I am Harold Varmus, Director of the National Institutes of Health (NIH), and I am pleased to appear before you to discuss the revitalization of the NIH.
Organization and Purpose of the NIH
The NIH is a confederacy of twenty four organization units that
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
often attempts to understand complex biological systems by
examining individual molecules, cells, or tissues; some addresses
normal human biology and disease in the context of living
subjects; and some is based on the study of human populations.
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 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 (IC's), each of
which has authorities defined by earlier legislation. Seven IC's
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, and the National Institute of
Arthritis and Musculoskeletal and Skin Diseases. Four IC's 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 IC's focus on stages
of human development: the National Institute of Child Health and
Human Development and the National Institute on Aging. Five
other IC's study particular aspects of human health or area of
science: the National Institute of Mental Health, the National
Institute of Environmental Health Sciences, the National
Institute of General Medical Sciences, the National Institute for
Nursing Research, and the National Center for Human Genome
Research.
Other IC's 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 collects, disseminates, and exchanges
biomedical information. The NIH organization also includes three
independent Divisions without budgetary authority. The Division
of Computer Research and Technology and the Division of Research
Grants carry out research management functions involved in 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 advance human health.
A Seamless NIH
Although each of the IC's 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, IC's often address different aspects of the major
health problems faced by our citizens. This feature requires
close interactions among the IC's; 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 IC's 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.
My colleagues and I will attempt to display these attributes of
the NIH in the presentations to be made by each of the five
panels that will testify during the remainder of this hearing.
The Committee will hear about four important problems in medical
science --- cancer, degenerative diseases, neuroscience, and
infectious diseases --- and will learn about the physical and
intellectual infrastructure that supports our work. In each
presentation, we will emphasize the multidisciplinary approach
that is undertaken by IC's working collaboratively to address the
Nation's health.
An Illustrative Example
I will begin with an illustration of how the NIH does research,
describing a common condition that almost everyone in our country
worries about --- obesity. To some, obesity may appear to be a
simple problem: too much fat in a body that ingests too much
food. But, in fact, obesity is a problem with complex origins
and complex manifestations; as a result, it engages the energies
of many of our IC's, as well as other government agencies, and
demands a wide variety of technical approaches.
At least six major issues need to be confronted (Chart 1): the
definition and prevalence of obesity; the factors that contribute
to its cause; the other medical conditions to which it
predisposes; and the preventive and therapeutic strategies that
can be used to control it. At the NIH, the National Institute of
Diabetes, Digestive, and Kidney Diseases (NIDDK) leads the
efforts to confront most of these issues, both by supporting a
great deal of research on obesity and diabetes and by housing
several organizations --- the National Task Force on Prevention
and Treatment of Obesity, the Weight-Control Information Network,
and the Office of Nutrition--that help to coordinate research
activities and interpret and disseminate the findings. But at
least ten other IC's support studies of obesity and its
complications and participate in the coordinating functions. In
addition, several program offices in the Office of the Director,
NIH --- the Office of Research on Minority Health, the Office of
Research on Women's Health, the Office of Disease Prevention, and
the Office of Behavioral and Social Sciences Research --- help to
guide obesity research in the areas of their expertise.
Largely through the work of the National Health and Nutrition
Examination Surveys, conducted by our sister agency, the Centers
for Disease Control and Prevention, we know that obesity, as
currently defined, afflicts about 50 million adults, roughly one
third of the population over 30 years of age. The condition
disproportionately affects women, minorities, and the poor.
Unlike most other risk factors for cardiovascular disease, such
as smoking, hypertension, and blood lipid levels, obesity has
become substantially more common in the past decade, especially
among children and adolescents.
The importance of obesity as a subject for research by the NIH is
underscored by its impact on the morbidity and mortality of our
citizens (Chart 2). Obesity is second only to tobacco as a risk
factor for disease, accountable for about 300,000 deaths per year
and an economic cost of between 50 to 100 billion dollars. Of
the diseases promoted by obesity, cardiovascular disorders and
diabetes (non-insulin dependent diabetes mellitus NIDDM ) are
probably best known; but obesity also increases the likelihood of
several cancers, stroke, gall bladder disease, gout, and
osteoarthritis, and is associated with eating, sleep, and mood
disorders. For these reasons, obesity is studied from many
vantage points by a large number of the organization units at the
NIH.
The rising prevalence of obesity attests to our inability to
control it effectively, despite the fact that at any one time
about one third of our adult population claims to be engaged in
weight control activities --- dietary, pharmaceutical, and
behavioral modification programs. A recent NIH Consensus
Conference, organized by the Office for Disease Prevention in
collaboration with the White House Council on Physical Fitness,
strongly recommended greater attention to increased physical
activity as a means to control weight, in part because it
provides health benefits even in the presence of obesity. In
addition, behavioral research shows long-term benefits to obese
children receiving family-based therapies. But, in general,
weight loss is transient with the methods now in widespread use,
and the dangers of frequent cycles of weight gain and loss have
not been fully assessed.
In the long run, the best prospects for control of obesity reside
in a better understanding of its origins. Many factors are now
known to contribute to obesity (Chart 3). Several of these
(such as gender or socioeconomic status) are difficult or
impossible to alter, but others (such as dietary habits and
physical activity) should be amenable to change through
instruction. The difficulty in achieving long-term behavioral
changes accounts in part for the public excitement about some
remarkable recent discoveries of genetic factors controlling
obesity and obesity-associated NIDDM in animals.
Mice and rats with certain inherited mutations that predispose to
obesity and NIDDM (Chart 4) are now known to lack a hormonal
mechanism for maintaining healthy patterns of eating and
activity. Through this mechanism, the animals --- and,
presumably, human beings-- regulate diet and exercise through the
brain's response to a hormone, called leptin, that is produced by
fat cells. Although it appears unlikely that this hormone is
itself deficient in a significant number of obese people, the
isolation of the genes for leptin and the leptin receptor has
already deepened our understanding of metabolism and stimulated
additional fundamental research. Furthermore, applied studies
already underway in the private sector may yield more potent ways
to control body fat and thereby prevent NIDDM and other
complications of obesity.
Challenges to the Continued Productivity of American Medical
Research
Throughout the course of these hearings, we will present many
examples of excellence in NIH-supported research programs, the
basis for our Nation's uncontested role as the world leader in
medical research. But to remain strong, the NIH --- and the
American research enterprise generally --- must be capable of
adapting to very substantial demographic, economic, and other
changes in our society. These changes are already beginning to
affect the kinds of problems we study, the way we finance medical
research, and the recruitment and training of new scientists.
Demographic changes and disease incidence. Although public
health has improved dramatically over the past half-century, due
in large part to NIH-supported biomedical research, current
demographic trends are creating new health problems. The aging
of the U.S. population, for example, is leading to an increase
in chronic and degenerative diseases, as will be presented by one
of tomorrow's panels. More people are surviving acute illnesses
and injuries that were once invariably fatal. As the number of
minorities in the U.S. grows, diseases such as diabetes
mellitus, which disproportionately affects members of some
minority populations, will become more prevalent. These changes
and many others that affect the distribution of illness must
inevitably affect the emphasis we place on the study of various
diseases. They also demand that we have the flexibility to
respond as an institution to new health threats and to
recurrences of old ones. Current concerns about emerging and
re-emerging infections, as discussed by another of tomorrow's
panels. illustrate this problem well.
Changes in health care delivery and clinical research. Systemic
changes in the financing and delivery of health care also may be
producing substantial effects on the Nation's biomedical research
capacity. Most NIH-supported medical research, especially
clinical investigation, is conducted at academic health centers.
During the 1980s, these centers began to rely heavily on clinical
revenues to subsidize the costs of both teaching and research.
As more patients enroll in managed care organizations, however,
referrals to the centers could decline, because their multiple
missions drive up service costs. As a result, less clinical
revenue may be available to support biomedical research. In
addition, managed care providers are reluctant to support the
costs of clinical research by covering hospitalization and other
health care needs for patients enrolled in clinical trials.
These changes will affect the capacity of some academic medical
centers to conduct research, particularly patient-oriented
research. They may also affect the availability of research
subjects for clinical trials. In addition. as the States
increasingly adopt managed care plans under their Medicaid
Programs, recruitment of minorities and underserved populations
into clinical trials may be more difficult. These trends could
slow the discovery of new treatments for many diseases.
The NIH is attempting to respond to these changes by providing
better oversight of clinical research in both the extramural and
intramural sectors. The NIH Director's Clinical Research Panel is
seeking new sources of funds to support clinical research,
evaluating the programs for recruitment and training of clinical
investigators, and determining where clinical research can be
most effectively conducted. The NIH Clinical Center is also
undergoing major changes in governance, financing, and daily
function, as a result of a recent REGO II evaluation, and it has
strengthened its training programs in clinical research.
Yesterday, the NIH and Department of Defense announced a
demonstration project that we believe could serve as a model for
future partnerships in health care between the health insurance
industry and medical research community. The National Cancer
Institute and the DoD signed an agreement that formalizes the
process by which patients who are beneficiaries of DoD's health
benefits program can participate in NCI-sponsored clinical
trials.
Changes in the recruitment of new scientists. The number of
scientists working in fields supported by the NIH has increased
in the past decade. As a result, research scientists face more
competition for jobs, especially in the academic sector; a lower
likelihood of success when applying for NIH grants; longer
periods of graduate and post-doctoral training; and considerable
and justifiable anxiety about their long-term productivity and
career prospects. These problems have been offset somewhat by
increased hiring in medical research industries-including
biotechnology, research supplies, and pharmaceutical companies.
In addition, new Ph.D.s and M.D.s have pursued new career
options, including patent law, science policy, journalism and
business.
The need for research in the health sciences is unlikely to
diminish in the decades ahead. Our ability to maintain the
momentum of recent scientific progress and our international
leadership in medical research depends on the continued
production of new, highly trained investigators. We do not plan
to reduce our efforts to recruit new investigators, especially
from under-represented sectors of the population, or to curtail
our training programs for graduate and post-graduate students.
We do, however, agree with a recent report from the National
Research Council that argues that trainees should be better
acquainted with the wide variety of new career opportunities that
have been created by the remarkable success of medical science.
Proposed Authorization Legislation
I support the authorization process. and am pleased the Committee
has undertaken these hearings. Authorization can play a strong
role in facilitating NIH's ability to conduct research. NIH has
been working with the Department to develop authorization
proposals that will help NIH advance scientific excellence in
basic and clinical research. We look forward to sending the
Committee a letter from Secretary Shalala outlining these
authorization proposals in the coming weeks.
Our proposals will likely fall into four broad areas: research
training; improving NIH' s administrative efficiency and
flexibility, ensuring that all of NIH's Institutes, Centers, and
Divisions, including the National Center for Human Genome
Research, possess similar authorities; and extending the
authorization of the NIH Office of AIDS Research. Each of the
authorization proposals HHS submits to the Congress will help NIH
capitalize on new areas of scientific opportunity. Extending the
authorization of the Office of AIDS Research, which plans,
coordinates, and funds all NIH AIDS research, will guarantee that
NIH has the flexibility to respond immediately to the many
promising new avenues of research that will help us fight AIDS.
Central to this flexibility is retention of the Office of AIDS
Research's budgetary authority.
Conclusion
When I first appeared before this Committee on November 2, 1993,
as part of the process leading to my confirmation as Director of
the NIH, 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. I believe
that you will see many examples of the fruits of that pledge in
the course of our testimony over the next two days. I hope we
will convince you that the NIH continues to thrive and that its
reauthorization is richly deserved.
I look forward to working with the Committee on the
reauthorization of NIH and would be pleased to answer any
questions you may have.
**Attached are 3 charts.
Chart 1
Obesity Issues
Definition
Prevalence
Causative Factors
Associated conditions
Prevention
Treatment
Chart 2
Conditions Associated with Obesity
Obesity is in the middle with the following conditions pointing
to and from it.
- Hypertension
- Stroke
- Heart Disease
- Hyperlipidemia
- Non-Insulin dependent Diabetes Mellitus
- Osteroarthritis
- Mood Disorders
- Sleep Disorders
- Eating Disorders
- Gout
- Gall Bladder Disease
- Some Cancers
Chart 3
Causative Factors
Obesity is in the middle with the following conditions pointing
to and from it.
- Nutrition
- Smoking Cessation
- Gender
- Race
- Socio-economic Status
- Age
- Genetic Factors
- Metabolic and Endocrine Status
- Pregnancy
- Activity Level
Chart 4
is omitted from this version.
