Mr. Chairman and Members of the Subcommittee, I am Harold Varmus,
Director of the National Institutes of Health. Accompanying me today, at
the Subcommittee's request, are: Francis Collins, Director, National Human
Genome Research Institute; Donald Lindberg, Director, National Library of
Medicine; David Lipman, also from the National Library of Medicine; Zach
Hall, Director, National Institute of Neurological Disorders and Stroke;
Richard Hodes, Director, National Institute on Aging; and Anthony Fauci,
Director, National Institute of Allergy and Infectious Diseases. We are
pleased to have this opportunity to discuss with you some of the research
supported and conducted by the NIH, what we are learning from it about
human health and disease, and some of the research tools we are developing
to not only facilitate that research, but to ensure that knowledge gained from
it is accessible to the scientific community and to the public.
The NIH seeks to expand fundamental knowledge about the nature and
behavior of living systems and to apply that knowledge to improve the health
of human beings. The research undertaken by the NIH assumes many forms,
occurs in many places, and employs many techniques. Some research is
confined to the laboratory and attempts to understand complex biological
systems by examining individual molecules, cells, or tissues. Other research
addresses normal human biology and disease in the context of living subjects
and some is based on the study of human populations. This continuum of
research provides the knowledge base for the development of new treatment
and prevention strategies.
About ten percent of NIH-funded research takes place in the NIH intramural
program; the rest is conducted at nearly 2000 institutions which receive
grants, contracts, and cooperative agreements awarded by the NIH after
competitive expert review. Both intramural and extramural research
activities address a wide spectrum of biological and medical questions with
methods that range from structural analysis of macromolecules to clinical
trials to behavioral studies. In addition, the NIH takes responsibility for the
training of new medical scientists through programs designed to assist
undergraduates, graduate, and post-graduate students in both extramural and
intramural settings.
These several genres of research activity are supported by funds allocated to
twenty-one Institutes and Centers (ICs), each of which has authorities
defined by earlier legislation. Eight ICs address specific health problems:
the National Cancer Institute, the National Institute of Allergy and Infectious
Diseases, the National Institute of Diabetes and Digestive and Kidney
Diseases, the National Institute of Neurological Disorders and Stroke, the
National Institute on Drug Abuse, the National Institute on Alcohol Abuse
and Alcoholism, the National Institute of Arthritis and Musculoskeletal and
Skin Diseases, and the National Institute of Mental Health. Four ICs are
organized around biological systems: the National Heart, Lung, and Blood
Institute, the National Eye Institute, the National Institute on Deafness and
Other Communication Disorders, and the National Institute of Dental
Research. Two ICs focus on stages of human development: the National
Institute of Child Health and Human Development and the National Institute
on Aging. Four other ICs study particular aspects of human health or area of
science: the National Institute of Enviromnental Health Sciences, the
National Institute of General Medical Sciences, the National Institute for
Nursing Research, and the National Human Genome Research Institute.
Other ICs provide research infrastructure. The National Center for Research
Resources supports research infrastructure including shared instrumentation
programs and centers for clinical research located across the Nation; the
Fogarty International Center fosters international scientific collaborations;
and the National Library of Medicine acquires, organizes, and disseminates
health information and engages in research and development in biomedical
communications. The NIH organization also includes three independent
Divisions without budgetary authority. The Center for Scientific Review
(formerly the Division of Research Grants) and the Division of Computer
Research and Technology carry out research management functions involved
in the review of grant applications and maintenance of our information
infrastructure, while the NIH Clinical Center supports nearly 50 percent of
all the federally-funded clinical research beds in the Nation and helps
translate basic science discoveries of intramural and extramural investigators
into clinical applications that improve human health.
Although each of the ICs has a specific research orientation, there are many
commonalities. Most obvious are the shared technical approaches to medical
research and the common locations for research within the intramural and
extramural programs. In addition, ICs often address different aspects of the
major health problems faced by our citizens. This feature is strengthened by
close interactions among the ICs; these may be informal or they may be
guided by inter-IC committees or by NIH-wide coordinating offices, some of
which are located within the Office of the Director, NIH. This rich matrix of
research activity requires collegial relations among the ICs and thrives in an
atmosphere that maximizes flexibility in the management of research
programs. A major objective of my administration at the NIH has been the
enrichment of these interactions and a strengthening of the sense of unified
purpose.
Conclusion
When I began as Director of the NIH nearly four years ago, I pledged to
remain firmly committed to scientific excellence, to defend open-ended basic
science, and to encourage the extension of discoveries to clinical settings.
These goals are shared by all of the NIH leadership, including the Institute
Directors you will hear from today. I believe that you will see many
examples of the fruits of that commitment, not only in our presentations
today, but in the months and years that follow. I would be pleased to answer
any questions you may have.
NATIONAL INSTITUE ON AGING
In creating the National Institute on Aging in 1974, Congress recognized the
potential for aging research to extend the healthy lifespan and improve the
quality of life of generations of older Americans. In the intervening years,
the NIA has made significant strides toward understanding the biological,
behavioral, and social aspects of aging, discovering factors that lead to age-related disease and
disability, and developing strategies for maintaining
health and independence in old age. This knowledge is benefitting all
generations. Knowing that aging does not equate to inevitable decline,
individuals of all ages are devoting more effort to maintaining fitness and
preventing disease. Despite the unprecedented growth of the older
population, studies have shown declines in a number of chronic disease since
the early 1980s, and analyses suggest a concomitant decline in overall
disability rates in older people.
The NIA is the primary federal agency conducting and supporting biological,
behavioral, and social research on aging, age-associated disease and
disability, and the special problems and issues of the aged. The Institute is
composed of four extramural programs: the Biology of Aging Program, the
Behavioral and Social Research Program, the Geriatrics Program, and the
Neuroscience and Neuropsychology of Aging Program. In addition, NIA
scientists conduct intramural research in laboratories located in Bethesda and
Baltimore, Maryland, site of the nearly 40-year-old Baltimore Longitudinal
Study of Aging. Following is a brief description of selected areas of
investigation supported by the NIA:
Alzheimer's Disease. The NIA leads the national research effort on
Alzheimer's disease, the most common cause of dementia in older people.
This devastating condition destroys the lives of those who have the disease
and disrupts the lives of their caregivers. Over the last five years, research
has resulted in major advances in our understanding of the disease, including
the discovery of genetic components, detection of risk factors, and
identification of potential protective interventions. Several of these findings
have stimulated plans for new clinical trials to prevent or delay the onset of
Alzheimer's disease. For example, compelling evidence suggests that
candidate compounds, such as anti-oxidants, anti-inflammatory agents, and
estrogen, may delay or prevent AD, and additional therapeutic leads are
expected from preliminary trials now in progress.
As the pace of research accelerates, new findings will make possible better
understanding of factors contributing to nerve cell death and will improve
our ability to predict who is at risk for developing Alzheimer's disease.
Further discoveries will lead to more accurate methods of diagnosis, and to
the development of more effective treatments and preventive interventions to
reduce the scourge of Alzheimer's disease.
Biology of Aging. NIA's basic research on the biology of aging investigates
the gradual or programmed alterations of structure and function that
characterize normal aging and the abnormal changes that accompany, or
serve as risk factors for, disease states. The ultimate goal is to develop
interventions, based on an understanding of molecular and cellular
processes, to reduce or delay age-related degenerative processes in humans.
For example, in a number of disease conditions, the ability of cells to divide
or replicate is altered. In some conditions, such as cancer, cells divide in an
excessive and uncontrolled manner. In other circumstances, a deficiency in
the ability of cells to divide may contribute to disease and disability. NIA is
making progress in understanding the molecular mechanisms that regulate
cell replication. This knowledge may lead to interventions that will correct
such abnormalities and provide new therapeutic approaches to cancer and
other disease processes.
NIA researchers have discovered in mamnmals and lower organisms several
"longevity genes" that have provided insight into biologic control of life
span. Continued research on longevity assurance genes is viewed as a
critical first step in the design of biologically based interventions to promote
human longevity, extend health span, and improve quality of life in older
individuals. Research is also continuing on caloric restriction, which has
been shown to extend lifespan in rodents by as much as 35 percent, as well
as reduce their incidence of age-associated diseases.
Musculoskeletal Research. The loss of bone mass due to osteoporosis is a
major public health threat, contributing to 1.5 million fractures annually.
Osteoarthritis and age-related loss of muscle mass also lead to frailty and
injury in millions of older people. The NIA supports several initiatives to
unravel the underlying mechanisms of musculoskeletal aging and to design
and evaluate effective prevention and intervention strategies for age-related
musculoskeletal decline.
Cardiovascular Aging. Cardiovascular diseases are the leading cause of
hospitalization and death in older Americans. NIA research has provided
important insights into age-related changes of the cardiovascular system and
their relation to disease and disability. Ongoing research emphasizes
preventive and therapeutic interventions designed to reduce cardiovascular
disease.
Aging and Cancer. Cancer is the second leading cause of death among the
elderly. NIA's program on aging and cancer aims to apply scientific and
technologic advances on malignancies to the needs of older people. Areas of
study include biology, clinical medicine, epidemiology, and the behavioral
and social sciences. Special initiatives are directed at prostate cancer and
breast cancer in men and women over age 65.
Aging and Disability. NIA studies are demonstrating the benefits of a
healthy lifestyle for maintaining physical and mental vigor into old age, and
are developing innovative strategies to help prevent disability that leads to
long-term care. One cost-effective controlled trial conducted in one of NIA's
Claude Pepper Older Americans Independence Centers reduced falls in older
people by nearly 50 percent in a one-year period. Since older persons
sustain 250,000 hip fractures each year, a substantial national cost savings
could result from incorporating risk factor interventions into the usual health
care of older persons.
Based upon data from National Long Term Care Surveys in 1982, 1989, and
1994, prevalence rates for chronic disability were shown to decline
significantly in the U.S. elderly population, ages 65 and older. In absolute
terms, the differences in prevalence suggest that there were approximately
1.2 million fewer disabled persons in 1994 than would have been predicted if
the 1982 rates had remained the same. NIA plans to analyze the dynamics
underlying this apparent decline to enhance this trend.
Behavioral and Social Research. NIA's Edward R. Roybal Centers of
Research on Applied Gerontology conduct research with the goal of keeping
people independent, active, and productive in later life. Investigators at
these centers focus on translating promising social and behavioral research
findings into strategies to help improve the lives of older people and their
families in such areas as computer skills, driving, caregiving, and nursing
home care.
Difficulty in remembering is one of the most commonly reported problems
that troubles Americans as they age. NIA has made a substantial investment
in basic research on age-related changes in cognitive fuction in the absence
of detectable brain disease. Studies have shown that age-related decrements
in cognitive function could be reversed with targeted training. Research
continues to develop and test new cognitive interventions to promote
independent functioning among older adults.
Health and Long-Term Care. NIA research also emphasizes improved
understanding of the interactions between older patients and health systems.
The Institute studies ways of improving acute health care for older people,
including improving older people's compliance with medical regimens.
Researchers are studying ways to enhance the quality of long-term care, ease
the burden of family care, and forecast the requirements for long-term care.
Health and Retirement. The unique Health and Retirement Survey, which
is following nearly 13,000 people for at least 12 years, will provide the first
up-to-date picture of work and retirement and how these factors relate to
health and midlife family roles in the 1990s. This study will examine the
transition between work and retirement, with emphasis on sources of
retirement income and health care needs. Survey data will be critical for
analyzing social security and health care issues.
Women's Health. After menopause, women lose bone density and strength,
and become more prone to developing diseases and disorders, such as
osteoporosis, osteoarthritis, cardiovascular disease, urinary incontinence, and
Alzheimer's disease. There is also evidence that women of various ethnic
and racial groups experience and respond to menopause differently. NIA's
recently initiated Study of Women's Health Across the Nation (SWAN), co-funded by the
National Institute on Nursing Research and the Office of
Research on Women's Health, will gather valuable new information on
aspects of menopause from women in diverse populations. This information
will help in designing future clinical interventions on health conditions
associated with menopausal changes.
Minority Aging. NIA's minority aging activities comprise clinical and
epiderniologic research on the health and well-being of minority elders,
demographic studies on the growth of minority populations, and efforts to
facilitate recruitment of minority individuals into clinical studies. Six NIA
centers have been funded to improve the health status of older minority
populations through research and programs of health education and
community outreach.
Additional information on NIA programs and research advances can be
accessed on the internet
at www.nih.gov/nia/.
NIAID OVERVIEW
The NIAID has its origins in the earliest days of the Public Health Service.
In 1948, the Rocky Mountain Laboratory and the Biologics Control
Laboratory, both dating to 1902, joined the Division of Infectious Diseases
and the Division of Tropical Diseases of the National Institutes of Health to
form the National Microbiological Institute. Six years later, Congress gave
the Institute its present name to reflect the inclusion of allergy and
immunology research. Today, NIAID provides the major support for
scientists conducting research aimed at developing better ways to diagnose,
treat and prevent the many infectious, immunologic and allergic diseases that
afflict people worldwide.
NIAID is composed of four extramural divisions: the Division of AIDS; the
Division of Allergy, Immunology and Transplantation; the Division of
Microbiology and Infectious Diseases; and the Division of Extramural
Activities. In addition, NIAID scientists conduct intramural research in
laboratories located in Bethesda, Rockville and Frederick, Maryland, and in
Hamilton, Montana.
Acquired Immunodeficiency Syndrome (AIDS). NIAID is responsible for
conducting and supporting basic research on the pathogenesis of human
immunodeficiency virus (HIV), which causes AIDS; developing new drug
therapies; conducting clinical trials of promising experimental drugs for HIV
infection and related opportunistic infections and cancers; carrying out
epidemiologic studies to assess the impact of HIV on the populations most
severely affected by the epidemic; and developing and testing HIV vaccines.
Asthma and Allergic Diseases. Research on asthma and allergies has
revealed much about their underlying mechanisms and contributed to the
development of new ways to help affected individuals. NIAID has
established a network of asthma, allergic, and immunologic diseases research
centers to transfer results rapidly from fundamental studies in immunology
and clinical studies of allergy to clinical practice. The Institute also supports
the National Cooperative InnerCity Asthma Study to define factors that
influence the disease's severity and to design and evaluate programs to
reduce asthma episodes and deaths among African-American and Hispanic
children.
Emerging diseases. New diseases are arising worldwide and old diseases
are re-emerging as infectious agents evolve or spread and as changes occur
in ecology, socioeconomic conditions, and population patterns. NIAID
conducts and supports research on Lyme disease, hantavirus, multidrug-resistant tuberculosis,
and other emerging diseases to develop new or
improved diagnostics, treatment, and vaccines.
Enteric Diseases. Worldwide, diarrheal diseases such as cholera and
rotavirus infection are major causes of illness and death in infants and
children. In contrast, viral hepatitis in its various forms, can cause severe
disease in older children and adults, although it produces few symptoms
among younger age groups. NIAID supports basic research on how enteric
agents cause illness as well as studies aimed at developing and testing
vaccines to prevent enteric infections.
Genetics and Transplantation. NIAID supports studies aimed at
improving immunosuppressive therapies, further developing reagents needed
for precise tissue matching, defining the genetic regulation of the immune
response, and understanding the molecular mechanisms that control immune
system genes. NIAID is participating in the first NIH cooperative clinical
trial in kidney transplantation, designed to translate developments in basic
research into new therapies to prevent graft rejection.
Immunologic Diseases. The immune system is a complex network of
specialized organs and cells that has evolved to defend the body against
attacks by foreign invaders. When functioning properly, the system fights
off infections by such agents as viruses and bacteria. A malfunction,
however, can unleash an enormous variety of diseases from allergy to
arthritis to cancer. NIAID research focuses on the basic biology of the
immune system and mechanisms of immunologic diseases including
autoimmune disorders.
Malaria and Other Tropical Diseases. Diseases such as malaria, filariasis,
trypanosomiasis, and leprosy disable and kill millions of people worldwide.
NIAID's research efforts in tropical medicine are conducted by U.S. and
foreign investigators receiving Institute support and by NIAID scientists in
Bethesda. NIAID supports a number of centers for tropical medicine
research in countries where such diseases are endemic.
Sexually Transmitted Diseases. More than 13 million Americans each year
acquire infectious diseases other than AIDS through sexual contact. Such
STI)s as gonorrhea, syphilis, chlarnydia, genital herpes and human
papillomavirus can have devastating consequences, particularly for young
adults, pregnant women and newborn babies. NIAID-supported scientists in
STD Cooperative Research Centers, NIAID laboratories, and other research
institutions are developing better diagnostic tests, improved treatments, and
effective vaccines.
Vaccine Development. Effective vaccines have contributed enormously to
improvements in public health in the United States during the last century.
Research conducted and supported by NIAID has led to new or improved
vaccines for a variety of serious diseases, including rabies, meningitis,
whooping cough, hepatitis A and B, chickenpox, and pneurnococcal
pneumonia, to name a few. NIAID supports vaccine evaluation units for the
testing of new vaccines in people at a number of U.S. medical centers.
Other areas of research include fungal diseases, hospital-associated
infections, chronic fatigue
syndrome, respiratory diseases, and antiviral and antimicrobial drug
development.
NATIONAL INSTITUTES OF HEALTH
The National Human Genome Research Institute (NHGRI) was
established in 1989 and originally named the National Center for Human
Genome Research (NCHGR). Its chief mission is to lead the NIH's
contribution to the Human Genome Project-a worldwide research effort to
determine the location of the estimated I 00,000 human genes and to read the
entire sequence of genetic instructions encoded in human DNA. NHGRI
carries out this task by providing financial support to investigators at
university and other research laboratories throughout the United States. The
Institute also has inhouse genetics research laboratories, created in 1993, to
develop and use genome technologies to understand and treat inherited
disease.
HUMAN GENOME PROJECT
The Human Genome Project (HGP) is an international research program
launched seven years ago, carried out in the US by the NHGRI and the US
Department of Energy (DOE). The ultimate HGP task of sequencing all 3
billion base pairs in the human genome will provide scientists with a virtual
instruction book for a human being. From there, researchers can begin to
unravel biology's most complicated processes, including the cause of many
human diseases.
The first five years of the HGP were primarily devoted to the development
of genetic and physical maps that allow precise localization of genes, and the
exploration of technologies capable of sequencing very large amounts of
DNA at high accuracy and low cost.
Pilot projects were initiated in 1996 to address and resolve issues that will be
confronted in large-scale sequencing of human DNA. These pilot projects
will generate between 50 and 100 million base pairs of human DNA
sequence by 1998 and, in doing so, will develop and test the methods that
will be used in the determination of the complete human DNA sequence. To
date, about 2% of human DNA has been sequenced from these projects. The
goal is to sequence the entire genome by 2005.
Analysis of the genomes of several important model organisms is also
included in the Project's goals. The genomes of 8 micro-organisms have
been sequenced so far, including most recently the well-studied bacterium E.
coli. The complete sequence of the genome of baker's yeast was completed
in the spring of 1996, an important step because yeast resemble human cells
more closely than do bacteria. The sequence of the 100 million base pairs of
the roundworm C elegans, an important model of development, will be
completed in 1998.
GENE DISCOVERY
Already as a result of the HGP, new disease genes are discovered almost
weekly. Recent successes include genes for breast cancer, diabetes,
Alzheimer's disease, and colon cancer. When scientists identify a disease
gene, they can begin to understand the illness at a molecular level, and
therefore over time can develop appropriate strategies for treatments and
even cures. In addition, the development of accurate diagnostic tests can, in
some instances, be life-saving. To date, over 80 disease genes have been
identified by positional cloning, the gene hunting strategy that uses HGP
tools.
The NHGRI intramural program is a leader in this gene discovery process.
In just the past year, NHGRI investigators have located a gene for prostate
cancer, and precisely identified genes for Parkinson's disease, a cancer
syndrome called MENI, a breast cancer gene called AIB I, and the childhood
disorders Niemann-Pick type C and Alagille syndrome.
TECHNOLOGY DEVELOPMENT
The development of novel technologies for DNA analysis is an integral
component of the HGP. Of the many such advances over the past seven
years, two examples are presented here:
Spectral Karyotyping (SKY), developed by NHGRI Intramural scientists,
translates computer-gathered light waves into a full-color palette and assigns
each chromosome its own distinct hue. With all 23 pairs of human
chromosomes identified by a different color, scientists can more easily
examine the entire group of chromosomes for subtle changes that could lead
to disease, such as missing or extra pieces, or parts from different
chromosomes that have swapped places. The technique is already proving to
be extremely valuable in diagnosis of disease based on chromosome
alterations.
DNA Microchip Analysis: Borrowing from semi-conductor science,
scientists have been working to develop miniature devices that will allow
hundreds, thousands, or millions of DNA assays to be carried out on a device
smaller than a credit card. Robots produce arrays of thousands of
microscopic spots of DNA that represent parts of genes on a "DNA array
chip." All cells of an organism contain the same genes, but the pattern of
genes being turned on or off is critical to the health of that tissue.
Researchers can use this technology to characterize the differential
expression of genes in different tumor types, or to identify specific gene
mutations. This allows the development of more precise diagnostic criteria
for different cancers and more individualized and effective treatments.
COMPLEX DISEASES
In addition to studies of disorders that arise from errors in one gene, NHGRI
scientists are investigating new strategies to tease apart the genetic and
environmental contributions to common complex disorders, such as many
cancers and diabetes. Impressive progress has been made for several
disorders.
The Center for Inherited Disease Research: Virtually all of us are
predisposed by our inheritance to at least one illness-cancer, heart disease,
diabetes to list a few. We are striving to learn more about the complex gene
interactions that confer disposition to these common diseases. CIDR was
established in 1996 through an agreement among 8 NIH
Institutes, with NHGRI serving as the lead. The CIDR facility, located at the
Johns Hopkins Bayview Medical Center, is dedicated to providing the
research community with the infrastructure to successfully map the genes
responsible for complex diseases. This marks a transition from "one gene-one disease" research
into the study of gene-gene and gene-environment
interactions.
ETHICAL, LEGAL, AND SOCIAL IMPLICATIONS (ELSI)
As an integral part of the HGP, the NHGRI has set aside a portion of its
funding to anticipate, analyze, and address the ethical, legal, and social
implications (ELSI) of the Project's new advances in human genetics.
The ELSI program has established four priority areas: privacy and fair use of
genetic information; responsible clinical integration of new genetic
technologies; ethical issues surrounding the conduct of genetics research;
and professional and public education about these issues.
A major focus of the ELSI project over the past year has been to work to
ensure the responsible use of genetic information. The number of genetic
tests available to consumers is increasing at a rapid rate. Although these
tests have great potential to be beneficial to patients and their families, there
is also potential for misinterpretation or misuse. Safeguards must be in place
to protect individual privacy and prevent insurance and employment
discrimination.
On July 14, 1997 President Clinton announced that the Administration will
support specific legislation to prohibit health insurers from using genetic
information to discriminate. The Administration's position is modeled on the
recommendations developed by the NIH-DOE Joint Working Group on the
Ethical, Legal, and Social Implications of Human Genome Research (the
ELSI Working Group) and the National Action Plan on Breast Cancer.
More information about NHGRI research can be found on the Internet at www.nhgri.nih.gov.
NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
The National Institute of Neurological Disorders and Stroke (NINDS)
supports basic and clinical research on brain and nervous system disorders.
There is a growing awareness of the importance of diseases of the brain in
our society. In part this arises because our population is aging, and diseases
of the brain become more prevalent as one gets older. It is also due to the
growing awareness of the importance of a healthy nervous system in early
childhood and the brain's role in many problems that have not traditionally
been considered as biologically based diseases, conditions such as autism or
addiction or Tourette's syndrome. NINDS shares with a number of other
Institutes and Centers at NIH responsibility for research on the brain, and
cooperates with them in areas of mutual research interest.
NINDS has responsibility for more than 600 neurological disorders that
affect every age of the life span, ranging from well-known disorders such as
stroke, Alzheimer's disease, and epilepsy, which affect millions of
Americans, to a host of less well-known disorders that may affect a only few
hundred Americans, but are nevertheless devastating to those with the
disease and to their families. Most NINDS-funded research is conducted by
extramural scientists in public and private institutions, such as universities,
medical schools, and hospitals. They compete for grants and contracts that
account for more than 80 percent of the Institute's annual budget. NINDS
intramural scientists, working in 22 Institute branches and laboratories, also
conduct a wide array of neurological research, ranging from studies
uncovering structure and function in single brain cells to tests of new
diagnostic tools and treatments for those with neurological disease. By
supporting and conducting neurological research, the NINDS seeks better
understanding, diagnosis, treatment, and prevention of these disorders.
To achieve this goal, the Institute relies on both clinical and basic
investigations. Clinical research applies directly to disease detection,
prevention, and treatment, as in studies of brain imaging techniques and in
trials to test new drugs or surgeries for stroke. Although scientists studying
the brain have made astounding progress in recent years, a great deal is still
not known about its complex functions. Basic research pursues an
understanding of the structure and activities of the human nervous system.
The answers gained through this research can create the foundation for
diagnosing and treating brain disease in the future. Learning how the brain
stores memory, for example, may help scientists determine what happens
when memory fails and may even suggest possible ways to treat certain
dementias.
NINDS sponsors a rich portfolio of research focusing on disease and
disability associated with the aging brain, including Parkinson's disease and
stroke, two major areas of need and opportunity.
Parkinson's Disease. Parkinson's disease (PD) usually strikes in late middle
age and affects more than a half million Americans. It impairs control of
movement, progressing from symptoms such as tremor and muscular rigidity
to total disability and death. Parkinson's disease, like Alzheimer's disease,
amyotrophic lateral sclerosis (ALS), and Huntington's disease, is a
neurodegenerative disease, the causes of which remain largely unknown.
Clinical trials are underway to evaluate several pharmaceutical and surgical
interventions to treat PD. Promising studies of new drug therapies for PD
are continuing. Scientists conducting basic research studies are investigating
the genetic and cellular origins of the disease, and have discovered the gene
for one form of PD. These genetic findings open up the possibility for new
understanding of the disease and development of new therapies.
Stroke. For several years, NINDS has been reporting significant new
findings in the prevention of stroke. In 1995 NINDS-supported research led
to the identification of the first emergency treatment for stroke in which a
clot blocks a major brain artery. Clinical trial results showed that the drug,
tissue plasminogen activator (t-PA), increases chances for recovery by at
least 30 percent if given within three hours. The trial findings will guide
future attempts to develop additional treatments for stroke. Moreover, the
trial demonstrated how community health care systems can organize to
provide swift high quality care. To insure such prompt treatment, NINDS is
working with patient and professional organizations to publicize the research
results, helping public and health care professionals organize acute stroke
treatment in a variety of settings.
NINDS also supports research on many neurological disorders that affect the
entire lifespan. Examples include:
Epilepsy. Epilepsy refers to a group of disorders which have in common
recurrent seizures that are usually unprovoked and unpredictable. Seizures
are caused by abnormal activity in the brain and take many forms depending
on what parts of the brain are involved. In about half the cases no cause can
be found, but head injuries, brain tumors, lead poisoning, problems in brain
development before birth, and certain genetic and infectious illnesses can all
cause epilepsy. Medication controls seizures for the majority of patients,
who are otherwise healthy and able to live full and productive lives. On the
other hand, at least 200,000 Americans have seizures more than once a
month. Their lives are devastated by frequent, uncontrollable seizures or
associated disabilities. As part of an international coalition including the
Human Genome Project and scientists from Finland, NINDS-supported
investigations discovered a gene for one form of epilepsy. Understanding
the processes involved in this form of epilepsy opens up an entirely new area
of research that may provide insights about the cause of many forms of
epilepsy. This discovery should lead to a screening test, and perhaps to a
better understanding of what causes epilepsy and to new treatment
approaches. In addition, NINDS is conducting and supporting many
ongoing research efforts to identify and test new therapies.
Brain and Spinal Cord Injury. One reason trauma to the central nervous
system has such severe consequences is that neurons in the brain and spinal
cord fail to regenerate after damage. Now we know they make unsuccessful
attempts to regenerate, and in some circumstances can be coaxed to regrow.
NINDS is encouraging research in several areas with potential for success:
- High dose methylprednisolone, the first therapy to improve the
outcome of spinal cord injury, is now regularly used in emergency
rooms. The effects of longer methylprednisolone treatment and of a
new class of drugs are now being studied.
- Efforts to understand and repair trauma of the brain and spinal cord are
continuing, using grafts, nerve bridges, cell implants, cell survival
factors, antibodies, and genetic engineering. The potential use of
newly-discovered neural progenitor cells, nerve cells that may have the
capacity to replace cells lost because of trauma, is also under
investigation.
- Neuroprosthetic devices connect with the nervous system via electrodes
to stimulate muscles or provide sensory input. For example, a neural
prosthesis developed with NINDS support and recently recommended
for approval by the FDA restores hand function to quadriplegics.
Future research goals include a splint-free system to allow a paraplegic
person to rise, stand and sit again without assistance, and technologies
to control muscles using direct brain signals instead of a functional
neuromuscular stimulation implant.
Disorders of the Developing Nervous System. More than a third of all
genetic disorders affect the nervous system, and hundreds of these first show
symptoms in children. In the past several years, research has rapidly
progressed in identifying genes for a number of these disorders.
Approximately 50 genes have been identified. Finding the defective gene
that causes a disease is only a beginning towards developing a therapy, but it
allows scientists to develop diagnostic tests, create animal models, learn how
the gene and its protein function to promote health or disease, and pursue a
reasoned strategy towards counteracting the defect. Another very exciting
area of research addresses the development of the brain in early life.