Environmental Factor, March 2006, National Institute of Environmental Health Sciences
NIEHS, NHGRI Take Lead in New Genes-Environment Initiative
By Colleen Chandler
At a press conference on Feb. 8, NIH Director Elias Zerhouni, along with NIEHS Director David Schwartz and NHGRI Director Francis Collins, unveiled two new initiatives that will take advantage of recent technological advances to move healthcare research to the next level.
The President's fiscal year 2007 budget calls for $40 million a year for the multi-year Genes and Environment Initiative, which will combine genetic analysis with the development of new environmental monitoring technology to accelerate research on common diseases like asthma, arthritis and Alzheimer's disease.
Collins and Schwartz will serve as co-chairs for the GEI coordinating committee.
The FY 2007 budget represents a $40 million increase above the $28 million already planned for these efforts in the NIH budget. Of the first year's funding, $26 million will go to genetic analysis and $14 million for the development of new tools to measure environmental exposures that affect health. As a result, GEI will have two main components: a laboratory procedure for efficiently analyzing genetic variation in groups of patients with specific illnesses, and a technology-development program to devise new ways of monitoring personal environmental exposures that interact with genetic variations and result in human diseases.
The other initiative, the Genetic Association Information Network, is a partnership between private industry and government researchers to determine genetic contributions to seven common diseases, and includes pledges of $25 million from Pfizer and Affymetrix. This initiative includes plans to raise more money from private industry and non-profit organizations to fund research on additional diseases. The GAIN initiative, Zerhouni said, complies with one of the objectives of the NIH Roadmap for Biomedical Research: accelerating public-private partnerships.
"We have not yet found the very fundamental molecular events that start the disease process," Zerhouni said at the Feb. 8 press conference. "The paradigm has always been to wait for somebody to be struck by a disease, and then we intervene to bring that patient back from illness to health. The vision has always been to reverse that process, to understand enough of the fundamental determinants of disease, understand their regulation, understand their interaction with the environment, and hopefully, to usher in a new era in medicine."
Schwartz said the two initiatives will work together with a joint objective of identifying the genetically determined differential responses to environmental exposures that underlie the pathogenesis of complex diseases.
The GEI and GAIN initiatives will impact both the scientific community and the public health community, Zerhouni said. With 75 percent of the nation's health care costs associated with common chronic, long-term diseases, he said, the initiatives provide the nation's greatest hope to control these skyrocketing healthcare costs.
Both the GEI and the GAIN initiatives focus on genetic analysis of single nucleotide polymorphisms, or SNPs, that normally occur within the 3 billion DNA base pairs that make up a person's genome. While most of the genetic variations are biologically meaningless, one-tenth of 1 percent of these SNPs alter the function of a gene, and the combination of many slightly altered genes may significantly increase the risk of developing a specific disease, according to an HHS press release.
Data gained from the new initiatives will be freely available for the scientific community in both public and private sectors. The National Center for Biotechnology Information, a part of the National Library of Medicine at NIH, will maintain databases to manage the vast amount of data generated by these initiatives.
In 2003, the human genome was decoded, and in 2005 the National HapMap Project was completed, decoding the genome of all humans, enabling a better understanding of genetic variations across the population. Comparing genetic maps of patients with specific diseases with genetic maps of people without those diseases will enable researchers to find the genetic differences by matching SNPs across the genetic 'map.' As a result of these breakthroughs, there has been an exponential improvement in the ability to identify genetic variations that may be linked to disease, and a corresponding exponential drop in cost. However, researchers need to be able to measure exposure at an individual level, and that will require new tools.
The GEI initiative will provide $14 million per year for five years to develop high-tech tools to measure environmental exposure and the biological responses to these exposures. These new tools could include small, wearable sensors. Schwartz said researchers need tools to measure individual exposure to environmental agents, a precise measure of individual biological response in order to better understand the relationship between environmental exposures and human health.
"We need better tools to evaluate environmental exposures, dietary intake and activity levels, and then to determine how those risk factors interact with specific genotypes to either maintain health or lead to disease. Without these more precise measures of exposure, it will be very difficult to figure out why certain people develop disease and others do not. We also need to find out why a disease has such a different prognosis from one person to the next," said Schwartz.
HHS and NIH officials agreed that the time is right for these initiatives to build on recent biomedical research accomplishments. The NIH strategy, as described by Zerhouni, is to use the existing NIH institute cohorts of patients well characterized for specific diseases to determine if this approach will lead to prototype discoveries related to specific diseases. The confidentiality and privacy of the subjects, of course, will be protected, he said.
Meanwhile, NIEHS will hold a planning workshop in mid-May to discuss what technologies can be developed to measure common exposures, such as organic solvents, pesticides and metals associated with neurodegenerative diseases and metabolic disorders, and phthalates, which are known endocrine disrupters that may affect reproductive health.