Mr. Chairman:
I am pleased to participate in this important hearing and to tell
you about our efforts to improve the Nation's health through
medical research sponsored by the National Institutes of Health
(NIH).
Organization and Role of the NIH
In 1940, President Franklin Roosevelt dedicated the grounds of
the NIH and first few buildings of the new Bethesda campus. As
the Nation braced itself against a world defending into war, the
President reminded America that our "total defense involves a
great deal more than building airplanes and ships, bombs and
guns. . . .We cannot be a strong nation," he said, "unless we are
a healthy nation."
After five and a half decades of growth, the NIH of today is the
largest and most successful medical research institution in the
world, with a budget of nearly $12 billion and a major impact not
only on this Nation's health, but on health status worldwide.
More than eight out of every ten research dollars appropriated to
the NIH flow out to the scientific community across the Nation,
primarily in the form of peer-reviewed research grants. Today
that community numbers more than 50,000 investigators affiliated
with nearly 2,000 universities, hospitals, and other research
facilities located in all 50 states, the District of Columbia,
Puerto Rico, Guam, the Virgin Islands, and points abroad.
Approximately 10 percent of the NIH budget supports a program of
basic and clinical research activities administered and staffed
by our own physicians and scientists. In addition to basic
research laboratories, this in-house, or intramural, research
program includes a research hospital, the NIH Clinical Center,
Each year, more than 20,000 children and adults from all over the
country, and some from abroad, are referred to the Clinical
Center for experimental treatment and study.
Today's NIH is a federation of 24 Institutes, Centers and
Divisions that seek to expand knowledge about living systems and
apply that knowledge to improve human health. Perhaps the bed
known NIH research institutes are those that focus either on a
particular disease, such as the National Cancer Institute, or on
an organ system, such as the National Heart, Lung, and Blood
Institute. Other Institutes and Centers attend to overarching
scientific needs and opportunities, such as the National Center
for Human Genome Research, while others focus on stages of human
development, such as the National Institute on Aging. Other NIH
components are responsible for developing the array of
technologies and resources that are vital to innovative and
efficient research; for example, the National Center for Research
Resources oversees the General Clinical Research Centers, which
provide core resources, such as specialized personnel and
sophisticated laboratories, to clinical investigators around the
country.
Multiple Institutes and Centers often address different aspects
of a single health problem faced by our citizens. For example,
research on Alzheimer's disease takes place in Institutes devoted
to neurology, aging and mental health, This feature, witch is
essential to the research effort, requires dose interactions
among the Institutes and Centers; these may be informal (such as
scientists talking with one another), or they may be guided by
inter-Institute committees or by NIH-wide coordinating offices
that are located in the Office of the Director (e.g., the Office
for Research on Women's Health.) This rich matrix of research
activity requires open and Collegial dialogue among the
Institutes and Centers and thrives in an atmosphere that
maximizes flexibility in the pursuit of knowledge. 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.
How NIH Works Toward the Goal of Improved Health
The human body is complex and the diseases to which it is
susceptible are legion. So we approach the goal of improving the
Nation's health aware that many experimental strategies require
years, often decades, of effort to make major advances against
each disease.
While no single pathway can be described as the common route to
success, it is apparent that many advances demand the talents of
laboratory scientists who work on fundamental aspects of living
organisms; clinicians and epidemiologists who describe the
conditions we attempt to prevent or cure; clinical investigators
who use their knowledge of both disease and scientific advances
to devise and test new therapeutic or preventive strategies; and
industry-based scientists who finally develop new drugs and
devices and help to bring them to market. This means that NIH
must provide financial support for many lands of work and promote
training programs that develop talented people to do the work.
It is important to understand that most NIH-funded research is
"investigator-initiated,"That is, the research ideas we fund
are proposed by the scientists themselves, not by the NIH. By
mistaking our traditional standards of scientific excellence
through peer review, the NIH uses competition among the most
highly trained scientists in the world to ensure that Fed" funds
are distributed to the most promising research projects; at
present, only one out of four meritorious proposals can be
funded. However, because of the broad constellation of public
health needs, scientific opportunities, Executive and
Congressional interests, and other factors that bear on the
course of the Nation's investment in medical research, the NIH
must constantly reevaluate its programs and have the flexibility
to make necessary changes.
The process of examining research priorities is not reducible to
a simple flow chart or time line. It takes place at several
distinct levels in the NIH organization and is occurring all of
the time, Priorities are set both within the Institutes and
Centers by their Directors, but, as Director of the
NIH, I assume ultimate responsibility for the overall
distribution of funds among our research
program.
The NIH must also ensure that the cadre of scientists we fund
have adequate facilities and equipment to conduct their work. In
fact, many of the advances in medical research that are leading
to ever more effective treatments for illness reflect stunning
innovations in sophisticated but often costly, research
technologies that are far beyond the capacity of all but a
handful of institutions to purchase, construct, or maintain. NIH
recognizes that ensuring broad access to these research resources
creates efficiencies that make the research dollar go farther,
while providing critical resources to all scientists. Often,
access to the needed tools by the largest possible number of
scientists determines the pace of research on many devastating
illnesses.
A partial solution to the problem of expensive technologies and
scarce resources already exists, and is being practiced through
innovative "'shared resource" centers funded by NIH. For
example, NIH's National Center for Research Resources funds one
shared resource network, built around its Shared Instrumentation
Grant Program, that involves some 60 biotechnology centers around
the country. At present, more than 7,000 investigators use the
network for about 5,000 research projects. Another example is
the Frederick Biomedical Supercomputer Center in Frederick,
Maryland, a resource for the world's medical research community.
Through this center, scientists working out of their home
institutions can obtain assistance in the use of the latest
computational methods to exploit and refine biological research
techniques and amass data important to their research.
Emphasis on sharing research resources is a relatively new
phenomenon brought about by increased sophistication and cost,
but progress in medical research and the practice of medicine has
always required sharing of information. The NIH has a
longstanding tradition of providing a steady flow of information
about important research discoveries and other medical
information to the research community, to health care providers,
and to the general public.
For example, one of the primary mandates of NIH's National
Library of Medicine is to ensure that health professionals around
the world have access to the latest published medical knowledge.
Last year, users of MEDLINE, a database with eight million
references and abstracts to medical journal articles, conducted
7,5 million searches. Half of these searches were for purposes
of patient care and were conducted in hospitals, clinics and the
offices of individual health care providers. This vital
information base connects health care professionals in even the
most rural area of the country to the latest medical advances.
Another way in which the NIH communicates the results of medical
research is through "clinical alerts." These provide health-care
practitioners with immediate news of significant research results
that affect clinical care, The full range of electronic and print
media are employed in these instances to ensure immediate
attention to the lifesaving (or life-threatening) potential of
the latest research findings.
NIH is also an invaluable resource for the general public,
including the nearly two million people who directly request
medical and health information each year, NIH's Cancer
Information Service alone (1 -800-4-CANCER) handles more than
600, 000 telephone inquiries annually. The recently created NIH
Home Page on the World Wide Web will soon include 110 of the
"best selling" consumer health booklets from the NIH. In an
effort to explore new ways of reaching the public, NIH recently
funded two pilot episodes for Health Week, a Maryland Public
Television news magazine about health covering such topics as
spinal cord injury, angiogenesis in cancer and heart disease,
melatonin, and the obesity gene. A unique aspect of the program
is the provision of "access points"-phone numbers, Internet
addresses and mailing addresses--to give the public avenues
exploring the health issues covered in greater depth.
To fully reap health benefits from the knowledge gained through
fundamental investigations, NIM must have in place efficient
processes for transferring knowledge and technology from
NIH-funded program to the private sector, where biotechnology and
pharmaceutical firms are poised to translate what we produce into
products that improve health and prevent disease.
NIH's technology transfer effort in its intramural research
program relies on two principal mechanisms, Cooperative Research
and Development Agreements (CRADAS) and the patenting and
licensing of research inventions. Over the decade ending with
fiscal year 1995, NIH intramural scientists negotiated 269 CRADAs
with private organizations to support a wide range of research
activities. Between 1985 and 1995, NIH was awarded 560 patents
on inventions made by our intramural scientists, and we
negotiated 713 licenses to develop commercial applications based
on those patents. The products that resulted from these patents
include a simple, accurate and inexpensive screening test for HIV
infection that also can be used to monitor and ensure the safety
of public blood supplies, two major therapeutics against
HIV-infection, and vaccines for the treatment of Hepatitis A and
for treatment of chronic B-cell leukemia.
Recipients of NIH support in the extramural community promote
technology transfer by two analogous mechanisms. Each
institution is entitled under the Bayh-Dole Act to seek patent
protection and licensing arrangements for the inventions made by
their employees while working with NIH funds. In addition, many
of these institutions have negotiated agreements that allow NIH
grantees to receive additional support from industries for
separate research projects. Another extremely important means of
technology transfer involves the traffic of personnel, especially
from NIH-supported graduate and post-doctoral training programs
to jobs in the industrial sector. The vitality of NIH research
programs, therefore, has a direct impact on the strength of our
Nation's industry, since the workforce in the pharmaceutical and
biotechnology fields is trained to do science in the context of
our training and research activities.
Advances in Medical Research That Have Led to Chances in Clinical
Practice
To have an impact on improving health and combating disease,
scientists need to develop and work from a body of basic
knowledge. The path leading from now findings to changes in
clinical practice can be very long, often measured in decades.
Many of the dramatic changes that have occurred in American
medicine over the past fifty years are based on insights drawn
from the traditional biomedical sciences, such as microbiology,
physiology, pathology, immunology, and chemistry. The following
brief stories about important, relatively recent developments in
the prevention and treatment of disease illustrate some of the
ways in which new knowledge has gradually led to improvements in
the country's health.
Haemophilus influenzae type b (Hib) is a serious bacterial
infection that once affected almost 25,000 children in the U.S.
every year, especially infants. Of the nearly I 5,000 infants
affected by Hib-related bacterial meningitis, up to 10 percent
died and 20-30 percent of the survivors suffered permanent health
consequences, especially mental retardation. In 1985, based on
an understanding of the unique chemical nature of Hib antigens
and the epidemiology of Hib in children compared with adults,
scientists developed the first effective vaccine against Hib for
children older than two years. But to make a vaccine effective
for infants, it was necessary to exploit decades of research in
chemistry and immunology to develop a novel technology that
linked sugars from the outer coat of the Hib bacterium to an
immunity-boosting protein. Today, thanks to the new vaccines,
Hib disease has decreased by over 95 percent among infants as
well as children; the vaccines have been estimated to save more
than $400 million per you.
Cancer of the testis is a relatively rare cancer afflicting about
5,000 men annually, but it usually strikes young men, 20-40 years
of age. In 1965, a biophysicist working at Michigan State
University made an unexpected observation that ultimately changed
the outlook for men with testicular cancer: he found that when
an electric current was generated with platinum electrodes in a
bacterial culture, normal cell division was inhibited. The
inhibition of cell division was soon found to be caused not by
the electric current, but by the generation of a small amount of
a well-known chemical, cisplatin, from the platinum electrodes.
After much collaborative work with the National Cancer Institute
and a pharmaceutical firm, scientists found that cisplatin could
inhibit cell division in other cells, especially cancer cells.
Later, it was recognized that testicular cancers responded
especially dramatically to cisplatin. Today, after two decades
of medical research based on an observation in biophysics,
testicular cancer has been transformed from a nearly uniformly
fatal disease to one that is 80-95 percent curable. Cisplatin is
not only responsible for saving lives; a cost-benefit analysis of
cisplatin-based chemotherapy estimated an annual savings of $150
million, mainly due to savings from the future earning potential
of survivors.
A half million Americans each year suffer from strokes, four out
of five of which are caused by a blood clot that blocks blood
flow to the brain. Years of NIH-supported laboratory research on
the biochemistry of blood clotting was essential to the
development of clot-dissolving drugs such as
tissue-plasminogen-activator (t-PA), which has been successfully
used in treating
heart attacks triggered by blood clots. More recently,
researchers have shown that t-PA is an effective emergency
treatment for stroke caused by blood clots when given within
three hours of initial symptoms. Among stroke victim to whom the
drug was administered in rigorous clinical trials, the proportion
who made excellent recoveries after three months increased by
30-50 percent. This is the first effective therapy for stroke,
stimulating work toward better therapies with even greater
preservation of brain function.
Research begun as a study of cholesterol in a rare disease
ultimately led to an effective treatment for all people suffering
from high blood cholesterol, a condition that cm inhibit blood
flow and lead to heart attack or stroke. This built-up
cholesterol is derived from low density lipoprotein, or LDL, in
the blood. Basic research more than two decades ago revealed
that the level of LDL in the blood is regulated by the LDL
receptor. This receptor, which is found on the surface of many
cells, binds to circulating LDL and removes it from circulation
by taking it into the cell, where it is broken down and used by
the cell. In studying patients with familial
hypercholesterolemia, a rare inherited form of high blood
cholesterol investigators discovered that LDL receptors were
either nonfunctional or severely defective. The discovery of
this receptor has revolutionized the understanding of cholesterol
and lipoprotein metabolism. Each step in the cellular processing
of cholesterol has now been meticulously defined. For example,
it is now known that the enzyme HMG CoA reductase is required for
cholesterol synthesis. Inhibition of this enzyme by a class of
drugs called "statins" forces the body to make use of cholesterol
in the blood. Thus, these drugs significantly reduce blood
cholesterol levels, decrease heart attacks and strokes, and
extend life in patients with mildly to severely elevated
cholesterol.
A long-term investment by the NIH in the molecular composition of
viruses, especially retroviruses, is directly responsible for
recent successes in the production of drugs effective against
HIV, the cause of AIDS. The most potent of these drugs are
inhibitors of an essential viral enzyme called a "protease," an
enzyme that cuts viral proteins into their working components.
Retroviral proteases were first discovered in viruses found in
chickens and mice; later, research revealed that retroviruses
cannot replicate--or reproduce themselves --without proteases.
Because HIV is also a retrovirus, scientists theorized that,
inhibiting HIV protease might block replication of the virus and
could lead to a new treatment for AIDS. The pharmaceutical
industry subsequently identified and developed agents that can
inhibit HIV protease. These therapeutic agents appear to be the
most effective and least toxic drugs now available to combat HIV.
Fundamental Research Findings Presage Advances in Human Health
Many of the recent advances in the control of disease, such as
those described in the preceding section, emerged from
discoveries made in the past several decades, and even a century
ago, about microbes, the immune system, hormones, and metabolic
pathways. Today, we are in the midst of a scientific revolution
based on gene isolation, DNA sequencing, sophisticated molecular
and cell biology, neuroscience, and study of the
three-dimensional structure of proteins. Based on our collective
experience with clinical advances developed from earlier
discoveries, it is reasonable to anticipate that new and more
effective means to combat a host of diseases will emerge over the
next few decades from the Current transformation of biological
sciences. Although it is impossible to predict exactly what
those means will be, there are many signs of new trends in
clinical practice.
Efforts to map human genes and determine the sequence of the
human genome are progressing at a greater than anticipated pace.
Over the past few years, investigators have isolated and
characterized genes that cause or predispose patients to cystic
fibrosis and many metabolic disorders; several neurological
diseases, including Huntington's disease and some forms of
Alzheimer's disease; and cancers of the breast, colon, kidney,
and other tissues. These discoveries are paving the way to: (i)
the more widespread use of genetic testing, to assess the risk of
future disease, as well as to diagnose disease; (ii) the
development of methods to introduce genes into appropriate cells
to treat both acquired and inherited illnesses ("gene therapy");
and (iii) the design of new strategies against disease based upon
a more profound understanding of the mechanisms that cause
disease.
The advent of molecular cloning and the dramatic growth of the
biotechnology industry have already produced several extremely
valuable clinical tools. These include bacterially produced
hormones, such as human growth factor, that offer advantages of
safety and expense; blood growth factors, such as erythropoietin
and granulocyte and platelet stimulants, that can reverse bone
marrow failure and shorten hospital stays for patients with
cancer, AIDS, and kidney disease; and new vaccines for hepatitis
B virus and others.
New methods for determining protein structures and the
interactions of proteins with other molecules are reshaping
approaches to the development of new pharmaceuticals. For
example, the cocaine receptor, a protein that transports dopamine
into cells, has been found to interact with cocaine and dopamine
at different sites, suggesting new ideas for medications against
cocaine addiction.
The recent isolation of genes from mice, rats, and humans that
regulate appetite and energy utilization and cause obesity and
diabetes has revolutionized approaches to these common medical
conditions. The genes govern an unexpected hormonal circuit
dominated by the hormone called "leptin" that is produced by fat
cells and responded to by the brain. New pharmaceutical products
that interfere with this circuit are likely to become important
agents in the control of obesity and its complications.
Clinical Research in Transition
A healthy biomedical research enterprise requires financial
support excellent facilities and equipment, and talented
personnel for a wide range of activities, from fundamental
laboratory research to clinical trials. Only in this way can
discoveries in the laboratory be converted to health benefits for
our citizens. Yet clinical research, both at the NIH and in the
extramural community, is threatened by deteriorating physical
facilities, inadequate recruitment and training of patient-
oriented investigators, and declining populations of clinical
subjects. The increasing dominance of managed care networks,
with their emphasis on cost control, further challenges research
and teaching activities at the Nation's academic health centers,
where most NIH-supported clinical investigation is conducted. We
need to be prepared to respond to these trends if we wish to
sustain the integrity of patient-oriented research programs at a
time when advances in genetics and cell biology promise dramatic
changes in the practice of medicine. During the past two years,
I have worked closely with my colleagues in both the intramural
and extramural communities to develop a plan to mounter this
nationwide erosion of clinical research. Our accomplishments and
further strategies include:
- Establishment of a Clinical Research Panel, chaired by
Dr. David Nathan of the Dana Farber Cancer Center, to advise
NIH on the funding of clinical research the training of
clinical investigators, and the revitalization of sites at which
such research is done. The Panel and its subcommittees have
been meeting and gathering information for nearly a year and
are expected to deliver recommendations to the NIH
Director's Advisory Committee this June.
- Development and implementation of a pioneering core
curriculum at the NIH to help prepare young physicians
for careers as clinical investigators. The central feature
of this curriculum is a course that runs throughout the
academic year and consists of four modules. These modules
introduce clinical fellows to important topics in clinical
research such as epidemiologic methods, ethical issues,
monitoring and regulating patient-oriented research, and approaches for
funding clinical research studies. We are making course
materials available to interested investigators and
training program directors across the country w that this program
can serve as a model for other health centers. We are, also
now televising Clinical Center Grand Rounds via satellite to
100 academic hospitals around the U.S.
- Establishment of a loan repayment program, Translating
advances from frontiers in fundamental science to the
bedside requires a cadre of highly skilled clinical researchers
trained in both laboratory and clinical research
methods. However, just when the scientific Opportunities beckon
talented physicians, we have seen a serious decline in
the numbers of trainees entering and completing clinical
research training. Part of the reason for this decline is the
burden of debt from earlier education. The median debt for
medical graduates in 1995 was $65,000, and debt is often
$100,000. Students may well conclude that this level of debt is
incompatible with pursuit of an academic career. For
this reason, approximately a year and a half ago, the NIH
established a loan repayment program in clinical research
for physicians from poor and disadvantaged backgrounds. We
are just now beginning to reap the fruits of that
investment. Nineteen physicians currently enrolled in clinical
research training on the NIH campus are receiving repayments of
their educational loans at $20,000 per year.
- Rexamination of the review of clinical research
proposals. Two years ago, a panel of scientists from wadeniic
institutions examined the fate of clinical research gmt
applications at NIH and recommended significant changes
in the review process for these grants. Once a new
director is selected for the NIH Division of Research Grants, an
initial task will be to find innovative ways to implement some
of these recommended changes in peer review.
- Improved monitoring of NIH-funded and conducted clinical
trials. Last summer, the NIH Office of Extramural Research
evaluated clinical trials supported and conducted by the
NIH Institutes, Centers, and Divisions in order to spring
mechanisms for oversight of these trials. These
findings will be further considered by the Clinical Research
Panel.
- Negotiated agreements for reimbursement for participants
in clinical trials. Last month, the National Cancer
Institute (NCI) signed an important agreement with the Department
of Defense that will permit members of the armed forces and
their dependents to enroll in NCI clinical trials under
the CHAMPUS health care system. This could become a model
for reimbursement by other health care providers and
insurers for experimental treatments for many diseases and help to
reverse the trend that is drawing patients away from research
projects into forms of care thought to be less costly.
- Construction of a new NIH Clinical Research Center, In
the FY 1997 budget for NIH the President requests a total of
$310 million to replar-e the existing 43 -year old NIH
Clinical Center, much of which is now functionally obsolete,
inefficient and potentially unsafe to operate, and
expensive to maintain. The Clinical Center houses nearly half of
all federallyfunded clinical research beds in the country
and accounts for one-fourth of all federally funded
outpatient clinical research visits. These patients account for
approximately 65,000 inpatient days and 70,000 outpatient
visits for experimental treatment and for the study of
frequently occurring as well as rare or "orphan"
diseases.
- Improved NIH Clinical Center operations. This year, the
DHHS Secretary commissioned a review and report on options to
improve the efficiency of Clinical Center operations.
The review panel reconunended changes in the governance,
funding and management of the facility. Many of these changes
are already being made, but others can be fully implemented
only when the new Clinical Research Center is in operation.
- Increased clinical collaboration with physician-scientists
in academic health centers. NIH intramural scientists are
already collaborating with extramural scientists on
clinical projects, fbr example through sabbaticals at the
Clinical Center, via telemedicine, and through programs that
provide one-day-a-week use of the facility for extramural
researchers. Once the new 250-bed Clinical Research
Center with its associated laboratories is completed,
extramural-intramural collaborations will increase, thereby
strengthening both intramural NIH and the Nation's
overall medical research enterprise.
Economic Benefits of NIH-Sponsored Research
NIH-funded discoveries not only improve the Nation's health, but
also result in economic benefits to the nation and the
individual. NIH research helps support skilled jobs both at
academic institutions and in the many U.S. companies that provide
materials and instruments used in research. Many of the
successes in the biotechnology and pharmaceutical industries are
related to NIH support of clinical and laboratory research. In
1994, the 1,311 U. S. biotechnology firms employed 103,000
people and generated $11.2 billion in revenues. Recent research
suggests a direct linkage between the presence of highly
productive scientists, most of whom receive NIH support and an
increase in start-ups and the growth of new biotechnology
companies. In addition, the top 15 U.S. pharmaceutical
industries--whose work is based upon fundamental research funded
by NIH for decades--employed more than 350,000 people and earned
profits of $13.3 billion on sales of $84.8 billion.
NIH-supported research has also led to many "spin off"
technologies including: agriculture (genetically altered plants
and animals are improving yields and extending the shelf life of
common foods); manufacturing (genetically-engineered enzymes are
revolutionizing the production of many chemicals); and the
environmental sciences (modified bacteria and biophysical methods
are inexpensively restoring soil and water to their natural
states following industrial contamination).
In some cases, medical research does not yield marketable
products, but still contributes to public health and yields
substantial cost savings. For example, NIH-funded research has
demonstrated that weight training for the frail elderly reduces
the risk of falls and the associated costs of hospitalization.
By helping to create and sustain a healthy, productive
population, NIH provides immeasurable benefits to the Nation.
Economic studies will increasingly be called upon to demonstrate
how the Federal funds received by NIH significantly improve
public health, enhance the productivity of health-related
industries, and contribute more generally to the well-being of
society and the Nation. For example, the development of
law-based photocoagulation treatment for early stage diabetic
retinopathy can arrest impairment of vision at a later stage and
has been estimated to save the Nation over $1 billion per year.
The use of clozapine as maintenance treatment for schizophrenia
reduces the need for hospitalizations costing $1.4 billion per
year. Estrogen replacement therapy lowers the rate of hip
fractures among women aged 65 and older and is estimated to save
$333 million per year.
Conclusion
For more than five decades, medical science supported by NIH has
benefitted from the
unwavering support of our Nation's citizens and their leaders.
The resolve to create and sustain a program of superlative
medical research has yielded multiple benefits, including vast
improvements in human health and well-being; significant
contributions to the economy; and an extraordinary store of
knowledge related to basic biologic mechanisms, the causes and
course of disease, and innovative treatments.
The pace of progress in medical science is astoundingly rapid.
But it is clear that the most critical scientific discoveries and
the clinical applications of these discoveries still lie ahead.
I believe the great potential for continued progress merits
consistent federal support for medical research.
I will be pleased to answer any questions you may have.
