Mapping the Human Exposome
Our genetic blueprint charts the course for our life, yet we rarely achieve our full genetic potential, because of external forces that continually steer us off course. Many environmental influences are beneficial—good nutrition, education, and socialization—while others, such as malnutrition, pollution, and poverty, contribute to ill-health and the woes of humankind. We can now measure and utilize over a billion features of the genome—the sequence of DNA, epigenetic changes that turn genes on and off, and how genes interact with the biochemical machinery of cells—and that knowledge is enabling powerful new insights and therapeutic approaches. But genetics can explain less than 25 percent of most major disorders. And at present our ability to measure the complex environment in which we live and its impact on our bodies is very limited.
One measure of the potential environmental impact on health is the registry of nearly 80,000 industrial chemicals that is maintained by the Environmental Protection Agency. The interaction of each of these chemicals with living organisms can generate multiple chemical markers, which could be used to assess exposure and potential harm, if we knew what they were. One example that has generated widespread concern is the class of phthalate chemicals used as plasticizers in a wide range of products, from infant lotions and powders to credit card purchase receipts, markers from which are found in virtually every United States resident, and which have been implicated as hormone-like endocrine disrupters that can affect sexuality. Those aren’t the only powerful chemicals in consumer products—think suntan lotions and beauty creams, preservative additives in food products to extend shelf life, pesticide residues on fresh produce. Food itself generates many different metabolic chemicals found in our bodies, both directly and as a result of processing of food by our microbiome—the colony of bacteria that inhabit our gut and our skin and are very much part of who we are. Add in air pollution, workplace hazards, the markers left by allergens and disease agents and immune system reactions to them, the medicines we use—they all leave a biochemical marker. The number of such markers in our bodies is estimated to be as many as 1 million, but what they are and which ones indicate conditions or exposures harmful to health is still for the most part unknown.
As it turns out, there is no reason for knowledge of the environmental mediators of disease and health to lag so far behind that of the genome. When the concept of the exposome—the totality of our exposures from conception onward—was first put forward in 2005, it seemed an impossible challenge: How could we detect and measure a million different chemicals? But just as a single sample of blood contains the core of our genetic data (in the DNA within white blood cells), so that same blood sample contains hundreds of thousands of biochemical markers. And because of advances in high resolution mass spectrometry and high throughput screening, it is now possible to identify, catalog, and understand each marker, each constituent of the exposome, and link it to the process or environmental factor that produced it. Mapping and annotating these biochemical markers, creating reference databases that define the human exposome and to which individual profiles can be compared, using big data techniques to correlate genetic and environmental factors—all of this portends a revolution in how we understand the complex chemistry of life. That knowledge in turn is likely to lead to more specific insights into how environmental factors affect human health and how we might intervene to protect and enhance it. Within a decade, potentially, a truly precision approach to personalized medicine could be possible....MORE
The biochemical markers of the Exposome
The Exposome includes hundreds of thousands of biochemical markers from many different sources, including those shown here.
Currently, only about 20,000 of those have been mapped and categorized.
