutants in the air, water, and soil, and then inferring how they may affect human health (as well as the surrounding flora and fauna). This approach has led to public policies that have mitigated and remediated sources of pollution and vastly improved public and environmental health.

Imagine if bio-analytical monitoring had been simultaneously performed during these decades on people living where the air, water, and soil were routinely evaluated. Would our understanding of disease mechanisms and what causes disease be much improved? Would our primary focus still be on genetics, or would we be taking a more holistic approach that considered the environment and exposures as factors interacting with and influencing the genome?

Measuring the plethora of exposures that individuals experience over time and understanding how they influence disease is an extremely complex undertaking. Measurement can’t be a one-time event, because these exposures are in a constant state of flux, acutely and chronically influencing human health and biological processes continuously throughout our lives. One way to evaluate the exposome paradigm would be to collect biological samples from a large number of individuals at birth, at one year of age, five years, 12 years, 21 years, and then once every 10 years over the lifetime.

With such a vast repository of samples, researchers could then potentially link biomarkers and chemical predictors with various diseases. This information could eventually be translated to the clinic and used for both preventive and personalized medicine to improve the health and welfare of future generations.

Transformative research occurs perhaps only once in a generation. The last such occurrence was with the advent of the Human Genome Project. The exposome represents the next transformative area of research, and could completely change our understanding of disease mechanisms, and shift the health paradigm more towards preventative and personalized medicine.

In early November 2018, the Icahn School of Medicine at Mount Sinai Institute for Exposomic Research, in partnership with Agilent Technologies, the company for which I work, and others, will hold the New York City Exposome Symposium. This symposium will explore the nascent field of exposomics, from methodologies to use in studying it to the challenges this work poses.

At that meeting, I plan to establish a group of exposome researchers from academia, industry, and government to formulate a unified request to the U.S. and other governments for increased exposome research funding and to impress a new perspective on the underlying causes of disease that incorporates the genome and the exposome. I hope that this call to action will stimulate new and necessary discussions about how to properly integrate nature and nurture, and for this viewpoint to be taken into consideration as the beginning of a journey towards new and successful health care policies for all.

Anthony Macherone, Ph.D., is a senior scientist at Agilent Technologies; a visiting professor of biological chemistry at Johns Hopkins University School of Medicine; and co-editor, with Sonia Dagnino, of “Unravelling the Exposome: A Practical View” (Springer International Publishing AG, 2018).

  • I wish you success in your endeavor for I truly believe it could produce much-needed information that could profoundly change the way healthcare is viewed and how disease is treated. I am pessimistic, however, that you will be able to secure government funding since any recommendations resulting from your work would likely entail greater regulation of industries that essentially determine funding decisions.

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