The Nature of Nurture: Refining the Definition of the Exposome

Historical debates concerning human biology and behavior have frequently focused on contributions of nature, ie, the inherited characteristics with which we are born, and nurture, ie, life’s influences after birth. Indeed, the concept of nature vs nurture has guided our understanding of human biology for decades, if not centuries. A series of discoveries has greatly advanced the knowledge of our nature. Watson and Crick’s unraveling of the double helix revolutionized the understanding of our genetic makeup (Watson and Crick, 1953). The polymerase chain reaction allowed amplification and manipulation of genes (Saiki et al., 1988). Identified links between specific genes and disease (Saiki et al., 1985) led to new diagnostic tools and treatments. These advances spurred the Human Genome Project with success in sequencing the entire human genome (Lander et al., 2001; Venter et al., 2001). This epic undertaking of biomedical science and technology was completed with amazing speed and celebrated with great fanfare. But the limitation of genetics to predict disease rapidly became obvious; as noted by Dr Venter shortly after the completion of human genome sequence, “We simply do not have enough genes for this idea of biological determinism to be right (McKie 2001).” Genome-wide association studies (GWAS) have revealed genetic associations and networks that improve understanding of disease, but these still account for only a fraction of disease risk. With the majority of disease causation being nongenetic, the need for improved tools to quantify environmental contributions seems obvious. The simple distinction between genes and environment is blurred by knowledge that environmental exposures cause permanent genetic changes via mutagenesis and also have long-term impact on gene expression through epigenetic mechanisms. Importantly, epigenetic mechanisms are central to differentiation and development, impacting genome function before birth and throughout life. The epigenome is highly reliant on nurture, ie, the nature and timing of environmental exposures and external forces. Randy Jirtle, a pioneer in epigenomics stated “The nature vs. nurture argument is rapidly proving to be irrelevant, because we’re finding that the 2 forces interact in highly specific ways that alter gene behavior (Duke Health, 2006).” Although Dr Jirtle suggests the argument is becoming irrelevant, the reality is that biomedical research is overwhelmingly focused on the gene side of this debate. The tools and knowledge of our nature are far ahead of those for the environment. If we want to focus on the interaction between nature and nurture, we need better ways of cataloguing and integrating the complex exposures and forces that represent nurture. Such a framework is provided by the exposome.