Introducing the Pitch Day Finalists: The Human Genome + the Human Exposome = Your Health

Oct 7, 2013, 8:00 AM, Posted by Pioneer Blog Team

What if we could map the environmental exposures that affected someone’s health, starting from the moment of conception? And what if we could use that information to radically transform our ability to prevent disease? That’s the highly simplified version of the idea that a team helmed by Elise Miller. She was invited to present her idea live and in person at the first-ever Pioneer Pitch Day, along with seven other finalists. Read Miller’s 1,000-character proposal below, and join the discussion on Twitter at #pioneerpitch.

Elise Miller is the director of the Collaborative on Health and the Environment, which you can connect with on Twitter at @che_for_science and on Facebook. The other members of her pitch team include Frederica Perera, PhD, and Maida Galvez, MD, MPH.

Pioneer: Congratulations on being a Pitch Day finalist! What made you decide to submit your idea to Pioneer Pitch Day?

Elise Miller: I have become increasingly concerned that while a considerable investment has been made in mapping the genome (a truly extraordinary and highly valuable achievement), a similar investment has not been made in deepening our understanding of how an array of environmental factors (the “exposome”) can influence gene expression. The way genes are expressed, in turn, is critical for determining human susceptibility to disease and disability. By not prioritizing research on these other factors and their interactions with the genome, we are undermining our capacity as a society to address many of the major health concerns of our time. For these reasons, I decided to make a “pitch” to bring greater attention to the exposome in an effort to leverage the development of even more effective prevention strategies and upstream interventions, particularly for our most vulnerable populations.

Pioneer: Tell us about the origins of your idea.

Miller: …I’ll share three significant catalysts. First, whenever we go into a doctor’s office and fill out a personal information questionnaire, we are asked about various family members having heart disease, cancer, or some other illness that might be inherited. This is of course useful for health professionals trying to assess potential health risks. However, these questions miss an entire set of important data that likely has equal if not more bearing on one’s susceptibility to disease. What are rarely, if ever, asked…are questions that might solicit information about a patient’s exposome. Examples might include: What kinds of meals do you regularly eat—home cooked, or from fast food outlets? Do you work with pesticides or solvents in your occupation? Do you have a long daily commute in heavy traffic? Is your home next to an industrial park or diesel bus station? Does your office building have ventilation or mold problems? …Are you afraid to go out on the streets because of gang violence? Do you live with an alcoholic or drug addict? …These may not be the right questions, nor do they get at the kinds of exposures (in the broadest sense of that term) that may have occurred over time. That said, the narrow focus of most current medical questionnaires has left me wondering what other information my health practitioners should know if they were to more accurately assess health risks and provide more useful preventative counsel—not to mention, how valuable this kind of data would be for obstetricians working with women to improve pregnancy outcomes.

In addition, reading about the ACE (Adverse Childhood Experiences) study and the correlations that seminal research has made to the risk of various chronic diseases later in life, I became curious as to how social determinants of health might interact with a plethora of other exposures and stressors that can influence health, such as nutrition, toxic chemicals, the built environment, infectious disease, and so forth. In addition, I reviewed studies showing how psychosocial and nutritional factors coupled with a chemical exposure (such as to lead) had a far greater impact on a child’s health than any one factor individually… It occurred to me there was a real opportunity to overlay the social determinants of health with other exposures to get a more complete picture of a child’s health risks. (Editor’s Note: You can learn about RWJF’s work with ACEs here.)

Finally, like many, I eagerly followed the unfolding story about mapping the human genome and how that information could be used to help people understand their health risks and options to act in ways that might reduce those risks. Then I read Dr. Christopher Wild’s publication in 2005 in which he coined the term “exposome.” He argued that environmental exposures (including nutrition, chemicals, stress, etc.) from conception throughout life are as important to understand in terms of human health as the genome. Though this general idea had been posited by systems biologists, environmental justice advocates, and others in different ways for years, it seemed to me that the exposome provided a conceptual lens to understand how social determinants of health and other exposures need to be layered on top of the information the human genome provides if we’re going to effectively improve individual and public health.

Since my professional work has focused on preventing exposures that might lead to chronic disease and disability, and more recently on the interplay and influence of multiple environmental factors, it became clear to me that we need to devise research methods to understand how these other contributors to health (or illness) interact with the genome through epigenetic influences that determine how genes actually express themselves—and then figure out how health professionals can use this information in clinical settings. In short, this is an essential next step in science and medicine if we are going to have access to and the capacity to assess this additional information in order to make healthier choices in this new age of personalized medicine. (Editor’s note: With support from RWJF’s Pioneer Portfolio, Kaiser Permanente built one of the largest genetic databases in the world, called BioBank.)

Pioneer: What do you believe is the most innovative aspect of your idea?

Miller: Perhaps the most innovative aspect is the call to layer our emerging understanding of the exposome squarely on top of the human genome in order to accurately assess risk factors and promote upstream interventions for a healthier society.

Pioneer: Who is an innovative thinker who has inspired your own work – why and how?

Miller: Though I could point to a number of people, here I will mention Denis Noble, Emeritus Professor of Cardiovascular Physiology at the University of Oxford. His book, The Music of Life: Biology Beyond Genes, published in 2006, offers a provocative set of metaphors for understanding the dynamic interplay between genes and the rest of life. For example, he writes that the genome is like the “CD of life,” noting that the CD itself doesn’t serve any function (in terms of emanating music) unless it is read by a mechanism that knows how to read it. In addition, there needs to be a listener who interprets the reading of that sound. And every listener has a unique experience of the sounds being read for a variety of reasons—the frequency with which the listener has heard that particular music, long-term training in certain styles of music, what is going on for the listener emotionally or externally when the music is being played, etc. (In terms of human biology, those reasons would be various environmental exposures that interact with the genome in different patterns to determine that person’s health experience at a certain time and place as well as over a lifespan). The CD metaphor of course has its limits, as Noble makes clear, but his use of other everyday metaphors throughout this gem of a book demonstrates how a reductionist causal chain in which the genome is a kind of database that catalyzes a linear biological response misses much of what makes life, in fact, life.

Proposal Submission: The Human Genome + the Human Exposome = Your Health

In the push towards personalized medicine, the human genome should only be considered part of the equation. Epigenetic markers, influenced by a range of environmental factors, are also crucial to understanding a person’s susceptibility to disease. Recently there’s been a call to map the human exposome – i.e., all environmental exposures starting from conception, including nutritional, chemical, psychosocial, etc. With this information, health professionals will be better able to reduce risk and prioritize prevention. Widespread use of electronic health records provides an opportunity to develop standardized questions about people’s exposures. Since early life development influences health across the lifespan, obstetric records are a good place to start. Not only would this enhance health professionals’ ability to make recommendations early on, it would provide a database for studying correlations between exposures and diseases that appear later in life – and in turn, radically increase options for improving individual and public health.

Got a pioneering idea of your own? We’d love to hear from you.

This commentary originally appeared on the RWJF Pioneering Ideas blog.