Genes, Environment And Disease Converge In Two Major NIH Initiatives

The research initiatives will be sponsored by NIH, the Foundation for NIH, Pfizer and biotech company Affymetrix.

Building on the promise of recent advances in genomic research, NIH launched two major, multi-million dollar initiatives Feb. 8 to find the genetic and environmental roots of common diseases.

According to NIH officials, advocates and industry representatives, the research will lead to the identification of major genetic susceptibility factors for diseases with a substantial public health impact, such as heart disease, cancer, diabetes, stroke, Alzheimer's, schizophrenia, osteoporosis, asthma, cataracts, hypertension, Parkinson's, autism and obesity. The initiatives also will increase investments in the development of innovative technologies to measure environmental toxins, dietary intake and physical activity, and to determine an individual's biological responses to those influences.

The first project, dubbed the Genes and Environment Initiative (GEI), will cost $28 mil. in FY 2006, an amount that would be increased to $40 mil. in FY 2007, according to the President's budget request. The other initiative involves a unique public/private partnership between NIH, the Foundation for NIH, and several prominent drug companies.

"This initiative would not have been possible a year or two ago," said NIH Director Elias Zerhouni at a Feb. 8 briefing in Washington, D.C. The completion of both the Human Genome Project and the International HapMap Project, and the recent development of key tools that have significantly reduced the cost of genotyping, have increased our insight into the environmental factors of health and disease, Zerhouni said. The haplotype map, a tool to help researchers find genes associated with human diseases, was completed in October.

The $40 mil. for the GEI in FY 2007 would be split between two efforts: $26 mil. for genotyping studies and $14 mil. for the development of new tools to measure environmental exposures that affect health.

"All illnesses have some hereditary contribution," National Human Genome Research Institute Director Francis Collins said at the briefing. "It has been said that genetics loads the gun and environment pulls the trigger."

Each genotyping study, which will cost on average $3 mil.-$6 mil., will involve 1,000 to 2,000 patients with a specific disease and a similar number of disease-free subjects to serve as controls. Using new, low-cost technology to analyze single nucleotide polymorphisms, or SNPs, researchers will identify genes that contribute to an increased risk of illness, Collins explained.

With the $14 mil. annual investment in the environmental component of this initiative, NIH will develop measures of dietary intake, personalized measures of physical activity, and biological measures that identify prior exposures to potential toxins. "You can't change genes, but you can change your environment," said Schwartz.

The public/private partnership, called the Genetic Association Information Network (GAIN), involves NIH, the Foundation for NIH, Pfizer and Affymetrix, a biotech company based in Santa Clara, Calif. The collaboration is being launched with a $5 mil. donation from Pfizer to set up a management structure and $15 mil. worth of lab studies to determine the genetic contributions to five common diseases. Affymetrix will contribute lab resources to study two additional common diseases. John Porter, vice chair of the foundation's board of directors, is leading the search for additional industry partners in this initiative.

"Through the financial support of the private sector, NIH will now be able to launch into this exciting initiative immediately," said Porter, who as a former House representative chaired the Appropriations/Labor-HHS Subcommittee that oversaw the NIH budget doubling. "Moreover, the interaction of scientists from the public and the private sector dramatically increase the likelihood that this initiative will get off to a quick and efficient start that will genuinely produce important advances for all patients."

"It is our challenge to bring discoveries forward in a much shorter time frame," said Martin Mackay, senior VP of research and technology at Pfizer. By way of example, Mackay explained how early genetic information has already been translated into valuable medicines for HIV/AIDS, heart disease and the prevention of organ rejection.

The National Center for Biotechnology Information, a part of the National Library of Medicine, will develop databases to manage the vast amounts of genetic, medical and environmental information that will emerge from these projects. All data will be freely available to the public. Mackay confirmed that Pfizer would have no intellectual property interests in this effort.

- Andrew J. Hawkins