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not necessarily respond to it. Although there is considerable improvement in safety
and effi cacy of a limited number of drugs available now in combination with diag-
nostics, investigation of environmental factors must continue to identify other fac-
tors, which will vary from one patient to another and would still come under the
scope of personalized medicine.
A Committee on Environmental Exposure Technology Development of the NIH
has identifi ed a “toolbox” of methods such as biosensors and toxicogenomics for
measuring external (environmental) and internal (biologic) exposure to assess
human behaviors that infl uence the likelihood of exposure to environmental agents
at a personal level (Weis et al. 2005 ). The aim is to understand complex human
diseases using an integrated approach to exposure assessment to defi ne particular
exposure-disease relationships and the interaction of genetic and environmental fac-
tors in disease occurrence. Improved methods for exposure assessment will result in
better means of monitoring and personalized intervention and prevention
programs.
Most of the focus of research on causes of human diseases has been on genome-
wide association studies (GWAS). In 2014, NIH is funding research at Center for
Biomedical Informatics of Harvard Medical School for examining data from
environment- wide association studies (EWAS) and GWAS to fi nd out if and how
environmental and genetic factors act together to increase disease risk. Bioinformatics
methods will be applied to epidemiological data to identify interacting environmen-
tal exposures and genetic variants in cardiovascular risk traits, such as high blood
pressure, and then to design an epidemiological study to test the clinical utility of
using these tools to predict risk for coronary heart disease.
Human Intestinal Microfl ora
The human intestinal microfl ora is composed of 10^13 to 10^14 microorganisms whose
collective genome (microbiome) contains at least 100 times as many genes as the
human genome. A study has analyzed approximately 78 million base pairs of unique
DNA sequence and 2062 PCR-amplifi ed 16S ribosomal DNA sequences obtained
from the fecal DNAs of two healthy adults, one male and one female, who had not
received any antibiotic in the past (Gill et al. 2006 ). Using metabolic function analy-
ses of identifi ed genes, the human genome was compared with the average content
of previously sequenced microbial genomes. The gut microbiome has signifi cantly
enriched metabolism of glycans, amino acids, and xenobiotics; methanogenesis;
and 2-methyl-d-erythritol 4-phosphate pathway-mediated biosynthesis of vitamins
and isoprenoids. This study concludes that humans are super organisms whose
metabolism represents an amalgamation of microbial and human attributes. Without
understanding the interactions between human and microbial genomes, it is impos-
sible to obtain a complete picture of human biology. The next frontier in the fi eld of
genetic research called metagenomics. This has implications for clinical diagnosis
and treatment of many human diseases. With the knowledge gained in this area, one
8 Non-genomic Factors in the Development of Personalized Medicine