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Biomedical Research at the National Institutes
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Overview
The National Institutes of Health (NIH), one of the world’s
premier centers for biomedical research, lies at the heart of Federal efforts
to support and stimulate research aimed at improving health and fighting
disease. The mission of NIH is to uncover new knowledge that will lead
to better health for everyone.
NIH works toward its mission by:
- Conducting research in its own laboratories
- Supporting the research of scientists in universities, medical schools,
hospitals, and research institutions in the United States and throughout
the world
- Training research investigators
- Promoting the communication of medical information and research findings
NIH accomplishes its mission by conducting and funding both basic and clinical
research. Basic research involves the fundamental studies of molecules, genes,
proteins, cells, tissues, and organisms that lead to a better understanding
of the workings of our natural world. Basic research may not have an immediate
payoff, but it can help us understand the underlying principles of how biological
systems function. This sets the stage for later medical advances that depend
on this basic understanding of biology. Clinical research focuses on developing
and testing new approaches to the prevention, diagnosis, and treatment of disease.
Together, basic and clinical research are our most powerful weapons against
disease and disability.
Approximately 10 percent of the NIH budget funds research conducted through
the NIH Intramural Research Program. The intramural program supports more than
2,000 research projects conducted by more than 4,000 doctoral-level scientists
at NIH. NIH’s main campus is located in Bethesda, Maryland. The intramural
program also has laboratories at other locations in Maryland (Frederick and
Baltimore) and in other States, including the National Institute of Environmental
Health Sciences in Research Triangle Park, North Carolina; the National Institute
of Diabetes and Digestive and Kidney Diseases’ Epidemiology and Clinical
Research Branch in Phoenix, Arizona; and the National Institute of Allergy
and Infectious Diseases’ Rocky Mountain Research Station in Hamilton,
Montana.
The bulk of the NIH budget, approximately 82 percent, is invested in the extramural
program, which supports research through grants and contracts at more than
2,000 research institutions throughout the United States and abroad.
The rewards of this investment have come in the form of scores of scientific
discoveries that are already helping researchers and physicians better understand,
prevent, and treat cancer, diabetes, heart disease, and neurological disorders,
as well as AIDS and other infectious diseases. A small sampling of some of
the research advances made in recent years through the intramural program,
the extramural program, and collaborative efforts is outlined below.
Recent
Major Advances |
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Human Genome
In February 2001, scientists throughout the world achieved a monumental milestone:
they sequenced nearly all of the 3 billion or so base pairs that make up
the human genome, the DNA contained in all the human chromosomes in each
cell of the human body. This feat was achieved through the Human Genome Project,
an international consortium of scientists from the United States, England,
Japan, Germany, France, and China. The researchers published a draft sequence
of the human genome that represents an exact order of four nucleotide bases
that comprise the base pairs within DNA. The draft sequence represents more
than 90 percent of the total human DNA sequence.
In addition to determining the sequence of the human genome, the international
consortium published a nearly complete physical map of the human genome.
The sequence reveals the order of bases along a DNA strand, whereas the genome
map shows the position of the genes within the genome. The project turned
up a few surprises. For example, scientists found that the human genome contains
far fewer genes than previously predicted. Instead of the 100,000 genes thought
to exist, the human genome contains only about 35,000 genes. Researchers
also found that the human genome contains much more “junk” than
previously realized. About half of the genome consists of stretches of DNA
that do not code for any proteins.
The findings are already changing the face of genetics throughout the world.
For example, tens of thousands of new genes have been identified from the
human genome sequence, including more than 30 genes that play a role in human
disease. Scientists are also using the information to examine patterns of
genes expressed under certain conditions, such as cancer.
With research contributions from both extramural and intramural scientists,
the Human Genome Project, which was funded in large part by NIH, completed
the sequence and mapping of the entire human genome in 2003.
Cancer |
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DNA Microarray Technology
Physicians treating cancer patients have long been baffled by a mystery of sorts.
Among patients who seem to have similar symptoms with the same type and stage
of cancer, some respond to standard therapies and are cured, while others fail
to respond and die. But new research reveals that cancer cells that appear similar
through a microscope may be quite different on a molecular level.
Researchers at NIH and their collaborators have recently developed a powerful
technique that can distinguish between different types of closely related cancers.
The technique, known as DNA microarray technology, anchors thousands of specific,
known DNA sequences to a grid on a silicon microchip. Researchers can then
bind complementary sequences of unknown genes that are expressed in a cell
or tissue
to evaluate the pattern of gene expression from a patient’s cells. Different
subtypes of cancers can have different patterns of gene activation that are
characteristic of that cancer subtype.
Understanding these subtle differences may help physicians develop better ways
to understand, prevent, and treat different cancers.
Breast Cancer
Physicians treating patients with breast cancer have long sought a better way
of distinguishing hereditary forms of breast cancer from sporadic forms of the
disease. Approximately 5 percent of women with breast cancer inherit genetic
mutations that predispose them to the disease, whereas women with sporadic breast
cancer accumulate genetic changes over time that can eventually lead to cancer.
Hereditary breast cancers are often more aggressive, affect women at younger
ages, and may require a different course of treatment. Over the past decade researchers
discovered that mutations in two genes, BRCA1 and BRCA2, give rise to most cases
of hereditary breast cancer. However, the genes are very large, and it is difficult
to pinpoint the genetic mutations that are triggering disease.
Researchers at NIH’s National Human Genome Research Institute turned
to DNA microarray technology to see if different types of breast cancer cells
express
different patterns of genes. The researchers analyzed the expression of more
than 6,000 genes from breast cancer cells and found clear differences between
hereditary and nonhereditary breast tumors. The researchers found that the
pattern of genes activated was different among tumors with BRCA1, BRCA2, and
sporadic
mutations. The researchers distinguished the three categories of tumors by
analyzing 50 or 60 specific genes. Understanding how the activation of these
subsets of
genes results in different paths of cancer development may help researchers
develop new targets for treating and preventing breast cancer.
Childhood Cancers
Physicians also have difficulty distinguishing four types of closely related
childhood cancers: neuroblastoma, rhabdomyosarcoma, non-Hodgkin’s lymphoma,
and Ewing’s sarcoma. Under the microscope, cells from these four cancers
appear very similar and are difficult to differentiate. Because of their similarity,
these cancers are sometimes misdiagnosed and not treated appropriately.
Researchers at NIH collaborated with investigators in Sweden to study these cancer
cells using DNA microarray technology. They were able to distinguish the cancers
from each other by analyzing the expression of a set of 93 genes. Forty-one of
these genes were not previously known to be involved in the development of the
cancers. The researchers hope that studying these genes will help them better
understand the biology of these cancers and possibly serve as targets for developing
new cancer drugs.
Ovarian Cancer
Early detection is a critical concern for treating women with ovarian cancer.
More than 80 percent of patients are not diagnosed until the cancer has progressed
to later stages when they have a less than 20 percent chance of surviving for
5 years. In contrast, patients who are diagnosed at early stages have a 95 percent
survival rate at 5 years.
NIH researchers and their collaborators have developed a new test that can detect
ovarian cancer, even at early stages. The scientists combined another cutting
edge technology called proteomics with sophisticated artificial intelligence
computer programs. Whereas gene chip technology assesses gene expression in cells,
proteomics examines cells for the presence of particular proteins. The scientists
used computers to study the patterns of proteins present in samples from known
cancer patients, then looked for these same patterns in unknown samples. The
test was able to correctly identify all samples from patients with stage I ovarian
cancer.
The proteomics test can be used to detect ovarian cancer and potentially other
cancers as well, using a blood sample from a finger-prick. Researchers believe
the technology will go a long way toward helping women combat this devastating
disease.
Prostate Cancer Gene Discovered
Approximately 16 percent of American men will develop prostate cancer sometime
in their life. Scientists have been searching for the genetic mutations that
cause prostate cancer for several decades. This year, researchers at NIH and
their collaborators discovered a new gene on chromosome 1 linked with an inherited
form of prostate cancer. The gene, which codes for a protein called ribonuclease
L (RNASEL), is mutated in some families with a history of prostate cancer.
The RNASEL protein plays a role in targeting damaged or abnormal cells for
programmed
cell death. The mutated cells may become cancerous when this normal way of
ridding the body of damaged cells is inactivated. RNASEL is probably just one
of several
proteins that contribute to prostate cancer.
Novel Anticancer Drug Discovered
Until recently most cancer patients have had to endure painful rounds of chemotherapy
drugs aimed at killing their cancer cells. The problem with most chemotherapy
drugs is that they also kill normal cells and cause debilitating side effects.
The strategy has been able to give enough drug to kill the cancer but not enough
to kill the patient and hope that the cancer does not recur. For years, researchers
have been searching for drugs that will specifically target cancer cells without
harming normal cells or the patient.
In May 2001 the FDA approved the use of a member of a new class of anticancer
drug, Gleevec, to treat chronic myelogenous leukemia (CML). Gleevec produced
dramatic results in an early phase clinical trial, in which normal blood counts
were restored in 53 out of 54 patients given the drug.
The drug, developed by the pharmaceutical company Novartis, is the first of
a new generation of anticancer drugs that specifically target a protein known
to contribute to the development of cancer. CML is caused by the translocation
of a piece of chromosome 22, which fuses to chromosome 9. A gene called bcr
is broken off of chromosome 22 and fused to a second gene called abl on chromosome
9. This fusion creates a new gene called bcr-abl that codes for a protein
that belongs to a class of proteins known as tyrosine kinases. Tyrosine kinases
play important roles in regulating cell growth, but bcr-abl causes cells
to
divide uncontrollably, leading to leukemia. Gleevec specifically blocks the
action of the bcr-abl protein in leukemia cells but does not affect normal
cells.
In a recently completed Phase II study of Gleevec, designed to test both the
safety and the efficacy of the drug, 454 patients with CML who had not responded
to standard therapy took Gleevec on a daily basis. After 18 months, 95 percent
of the patients were alive and 89 percent were free of disease progression.
NIH has funded much of the basic research that led to the discovery of Gleevec
and is continuing to support and coordinate clinical trials of the drug. Currently,
clinical trials are being held to test the long-term effects of Gleevec in
CML patients, as well as the effect of Gleevec in patients with other types
of cancer, including glioblastomas and sarcomas.
AIDS Research |
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HAART
When AIDS first appeared in this country and throughout the world, the disease
was a virtual death sentence. Although there is still no cure, researchers
have made great strides in developing treatment regimens to combat the
devastating
disease. Over the past several years, an AIDS treatment strategy called highly
active antiretroviral therapy (HAART) has proven remarkably successful in
reducing HIV levels and preventing the progression of AIDS in HIV-infected
patients. Many
patients have experienced a reduction in HIV to undetectable levels in the
blood. However, the therapy, which consists of combinations of three or
four potent
antiretroviral drugs, can be toxic, difficult to adhere to, and prohibitively
expensive.
NIH researchers recently studied the feasibility of cycling on and off these
medications. The researchers showed that this approach, called structured
intermittent therapy, appeared to effectively control HIV replication while
reducing some
of the side effects of HAART. The study involved 10 patients who had been
receiving daily HAART. During the study, patients received a four-drug regimen
of the
anti-HIV drugs stavudine, lamivudine, indinavir, and ritonavir, administered
twice a day
for a period of 7 days, followed by a 7-day period with no drugs. This on-off
cycle was repeated 16–34 times, or 32 to 68 weeks. The researchers
found that study patients had no significant increases in the amount of HIV
in their
bodies and no reduction in CD4+T cells, important immune cells that are typically
depleted in HIV-infected patients. The researchers also found that patients
on structured intermittent therapy had reduced serum cholesterol and triglyceride
levels. Typically, HAART therapy increases serum cholesterol and triglyceride
levels, which can contribute to heart problems in patients.
The success of the initial pilot study has prompted larger clinical trials of
structured intermittent therapy. The researchers hope that the approach could
reduce the side effects and high costs of HAART, which have impeded its widespread
use, particularly in underdeveloped nations, where more than 95 percent of HIV-infected
individuals live.
HIV Vaccine Development
As a result of new scientific findings and new funding in the area of HIV vaccines,
many new approaches are being pursued from the basic research level through vaccine
product development. In the past several years, investigators have determined
that several AIDS vaccine strategies have been able to decrease the level of
the virus that was established shortly after challenge in animal models. Even
though these vaccines have not been totally effective in preventing virus infection,
the concept that control of viral load may be an equally important vaccine outcome
has been recognized because of data that suggest that partners of HIV-infected
subjects become infected far less frequently when there is a reduced level of
HIV transmission.
In November of 2002, NIH’s Vaccine Research Center (VRC) launched a
Phase I clinical study of a novel DNA vaccine directed at the three most
globally
important HIV subtypes, or clades. The vaccine, developed by VRC, incorporates
HIV genetic
material from clades A, B, and C, which cause about 90 percent of all HIV
infections around the world. This is the first multigene, multiclade HIV
vaccine to enter
human trials and marks an important milestone in the search for a single
vaccine that targets U.S. subtypes of HIV as well as clades causing the global
epidemic.
Reducing Mother-to-Child Transmission
In 2002 alone, approximately 800,000 children worldwide became infected with
HIV through mother-to-child transmission, with more than 90 percent residing
in resource-poor countries.
A regimen of the HIV drug AZT, administered to the mother during labor and
to the infant during the first week after birth, reduces the infection rate,
but
AZT is expensive and requires multiple doses due to its short half-life.
A recent NIH-funded study by Ugandan and U.S. researchers found that two
doses
of the
inexpensive antiviral drug nevirapine (NVP)—one dose to the mother and
one to the child—reduced HIV transmission by 41 percent over infants and
mothers who received an AZT regimen. At 18 months, 25.8 percent of children in
the AZT group were infected with HIV, compared with 15.7 percent in the NVP group,
yielding a difference of 41 percent when a time variable is considered. The cost
savings of using nevirapine in the study were substantial—approximately
70 times less than the AZT treatment.
Heart Disease |
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The scientific mainstream has long believed that certain types of cells, once
destroyed, are gone forever. For decades physicians have been telling their
patients that heart muscle damaged during a heart attack cannot be repaired
or regenerated.
But two recent studies now challenge the longstanding dogma.
NIH-funded researchers in collaboration with researchers at NIH in Bethesda discovered
that bone marrow cells can develop into cardiomyocytes and replace damaged heart
muscle in mice. The researchers induced myocardial infarction, or heart attack,
in mice by ligating, or tying off, the left main coronary artery, a major blood
vessel to the heart. They then injected bone marrow cells into the wall bordering
the damaged heart muscle. The bone marrow cells were selectively enriched for
a type of bone marrow progenitor cell with a high capacity to develop into a
variety of cell types. The researchers found that the injected cells homed in
on the damaged tissue and regenerated new myocardium, which occupied 68 percent
of the damaged portion of the heart muscle 9 days after injection. The results
indicate that bone marrow progenitor cells can replace dead or damaged myocardial
cells with functioning living tissue. The results indicate that the heart is
much more resilient than previously realized.
Diabetes |
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Diabetes Prevention
The Diabetes Prevention Program (DPP), a multicenter study sponsored
by NIH and conducted at clinics throughout the country, ended a year
early when it showed
that lifestyle changes can delay and possibly prevent the onset of type
2 diabetes. Seventeen million people in the United States have diabetes
today. Type 2 diabetes,
the most common form, occurs mostly in people who are older, overweight,
sedentary, and have a family history of diabetes. African Americans,
Latinos, and Native
Americans have an especially high risk of developing type 2 diabetes.
Diabetes greatly increases the risk of heart disease, kidney disease,
stroke, eye disease,
and nerve damage. In fact, it is the main cause of kidney failure, limb
amputation, and new-onset blindness and a main cause of heart disease
and stroke.
Diabetes, which is characterized by high blood glucose levels, is usually
preceded by prediabetes. People with prediabetes have blood glucose
levels that are
higher than normal, but not high enough to be considered diabetic. Physicians
and researchers have long known that regular exercise and changes in
diet can lower blood glucose levels in people with diabetes.
The DPP asked whether modest weight loss achieved with these same lifestyle
changes or a glucose-lowering medication could delay or even prevent
the onset of diabetes. The researchers randomly assigned 3,234 overweight
volunteers
with prediabetes to one of three groups:
- Lifestyle modification through diet and exercise, with the aim of reducing
weight by 7 percent
- Treatment with the drug metformin (an oral medication used to treat type
2 diabetes)
- A control group receiving a placebo in place of metformin
The results showed that people in the diet and exercise group who lost 5–7
percent of their weight lowered the incidence of diabetes by 58 percent. Metformin
reduced the incidence of diabetes by 30 percent. Among volunteers over the
age of 60, diet and exercise reduced the incidence of diabetes by 71 percent.
In addition to delaying or preventing the onset of diabetes, diet and exercise
also restored normal blood glucose levels in many people with prediabetes.
The researchers plan to continue to monitor study participants to see whether
diabetes can be delayed beyond the 3-year followup period in the study.
Islet Transplantation and Stem Cells
Type 1 diabetes, or juvenile-onset diabetes, results from the loss of the insulin-producing
islet cells of the pancreas. For unknown reasons, the body’s immune system
destroys its own islet cells and patients are unable to produce insulin. Without
insulin, the cells of the body cannot function. Researchers would like to find
a way to replace the insulin-producing cells of the pancreas in patients with
type 1 diabetes. They are finding new hope in islet transplantation.
Researchers are trying to determine whether the procedure can restore natural
insulin production in patients with type 1 diabetes. Despite its promise, however,
islet transplantation cannot be adopted for widespread use until two major obstacles
are overcome: the severe shortage of donor islets and the need for immunomodulatory
drugs that safely prevent rejection.
NIH is addressing the inadequate supply of islets by establishing the Beta Cell
Biology Consortium to pursue methods for growing an unlimited quantity of functional
insulin-secreting beta cells. Studies on immune tolerance, which would permit
transplantation without the need for chronic immunosuppressive drugs, are focusing
on the problem of rejection of transplanted tissue. In related work, NIH is funding
research resources, such as islet isolation centers, to obtain human islets from
donor pancreases for use in islet transplantation studies, as well as research
to find ways to prevent the immune system from rejecting the transplanted islets.
Stem cell research may also provide methods for developing a renewable supply
of islets. Recently, scientists at NIH induced mouse stem cells to develop into
insulin-producing islet clusters similar to those found in the pancreas. The
researchers started with embryonic stem cells of mice. The stem cells spontaneously
form aggregates called embryoid bodies, which contain all three primordial germ
layers. The researchers then selected a subpopulation of cells that express a
specific neural marker. After subjecting the cells to a five-stage culturing
technique, the cells formed islet-like pancreatic clusters. The cells responded
to normal glucose concentrations by secreting insulin and survived when transplanted
into mice. Researchers hope that this technique may lead to a way to develop
insulin-producing cells for people with type 1 diabetes.
Neurological Disorders |
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Spinal Cord Injury
Each year, approximately 100,000 Americans suffer an injury to the spinal cord,
often causing paralysis, muscle atrophy, breathing difficulties, and chronic
pain. An estimated 200,000 individuals in the United States live day-to-day with
the devastating consequences of such injuries.
Recently, NIH-supported researchers found that delayed treatment of spinal
cord injury may improve recovery. In the study, rats given an experimental
combination
therapy—consisting of fetal spinal tissue transplants and nerve growth
factors (neurotrophins)—several weeks after their spinal cords were severed
showed dramatically greater re-growth of nerve fibers and recovery of function
than rats treated immediately after injury. The finding suggests that the window
of opportunity for treating spinal cord injury may be wider than previously
anticipated.
Earlier
studies in animals have shown that fetal tissue transplants and neurotrophins
can improve regrowth of injured neurons in the adult spinal cord and that
some injured neurons can regrow even after long periods of time. However,
this study is the first to show that spinal cord regeneration is actually
improved when treatment is postponed until most of the initial injury-related
changes
in the rat spinal cord have taken place and the surrounding environment has
stabilized.
Translational Research
The Neurodegeneration Drug Screening Consortium—a novel partnership between
the National Institute of Neurological Disorders and Stroke and three voluntary
health organizations—was created to identify drugs that may be useful
for treating neurodegenerative disorders. Recently, the group met to discuss
results of the initial phase of the program—a large-scale, 6-month
project in which investigators from 26 laboratories tested 1,040 compounds.
They used
29 different assays to identify possible effects of the drugs on cell death,
protein aggregation, and other processes linked to neurodegenerative diseases.
Most of the tested compounds had previously been approved by the FDA for use
in treating other disorders. FDA-approved drugs generally have advantages over
newly identified compounds because they are already on the market and have
undergone years of testing in humans. More research is needed before the tested
compounds can be considered for clinical trials in patients with neurodegenerative
disorders.
Muscular Dystrophy
In a recent NIH-supported study, scientists identified a new kind of genetic
problem that underlies a common neuromuscular disorder called facioscapulohumeral
muscular dystrophy (FSHD). The study showed that deletion of repetitive DNA
sequences in people with FSHD causes overactivity in nearby genes. The finding
solves a decades-old mystery about the causes of this disorder and may ultimately
lead to the first effective treatments.
The researchers found that abnormally short strings of repeated DNA sequences
on chromosome 4 interfere with the function of a protein complex that controls
nearby genes, leading to overactivity of several genes that may play a role
in FSHD. This type of genetic problem has never before been identified in a
human disease.
FSHD is the third most common inherited neuromuscular disorder, affecting
1 in every 20,000 people. Symptoms include progressive muscle degeneration
that
primarily affects the face, shoulder blades, and upper arms. Despite intensive
efforts, researchers have been unable to identify any genes that are altered
in this disorder. Scientists can now focus on identifying which genes on
chromosome 4 contribute to FSHD and how to regulate gene activity.
Deafness Gene Discovered |
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NIH researchers, in collaboration with 21 other scientists in this country,
Pakistan, and India, have discovered a gene that, when mutated, causes two
forms of deafness
in both humans and mice.
The gene, called TMC1 for transmembrane cochlear-expressed gene, is located on
chromosome 9 in humans and codes for a protein that is thought to affect the
function of cochlear hair cells. Hair cells convert sound vibrations into electrical
signals that are transmitted to the brain. One type of dominant hearing loss,
called DFNA36, develops when one parent passes along a dominant mutation of TMC1.
Although the child will have normal hearing early on, severe deafness will generally
occur by the age of 30. A recessive form of deafness, called DFNB/B11, appears
to be caused by a different mutation of TMC1. A child who inherits two copies
of the recessive mutation will be deaf at birth. However, carriers with only
one recessive mutation of TMC1 have normal hearing.
The researchers also reported that in mice, a similar gene, Tmc1, is located
on chromosome 19. Mice with a recessive form of the mutant gene are profoundly
deaf, and their cochlear hair cells do not respond to sound. The findings suggest
that the protein encoded for by TMC1 in humans and Tmc1 in mice plays an important
role in the function of cochlear hair cells. By identifying the role of this
protein, researchers can better understand the hearing process and why some inherited
hearing disorders arise.
Biodefense and Anthrax |
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The terror and fear felt by all Americans following September 11, 2001, has
been devastating. The incidents of anthrax poisoning that followed raised the
specter
that the threat of bioterrorism is more real than perhaps anyone ever realized.
The attacks have underscored the importance of understanding the mode of
action of anthrax and other agents of bioterrorism.
Two teams of NIH-funded researchers recently reported key discoveries that
shed light on how the anthrax toxin destroys cells, often killing its victims.
In
the most dangerous form of anthrax poisoning, inhalation anthrax, bacterial
spores are inhaled and travel to the lungs, where they multiply and produce
a lethal
toxin. The anthrax toxin has three parts. Protective antigen (PA) binds
to a receptor on the surface of cells and ushers edema factor and
lethal
factor
into the cells of the host. Once inside the cell, edema factor and
lethal factor interfere with cell metabolism, ultimately leading to cellular
destruction.
In the recent studies, researchers discovered that the first step in the
attack of the anthrax toxin occurs when PA binds to a protein on the surface
of animal
cells that appears to be the anthrax toxin receptor. The researchers
identified the specific portion of the receptor protein that binds to the
toxin. Then they
manufactured a truncated, synthetic version of that part of the receptor—the
toxin-binding domain—that binds to the anthrax toxin. When they mixed
the receptor fragment with the anthrax toxin, the fragment blocked binding
of anthrax
to its receptor. This approach suggests a plausible route to developing
antidotes to the anthrax toxin.
Benefits
of Biomedical Research |
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NIH invests its research dollars with the ultimate goal of preventing and
treating disease and disability. This investment has benefited Americans by
saving lives, improving the quality of life, and reducing the costs of health
care and lost income due to disability.
Research Saves Lives. Over the past
several decades, biomedical research has led to countless improvements in the
health
of the Nation:
- Heart Disease—Although heart
disease is still the number one killer in the United States, the heart disease
death rate (number of deaths per
100,000 people) dropped by 36 percent between 1977 and 1999.
- Stroke—The death rate due
to stroke decreased by 50 percent between 1977 and 1999. And anticlotting
medications have cut the risk of
stroke due to atrial fibrillation, a common heart condition, by 80 percent.
- Cancer—Advances in understanding the genetic and environmental causes
of cancer have led to effective screening programs that prevent cancer, improve
detection, and increase the success of treatments. Between 1992 and 1998,
the overall incidence of cancer fell 1.1 percent each year. The number of
deaths due to cancer also fell 1.1 percent per year during the same period.
- Mental Illness—New treatments for schizophrenia can reduce or eliminate
the symptoms of schizophrenia—including hallucinations and delusions—in
80 percent of patients.
- Spinal Cord Injury—High doses of steroid given within the first 8
hours after injury can prevent paralysis and increase the likelihood of recovery
in patients who have lost sensation or mobility.
- Diabetes—Maintaining tight control of blood glucose levels, blood
pressure, and LDL (bad) cholesterol in people with diabetes with the help
of new medications can lower the risk of debilitating complications of diabetes,
including heart disease, stroke, nerve disease, eye disease, and kidney disease
by more than 50 percent.
- Respiratory Distress Syndrome—Infant
mortality due to respiratory distress syndrome, a condition caused by immaturity
of the lungs, has decreased
significantly due to the development of a new treatment (lung surfactant)
that prevents lung collapse in premature infants.
- Infectious Diseases—Vaccines
now prevent diseases that once killed and disabled millions of children and
adults.
- Life Expectancy—In general, an infant born today can expect to live
three decades longer than one born at the turn of the last century.
Research Saves Money. Not only does biomedical research save lives, it also
reduces the costs of health care and the impact of lost earnings. For example,
estrogen therapy can reduce the incidence of osteoporosis and hip fractures
in postmenopausal women for an estimated annual savings of $333 million in
patient-care costs.
Men with testicular cancer can now expect a 91 percent cure rate and an increased
life expectancy of 40 years. Thus, a 17-year, $56 million investment in research
on testicular cancer has led to an annual savings of $166 million.
The
NIH BUDGET |
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NIH’s important role in the Nation’s biomedical research enterprise
is reflected in the proposed fiscal year 2004 budget of $27.8 billion. In 2003,
Congress appropriated $27.2 billion to NIH, which supported nearly 46,700 research
project grants in universities, medical schools, and independent research institutions
across the country.
Several biomedical research priority areas were identified
in the President’s
proposed NIH fiscal year 2003 budget. They included:
Investigator-Initiated
Research—$15.2 billion for new, competing, and continuing grants to
fund research projects initiated by individual investigators.
Cancer Research—$5.5
billion for cancer-related research. Of particular interest is the use of
proteomics and sophisticated computer technology to
detect and diagnose cancers and new drugs that specifically target proteins
known to arise from genetic mutations that lead to cancer.
Biodefense Research—An increase by $1.47 billion to $1.75
billion for biodefense research. Most of this money was targeted
to expand the effort to develop countermeasures that will be
needed to respond to bioterrorism attacks.
Clinical Research—NIH hopes to benefit from unprecedented advances
in genomics, proteomics, and advanced imaging technology to test new ways
to prevent, diagnose, and treat many diseases through clinical trials involving
patients and healthy volunteers. The fiscal year 2003 budget placed particular
emphasis on clinical research. For example, funds for the Extramural Loan
Repayment Program for Clinical Researchers doubled to approximately $50 million
over the previous year’s request.
Research on Disease Prevention—More than $6.8 billion to launch new
initiatives to develop strategies to prevent disease. The cornerstone of
disease prevention remains vaccine development. New vaccines to prevent otitis
media, Ebola, HIV/AIDS, Leishmania, and malaria will be pursued.
Diabetes—More than $845 million to support research into the treatment
and prevention of diabetes, a chronic disease that affects more than 17 million
people in the United States today. Research into preventing type 2 diabetes
through changing lifestyle factors as well as developing technology for islet
cell transplantation to treat patients with type 1 diabetes will be emphasized.
Minority
Health and Health Disparities—NIH remains committed to eliminating
disparities in health among minorities and other disadvantaged populations.
The proposed budget will support improvements to infrastructure in minority
institutions and foster partnerships with minority research institutions. In
2000, Congress authorized the establishment of the National Center on Minority
Health and Health Disparities, which aims to promote minority health and to
lead the NIH effort to reduce and ultimately eliminate health disparities.
Parkinson’s Disease—NIH will continue to fund research to treat
Parkinson’s disease, based on advances in understanding the genetics,
cell biology, and pharmacology of the disease. Methods for replacing damaged
dopamine-releasing neurons, as well as testing neuroprotectant drugs, which
slow progression of the disease, will be actively investigated. The $215 million
budget for this disease seeks to carry out the NIH Parkinson’s Disease
Research Agenda, the result of a 2000 workshop attended by patients, doctors,
and scientists from academia, government, and industry.
Future
Directions |
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Although NIH-supported scientists have made many important discoveries in
recent years, much remains to be done. Researchers are trying to find better
ways to prevent and treat a wide range of diseases, including brain disorders,
diabetes, cardiovascular disease, asthma, childhood diseases, and those associated
with aging. Efforts to understand how organisms function under normal and abnormal
conditions will lead to biomedical research advances that result in improved
health for all Americans, and for people worldwide
In September 2003, NIH Director Elias A. Zerhouni, M.D., announced a series of
far-reaching initiatives known collectively as the NIH Roadmap for Medical Research.
The Roadmap aims to transform the Nation’s medical research capabilities
and accelerate medical discoveries to improve health.
In setting forth an ambitious vision for a more efficient and productive system
of medical research, the NIH Roadmap focuses on the most compelling opportunities
in three main areas: new pathways to discovery, research teams of the future,
and re-engineering the clinical research enterprise.
NIH
Research Training Programs |
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Programs for Undergraduate Students
Undergraduate Scholarship Program (UGSP)–The
NIH UGSP offers scholarships to undergraduate students from disadvantaged
backgrounds who are committed to careers in biomedical, behavioral, and social
science health-related research. Applicants must be academically gifted and
have earned an overall 3.5 grade point average, or be within the top 5 percent
of their class. The yearly renewable scholarships pay for tuition and related
educational and reasonable living expenses up to $20,000 per academic year.
Two kinds of service obligations are required from each scholarship recipient:
after each scholarship year, recipients train for 10 weeks during the summer
at the NIH laboratories as paid Federal employees, and after graduation recipients
serve as NIH employees 1 year (52 weeks) for each year of scholarship support.
Although these are required service obligations to NIH, the obligations themselves
can be considered benefits—providing students with valuable research
experiences. Additionally, students receive stipends during their service at
NIH. The amount of the stipend varies according to the research experience
of each participant.
Unique features of the UGSP include its mentoring activities and communication-skills
training, which are designed to nurture the undergraduates’ career development,
and practical experience in a state-of-the-art research setting.
Summer Internship Program in Biomedical Research (SIP)–NIH’s
SIP offers opportunities for high school, undergraduate, and graduate students
to spend at least 8 weeks conducting research in one of NIH’s research
laboratories during the summer months. Students are encouraged to participate
in meetings in their individual laboratories and have the opportunity to present
the results of their research at the Summer Research Program Poster Day. Stipends
range from $1,100 for high school students to $2,400 per month for advanced
graduate students. Candidates must be permanent residents or citizens of the
United States.
Programs for Predoctoral Students |
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The NIH Academy–The NIH Academy is a year-long postbaccalaureate research
training program for recent college graduates who have demonstrated a well-defined
interest in health disparities. The mission of the Academy is to enhance health
disparities research through the development of a diverse cadre of biomedical
researchers.
In addition to biomedical research training, there are two educational components
to the program: seminars and workshops on topics related to health disparities
and general knowledge workshops.
Predoctoral Intramural Research Training Awards–The goal
of these awards is to introduce recent college graduates to biomedical research,
as well as
to provide additional time to pursue successful application to a doctoral-degree
program. Participants receive training and gain research experience under
the mentorship of an experienced clinical or laboratory investigator. Candidates
must be U.S. citizens or permanent residents and have graduated from an accredited
college or university no more than 12 months prior to arriving at NIH. Applicants
must intend to apply to graduate or medical school within the next year.
Interim or Year-Off Intramural Research Training Awards–These awards
are for graduate students or medical students who desire an interim or year-off
research experience at NIH. Awards may be granted to students who have been
accepted into graduate or medical school and who wish to delay matriculation.
Students currently enrolled and attending graduate school are also eligible.
Awards initially made for less than 1 year may be extended, but the cumulative
period will not exceed 1 year.
Clinical Research Training Program (CRTP)–The CRTP is an individualized,
1- to 2- year tutorial for third-year medical and dental students. The program
emphasizes clinical research training and coursework. It offers training with
a senior research clinician in the student’s field of research interest.
CRTP scholars receive stipends of $25,300 per year, health insurance, and reimbursement
for traveling and moving costs. Clinical research scholars must be U.S. citizens
or permanent residents and gain their dean’s permission to take a leave
of absence from their studies.
Programs for Physicians and
Postdoctoral Researchers |
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Loan Repayment Programs (LRPs)–The
NIH LRPs offer educational loan repayment assistance to recent medical school
graduates and postdoctoral scientists.
NIH offers both intramural LRPs for researchers employed at NIH and extramural
LRPs for investigators conducting qualified research at nonprofit institutions,
funded by nonprofit or U.S. Government (Federal, State, or local)
entities.
The LRPs can repay up to $35,000 per year for each year of support (with a
minimum 2- or 3-year contract), depending on total debt. The LRPs also provide
reimbursement for any Federal and State tax liabilities that result from the
loan repayments.
There are currently five extramural LRPs, each of which seeks to attract investigators
to a particular area of research: clinical (two programs), pediatric, health
disparities, and contraceptive and infertility research.
There are three intramural LRPs (for AIDS, clinical, and general research),
which repay up to $35,000 in debt per year, depending on total debt, as well
as a special initiative for the Accreditation Council for Graduate Medical
Education (ACGME) Fellows, which offers $15,000 per year in loan repayment
to fellows in subspecialty
and residency training programs accredited
by the ACGME.
A primary goal of the intramural LRPs is to attract the best and brightest
postdoctoral and medical school graduates to NIH.
Laboratory Research Pathway–Participants who enter this postdoctoral
training pathway engage in pure laboratory research. Applicants must have
either a graduate doctoral degree (e.g., Ph.D. or M.D/Ph.D.) or a professional
degree (e.g., M.D., D.O., D.D.S., D.M.D., or D.V.M.) accompanied by previous
research laboratory experience.
Combined Clinical and Research Pathway–In
this postdoctoral training pathway, participants often receive clinical
subspecialty training as well
as training in basic research. Applicants must possess a degree in medicine
or dentistry. In general, candidates must have 2 or 3 years of postgraduate
clinical training and ideally should apply 1 or 2 years before the desired
date of the appointment. In the first year of training, the Clinical Associate
is involved in clinical research and care on the wards of the NIH Clinical
Center. In the second and optional
third years, the Clinical Associate may choose a training program that
will involve clinical research, basic research, or a combination of the
two. The Clinical Associate experience in many cases is creditable toward
board certification.
Additional
Information |
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NIH maintains a comprehensive site on the World Wide Web at http://www.nih.gov.
The site contains information about the agency’s scientific research
programs, the Institutes and Centers that conduct intramural research and administer
extramural
grants, news about recent research findings, health resources for the public,
and information about research training programs.
For more information about training opportunities at NIH, visit the following
individual Web sites:
NIH Undergraduate Scholarship Program: http://www.ugsp.nih.gov
NIH Loan Repayment Program: http://www.lrp.nih.gov
List of training programs at NIH and general information from the NIH Office
of Education:
http://www.training.nih.gov
Disclaimer
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