|Two NIH Initiatives Launch Intensive Efforts to Determine
Genetic and Environmental Roots of Common Diseases
President’s FY07 Budget Calls for $40 Million a Year Boost for Multi-Year Effort;
Companies to Commit More Than $25 Million to Launch Genetics Project This Summer
The Department of Health and Human Services (HHS) today announced the creation
of two new, closely related initiatives to speed up research on the causes of
common diseases such as asthma, arthritis and Alzheimer’s disease.
One initiative boosts funding at the National Institutes of Health (NIH) for
a multi-institute effort to identify the genetic and environmental underpinnings
of common illnesses. The other initiative launches a public-private partnership
between NIH, the Foundation for the National Institutes of Health (FNIH) and
major pharmaceutical and biotechnology companies, especially Pfizer Global Research & Development
of New London, Conn.; and Affymetrix Inc. of Santa Clara, Calif., to accelerate
genome association studies to find the genetic roots of widespread sicknesses.
The genetic analysis component of the two initiatives is highly complementary.
Genes and Environment Initiative
HHS Secretary Mike Leavitt announced on Monday that the President’s budget proposal
for fiscal year (FY) 2007 includes $68 million for the Genes and Environment
Initiative (GEI), a research effort at NIH to combine a type of genetic analysis
and environmental technology development to understand the causes of common diseases.
The FY 2007 budget represents a $40 million increase above the $28 million already
planned for these efforts in the NIH budget.
If approved by Congress, this additional federal funding will begin in FY 2007
and continue for multiple years. 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.
“The discoveries made through these efforts will ultimately lead to profound
advances in disease prevention and treatment,” Secretary Leavitt said. “These
are the kinds of innovative efforts that we should support. We must seize the
historic opportunity provided by the Human Genome Project and the International
HapMap Project, to speed up the discovery of the genetic causes of common diseases
like diabetes and hypertension. At the same time, it’s critical that we also
understand the environmental contributors to sickness, and the interplay among
genes and environment. There is not a moment to be lost.”
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 proposed federal funding level will enable GEI to perform genetic analysis — or
genotyping — studies for several dozen common diseases. The exact diseases
to be studied will be determined by peer review. An initial survey of existing
NIH-supported clinical studies identified more than 100 with sufficient numbers
of already characterized patients to get this effort started. In addition, NIH
expects to develop four new environmental monitoring devices a year.
“This initiative would not have been possible a year or two ago,” said Elias
A. Zerhouni, M.D., Director of the National Institutes of Health, an agency within
the Department of Health and Human Services. “This is a tangible result of the
nation’s increased investment in medical research over the past 10 years. We
are now poised to combine what we have learned from years of population studies,
with newly available technologies, developed with NIH support. These technologies
reduced the cost of genotyping by more than 100-fold, making such a comprehensive
effort affordable. Equally important, this effort will dramatically increase
our understanding of the environmental factors of health and disease, and help
us develop novel measures of gene-environment interactions. We stand on the threshold
of creating a future that will revolutionize the practice of medicine by allowing
us to predict disease, develop more precise therapies and, ultimately, pre-empt
the development of disease in the first place.”
At the same time, a public-private partnership between NIH, FNIH, which is a
non-profit foundation established by Congress to support the mission of the
NIH; Pfizer and Affymetrix is being created to further accelerate this important
research on the genetic association studies.
The new partnership, called the Genetic Association Information Network (GAIN),
is being launched with a $5 million donation from Pfizer to set up the management
structure and $15 million worth of laboratory studies to determine the genetic
contributions to five common diseases. Affymetrix, a biotech company that develops
the types of tools used in these kinds of genetic studies, will contribute enough
laboratory resources to study two additional common diseases. On average, it
costs about $3 million to carry out one study.
“We’ve translated early information from genetic research into valuable medicines
for HIV/AIDS, heart disease and the prevention of organ rejection,” said Martin
Mackay, Ph.D., Senior Vice President Worldwide Research & Technology, Pfizer
Research & Development. “But these advances have only scratched the surface of
possible revolutionary approaches to treat and cure diseases. Pfizer, the NIH
and other public/private biomedical research interests have complementary missions
greater than the sum of their parts. Our hope is that this public/private initiative
will encourage a deeper collective understanding of the genetic factors of disease
for major new therapeutic advances.”
GAIN will be an FNIH-managed partnership that includes NIH, industry, foundations,
individuals and advocacy groups. Governance will include an executive committee,
a steering committee, as well as peer review and data access committees.
“Our partnership with pharmaceutical and biotech companies to speed up this
research exemplifies the aim Congress had in mind when it established the Foundation
for the National Institutes of Health to support the mission of NIH,” said John
E. Porter, Vice Chairman of the foundation’s Board of Directors. “Through the
financial support of the private sector, NIH will now be able to launch into
this exciting initiative immediately. 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.”
The genetic analysis of both GAIN and GEI will focus on the alternative spellings — called
single nucleotide polymorphisms or SNPs — that normally occur in the order
of the 3 billion DNA base pairs or letters that make up a person’s genome. SNPs
are like single-letter misspellings of a word. Most of these genetic variations
are biologically meaningless. But a small fraction of these SNPs alter the function
of a gene — often only slightly. The combination of many slightly altered
genes may significantly increase the risk of a specific disease, but identifying
such a complex set of genetics changes is challenging. Finding these disease-causing
variants is one of the highest priorities of current biomedical research.
“Virtually all diseases have a hereditary component, transmitted from parent
to child through the three billion DNA letters that make up the human genome,” said
Francis S. Collins, M.D., Ph.D., Director of the National Human Genome Research
Institute at NIH and chairman of the GAIN Steering Committee and co-chairman
of the NIH Coordinating Committee for GEI. “But progress in identifying the genetic
factors that influence health or disease, or even the response to treatment,
is difficult. Both initiatives promise to rapidly identify the myriad genes in
an individual that, taken together, contribute to an increased risk of illness — or
that increase the chances of a healthy life. As the genetic underpinnings of
health and common diseases become clearer, researchers will be empowered to develop
targeted treatments that either prevent illness from occurring or treat it effectively
once it does.”
There are about 10 million common SNPs in the human population. Scanning the
genomes of large numbers of patients for such a large number of variants would
be prohibitively expensive. Fortunately, a major shortcut has been discovered
that reduces the workload about 30-fold. The International HapMap Project, led
by the NIH and completed in October 2005, demonstrated that the 10 million variants
cluster into local neighborhoods, called haplotypes, and that they can be accurately
sampled by as few as 300,000 carefully chosen SNPs. New technological systems
allow these SNPs to be systematically studied in high-throughput facilities that
dramatically lower the cost.
For each study of 1,000 to 2,000 patients with a specific disease and a similar
number of people who do not have the illnesses (controls), an investment of $3
million to $6 million (depending on the number of patients and controls) is needed
for the first stage of genotyping. Follow-up studies to validate the results
with additional patients and controls, data analysis, and patient management
expenses will add to these basic costs. It is important to note, however, that
these costs are a small fraction of what has already been invested in enrolling
these study subjects, examining them, carrying out extensive laboratory investigations,
and collecting their DNA.
The genotyping work itself will be performed by either commercial or government
laboratories. The initial GAIN genotyping supported by Pfizer will be carried
out by Perlegen Sciences, Inc., of Mountain View, Calif., and will start in late
summer 2006; Pfizer is contributing these Perlegen-produced genotypes as an “in
kind” donation to the project. A similar arrangement will be worked out with
Affymetrix. Federally funded genotyping for GEI will be managed by an NIH coordinating
committee under the usual government rules, subject to competition between research
facilities, and begin in FY 2007.
The research will lead directly to the identification of major genetic susceptibility
factors for common diseases of substantial public health impact — disorders
such as heart disease, diabetes, cancer, stroke, Alzheimer’s disease, schizophrenia,
osteoporosis, asthma, cataracts, hypertension, Parkinson’s disease, autism and
obesity. The target diseases and the populations studied have yet to be selected
and will be subject to a peer-review process.
Genes alone do not tell the whole story. Recent increases in chronic diseases
like diabetes, childhood asthma, obesity or autism cannot be due to major shifts
in the human gene pool. They must be due to changes in the environment, including
diet and physical activity, which may produce disease in genetically predisposed
persons. Therefore, GEI will also invest in innovative new technologies to
measure environmental toxins, dietary intake and physical activity, and to
determine an individual’s biological response to those influences, using new
tools of genomics, proteomics and metabolomics.
“Differences in our genetic makeup certainly influence our risks of developing
various illnesses,” said David A. Schwartz, M.D., Director of the National Institute
of Environmental Health Sciences, also part of NIH, and co-chairman of the NIH
Coordinating Committee for GEI. We only have to look at family medical histories
to know that is true. But whether a genetic predisposition actually makes a person
sick depends on the interaction between genes and the environment. 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. Given the recent advances in
biomedical research, this is the right time to take on this challenge.”
To determine how the environment, diet and physical activity contribute to
illness, investments will be made in emerging technologies, such as small, wearable
sensors that can measure environmental agents that have contact with the body
and individual measures of activity. Devices also will be developed that measure
changes in human biology, which can be observed in samples of blood or urine.
In aggregate, these new tests will provide the precision needed to help determine
how these factors influence the genetic risk of developing disease. The goal
is to produce devices for application to eventual population studies, to speed
up data processing, to enhance accuracy and to reduce cost.
With the $14 million annual investment in the environmental component of this
initiative, NIH will develop technologically advanced measures of dietary intake,
precise personalized measures of physical activity, and biological measures that
identify prior exposures to potential toxins such as metals and solvents. NIH
also will assess disease indicators like inflammation and oxidative stress that
are known to be influenced by environmental toxins.
The National Center for Biotechnology Information, a part of the National Library
of Medicine at NIH, will develop databases to manage the vast amount of genetic,
medical and environmental information that will emerge from these initiatives.
To encourage rapid research advances, and in keeping with the principles pioneered
by the Human Genome Project and increasingly common in such pre-competitive public/private
partnerships, all data generated through these initiatives will be placed in
the public domain.
Background information on whole genome association studies can be found at www.genome.gov/17516714.
Background information on environmental impacts on health can be found at www.genome.gov/17516715.
The Foundation for the National Institutes of Health is a nonprofit organization
authorized by Congress to raise private funds and establish public-private partnerships
to support the NIH mission. More information about FNIH can be found at http://www.fnih.org/.
Pfizer Global Research & Development is the world's largest privately owned
biomedical research organization. Pfizer Inc discovers, develops, manufactures
and markets leading prescription medicines, for humans and animals, and many
of the world's best-known consumer brands. More information about Pfizer can
be found at http://www.pfizer.com.
NOTE: The initiatives will be announced at a press conference at 9 a.m.
Wednesday, Feb. 8, 2006, in the Murrow Room of the National Press Club, 529
14th Street NW, Washington, D.C. A webcast of the press conference will be
available two to three hours after its conclusion at http://videocast.nih.gov/ram/nhgri020806.ram.
The National Institutes of Health (NIH) — The Nation's Medical Research
Agency — includes 27 Institutes and Centers and is a component of
the U. S. Department of Health and Human Services. It is the primary Federal
agency for conducting and supporting basic, clinical, and translational medical
research, and it investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.