Bob from Houston
Thought this might be of interest to some of you. There is a section
which briefly discusses potassium channel proteins. Since 4-AP is a
"potassium channel blocker" I thought that section might have something
to do with sci research. If you are not interested in reading it all,
the paragraph that discusses potassium proteins starts with the
sentence, "Another important means for gathering critical intelligence .
. ."
Also, Mr. Varmus mentions a few times President Clinton's plan to raise
the NIH budget by 50% in five years. That was Clinton's plan, but
various groups and Senators Harkin and Specter have been working to
double it in five years, not just raise it by 50%.
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Statement by
Dr. Harold E. Varmus, NIH Director, before the LHHS subcommittee
National Institutes of Health on Fiscal Year 2000 President's Budget
Request
Mr. Chairman and Committee Members:
I am pleased to be here today to represent the NIH for the sixth time in
the annual appropriations process. In his budget plan for FY2000, the
President is requesting $15.933 billion for the NIH, an increase of $320
million or 2.1 percent above the amount appropriated to us in FY 1999.
By any measure, the amount we received in FY 1999 from the Congress and
the Administration =97 an increase of $2.030 billion or 15 percent above
our FY 1998 level =97 was dramatic, especially in an era of fiscal
austerity. This generous FY 1999 budget has allowed us to initiate many
new and important programs, which I will discuss later, and to improve
conditions throughout the medical research enterprise. The funds
requested for FY 2000 will permit us to continue our FY 1999 initiatives
and will bring us just above the level outlined last year in the
President's plan to increase the NIH budget by 50 percent over five
years.
Rationale for Support of the NIH: Winning the War Against Disease
Throughout the world, the NIH is considered the leading force in
mankind's continuing war against disease. Over several decades of
medical research, we have learned that disease is a complex and evolving
enemy =97 one that draws upon the combined forces of heredity,
environmental insults, infectious agents, the aging process, personal
habits, and other factors, and acts upon a variety of tissues and
organs. And we have also learned that disease can be fought in many
different ways =97 with medicines and vaccines, with surgical procedures
and medical devices, with behavioral modification and environmental
remediation.
Our enlarging conceptions of disease and the means to control it
underscore the magnitude of the war that needs to be waged. As in
military encounters, the strategy includes the gathering of intelligence
about the enemy =97 the causes of disease, its distribution in the human
population, and its progression in individuals =97 and about the terrain
on which the battle will be fought =97 the cells and organs of the human
body. In addition, the battle demands the development of weapons (drugs
and procedures to prevent and treat disease) and the training of
soldiers (laboratory and clinical scientists). All of these are
functions that the NIH has assumed, often in collaboration with our
partners abroad, in other agencies and funding organizations, and in the
private sector.
At the end of a century in which the average life expectancy in the
United States has increased by nearly thirty years, victory over disease
and disability has become an understandably popular and realistic goal.
Support for this goal has been further enhanced by the advent of an era
in which the world is largely at peace and our nation is experiencing
remarkable economic prosperity. These factors have contributed greatly
to the growth of our budget over the past few years. But interest in the
work of the NIH has also expanded as the public learns more about the
evolving threats to health that accompany the aging of our population,
the appearance of new and altered infectious agents of disease, the
growth of components of our population that have traditionally
experienced the poorest health, and the unequal distribution of medical
resources among nations and segments of our own society. Because the
burdens of illness =97 the cost of care, the loss of manpower, the
psychological impact, and the raw suffering =97 have such detrimental
effects on social groups, the fight against disease is increasingly
viewed as one of the great communal responsibilities of advanced
nations.
The Administration recognizes the several responsibilities assigned to
the NIH in this fight: to amass intelligence about biological systems
and about the mechanisms by which they fail; to develop defenses and
weapons against disease; to train the personnel who will wage the war;
and to transmit news of progress on the battle fronts to the public and
providers of health care.
Progress Against Disease: Intelligence Gathering
The NIH has a rich history of success in its many roles in the battle
against disease. In their opening statements, the Institute and Center
Directors will provide many examples of new weapons that they have
developed for preventing and fighting disease effectively. I will
instead highlight some recent accomplishments that illustrate the
stunning power of our intelligence gathering devices and the speed with
which new intelligence is translated into new battle strategies.
The first =97 the result of a ten year project sponsored jointly by the
NIH and the Welcome Trust in England and a watershed event in the
history of biology =97 is the complete deciphering of all of the genes of
a multicellular organism, the intensively studied roundworm,
Caenorhabditis elegans. This tiny organism has a delicious anatomical
simplicity; the adult form contains only 959 cells, each with known
physiological functions and an origin precisely traceable back to the
fertilized egg (Figure 1). Despite its small size, C. elegans performs
many of the activities enjoyed by mammals =97 digestion, sensation, sexua=
l
reproduction, muscular movement =97 and has fully one-quarter as many
genes (19,099 compared to the 80,000 estimated for man) (Figure 2). Most
significantly, the similarity of many worm genes to human genes is
readily recognizable: over 70 percent of the human genes catalogued to
date are related to genes present in the worm. These include several
genes implicated in important human diseases, including Alzheimer's
Disease, diabetes, cancer, and musculoskeletal disorders. Because gene
functions and interactions are much easier to decipher in worms than in
mammals, many important features of biological systems and their
disorders are being learned swiftly from this tiny organism, now that
every one of its genes is known.
Another important means for gathering critical intelligence about
biological systems depends on the increasingly powerful set of tools
used to survey the three dimensional organization of proteins. This
year, two dramatic discoveries have been made about proteins that are
associated with cell membranes and therefore notoriously difficult to
decipher. One such class of proteins =97 the potassium channel proteins =97
form a conduit that allows the efficient passage of potassium, the
charged atom (ion) needed for electrical impulses in the brain, muscle,
and sensory organs, from the outside to the inside of cells. The
structural features of one such potassium channel, isolated from the
soil bacterium, Streptomyces lividans (Figure 3), can explain how
potassium can move so quickly through these fatty membranes and how the
channel can discriminate so precisely between potassium and very similar
ions, like sodium and calcium. Because the makeup of potassium channels
is so similar from one to the next, the structure determined this year
can be used to predict what others will look like, including the several
hundred potassium channels in man and other mammals and the 80 or so
known from genomic sequencing to exist in the worm, C.elegans. This is
important because mutations in human genes that instruct cells to make
potassium channels cause certain forms of epilepsy, abnormal heart
rhythms, congenital deafness, and likely other disorders. And the
recently deciphered shape of the channels can now serve as a guide to
the design of drugs that might beneficially affect their behavior.
Equally complex information has been obtained about another group of
membrane proteins =97 two proteins on the membranous surface of HIV and
two on the surface of susceptible human cells (Figure 4). These are the
four proteins that interact to allow HIV to gain entry to cells,
initiating infection and ultimately disease. Studies of the shapes and
interactions of these proteins =97 and of the crucial changes in shape
that accompany the steps in viral entry =97 have provided new ideas for
the design of vaccines and the synthesis of drugs intended to block the
virus from entering cells. Indeed, in just the few months since these
changes in shape were described, vaccine strategies for attacking the
virus during its journey into cells have been successfully tested in
model systems, and chemicals that interfere with the entry process have
been synthesized. Thus, intelligence gathering through structural
biology provides promising ways to fight viral infection =97 by HIV or
other viruses =97 with immune responses and chemistry.
Spending the FY 1999 Appropriation
These and many other recent successes of biomedical science have helped
to inspire increased appropriations for the NIH. Nevertheless, the $2
billion increase awarded to the NIH in FY 1999 has understandably
prompted concerns about our planning practices; some have even wondered
openly whether we could usefully spend the new funds in one year. Under
the President's Budget for FY 2000, the NIH will mainly continue FY 1999
programs, so it is especially appropriate to review here the spending
patterns and initiatives undertaken this year in order to demonstrate
that we are spending the increase wisely now and will continue to do so
in FY 2000.
To facilitate the presentation of so many scientific activities,
conducted through a wide variety of mechanisms in many Institutes and
Centers, I have displayed the categories of spending in a series of
charts (Appendix A) that indicate the amounts of new money devoted to
research project grants, centers, research and development contracts,
intramural research, training awards, and other mechanisms, and I have
listed some of the specific programs that will be initiated or expanded
through each mechanism. The charts also indicate the amounts that will
be spent on inflationary increases, salary and stipend increases, and
increases in average size of awards in FY 1999. Additional new
initiatives, to be undertaken in FY 2000, are described in our
Congressional Justification documents, classified within several NIH
Areas of Research Emphasis; these include contributions to the
Administration's trans-agency plans to improve information technology
and bolster defenses against bioterrorism. To maximize funds available
for these programs within the President's Budget Proposal for FY 2000,
we do not anticipate increasing the sizes of competing or non-competing
awards or augmenting salaries or stipends.
The charts that depict our spending of the increase in appropriated
funds in FY 1999 and the lists of programs to be added or expanded in FY
2000 are telling reminders of the long- and short-term planning
undertaken annually throughout the NIH. Because of the number and
variety of research objectives, it is not possible to provide a full
account of the programs here. However, many of their goals can be
encompassed within four large themes:
(1) Exploiting genomics. All of biology is undergoing fundamental change
as a result of new methods
that permit the isolation, amplification, and detailed analysis of
genes. The completion of the analysis of
genomes of viruses, bacteria, and yeast, as well as C.elegans, has
dramatically demonstrated the utility
of such information and inspired new technologies for analyzing genetic
variations and the roles of
genes, and the proteins they encode, in health and disease. The NIH is
pursuing an accelerated plan to
complete a rough draft of the human genome by 2001 and to deliver a
finished product by 2003. We
have initiated a program to sequence the genome of the mouse, arguably
the most significant animal
model for human disease, and we are assembling genetic information
about several other
disease-causing and model organisms as well. This new information will
be used to assess
predisposition to disease, predict responses to environmental agents
and drugs, design new medicines
and vaccines, and detect infectious agents, including the agents of
bioterrorism.
(2) Reinvigorating clinical research. New developments in genetics,
drug discovery, stem cell research,
and other fields are creating opportunities for revolutionary change in
the practice of medicine =97 but at
a time when clinical research is perceived to be under siege and
perhaps even in decline. To confront
this situation, the NIH has initiated several new training and career
development programs for clinical
investigators; intensified our clinical trials activities, including
the establishment of clinical trials
networks; augmented funding of the General Clinical Research Centers
and created other Centers for
clinical research on diseases such as asthma, Parkinson's Disease, and
mental illness; taken steps to
strengthen clinical research in the intramural program, including
continued construction of the new Mark
O. Hatfield Clinical Research Center; and developed an NIH clinical
trials database, in accord with the
FDA Modernization Act of 1998. To further expand patient access to
clinical research protocols, we
have worked with the American Association of Health Plans to begin to
define acceptable terms under
which their member organizations would refer patients to clinical
trials and agree to pay the costs of
care for those enrolled in NIH trials.
(3) Harnessing other disciplines. Medical research has traditionally
depended heavily on discoveries
made by physicists (e.g. isotopes and X-rays), engineers (e.g.
biomaterials and instruments), and
chemists (e.g. synthetic drugs and laboratory reagents). Recent
advances have further increased our
needs for scientists in these disciplines and others, including
computer science, mathematics, and
subfields of engineering. We are trying to meet these needs by
attracting scientists in other fields to
biology and medicine through program announcements that invite
applications from such investigators;
the creation of the Bioengineering Consortium (BECON); investment in
instrumentation development;
participation in the President's Information Technology Initiative
(ITI); construction of new beam lines
for structural biology at DOE's Synchotron facilities; and development
of interdisciplinary training
programs and centers for drug development and other purposes.
(4) Eliminating health disparities. Recent epidemiological surveys
indicate that the benefits of healthy living conditions and advanced
medical knowledge have not reached all components of our own society or
all nations on the globe. Varying rates of disease, disability, and
mortality exist among people belonging to different ethnic and racial
groups, living in different parts of the United States, experiencing
different socio-economic status, and engaging in different patterns of
behavior. These differences are important points of departure to learn
what accounts for the variable burden of disease and to identify
targets for efforts to eliminate disparities in health status. Many new
research programs at the NIH are intended to understand and to remove
the origins of these disparities in the United States and abroad. In
our efforts abroad, we are working closely with the World Health
Organization, under the new leadership of Dr. Gro Brundtland, and we
are giving special attention to infectious diseases (including malaria,
HIV, emerging infections, and tuberculosis) as well as many chronic
illnesses that pose increasing problems in developing countries as
their populations age.
Administrative Functions at the NIH
The large increase awarded to the NIH in FY 1999 has also focused
attention on our administrative practices, as well as on our plans to
spend the funds, with the legitimate concern that an organization of
such size should be operating with efficiency, fairness, and rigor.
In response to similar concerns raised by the House Appropriations
Subcommittee in 1997, the NIH contracted with Arthur Andersen and
Associates to undertake an extensive review of our administrative
functions. The outcome of that study was presented to the Subcommittee
last year. This year we can report that implementation of 72 of the 80
recommendations is either complete or in progress. These changes range
from the mundane but vital (e.g. marked improvements in mail delivery)
to the fundamental (e.g. creating a Center for Information Technology).
The CIT, headed by our first Chief Information Officer, is performing
several essential roles in response to needs for streamlined
administrative practices and to changes in biology that demand more
computer science. For example, the NIH has met all of its milestones for
achieving Year 2000 compliance for its computer systems, it is improving
its methods for preserving clinical and research data in the intramural
program, and it is undertaking an extensive review of future computer
needs in biomedical sciences. This review, to be completed by June,
1999, has informed our choice of projects within the Administration's
Information Technology Initiative for FY 2000.
The organization of our peer review system, largely under the direction
of the Center for Scientific Review, is a traditional focus of attention
for NIH-supported scientists and advocacy groups; this is especially so
with the recent changes that have occurred in biomedical science and the
need to design review mechanisms for novel and interdisciplinary
research. The CSR has begun a comprehensive reorganization of its study
sections, with advice from an external Panel on Scientific Boundaries
for Review. In addition, with the advice of the Peer Review Oversight
Group, public representatives have been added to review panels, when
appropriate.
The NIH has been seeking other ways to extend the already numerous
interactions with our various public constituencies. Responding both to
the interests of many disease advocacy groups and to the
Congressionally-mandated Institute of Medicine report entitled
"Scientific Opportunity and Public Need," we have designated Offices of
Public Liaison in all Institutes and Centers and in the Office of the
Director; established an NIH Director's Council of Public
Representatives; begun a revision of our booklet describing the priority
setting process; expanded the budget planning activities for FY 2001 to
include more public opinion; and planned workshops to examine ways to
measure and interpret the burden of disease. In addition, public
representatives will participate in the drafting of strategic plans for
each Institute and Center and in the review of our GPRA Performance
Plan.
Under FY 1999 appropriation law, the NIH is required to establish a
National Center for Complementary and Alternative Medicine. We have
rapidly formed the Center (final approval was provided by Secretary
Shalala on February 1, 1999), chartered a new Advisory Council, nearly
finished the search for a permanent Director, and expanded the research
portfolio to make full use of the new funds provided for the NCCAM in FY
1999.
Conclusion
In proposing the NIH increase for FY 2000, which is consistent with the
goal of increasing NIH's budget by nearly 50 percent over 5 years, the
Administration has voiced its support for the NIH's many roles in a
multifaceted war against disease. With your continued help, we can
insure that these advances occur on many fronts.
I will be pleased to answer any questions you might hav