Exposome workshop uncovers the devil in the details
By Eddy Ball
For many environmental health scientists, it is self-evident that the totality of internal and external exposures, the exposome, is more significant than any single exposure in the overall health of an organism. But, as the NIEHS Exposome Workshop Jan. 14-15 made abundantly clear, the process of putting the emerging exposome approach to work in scientific research is hardly straightforward.
The 2 days of breakout workgroups and animated discussions highlighted the philosophical, practical, technical, and financial challenges that lie ahead. David Balshaw, Ph.D., chief of the NIEHS Exposure, Response, and Technology Branch, emphasized that holistic approaches to exposure biology require global involvement.
“Although NIEHS has a significant role in implementing the exposome,” Balshaw told attendees, “it’s going to have to be an international EHS [environmental health science] community program.”
NIEHS and National Toxicology Program (NTP) Director Linda Birnbaum, Ph.D., pointed to the importance of crafting creative solutions, adopting new approaches in training, and reaching across the social, financial, and intellectual spectra. “We need partners,” she said. “I think one of the important things about the exposome is that it requires integrated methods.”
One chemical – one set of outcomes no longer suffices
In planning their meeting, Balshaw and his colleagues across NIEHS underscored the role of work in the term workshop. Participants spent 5 months preparing for the workshop, hashing out the troublesome details behind the self-evident truth of the exposome. They discussed promotion strategies, including the development of exposome case studies, or use cases, as proof of principle. They also worked toward papers to submit to peer-reviewed journals.
A number of developments in 21st century environmental health science parallel themes and goals in the NIEHS 2012-2017 strategic plan. Attendees engaged in virtual workgroups before meeting face-to-face at NIEHS to frame the following developments within the exposome concept:
Appreciating variation in host susceptibility and response — Individuals experience a complex mixture of chemical, natural, and social exposures. A range of external and internal factors shapes how an organism responds as it struggles to maintain metabolic balance, or homeostasis.
Gary Miller, Ph.D., of Emory University and chair of the Biological Response Workgroup, introduced the concept of allostatic load as a way to discuss this variation. The term refers to the cumulative cost of correcting perturbations to homeostasis, and a way to frame resilience against further stress.
Understanding critical windows of development — In a dynamic matrix, time is a key determinant in host response to internal and external exposures. Exposures vary in effect depending on when they occur during the lifetime. Exposures may also trigger changes in gene expression linked to the onset of disease later in an individual’s life.
“We have to have life course information,” said Epidemiology Workgroup member Roel Vermeulen, Ph.D., of Utrecht University, Utrecht, The Netherlands.
Making fundamental changes in scientific method and promoting interdisciplinary approaches — “The exposome is really about changing the way we do science, moving from a reductionist approach to an integrated complex exposure approach,” argued the chair of a breakout group on refining recommendations, Dean Jones, Ph.D., of Emory University.
Several researchers argued for the need to directly challenge disciplinary silos and reengineer training — and retraining — for the scientific workforce across the physical, medical, chemical, biological, and social sciences.
Exploiting big data to survey the exposome — Immediate goals include data mining and integration of existing epidemiological cohorts. Data Workgroup chair Chirag Patel, Ph.D., of Harvard University, floated the idea of establishing databases of databases and pursuing partnerships with private-sector information companies.
Exposome theorist Martyn Smith, Ph.D., of the University of California, Berkeley, proposed a global database of exposure, GHANES, modeled on the U.S. National Health and Nutrition Examination Survey (NHANES). Smith was a member of the response work group and chaired a breakout group on use cases.
These represent only a few of the many ideas attendees discussed during the workshop, but they are important components of what may one day become a cohesive theory of exposure biology.