DEPARTMENT OF HEALTH AND HUMAN SERVICES

NATIONAL INSTITUTES OF HEALTH

Fiscal Year 2006 Budget Request

Witness appearing before the

House Subcommittee on Labor-HHS-Education Appropriations

Dr. Judith L. Vaitukaitis

Director, National Center for Research Resources

National Institutes of Health

March 9, 2005

William Beldon, Deputy Assistant Secretary, Budget

Mr. Chairman and Members of the Committee:

I am pleased to present the President=s budget request for the National
Center for Research Resources (NCRR) for Fiscal Year 2006, a sum of
\$1,100,203,000, which reflects a net decrease of \$14,887,000 over the
comparable Fiscal Year 2005 appropriation. Within the total is
\$162,618,000 for AIDS research.

I am delighted to have this opportunity to share with you the scientific
advances achieved by NCRR-supported investigators and the future
directions for NCRR programs. As the Aresearch resources@ component of
the National Institutes of Health, NCRR=s mission is to ensure that
scientists have the necessary tools and access to research environments
to conduct their progressively more complex research on human disease.
With ready access to essential tools, our nation=s top scientists may
creatively explore promising new research avenues that will ultimately
enhance human health.

Because of its cross-disciplinary programs, NCRR supports research tools
and infrastructure that enable all lines of biomedical inquiry, from
studies of molecular structures to clinical trials that evaluate
potential therapies. Most NCRR-supported research resources are shared
and accessible to scientists nationwide. These shared resources include
advanced instrumentation and novel technologies, animal models of human
disease, and electronic networks for collaborations among investigators
in less populated areas. In addition, through the Institutional
Development Award program, NCRR provides support to institutions in 23
states and Puerto Rico to develop new research facilities, equipped with
state-of-the art research tools.

NCRR encourages resource sharing because it broadens access to essential
tools and is cost effective and leverages precious federal research
support. Each year, NCRR-funded research resources are used by more than
35,000 investigators who receive their primary research support from
other NIH components, other federal agencies, and the private sector.
Let me briefly describe just a few of the science advances that these
researchers achieved over the past year.

**OBESITY STUDIES AIDED BY ANIMAL AND CLINICAL RESOURCES**

Scientists who seek to determine the genetic defects of many human
diseases are often stymied by the fact that common conditionsCfrom
obesity to psychiatric disordersCare influenced by multiple genes.
Therefore, researchers have turned to inbred mice as a model system for
detecting genetic regions that contribute to complex disease. Using
unique mouse strains available through an NCRR resource, scientists
examined genetic factors that affect many complex traits, including
obesity and anxiety. With this approach about 150 previously
undiscovered genetic regions were discovered. This effort may narrow the
search for specific genes that contribute to obesity and also pave the
way for finding similar genes in humans.

NCRR=s General Clinical Research Centers (GCRCs) provide an ideal
research environment for studies of obesity, an increasing public health
concern. Particularly valuable are the GCRCs= highly trained staff and
state-of-the-art equipment that can analyze a patient's metabolism and
track consumption of all foods, down to the level of micronutrients. At
the University of California, Los Angeles, researchers depend on the
GCRC for their carefully controlled studies of the hormones that affect
appetite and metabolism. One study found that injections of the hormone
leptin can reduce body weight by more than 50 percent in obese
individuals born with leptin deficiency. At Yale University=s GCRC,
scientists evaluated hundreds of overweight children and adolescents and
found that about half of the severely obese have a condition that raises
their risk of heart disease and type 2 diabetes. Ultimately, better
understanding of the risk factors and potential therapies for obesity
could lead to a leaner, healthier population.

**ADVANCES IN TRANSPLANTATION RESEARCH**

As mentioned earlier, the GCRCs continue to have a significant role for
advancing human health. For instance, the GCRCs enabled pioneering
clinical studies related to transplantation, from the earliest successes
with organ transplants in the 1960s to the current microtransplants of
genes into cells. One recent success, reported in the *Journal of the
American Medical Association* this past February, showed that islet
cells from a single human pancreas can be transplanted into up to eight
patients with type 1 diabetes, a condition in which the pancreatic islet
cells do not make insulin. All eight transplant recipients achieved
normal glucose levels without the need for insulin injections. Ongoing
advances in transplantation illustrate how federally funded
effortsCamong molecular biologists, geneticists, animal researchers, and
clinical investigatorsClay a solid foundation for improving human health
through the effort of a team of investigators.

**BIODEFENSE AND TECHNOLOGY RESOURCES**

Besides clinical and comparative medicine resources, NCRR also supports
biomedical technology centers that develop and provide scientists with
access to innovative instruments, technologies, and computational tools.
These technology centers have enabled recent advances to help scientists
determine how infectious agents, like anthrax, induce their deleterious
clinical effects. The anthrax bacterium is unusual because it produces
large amounts of a toxin that can kill a patient even after the
bacterium itself has been destroyed by antibiotics. A research team used
x-ray data collected at an NCRR-supported synchrotron resource to
examine the structures of molecules that might disarm the deadly toxin.
Synchrotrons are large machines (about the size of a football field)
that accelerate electrons to almost the speed of light to produce
intense X-rays with adjustable wavelengths that can be exploited to
reveal the 3 dimensional structures of molecules. Further structural
studies may lead to the development of effective toxin-blocking
therapies for inhalational anthrax infections.

In another study, scientists developed improved techniques for
identifying microbes by their DNA Afingerprints"---a critical advance in
this age of bioterrorism and emerging diseases---and shorten the
timeframe needed to identify the toxic agent. Using laser technology at
an NCRR-supported flow cytometry resource, scientists analyzed and
measured tiny samples of DNA from a *Staphylococcus aureus* bacterium.
The analysis can be completed in just 30 minutes, compared to the 24
hours normally required to analyze DNA. Advanced computational methods
linked to the new technology may boost efforts to detect and track
microbial threats and provide sufficient time to alert individuals at
risk.

**INFORMATICS AND INTERDISCIPLINARY SCIENCE**

NCRR=s shared resources provide a fertile environment for
interdisciplinary collaboration. Such studies are essential for
addressing important but complex research problems that scientists
grapple with today. For instance, NCRR supports a large-scale
interdisciplinary effort known as the Biomedical Informatics Research
Network (BIRN). That effort draws on multiple resources to examine
increasingly complex problems in neuroscience. BIRN is the nation=s
first test bed for online sharing of research resources and expertise,
and for effective data mining for both basic and clinical research. The
initial effort focuses on neuroscience, since that discipline holds the
largest data sets and requires the capacity to transmit large,
information-rich images of the brain BIRN will be extended to other
research areas. Ultimately, the network will enhance the translation of
basic research to the patient.

**NIH ROADMAP**

NCRR=s programs complement a variety of the Roadmap initiatives that can
be implemented with the help of NCRR research resources, repositories,
and centers progress. NCRR also leads the NIH institutes and centers in
support of Exploratory Centers for Interdisciplinary Research that seek
to lower artificial barriers that divide researchers and the National
Technology Centers for Networks and Pathways that aim to develop new
technologies to study the dynamics of molecular interactions within
intact cells. NCRR program staff also have a significant role in another
Roadmap initiative, the National Centers for Biomedical Computing. This
effort will provide the computational infrastructure for biomedical
computing, ranging from basic research in computational science needed
for biomedical and behavioral research.

**STRATEGIC PLANNING AND FUTURE INITIATIVES**

This past year, NCRR published a new strategic plan for 2004-2008.
Titled *Challenges and Critical Choices,* the plan was developed based
on input from thousands of researchers and administrators for
research-intensive organizations nationwide. This strategic plan now
guides NCRR=s priorities for programmatic investments. I would like to
briefly describe just a few of the initiatives that NCRR has launched,
or plans to launch, to address the plan=s recommendations.

**Informatics for Clinical Research**

The scientists who participated in NCRR=s strategic planning process
highlighted cyberspace infrastructure that would significantly enhance
information sharing, access to and management of vast datasets, and
transmission of large data objects like brain images as a priority. NCRR
has initiated an assessment to determine current capabilities and future
requirements for electronic communication and information management
across research centers, including the GCRCs, Research Centers in
Minority Institutions, and biomedical technology research centers. One
long-term goal is to support collaborations among investigators located
in less densely populated states.

**Enhance Protection of Clinical Research Subjects**

Another important trend identified during NCRR=s strategic planning
process involves the public=s growing concern for the safety of
participants in clinical research studies. NCRR created a Research
Subject Advocate (RSA) program to assure appropriate safety monitoring
of research subjects for GCRC-based studies and ensuring that
investigators are aware of their responsibilities under State and
Federal law. Because the RSA program has had such a positive impact,
NCRR remains committed to strengthening the program

**Expand Availability of Nonhuman Primate Stem Cells**

Another NCRR initiative will focus on stem cells, which hold the
potential for treating a variety of disorders. But extensive animal
studies are needed to identify the molecules, cytokines or other agents
that modulate stem cell differentiation. NCRR proposes to support
research to identify these factors and to isolate several different
embryonic stem cell lines from the rhesus macaque, baboon, and a few
other nonhuman primate species. Isolated cell lines will be distributed
to qualified scientists via a national resource, and a companion
database will track relevant data for each cell line. Information
gleaned from these studies may be applicable to the study of human stem
cells.

**CONCLUSION**

In closing, as biomedical research becomes more complex, specialized
research resources are required to address emerging trends and build
bridges across disciplines. NCRR plays a cross-cutting, trans-NIH role
in biomedical research, supporting state-of-the-art resources that
enable collaboration and stimulate scientific discovery. These research
resources play an essential role in advancing human health.

Thank you, Mr. Chairman. I would be pleased to answer any questions that
the Committee may have.

NAME: Judith L. Vaitukaitis, M. D.

POSITION: Director, National Center for Research Resources (NCRR)

National Institutes of Health

BIRTHPLACE: Hartford, Connecticut

EDUCATION: B.S., Tufts University, 1962

M.D., Boston University, 1966

EXPERIENCE:

Following house staff training in internal medicine at Bellevue Hospital
(Cornell), the Memorial-Sloan Kettering Hospital in New York City and
University Hospital in Boston (1966-69), Dr. Vaitukaitis completed
postdoctoral training in reproductive endocrinology at Boston University
School of Medicine and at the National Institute of Child Health and
Human Development. She also served as a Senior Investigator in the
National Institute of Child Health and Human Development=s intramural
program in Bethesda. She returned to Boston in 1974 as an Associate
Professor of Medicine at Boston University School of Medicine where she
conducted basic and clinical research studies in reproductive
endocrinology. She served as Professor of Medicine at Boston University
School of Medicine (1977-86). She also directed Boston University\'s
General Clinical Research Center (1977-86) and headed the Section on
Endocrinology and Metabolism at Boston City Hospital (1974-86).

In 1993, Dr. Vaitukaitis became the Director of the National Center for
Research Resources. Prior to that she served as Director of NCRR\'s
General Clinical Research Centers Program, a position she initially
assumed in July 1986, and subsequently became NCRR\'s Deputy Director in
1991.

She has delivered nearly 300 invited lectures and has published over 165
scientific papers in both basic and clinical research and has had four
publications selected as Citation Classics. She is Editor of one book,
[Clinical Reproductive Neuroendocrinology]{.underline}. She has served
as a member of numerous editorial boards of scientific journals and has
served on many advisory boards and committees for the National
Institutes of Health, other Federal agencies, universities, private
foundations as well as scholarly societies. She has served as a member
of the Liaisons of the Board of Health Sciences Policy, Institute of
Medicine; and International Scientific Advisory Board, Joint
Infrastructure Fund, The Wellcome Trust and Office of Science and
Technology, UK. She is a charter member of the NICHD's Hall of Honor, in
recognition of her research contributions while an intramural
investigator with NICHD.

She is an elected member of the American Society for Clinical
Investigation, Association of American Physicians, The Endocrine Society
and the Institute of Medicine of the National Academy of Sciences.

Department of Health and Human Services

Office of Budget

William R. Beldon

Mr. Beldon is currently serving as Deputy Assistant Secretary, Budget in
the Department of Health and Human Services. He has been a Division
Director in the Budget Office for sixteen years, most recently as
Director of the Division of Discretionary Programs. Mr. Beldon started
in federal service as an auditor in the Health, Education and Welfare
Financial Management Intern program. Over the course of more than 30
years in the Budget Office, Mr. Beldon has held Program Analyst, Branch
Chief and Division Director positions. Mr. Beldon received a Bachelor=s
Degree in History and Political Science from Marshall University and
attended the University of Pittsburgh where he studied Public
Administration. He resides in Fort Washington, Maryland.