I am pleased to present the President's budget request for the National Institutes
of Health for Fiscal Year 1998, a sum of $13.078 billion, an increase of $337 million (or
2.6%) above the FY1997 appropriation.
The pace of medical research: Retrospective
This is the fourth year that I have been privileged to represent the NIH at this
Committee's proceedings. As on previous occasions, the Institute Directors and I will
soon provide you with a summary of remarkable scientific accomplishments from the
past year and a description of some exciting paths our research is likely to take in the
coming year. This annual process of recounting our performance and predicting future
productivity is important, stimulating, and necessary. But it should not obscure some
essential features of our activities: that our ultimate task, the conquest of disease, is
formidable; that the course of progress is best measured over many years or decades,
rather than over a single year; that scientific advances require a long-term investment in
training and facilities, as well as research projects; and that the benefits of research are
unpredictable, demanding work on a broad range of topics to achieve success with even
a single problem.
Some of these features are dramatically illustrated by recent events in our battle
against the human immunodeficiency virus (HIV) and the acquired immunodeficiency
syndrome (AIDS). In the past year, the world has learned that many people with AIDS
can experience dramatic improvement after treatment with a new class of anti-HIV
drugs, called protease inhibitors, especially when combined with another class of drugs,
called reverse transcriptase inhibitors. Although far from perfect, such potent anti-viral
agents are unprecedented in the history of virology, and the achievements have been
appropriately heralded in many news stories, including New Year cover stories in the
lay press (Time magazine) and the science press (Science magazine).
But the history of these accomplishments encompasses much more than a single
year; it reaches back over many years and in many directions. It extends to the early
isolation of retroviruses from birds and rodents, as long ago as 1910. To the
identification in the 1970's of retroviral enzymes---reverse transcriptase and protease---that
now serve as targets for the anti-viral drugs. To the determination of the three-dimensional
structure of these enzymes a few years ago. To the development of
inhibitors of cellular proteases over twenty years ago for the treatment of hypertension.
To the lengthy training of investigators competent to pursue basic science, drug
discovery and development, and clinical testing. And to the strength of our nation's
laboratories, developed over decades, in governmental, academic, and industrial sectors.
The pace of medical research: Prospective
The breadth and depth of the investments required for the success of protease
inhibitors underscore the importance of the strong bipartisan support that the NIH has
received for the past fifty years. It is our responsibility to bring here each year new
signs that such continued confidence is warranted and likely to produce future
dividends. Thus, while we can take pride in end products, such as protease inhibitors, it
is even more important to showcase recent discoveries, especially those findings from
which many lines of investigation are likely to grow and measures to combat disease are
likely to develop.
To illustrate this point, I would like to refer again to the field of HIV research,
this time to describe a recent, long-awaited finding that holds special promise. Soon
after the discovery of HIV in the early 1980's, investigators found that CD4, a well-known
protein on the surface of certain T lymphocytes, was required for HIV to attach
to and infect target cells. But it was also learned that at least one other protein was
required, and those proteins---the so-called co-receptors---remained elusive for many
years.
About one year ago, a research group in the NIH intramural program used an
ingenious detection method to unveil co-receptors as members of a class of cell-surface
proteins we already knew a great deal about---proteins that normally allow cells to
detect secreted signaling molecules called chemokines. This discovery was especially
exciting because another group of NIH intramural scientists had shown that certain
chemokines could interfere with infection by HIV. Now we recognize that the
interference is due to blockade of a co-receptor. Recently, some individuals were found
to carry mutations that prevent production of a co-receptor. Because these people are
actually resistant to infection by HIV, yet otherwise normal, co-receptors have emerged
as prime targets for therapeutic and preventive strategies against HIV, stimulating a
frenzy of experimental activity towards those goals.
Recent culminations and inspirations
For dramatic purposes, I have chosen to present in detail two paradigms of
success---one representing culmination, another inspiration---from the domains of AIDS
research. But other examples abound.
The culminations are visible as practical health benefits, often accompanied by
economic benefits:
- The first successful treatment for stroke, using recombinant tissue plasminogen
activator (tPA).
- Increasing use of cell growth factors to protect patients against the bone marrow
toxicities of cancer and AIDS therapies.
- Declining mortality rates for many cancers, including some common ones.
- Reduction in disability rates among the elderly.
- The virtual elimination of Hemophilus influenza as a cause of childhood
meningitis, due to widespread use of a new vaccine.
- Recent inspirational discoveries are also legion, especially in the fields of
genetics, molecular biology, and neurosciences:
-
The genomes of baker's yeast and several bacteria (including the experimental
warhorse, Escherichia coli) have been fully sequenced; a detailed map of the human
genome as been assembled and posted on the Internet; and innovative technologies are
being harnessed to understand this genetic cornucopia.
- The locations of still unknown genes implicated in Parkinson's disease, prostate
cancer, and other diseases, have been narrowed to small chromosomal regions, implying
imminent isolation; and genes involved in many other disorders (such as retinitis
pigmentosa, polycystic kidney disease, many birth defects, basal cell carcinoma,
hemochromatosis, and some forms of diabetes) have been isolated and characterized.
- The precise changes that occur in genes during our lifetimes are telling us how
environmental agents, like tobacco and sunlight, cause cancer by inducing mutations,
and how normal mechanisms for correction of DNA can fail, allowing harmful mistakes
to persist in our genetic material.
- Experimental manipulation of genes in mice has produced new animal models for
studying many diseases (including Alzheimer's Disease, cardiac and vascular diseases,
developmental defects, drug abuse, cancers, and others).
- New imaging methods are informing our understanding of the central nervous
system during early development, behavioral change, learning, pain, and emotion, and in
a variety of disease states, including drug addiction.
Recently-identified molecules that govern the behavior of nerve and muscle cells
are providing new prospects for repairing injury and degeneration in the brain and spinal
cord.
- Such advances inspire further work and support our request for appropriated
funds for FY1998. To help you see what these funds are likely to accomplish in the
immediate future, the Institute Directors and I have identified many of the most exciting
topics of on-going and anticipated research and grouped them within six broad Areas of Research Emphasis: the biology of brain disorders, new approaches to pathogenesis,
preventive strategies against disease, therapeutics and drug development, genetics of
medicine, and advanced instrumentation and computers. These categories of research
reach beyond Institute boundaries to highlight the disciplines that we judge to show
special promise for further discovery and practical application. You will be hearing
from individual Institute Directors during the next two weeks about many specific
examples that illustrate why we believe these topics to warrant such high priority.
Clinical research and the new Clinical Research Center
In my appearance before this Committee last year, I emphasized my concerns
about several aspects of clinical research, especially the need to reinvigorate, reorganize,
and rebuild the Clinical Center at the NIH. Since then, we have received $90 million in
FY1997 appropriated funds that allow us to proceed with the detailed planning and
initial construction of what will be the Mark O. Hatfield Clinical Research Center. We
have established a Board of Governors to oversee management of the Clinical Center, in
accord with the recommendations of last year's report by Dr. Helen Smits and her
colleagues to the Secretary of HHS and we have initiated plans to collect third party
payment for care at the Clinical Center. We have continued to recruit outstanding
clinical scientists, improve instruction in clinical research, toughen the review of
protocols for clinical experiments, expand outreach to extramural clinical investigators,
and forge stronger ties with nearby academic health centers. In the past few months, we
have also developed a program to bring medical students to the NIH campus for one or
two years to participate in patient-oriented research, in accord with a recommendation
by the NIH Director's Panel for Clinical Research. (This important training program, to
begin this Fall, is our first collaborative effort with the newly-constituted Board of the
National Foundation for Biomedical Research, which received its first appropriated
funds, $200 thousand, in FY1997.)
The prospect of a new Clinical Research Center has re-energized clinical
investigators at the NIH. Two weeks ago, we held a full-day celebration of our clinical
research activities, with many presentations of past, present, and future projects on
metabolic, infectious, and genetic diseases; diagnostic methods developed with
molecular and novel imaging tools; therapies involving immune manipulation and gene
transfer; and various approaches to disorders of the nervous system. For this occasion,
Institute Directors prepared statements of their goals for patient-oriented research for the
next several years; post-doctoral fellows showed posters outlining recent work; and
architects and administrators described plans for the form and function of the new
facility. In addition, the intramural clinical research community has proposed measures
to strengthen our ability to recruit clinical investigators and to ensure a nurturing
environment for them at the NIH.
Other aspects of administrative oversight
Clinical research is only one of many areas that have benefitted from increased
administrative oversight during the past few years. The Institutes have recently pledged
to develop more interactive information systems, and the NIH is in the process of hiring
a Chief Information Officer. Directives from both this Committee and the
Administration to limit administrative costs have stimulated the adoption of streamlined
methods for peer review, accounting, and other activities; more widespread use of
electronic communication; sharing of resources through service centers; and reduced use
of FTE positions. In response to your request, Mr. Chairman, we are currently
undertaking an extensive study of all of our administrative functions, looking for
opportunities to achieve even greater efficiency, without impairing support of the
research enterprise and our traditional stewardship of Federal funds.
We have also been vigilant about oversight of our research activities. In the
spirit of the 1994 report on intramural research by the Marks-Cassell Committee and the
1995 Bishop-Calabresi report on the NCI, we have continued to review individual
intramural research programs; a report on the NIMH program was recently completed,
and four others are in progress. Complex activities--- gene therapy, the AIDS program,
and clinical research---have been subjected to detailed review, and many trans-Institute
areas of investigation---nutrition, pain, sleep, and several specific diseases---are being
monitored by special coordinating committees. In addition, we have initiated a process
for evaluating the performance of Institute and Center Directors every five years; panels
are currently reviewing the activities of the seven Directors with the longest terms of
service.
Plans for the proposed budget for FY1998
The President's FY1998 budget for the NIH provides an increase of $337 million
over the current NIH appropriation. In line with our traditional priorities, we plan to
allocate about 80% of the additional funds ($271 million) to research project grants
(RPGs), increasing support for these awards by nearly 4% over FY1997. We expect to
increase the average size of both continuing and new awards by 2%, rather than the
usual 4%, allowing us to support about 7100 new and competing grants and to achieve
an all-time high total of nearly 27,000 research grant awards. (Note that the Department
of Commerce has determined the Biomedical Research Development and Price Index
[BRDPI] to have been 2.6% in 1996, the lowest rate in many years, consistent with the
recent decline in the consumer price index ; we project BRDPI values of about 3% for
1997 and 1998.) The Budget also requests a $30 million increase for the National
Institute for Drug Abuse as part of the Administration's efforts to address the problem of
drug use.
We also request $90 million to support continued construction of the Mark O.
Hatfield Clinical Research Center in FY1998, along with advanced appropriations of
$90 million for FY1999 and $40 million for FY2000, for a total of $310 million, which
is required to complete the project by 2002.
I will be pleased to answer any questions you and your colleagues might have.
