    [Senate Hearing 110-]
    [From the U.S. Government Publishing Office]

      DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND
              RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2008

                                  ----------

                              MONDAY, MAY 21, 2007

                                           U.S. Senate,
               Subcommittee of the Committee on Appropriations,
                                                        Washington, DC.
        The subcommittee met at 2 p.m., in room SD-116, Dirksen
    Senate Office Building, Hon. Tom Harkin (chairman) presiding.
        Present: Senators Harkin, Cochran, and Stevens.

                    DEPARTMENT OF HEALTH AND HUMAN SERVICES

                         National Institutes of Health

    STATEMENT OF DR. ANTHONY S. FAUCI, DIRECTOR, NATIONAL
                INSTITUTE OF ALLERGY AND INFECTIOUS
                DISEASES

                    OPENING STATEMENT OF SENATOR TOM HARKIN

        Senator Harkin. The Subcommittee on Labor, Health and Human
    Services, and Education, and Related Agencies will come to
    order.
        I just thought that before we begin today's hearing I want
    to take a moment to offer my condolences to everyone, through
    you, at NIH over the recent passing of Dr. Steve Straus, the
    founding Director of the National Center for Complementary and
    Alternative Medicine. It's an enormous loss to science and to
    his many friends and colleagues at NIH where he worked for 27
    years. We always knew that Steve was a man of great integrity
    and skill and dedication. That was apparent from his many
    scientific accomplishments.
        But during his 2\1/2\ year battle with brain cancer we also
    witnessed his courage and his grace. He fought a valiant fight
    and was a teacher until the end. We were lucky to have him as
    NCCAM's founding director.
        He and I had many, many conversations and meetings on
    alternative medicine, complementary medicine, where we're going
    and how we fold that in with other mainstream research. I think
    he's one of those people of whom we can truly say that he did
    make the world a better place.
        So, this is the fifth of six hearings on the National
    Institutes of Health that the subcommittee will hold this year.
    We've heard from 13 Institutes so far. Today we'll hear from
    five more: the National Institute of Allergy and Infectious
    Diseases, the National Cancer Institute, the National Center
    for Research Resources, the National Institute of Nursing
    Research and the National Center on Minority Health and Health
    Disparities.
        I'll ask each Director to speak 5 to 7 minutes. In the
    spirit of how we've been doing this if I think of something
    while you're doing it I may even ask you a question at that
    time or--I excuse myself right now for interrupting. But we'll
    try to go through all of the testimonies and we'll just open up
    for general discussion after that.
        I kind of like this format a little bit more than the
    formal one of sitting at a dais and that type of thing. I'd
    rather have more of a free flow of a discussion, sometimes even
    amongst you sitting across the table from me.
        I think we learn a lot more and we get a better flavor for
    exactly what we're doing here. I know that C-SPAN and others
    pick this up. I look upon this as a way of also of teaching the
    public, getting information out to the public in a format in
    which they can get a better handle on just exactly what NIH is
    doing and what the different Institutes are doing.
        So with that I'll start us here on my left. Dr. Anthony
    Fauci has served as Director of the National Institute of
    Allergy and Infectious Diseases since 1984. He received his MD
    degree from Cornell University Medical College. He has
    testified before this subcommittee many, many times over the
    years on everything from AIDS to pandemic flu to bioterrorism.
    I took over the Chair of the subcommittee in 1989. That was the
    first time I met Dr. Fauci.
        So, welcome back, Dr. Fauci. All your statements will be
    made a part of the record in their entirety. Like I said if you
    could take 5 to 7 minutes or so, sum it up. I'd sure appreciate
    it.

                   SUMMARY STATEMENT OF DR. ANTHONY S. FAUCI

        Dr. Fauci. Thank you very much, Mr. Chairman and thank you
    for the opportunity to talk to you today a little bit about the
    activities of the National Institute of Allergy and Infectious
    Diseases.
        I'm going to talk from some visuals that are right in front
    of you--right in front of you there.
        Senator Harkin. Okay.
        Dr. Fauci. I believe that's the top one. If you turn the
    page and look at the first slide.

    [GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

        I want to use that to tell you something that I know that
    you're familiar with. But for the sake of the record I will
    just mention very briefly what the mandate and the mission of
    the National Institute of Allergy and Infectious Diseases is.
    As you know it's responsible for the bulk of NIH research in
    the disciplines of immunology, microbiology and infectious
    diseases.
        We're driven by two major issues. One is the scientific
    opportunity and the other is the public health need. You know
    about what we do from the much publicized issues such as HIV/
    AIDS, pandemic influenza and bio-defense. But we also have
    responsibility for emerging/re-emerging microbes, vaccinations
    and immunizations for adults and children, the development of
    antibiotics, vaccines as well as the study of diseases of the
    immune system, including the important issue of immunological
    tolerance, which has a great potential in many areas of
    medicine that go well beyond our Institute's mandate.
        If you look at the next slide--I talk also here about what
    I call the dual mandate. Because in addition to all that we do,
    as every other Institute does, maintain a robust, basic and
    clinical research portfolio. For us it's microbiology,
    infectious diseases and the immune system. For Dr. Niederhuber,
    it's cancer and down the line. They each have what they do and
    what their Institute is responsible for.

    [GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

        When I refer to our dual mandate I mean that we also need
    to be able to respond very rapidly to new infectious disease
    threats. You know we've discussed this at many hearings that
    we've had together on issues such as: HIV/AIDS, SARS, et
    cetera.
        In fact if you go to the next slide. This is a slide I must
    have shown to you, Mr. Chairman, over the years since 1989
    about 10 different times. The reason I can show you this--I
    hope without your getting bored, is that each year we add one,
    two and sometimes three, new emerging infectious diseases. In
    fact the print has gotten so small there that we're sort of
    running out of space. We started out with HIV/AIDS there, but
    you see there are many others that are emerging and re-emerging
    infectious diseases.

    [GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

        Of particular note this time is one that we've just
    recently added, which I hope we get a chance to discuss in the
    question period. That is extensively drug resistant
    tuberculosis, which is an issue that poses a significant threat
    to us. Also there are multiple drug resistant microbes like
    staphylococcus and enterococcus as well as things like the E.
    coli contamination of our spinach and our lettuce that was a
    major challenge just some months ago.
        If you go to the next slide it really describes
    schematically, how we accomplish this. The NIAID research, for
    example on emerging and re-emerging infectious diseases is, as
    with all Institutes, based on a fundamental matrix of basic
    research which we hopefully then apply to the things that we
    need to do for the American public. In our case, it's the
    development of countermeasures, for example, in the forms of
    diagnostics, therapeutics and vaccines.

    [GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

        What I'd like to do in the next couple of slides is just go
    over with you some of the selected accomplishments which are
    also selected opportunities. So I'll go through them rapidly
    with you. If you look at HIV/AIDS, there has been this year, in
    addition to the great accomplishments of drugs that have
    essentially transformed the lives of HIV infected individuals.
    We know now that there have been a total, in a conservative
    estimate of about 3 million years of life saved in the United
    States on the basis of the anti-HIV therapeutic regimens that
    have been used.

    [GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

        This year we have a couple of new drugs that are very
    exciting and will in fact, even improve that menu of drugs that
    we have available. In addition we have expanded HIV vaccine
    trials that we have embarked upon: one in collaboration with
    Merck and one with the Vaccine Research Center at the National
    Institutes of Health. In addition there are new tools for
    improvement such as the announcement that you probably heard of
    a few months ago about the protective effect of medically
    supervised adult circumcision for the prevention of HIV
    infection.
        If you move on to malaria there have been some exciting new
    issues that have come up. For example, the sequencing of the
    parasite itself, and at least two or three of the vectors,
    namely the mosquitoes that cause it, allow us to get a greater
    insight into transmissibility, as well as drug resistance to
    the standard malaria anti-parasitic drugs.
        In influenza we're pleased to mention to you something that
    was announced just a short time ago, is that at our last
    hearing I mentioned to you that we were in the process of
    developing a pre-pandemic influenza vaccine. Just last month
    the FDA has approved that as an approved vaccine. We still need
    to make better vaccines for pandemic flu but we have at least
    one that's approved by the FDA.

                          UNIVERSAL INFLUENZA VACCINE

        Senator Harkin. That's not a universal?
        Dr. Fauci. No, no. We'll get to that, hopefully, in the
    questions. This isn't a universal--this is for the H5N1 bird
    flu.
        Senator Harkin. Specifically.
        Dr. Fauci. Specifically for the bird flu.

                    EMERGING/RE-EMERGING INFECTIOUS DISEASES

        Then on the next slide I mention tuberculosis. I mentioned
    in my very earlier comments the real threat that we're seeing
    with this extensively drug resistant tuberculosis. NIAID has
    developed a strategic plan, very rapidly, which just this
    morning, at our National Advisory Council was presented to them
    for their final comments before we actually make it public.
    We'd be happy to provide that to you and your staff if you'd
    like it.

    [GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

        Then finally potential bio-terror agents, we've enhanced
    the infrastructure. Again a year or two ago I showed you the
    blueprints for the physical infrastructure that we were going
    to do. Several of those buildings are either near completion or
    actually up or--and operational such as the building on the NIH
    campus, building 33.
        So if we go now to the last slide. I just want to close by
    saying that I've been talking to you about the threats of
    emerging and re-emerging infections and how the NIH research
    endeavor can meet these challenges, hopefully. I refer to it on
    this slide as a perpetual challenge because microbes will
    continue to emerge and re-emerge and nothing that we can do
    because of their evolutionary capability is going to allow us
    to completely eliminate the threat.

    [GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

                               PREPARED STATEMENT

        Dr. Fauci. The best that we can do and I think it's
    something very important, is to maintain that balance by a very
    robust, research portfolio that can be wedded to our public
    health endeavors. We appreciate you and the committee for the
    support that you've given us over so many years. Thank you very
    much.
        [The statement follows:]
                   Prepared Statement of Dr. Anthony S. Fauci
        Mr. Chairman and Members of the Committee: I am pleased to present
    the President's budget request for the National Institute of Allergy
    and Infectious Diseases (NIAID) of the National Institutes of Health
    (NIH). The fiscal year 2008 budget includes $4,592,482,000.
        The mission of NIAID is to conduct and support research to
    understand, treat, and prevent infectious and immune-mediated diseases.
    Infectious diseases include well-known killers such as HIV/AIDS,
    malaria, tuberculosis, lower respiratory infections and diarrheal
    illnesses; naturally emerging or re-emerging threats such as pandemic
    influenza and SARS; and ``deliberately emerging'' threats from
    potential agents of bioterrorism. Preemptive medicine, in the form of
    vaccines and other prevention tools, is a major focus of the NIAID
    research portfolio in infectious diseases. Immune-mediated disorders
    include autoimmune diseases such as type 1 diabetes, lupus, and
    rheumatoid arthritis as well as asthma, allergies, and problems
    associated with transplanted tissues and organs. Here again, preemptive
    medicine is an important component of our research efforts, as NIAID
    extramural scientists work to predict, prevent, and treat immune-
    mediated diseases more effectively.
        The NIAID mission has two distinct mandates. First, NIAID must plan
    and execute a comprehensive, long-term program of basic and clinical
    research on well-recognized endemic infectious and immune-mediated
    diseases. Second--and in this case distinctive among the NIH
    Institutes--NIAID must respond quickly with targeted research to meet
    new and unexpected infectious disease threats as they arise, often in
    the form of public health emergencies.
                  emerging and re-emerging infectious diseases
        Despite advances in medicine and public health such as antibiotics,
    vaccines, and improved sanitation, the World Health Organization (WHO)
    estimates that infectious diseases still account for approximately 26
    percent of all deaths worldwide, including about two-thirds of all
    deaths among children younger than 5 years of age. Moreover, the
    pathogens we face are not static, but change dramatically over time as
    new microbes emerge and familiar ones re-emerge with new properties or
    in unusual settings.
        Influenza is a classic example of a re-emerging disease. Because
    circulating human influenza viruses continually accumulate small
    changes, a new vaccine must be made for each influenza season. When an
    influenza virus emerges that has undergone a major genetic shift such
    that the global population has limited natural immunity but the virus
    can be easily transmitted among people, a worldwide pandemic can
    result. Three influenza pandemics occurred in the 20th century,
    including the 1918 pandemic that killed more than 50 million people
    worldwide.
        It is imperative that we take a preemptive approach to the
    possibility that a new influenza virus will emerge to cause a 1918-like
    pandemic. How well we do that, however, depends to a large extent on
    improving how we cope with seasonal influenza, which kills an average
    of about 36,000 people in the United States each year. Control of both
    seasonal and pandemic influenza requires development of and access to a
    sufficient supply of effective vaccines and antiviral drugs, effective
    infection control measures, and clear public communication. In this
    regard, NIAID research has directly laid the foundation for improved
    influenza vaccine manufacturing methods, new categories of vaccines
    that may work against multiple influenza strains, and the next
    generation of anti-influenza drugs. Certain of these goals will be
    accomplished through basic research projects intended to increase our
    understanding of how animal and human influenza viruses replicate,
    interact with their hosts, stimulate immune responses, and evolve into
    new strains. Other goals will be accomplished through targeted
    projects, such as a program to screen compounds for antiviral activity
    against influenza viruses.
        Since last year, we have made substantial progress in influenza
    vaccine research. The inactivated-virus H5N1 vaccine currently
    stockpiled by the Department of Health and Human Services has been
    shown in NIAID-sponsored clinical trials to be safe and capable of
    inducing an immune response predictive of being protective against the
    H5N1 virus in healthy adults, children, and seniors. Although the
    vaccine dose required to induce this response is high, studies on
    enhancing the immune response to lower doses by employing immune
    enhancers called adjuvants are showing promising preliminary results.
    NIAID also is collaborating with industry to pursue several other
    vaccine strategies in addition to inactivated virus H5N1 vaccines. For
    example, trials of cold-adapted, live-attenuated H5N1 vaccine
    candidates are underway, as is a Phase I clinical test of a novel DNA
    H5N1 vaccine candidate developed at the NIAID Vaccine Research Center.
        We also have made progress in antiviral drug and diagnostic test
    research over the past year. An NIAID program that screens both
    licensed drugs and new drug candidates--first in cell culture systems
    and then in animal models--has identified several promising anti-
    influenza candidates that are now being further developed in
    partnership with industry sponsors. These include FluDase, which binds
    host cell receptors to prevent viral entry; T-705, which inhibits
    replication of viral RNA; and Peramavir, which inhibits an influenza
    enzyme called neuraminidase. Research into influenza diagnostics is
    being vigorously pursued. For example, NIAID-funded researchers,
    working in collaboration with scientists at the Centers for Disease
    Control and Prevention, have reported encouraging results with a
    potentially revolutionary diagnostic device called the MChip, which is
    capable of quickly and accurately identifying many influenza viruses,
    including H5N1.
        Tuberculosis (TB) is another emerging threat, especially with
    regard to new and dangerous drug-resistant forms of Mycobacterium
    tuberculosis that are being seen with increasing frequency. About one-
    third of the global population is latently infected with the TB
    bacterium. WHO estimates that 8.9 million TB cases occurred in 2004, as
    did 1.7 million TB deaths; active TB is especially common among people
    with HIV. Currently, about 20 percent of new TB cases are a multi-drug
    resistant form (MDR-TB), meaning that they are resistant to two common
    and inexpensive antibiotics and are thus far more difficult to treat
    than uncomplicated TB cases. However, an even more resistant form,
    called extensively-drug resistant TB (XDR-TB), has appeared. XDR-TB
    already accounts for about 10 percent of all MDR-TB cases, that is, two
    percent of all new TB cases.
        The emergence of XDR-TB was not unexpected, but was a predictable
    consequence of imperfect compliance with the long and complex regimens
    needed to treat TB. We have long supported a large portfolio of
    research to develop new drugs, vaccines, and diagnostics for TB and to
    evaluate improved treatment and prevention regimens. As a result of
    that sustained effort, the ``pipeline'' of new countermeasures for TB
    is robust. At least nine new drugs are currently in clinical trials,
    including SQ-109, a promising candidate being developed in a private-
    public partnership with Sequella, Inc. After a hiatus of 60 years in
    which no new TB vaccines were clinically tested, nine candidates are
    now in human trials, and at least ten more are in preclinical
    development. In addition, to ensure that the NIAID TB research program
    continues to contribute effectively to the global response to this
    increasing threat, the Institute has developed a comprehensive
    strategic plan for MDR/XDR-TB that will help guide our research
    efforts. .
        Influenza and TB are just two of many emerging and re-emerging
    infections on which NIAID conducts research. Malaria, long a leading
    cause of death worldwide, has become even more problematic because of
    the emergence of drug-resistant malaria parasites and insecticide-
    resistant mosquito vectors. NIAID supports a large portfolio of malaria
    research that has generated many promising drug and vaccine candidates,
    some of which are now in clinical trials; this research is related to
    the President's Malaria Initiative, which was discussed at the December
    2006 White House Malaria Summit. In addition, NIAID conducts research
    on many other less common, but nonetheless important tropical diseases
    such as leishmaniasis, trypanosomiasis, hookworm, and lymphatic
    filariasis, which exact an enormous toll worldwide.
                               hiv/aids research
        In the almost 26 years since it was first recognized, the acquired
    immune deficiency syndrome (AIDS) has become a global catastrophe. An
    estimated 39.5 million people worldwide are infected with HIV, the
    virus that causes AIDS. In 2006 alone, an estimated 4.3 million people
    were newly infected with HIV, and 2.9 million died of AIDS.
        Although the global HIV situation remains grim, our government's
    investment in HIV research has generated many solid successes, and the
    healthy pipeline of new drugs, vaccines, and other prevention methods
    promises more successes in the future. Antiretroviral therapies made
    possible by NIAID-supported research have transformed HIV from an
    almost uniformly fatal infection into a manageable chronic condition.
    In this regard, a recent study concluded that since 1996 these
    antiretroviral medications have saved at least 3 million years of life
    in the United States alone. These life-saving therapies are now
    reaching the developing world: 1.6 million persons are now receiving
    antiretroviral therapy, more than half of them with support from the
    President's Emergency Plan for AIDS Relief (PEPFAR). In addition to
    these accomplishments, several new generation antiviral drugs that
    target HIV in novel ways are in the final stages of development.
        Prevention efforts continue to be a major component of NIAID's HIV
    research program. We have improved our ability to prevent mother-to-
    child transmission. Research to develop topical microbicides capable of
    blocking HIV transmission during sexual contact is proceeding
    vigorously. And in December 2006, two NIAID-supported trials in Kenya
    and Uganda showed that medically supervised circumcision of adult males
    can significantly lower their risk of contracting HIV through
    heterosexual intercourse. The most powerful tool to prevent HIV
    infection would be a safe and effective HIV vaccine. NIAID is currently
    supporting 20 clinical trials of HIV vaccine candidates. Seven of these
    have moved beyond initial Phase I safety and immunogenicity testing.
    For example, in January 2007, a Phase IIb ``proof of concept'' trial of
    a non-replicating adenovirus vector modified to contain three HIV genes
    opened in South Africa. A related trial of the same candidate is
    ongoing in volunteers from North America, South America, Australia, and
    the Caribbean in collaboration with Merck pharmaceutical company. The
    NIAID Vaccine Research Center has also developed an HIV vaccine
    candidate that is currently being tested in Phase II trials, with an
    international Phase IIb efficacy trial set to begin later in 2007.
    Because of the enormous need for human testing of HIV drug, vaccine,
    and other prevention strategies, we recently reorganized our HIV/AIDS
    clinical trials network to make our clinical research capacity more
    efficient so that we can continue to meet evolving global AIDS research
    challenges. Additionally, NIH will contribute $300 million to the
    Global Fund to Fight HIV/AIDS, Tuberculosis and Malaria in fiscal year
    2008.
                              biodefense research
        The possibility that terrorists will use a biological agent to
    mount an attack is a serious threat to the citizens of our nation and
    the world. Research to preempt and mitigate this threat is a key focus
    of NIAID, and complements our role in meeting the challenges of
    naturally emerging and re-emerging infectious diseases. Our strategic
    planning for biodefense research includes three essential pillars:
    infrastructure needed to safely conduct research on dangerous
    pathogens; basic research on microbes and host immune defenses that
    serves as the foundation for applied research; and targeted, milestone-
    driven development of medical countermeasures to create the vaccines,
    therapeutics and diagnostics that we would need in the event of a
    bioterror attack. These efforts enhance not only our preparedness for a
    bioterrorism attack, but for naturally occurring endemic and emerging
    infectious diseases as well.
        NIAID has undertaken a substantial expansion of biocontainment
    research facilities, which will greatly enhance our ability to safely
    and efficiently conduct research on infectious agents. For example,
    through its extramural program, NIAID is supporting the construction of
    two National Biocontainment Laboratories capable of safely containing
    the most deadly pathogens, as well as thirteen Regional Biocontainment
    Laboratories nationwide. Three intramural biocontainment labs--on the
    NIH campus, on the National Interagency Biodefense Campus at Fort
    Detrick in Fredrick, Maryland, and at the NIAID Rocky Mountain
    Laboratories in Hamilton, Montana--are either complete or well under
    construction. In addition to these facilities, NIAID has established a
    nationwide network of ten Regional Centers of Excellence (RCEs) for
    Biodefense and Emerging Infectious Diseases Research, which conduct
    research and development activities and provide training for future
    biodefense researchers.
        The Institute's efforts have already yielded substantial dividends
    as described in our periodic progress reports, the latest of which was
    issued in January 2007. For example, new or improved vaccines and
    therapies against anthrax, smallpox and Ebola virus have shown great
    promise; among these is ST-246, a promising smallpox drug candidate
    that protects both rodents and nonhuman primates from lethal challenge.
        NIAID also has been assigned the responsibility to coordinate
    research to develop countermeasures against a range of radiological and
    chemical threats. We have established eight Centers for Medical
    Countermeasures against Radiation and four Centers for Countermeasures
    against Chemical Threats; in addition, basic and applied research is
    moving rapidly. We continue to coordinate and collaborate on these
    important components of our national security with our sister
    Institutes at NIH as well as interagency partners, including the
    Department of Defense, Department of Energy, and Department of Homeland
    Security.
                      research on immune-mediated diseases
        Autoimmune diseases, allergic diseases, asthma and other immune-
    mediated diseases are significant causes of chronic disease and
    disability in the United States and throughout the world. NIAID-
    supported research in immune-mediated diseases has led to significant
    advances in our understanding of how to manage these diseases.
        One promising strategy to treat and prevent immune-mediated
    diseases is the induction of immune tolerance. Immune tolerance
    therapies are designed to ``reprogram'' immune cells to eliminate
    injurious immune responses, such as those seen in autoimmune diseases,
    while preserving protective responses needed to fight infection. NIAID
    has established a comprehensive program in immune tolerance research,
    including basic research, preclinical testing of promising strategies
    in nonhuman primates, and clinical evaluation through the Immune
    Tolerance Network (ITN). In an important study of people with severe
    diabetes, the ITN has shown that the transplantation of pancreatic
    cells can improve blood sugar control, protect patients from severely
    low blood sugar, and, in a few cases, relieve patients of the need for
    insulin injections; unfortunately, insulin independence was not
    sustained in most subjects. Further research is underway to improve
    this promising procedure.
        Last year, NIAID-supported scientists reported the identification
    of new ways to non-invasively assess the risk of kidney graft rejection
    by using gene-expression based biomarkers of immunologic activity
    present in urine. These investigators are now conducting a multi-center
    study to validate these approaches that potentially could allow
    physicians to predict, prevent, and treat kidney rejection more
    effectively.
        NIAID remains committed to improving the health of children with
    asthma, particularly those who live in our Nation's inner cities. The
    NIAID-supported Inner City Asthma Consortium (ICAC) has undertaken two
    important efforts in this area. The ICAC is conducting the Urban
    Environment and Childhood Asthma (URECA) Study. Five hundred and fifty
    inner-city children have been enrolled at birth and will be followed
    prospectively during childhood. The goals of the study are to identify
    the immunologic causes of the development of recurrent wheezing, a
    surrogate marker for asthma in children under three, and to monitor the
    development of food allergies in this patient population.
                                   conclusion
        The research conducted at NIAID and at NIAID-sponsored laboratories
    encompasses a broad array of basic, applied and clinical studies. This
    research has resulted in tangible benefits to the American public and
    to individuals throughout the world. By supporting talented researchers
    and emphasizing a balance of basic studies and targeted research, we
    will continue to develop innovative interventions to prevent, diagnose,
    and treat the wide range of infectious and immune-mediated diseases
    that afflict humanity.

                             COORDINATION WITH CDC

        Senator Harkin. Would it be safe to say, Dr. Fauci that
    your Institute probably intersects with CDC more than any other
    Institute?
        Dr. Fauci. I would think that would be safe to say. Several
    of the other Institutes do interact with CDC. But since CDC is
    responsible for the disease surveillance of those precise
    diseases, those emerging infections, that we are responsible
    for the research that develop the counter measures. There's a
    natural marriage between our Institutions in working together.

                    COORDINATION WITH DEPARTMENT OF DEFENSE

        Senator Stevens. Dr. Fauci, we've put up a lot of money
    through the defense bill for similar endeavors. Do you
    coordinate with them?
        Dr. Fauci. Indeed we do, Senator Stevens. In fact, we have
    very robust collaborations with them. A couple of examples have
    been influenza, the bio-defense, the HIV and malaria as just
    four examples of things that we work very, very closely with
    the Department of Defense.
        In fact, we have cooperative agreements with them. In our
    bio-defense area we actually have a facility that's with them
    up at Fort Detrick. So the Department of Defense, NIH, NIAID
    interaction is very, very healthy.
        Senator Stevens. So there's not a redundancy there. You are
    keeping that coordinated, so it's not going to be.
        Dr. Fauci. It's complementary as opposed to redundant.
        Senator Stevens. Thank you.
        Senator Harkin. Now we turn to Dr. John Niederhuber, who
    became Director of the National Cancer Institute in September
    2006. Also served as NCI's acting Director and Deputy Director.
    He received his MD from the Ohio State University School of
    Medicine and his research at the NCI has focused on the study
    of tissue stem cells as the cell of origin for cancer.
    Interesting.
        Dr. Niederhuber, thank you very much for being here. You
    may proceed.
    STATEMENT OF DR. JOHN E. NIEDERHUBER, DIRECTOR,
                NATIONAL CANCER INSTITUTE, NATIONAL
                INSTITUTES OF HEALTH, DEPARTMENT OF HEALTH
                AND HUMAN SERVICES
        Dr. Niederhuber. Chairman Harkin, Senator Stevens and
    members of the staff, thank you for the opportunity to testify
    today on behalf of the National Cancer Institute and the
    National Institutes of Health.
        Over the next few minutes, I would like to describe some of
    the progress NCI has made in cancer research along with some of
    the exciting opportunities we are pursuing.
        For 2 years now we have seen unprecedented decreases in the
    actual number of cancer deaths nationally. That is remarkable
    news considering cancer is largely a disease of aging and as
    you know our country is not only growing older, its population
    is also growing.
        Today's progress is occurring in no small part because
    researchers are coming to understand cancer's basic biologic
    processes. The sequencing of a human genome, a singular
    landmark in biomedical research, is providing a foundation for
    NCI's new Center of Human Cancer Genomics. Its mission is to
    systematically identify all important inherited and acquired
    genetic alterations that now contribute to a person's cancer
    risk and if cancer occurs, that cancer will behave. We are
    diligently working to understand these genetic changes and
    apply them to cancer prevention and to cancer treatment.
        Consider if you will that under the microscope, diffused,
    large B-cell lymphoma tumors from different patients look the
    same. However, when subjected to gene expression analysis, they
    have distinct genetic signatures. These differences in their
    genetic signature predict prognosis and enable us to
    individually characterize a patient's cancer and match him or
    her with the best treatment. Importantly, this is not a
    futuristic technique. We are already beginning to apply this
    technology in clinical settings such as lymphoma, lung and
    breast cancer.
        At the same time we are learning more about the mechanisms
    of a cancer cell including a small subset of cells within the
    tumor that drive the steps of invasion and growth. This subset
    of cells may enable the tumor to spread. Interestingly, these
    cells have stem cell like characteristics.
        Evidence is building that these so called cancer
    initiators, or transformed tissue stem cells are the driving
    force behind many tumors, and are the basis for long term risk
    of cancer recurrence. Clearly these cells will be a necessary
    target for treatment of the future.
        As we move toward an era of personalized medicine, advanced
    technologies will play a significant role in cancer prevention
    and preemption telling us in real time if a new drug treatment
    is reaching its target within the cell, if the novel drug is
    saturating that target, or if it is changing the function of
    the target. These early phase tests in patients will make go or
    no go decisions possible within hours, not within months for
    early cancer drug development, thus shortening development time
    and greatly decreasing cost.
        We also realize, however, that most cancer patients have
    yet to see the benefits of our science. Too many patients lack
    the means, the mobility or even the language capacity to travel
    to a premier facility. It is clear that access to care will be
    one of the greatest determinants of cancer mortality in the
    years ahead.
        Mindful of our mission to conduct research in all areas of
    science, including the behavioral sciences, such as how best to
    provide patient education and access to optimal care, NCI will
    in the next few weeks launch the pilot phase of a community
    cancer centers program that if fully implemented will bring
    state of the art cancer care to patients in community hospitals
    across the United States. This program will encourage and
    foster the collaboration of private practice medical, surgical
    and radiation oncologists with the opportunity for close links
    to NCI's research and to our NCI designated cancer centers.

                               PREPARED STATEMENT

        There is great cause for optimism in cancer science. But it
    must be tempered by an understanding of the hurdles we face.
    Cancer is a disease of staggering complexity with a singular
    name. Our progress is exciting. It is certainly encouraging,
    but we are continually challenged--challenged by our fellow
    citizens living with cancer to make faster progress.
        Thank you for the opportunity to testify before the
    Subcommittee this afternoon.
        [The statement follows:]
                 Prepared Statement of Dr. John E. Niederhuber
                                  introduction
        I am most pleased to be before you today to report on the Nation's
    progress in cancer research. While there has been a steady decline in
    the cancer mortality rate (the number of cancer deaths per 100,000
    people) since 1991, we now have the excellent news that--for the second
    year in a row--there has been a decline in the absolute number of
    cancer deaths. In 2003, there were 369 fewer cancer deaths reported in
    the United States than in 2002. In 2004 (the most recent year reported)
    the decrease was almost ten times greater, at 3,014 [Figure 1]. This
    decline is even more significant when you consider that cancer is
    largely a disease of aging, and our population is not only growing in
    numbers, it is aging at an even greater rate. Progress is, indeed,
    heartening, but our work is not done. Too many of our citizens--
    patients and families alike--continue to feel the pain and fear that
    come with the devastating news of a cancer diagnosis.

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      Figure 1.--The green line represents the cancer mortality rate per
     100,000 population. The bars represent the actual recorded number of
                      cancer deaths in the United States.

        While we measure our progress against cancer in terms of patients
    treated and lives saved, that effort also has a measurable economic
    impact. It has been projected that even a 1 percent decrease in cancer
    mortality will result in a $500 billion benefit to the U.S. economy
    (Murphy, K. and Topel, R., Journal of Political Economy, 2006; 114(5),
    871-904). In fact, such a benefit may ultimately be magnified many
    fold, because increasingly we recognize that cancer has become a model
    for developing our base of knowledge concerning many diseases. For
    example, the study of angiogenesis (blood vessel development)
    associated with tumor growth has been applied to greater understandings
    and treatment of macular degeneration, ischemic heart disease, diabetic
    wound healing, endometriosis and neurodegenerative illnesses.
    Furthermore, the unique capabilities of NCI's cancer researchers have
    been vital in other conditions. The identification of the AIDS virus
    and the development of assays to screen banked blood for the AIDS virus
    happened at the National Cancer Institute, where the current AIDS
    therapy regimen used around the world was also developed.
        Today, the NCI is leading the way in identifying the genetic,
    molecular, and cellular mechanisms associated with cancer--research
    fronts that hold great potential to enhance research and research
    collaboration against other diseases, as well. Building upon the
    sequencing of the human genome and working in our newly developed
    ``Center for Human Cancer Genomics,'' NCI is systematically identifying
    all the important inherited and acquired genetic alterations that
    contribute to cancer susceptibility. We are cataloguing genetic changes
    involved in the process of a normal cell becoming malignant, and we are
    applying this knowledge, in order to identify people at increased risk
    for developing cancer, prevent and detect cancer at its earliest, most
    treatable stages, and identify new targets for highly selective and
    specific therapeutic agents.
                            a record of real success
        The past year for cancer research and development has been one of
    substantial and heartening achievement. We are expanding both our
    knowledge and the technology tools to understand the mechanisms of
    cancer. Importantly, we are seeing scientific advances being rapidly
    applied to predict and preempt cancer.
      --We reached an important public health milestone in June 2006, when
            the FDA approved a vaccine that prevents infection by the two
            types of the human papillomavirus (HPV) responsible for up to
            70 percent of cervical cancer cases worldwide. We can all take
            great pride in the fact that our Nation's strong commitment to
            and investment in cancer research at NCI led to this approval.
      --Researchers have begun to survey the human genome for DNA variants,
            to identify genes that predict risk for common cancers.
            Capitalizing on new knowledge of human genetic variation and
            technical advances in whole-genome scanning, The Cancer Genetic
            Markers of Susceptibility (CGEMS) project is currently
            targeting genes that increase the risk of prostate and breast
            cancer [Figure 2]. Work is beginning on a similar study for
            pancreatic cancer. These studies of large numbers of patients
            will be useful both for understanding causal pathways and for
            developing preventive interventions. DNA variants found to be
            associated with cancer risk will rapidly be made available
            publicly to the scientific community through the NCI cancer
            Biomedical Informatics Grid (caBIG?) database.

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     Figure 2.--Previously developed technologies are used to analyze DNA
                     specimens from large patient cohorts.

      --Genomic technology is already being applied to explain why some
            patients with diffuse large B-cell lymphomas (DLBCL) live
            longer and respond better to therapy than others [Figure 3].
            Under the microscope, the DLBCL cancer cells from every patient
            look the same, but genetic differences have been shown to
            predict good versus poor prognosis. As a result of this
            research, it may be possible to determine which patients are
            most likely to respond to a specific treatment, thus sparing
            those patients unlikely to see a significant benefit the side
            effects of a failed treatment.

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     Figure 3.--Previously developed technologies are used to analyze DNA
                     specimens from large patient cohorts.

                delving deeply into the cancer cell environment
        Building on the success of the CGEMS project in identifying
    inherited genetic risks, the NCI and the National Human Genome Research
    Institute have launched a pilot phase of The Cancer Genome Atlas
    (TCGA), a collaboration designed to determine the feasibility of using
    large-scale genome analysis technology to identify important genetic
    changes involved in cancer. TCGA is currently studying lung, brain
    (glioblastoma), and ovarian cancers--which collectively account for
    more than 210,000 cancer cases each year in the United States.
        Other initiatives are expanding our study of the cancer cell--and
    the networks and the cellular microenvironment that also appear to be
    significantly involved in tumor development and metastasis. These
    studies of molecular carcinogenesis are being conducted at the single-
    cell or the subcellular level, using high-resolution, three-dimensional
    electron microscopy. These technologies allow us to look within the
    nucleus to study differences in chromosome movement and location during
    stages of abnormal cell growth.
        On another front, there is increasing evidence that cancer ``stem
    cells'' or ``cancer initiator'' cells are both the driving force behind
    many cancers and the basis for long-term risk. The presence of such
    cells, first demonstrated in acute myeloid leukemia patients, provides
    a different and exciting model with which to further explore cancer
    biology. NCI is establishing a group of scientists across the National
    Institutes of Health interested in embryogenesis and cancer stem cell
    biology, in order to advance the study of the underlying mechanisms in
    these processes.
                   advanced technologies accelerate progress
        It is clear that the area of advanced technologies development is
    absolutely essential and critical in creating tools for speeding up and
    enabling the discovery process. In addition to the genomic technology
    projects (CGEMS and TCGA), NCI is investing in the development of
    critical technology platforms in a number of other strategic areas,
    such as nanobiology, proteomics and computational biology.
        Recognizing the key role of biospecimens in all of biomedical
    research, not just cancer research, NCI has led a pioneering effort to
    provide the first guidelines that standardize and enhance specimen
    collection and biorepositories. These guidelines have made it possible
    for NCI to develop a common biorepository infrastructure that promotes
    resource-sharing and enables data comparison among research
    laboratories, while also ensuring patient protection and ethical
    integrity.
        We also believe that advanced imaging technologies will play a
    significant role in the prevention and preemption of cancer, as well as
    in making ``go or no-go'' decisions for early oncologic drug
    development. The NCI is working now in the aforementioned subcellular
    space, to be able to view--in real time--the interactions between drugs
    and cells and the resulting secondary functional changes. The NCI is
    developing new targeted and non-targeted molecular imaging agents for
    use as lymphatic markers, angiogenic markers, and surrogate markers for
    drugs that enhance quantitative methods to measure early, real-time
    tumor response. These technologies are further examples of NCI
    initiatives that produce benefits that will be realized across multiple
    areas of biomedical research.
                           interagency collaborations
        Addressing cancer requires work across institutional and sector
    boundaries, so members of the Department of Health and Human Services
    (DHHS) family of agencies, other federal offices, and the private
    sector can share knowledge and partner in the development of systems-
    based solutions. NCI has long been at the forefront of research and
    development of biomarkers for use in diagnosis and treatment for
    cancer. Now, a Biomarkers Consortium launched last year includes
    participants from the Foundation for the NIH, NIH, FDA, CMS, and
    private industry--with the goal of validating biological markers for a
    variety of diseases, including cancer. The first project approved by
    the Consortium is the evaluation of an imaging agent that detects an
    increase in cell metabolism characteristic of tumor growth. NCI is
    conducting trials in lung cancer and non-Hodgkin's lymphoma that use
    this ability to view cellular metabolism to monitor tumor masses for
    increased activity (cell growth) or decreased activity (cell death)
    during the early stages of anticancer treatment.
        The joint NCI-FDA Interagency Oncology Task Force (IOTF),
    established in 2003 to enhance and accelerate the overall process of
    developing new cancer interventions, released two new guidance
    documents and a final rule intended to streamline the early clinical
    development of new drugs and biologics for cancer and other diseases.
    This has enabled the first-in-human ``Phase 0'' trial (a step before
    the classic Phase 1 level of drug study) that measures the activity of
    a new drug in a limited number of patients using a single, small dose
    of the study agent, prior to the traditional dose-escalation, safety
    and tolerance studies. Phase 0 will substantially compress drug
    development time.
               training the next generation of cancer researchers
        Cancer is one of the most exciting and innovative areas of medical
    research. It takes a superbly trained, highly effective workforce to
    make discoveries, to translate them into new interventions, and to put
    the improved knowledge base and cutting-edge tools to work for
    patients. NCI will continue to play an important role in developing the
    cancer research workforce in the United States and in other countries.
    We stand firmly by the Institute's commitment to provide unparalleled
    training opportunities for talented researchers from a wide variety of
    disciplines to advance their careers. In fact, many of the current
    programs at NIH had their origins in the NCI.
        Of special significance are minority training programs, such as the
    Continuing Umbrella of Research Experiences (CURE), which begins with
    talented minority high-school students and continues progressively and
    selectively through long-term funding to qualified minority students
    interested in scientific, cancer research-related careers.
                       reaching the patient and community
        NCI must continue to make progress for each cancer patient. Yet,
    the recent report on cancer deaths that showed a decrease in deaths
    nationally also confirms a troubling fact: Minority and low-income
    populations shoulder a disproportionate cancer burden and are not
    benefiting equally from important advances. We must bring the best
    science to patients, 85 percent of whom are treated in the communities
    where they live. With that obligation in mind, NCI is launching a pilot
    of the Community Cancer Centers Program (NCCCP). This pilot project
    will study how best to provide easily accessible, state-of-the-art,
    multi-specialty cancer care and earliest phase clinical trials research
    to patients in their communities. Through this program we will also
    learn best how to educate patients concerning risk, healthier living,
    screening practices, clinical trial participation, survivorship, and
    end-of-life issues.
        This program is about bringing the newest science to patients where
    they live--a challenge that is more critical now than at any time in
    our history. Our nation's healthcare system faces many looming
    stresses, particularly in light of the fact that the first wave of baby
    boomers turns 65 in 2011. With the graying of a generation comes the
    need for a new way to confront the diseases of aging--and especially to
    anticipate what will be a marked increase in cancer incidence. That
    makes even more important our efforts to develop advanced technologies
    that will eventually lead to the genomic and proteomic breakthroughs
    essential to enable us to preempt disease at earlier stages.
        There is great cause for optimism, but an optimism that should be
    tempered by an understanding of the very real hurdles to progress we
    still face. These are challenges that we must address as a community.
    In doing so, the encouraging trends of decreasing death rates from
    cancer will become the rule, not the exception. We will learn how to
    deliver the best of our science to everyone--not just a few.

        Senator Harkin. Thank you, Dr. Niederhuber. Let's go on
    here unless you have a specific question right now.
        Senator Stevens. No.
        Senator Harkin. Dr. Barbara Alving was named as the
    Director of the National Center for Research Resources in
    April, although she served as acting Director before that. Her
    medical degree is from Georgetown University School of
    Medicine. Dr. Alving has published more than 100 papers in the
    areas of thrombosis and hemostasis.
        Dr. Alving, welcome to the committee.
    STATEMENT OF DR. BARBARA M. ALVING, DIRECTOR, NATIONAL
                CENTER FOR RESEARCH RESOURCES
        Dr. Alving. Thank you. Mr. Chairman, Senator Stevens, It's
    a great honor to discuss the mission and activities of the
    National Center for Research Resources today.
        The research center is very different from the two ICs that
    you've heard about earlier. They are categorical. They're
    focused on specific disease areas, specific missions. The
    National Center for Research Resources, which is greater than a
    $1 billion center. Is really focused on providing the
    infrastructure and support to investigators and institutions
    throughout the country. That can really provide the support for
    studies in the categorical diseases.

                      CLINICAL AND TRANSLATIONAL RESEARCH

        What we are focusing on at NCRR is clinical and
    translational research. By that, we're focusing on the ability
    to go from very basic studies, into preclinical studies, into
    clinical trials, and dissemination out into the public. The
    NCRR is very well situated for this.
        For example, we have a division of comparative medicine
    that provides animal resources for the preclinical studies that
    are needed to test drugs before they go into clinical trials.
    We fund the eight national primate centers. I might add we also
    support Chimp Haven for the long-term retirement of those
    chimpanzees that have been involved in research.
        We fund biomedical technology resources that provide
    cutting edge research in new imaging techniques that can then
    be used in clinical trials.
        We fund the General Clinical Research Centers that have
    been situated at academic institutions throughout the country
    to provide better ways to conduct clinical trials and the
    resources needed for biostatistics. What's very exciting is
    that this program of General Clinical Research Centers is now
    transitioning into a very large program known as the Clinical
    and Translational Science Awards.
        In addition we fund outreach programs through our Science
    Education Partnership Awards that allow investigators to
    actually partner with museums to have public displays on, for
    example, research opportunities, discussions of stem cell
    research, so that children throughout school systems can learn
    much more about the type of science, as well as the chronic
    diseases that are being studied in this country.
        On the second slide here you see a little swirly area which
    represents a clinical and translational science award for an
    academic health center. As we have said, the General Clinical
    Research Centers that are funded throughout the United States
    are now going to be the academic health centers transitioning
    into receiving these clinical and translational science awards.

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        This means that each academic health center that receives
    such an award agrees to form a home for clinical and
    translational science. This will make all of our studies much
    more efficient, so that we can bring new research and new drugs
    out into the public much more rapidly and train a new
    generation of clinical and translational researchers. So
    they'll know how to interact with the FDA and they'll
    understand the rules. They will know how to develop better ways
    of doing clinical trials so that we can have more rapid accrual
    and less time delay and less expense.
        Each of these academic health centers has agreed to form
    partnerships with the others, so this is really a consortium,
    and they will interact with industry as well as with other
    organizations such as Kaiser Permanente and the VA. These
    organizations are very rich in informatics and we want to bring
    interoperable informatics information systems throughout the
    country.
        The third slide shows the United States in yellow. The
    little red stars show the first 12 CTSAs that have been awarded
    throughout the country. This was done in October 2006, along
    with 52 planning grants. By 2012, we hope to have 60 CTSA
    awards at a total annual cost of $500 million per year. But we
    fund other large programs at NCRR, and we want to create a
    matrix of interactions with programs.

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                        INSTITUTIONAL DEVELOPMENT AWARD

        In the fourth slide you see the IDeA program. I think
    Senator Stevens is probably very well aware of this program. It
    is providing funding to 23 States and Puerto Rico that receive
    less--historically a lower amount of NIH funding. This is
    usually due because they have rural populations or small
    populations. These awards are allowing students from
    undergraduate colleges to have access to research training in
    some of the larger universities in these States.

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        We also realize they need to be connected because of their
    vast challenges of distance. So you see in the slide that shows
    the green States, those are the IDeA States red line which is
    Lariat. That's really a lasso to bring high speed information
    systems and fiber optic networks to six States that are very,
    very far apart that need to be connected. So through this
    Lariat project we've connected Hawaii, Alaska, Idaho, Nevada,
    Montana, and Wyoming. This provides the latest opportunities to
    conduct science through this high speed fiber optic system. It
    also has improved the economies of these States and allows the
    delivery of health care. We want to continue this in other
    areas.

                   RESEARCH CENTERS IN MINORITY INSTITUTIONS

        If you go to the fifth slide to the map of the United
    States, you see another picture. You see the Research Centers
    in Minority Institutions. These are centers that include
    historically black academic health centers and Hispanic
    centers. These too, need to be linked up and have the latest
    opportunities.

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        We provide funding to these centers to conduct clinical
    research and training as well as basic research. What we're
    doing now is encouraging them and they are very eager to link
    up into this new clinical and translational science program. So
    we have Meharry talking with Vanderbilt. Morehouse is talking
    with Emory. Charles Drew is talking with UCLA. How can they
    form partnerships? How can they provide outreach to the
    communities?

                            MATRIX OF OPPORTUNITIES

        Basically, at NCRR, we are now focusing throughout the
    center on translational and clinical sciences. We want to
    create a matrix of opportunities for this nationally,
    geographically and racially diverse matrix of academic health
    centers and other institutions. We want to include links to
    PHARMA, biotech, state and Federal agencies, as well as to CMS
    and the FDA, so that we can have a seamless interaction.

                               PREPARED STATEMENT

        The whole result of this will be to provide better access
    to health care to our diverse populations. We're very aware of
    the increased amount of money going to health care. We want to
    make this much more efficient. We want to train the new
    generations of investigators who have to carry out this work.
        Thank you for the opportunity to discuss this.
        [The statement follows:]
                  Prepared Statement of Hon. Barbara M. Alving
        Mr. Chairman and Members of the Committee: It is a privilege to
    present to you the President's budget request for the National Center
    for Research Resources (NCRR) for fiscal year 2008. The fiscal year
    2008 budget includes $1,112,498,000. I appreciate this opportunity to
    discuss with you our vision of the future of health and medicine and to
    share ways NCRR programs are transforming clinical and translational
    research.
        The NCRR, which is one of the 27 Institutes and Centers at the
    National Institutes of Health (NIH), provides NIH-supported laboratory
    and clinical researchers with the infrastructure, tools, and training
    they need to understand, detect, treat, and prevent a wide range of
    diseases. With this support, scientists engage in basic laboratory
    research, translate these findings to animal-based studies, and then
    apply them to patient-oriented research. Through innovative programs
    and resources that transcend geographical boundaries, NCRR connects
    researchers with one another, and with patients and communities across
    the Nation. These connections bring together innovative research teams
    and the power of shared resources, multiplying the opportunities to
    improve human health.
                         transforming clinical research
        Given its mission and support to more than 30,000 basic and
    clinical researchers, NCRR has become the leader of the NIH Roadmap for
    Medical Research effort to energize the discipline of clinical and
    translational research. To remove the barriers identified by the
    research community, NCRR launched the Clinical and Translational
    Science Award (CTSA) program, which is a national consortium designed
    to more rapidly and efficiently facilitate the transfer of discoveries
    made in the laboratory into new treatments for patients. Through the
    CTSAs, academic health centers are developing centers, departments, or
    institutions for interdisciplinary teams that cover the complete
    spectrum of research from basic biology to clinical medicine. These
    academic homes also will train the next generation of researchers in
    translational and clinical research.
        On September 30, 2006, we made the first CTSA awards to 12 academic
    health centers throughout the country. We will award the second group
    of CTSAs this fall. By 2012, the CTSA Consortium is expected to include
    approximately 60 CTSAs.
        The impact of the CTSA Consortium will be far greater than the
    number of awards made. The Consortium will develop better designs for
    clinical trials, forge new partnerships with health care organizations,
    and expand outreach to minority and medically underserved communities.
    The CTSAs will focus on both types of translational research--ensuring
    first that basic discoveries are applied to the clinic and second that
    they are further translated into community practice. Improving clinical
    research informatics will be a prominent focus of the Consortium.
    Institutions are taking steps to prioritize their efforts to ensure
    that standards are developed, interoperability is enhanced, and
    communication resources are accessible to researchers and their
    patients.
        To improve communication with the public and our stakeholders about
    our progress, as well as to foster collaborations within and beyond the
    Consortium, we recently launched the CTSAWeb.org site. I encourage you
    to visit the site and learn more about the CTSA Consortium. We also
    have started plans to evaluate the Consortium to ensure that the
    program spurs innovation, integration, inclusion, and dissemination.
        Already, we are starting to see significant changes within and
    across the CTSA institutions. As a result of this effort, academic
    health centers are developing new curriculums, revamping their
    organizational structures, creating unprecedented partnerships with
    other medical and research disciplines, and generating medical
    advances. For example, the Institute for Translational Medicine and
    Therapeutics (ITMAT) at the University of Pennsylvania--a trans-
    institutional endeavor with the Children's Hospital of Philadelphia,
    the Wistar Institute, and the University of Sciences in Philadelphia--
    is leading clinical and translational research and fostering
    interdisciplinary science. Now with the CTSA award, ITMAT will also
    become the home to new centers in bioinformatics, personalized
    medicine, imaging, and chemical biology. At the same time, the
    University of Texas Health Science Center at Houston CTSA is
    encouraging participatory research by connecting with Hispanic
    communities on the border. By linking with NCRR's Science Education
    Partnership Award program in Houston, this CTSA is improving the
    public's understanding of the importance of clinical trial
    participation. As the CTSAs begin to work together, the benefits of the
    program will extend to the greater research community and ultimately be
    incorporated into clinical care.
        I am pleased to report that this transformation is creating new
    energy and opportunities within NCRR and across the NIH. The CTSA
    initiative is further enhancing NCRR's long-standing investments in
    advancing translational research and providing new opportunities for
    community engagement. The addition of the CTSA Consortium to the matrix
    of NCRR programs is providing opportunities for increased cohesion and
    interaction throughout our entire research portfolio. Similarly, the
    truly trans-NIH nature of the CTSA program is facilitating interactions
    among the NIH Institutes and Centers and helping to ensure that the
    benefits of the Consortium are realized across the full spectrum of
    medical research.
                        advancing translational research
        Helping to propel the CTSA discovery engines are NCRR's
    translational research programs. Our readily available animal models
    and biomedical technology resources are fueling advancements in
    clinical care. We are exploring opportunities to enhance interactions
    among our translational programs and the CTSA Consortium to further
    capitalize on our research investments.
        Animal models are the bridge between basic science and human
    medicine. The NCRR provides such models through specialized laboratory
    animals, research facilities, and training. Linking NCRR's animal
    resources with CTSAs will allow for more seamless translation from pre-
    clinical findings to clinical trials. This is already underway at two
    CTSAs, the University of California-Davis and the Oregon Health and
    Science University, which are connecting with the NCRR-supported
    National Primate Research Centers at their institutions. To provide
    researchers with easier access to animal models, and thus further
    accelerate translational research, we sponsored a workshop in 2006 to
    explore approaches to develop a resource that would enable researchers
    to find and use animal and other biological resources more efficiently.
    Based on stakeholder recommendations, we are planning to fund a
    comprehensive electronic catalog of animal model resources in fiscal
    year 2008.
        Technologies are critical throughout all stages of biomedical
    research--from basic discovery to clinical application. The NCRR
    support for biomedical technology (BT) resource centers provides
    researchers with a broad spectrum of technologies, techniques, and
    methods. Across the nation, researchers depend on these centers for a
    wide variety of clinical and translational studies. For example,
    researchers at the University of Illinois are developing software to
    help analyze the motions of viruses, so that they can better predict
    the virulence of these organisms. At the University of Wisconsin-
    Madison, another BT resource center, researchers are using advanced
    nuclear magnetic resonance technologies to develop faster and more
    cost-effective methods for studying how biological systems work and
    respond to drugs. In the future, technologies developed at the BT
    resource centers may lead to discoveries that the CTSAs can translate
    into improved patient care.
                         enhancing community engagement
        The launch of the CTSA initiative has further enhanced our
    appreciation of the need to actively engage not only the researchers
    but also the American public. Our programs are providing opportunities
    for people in underserved communities to participate and shape medical
    research. Our innovative science education programs are inspiring
    children to pursue careers in biomedical research and are increasing
    the public's understanding of medicine. By reaching out to new
    collaborators and strengthening our partnerships, NCRR is facilitating
    connections that are sparking new discoveries and maximizing the
    effectiveness of the matrix of NCRR programs.
        NCRR has two successful programs that are creating new research
    opportunities for underserved communities. First, the Research Centers
    in Minority Institutions (RCMI) program increases the number of
    minority scientists engaged in biomedical research and enhances the
    research capacity and infrastructure at minority colleges and
    universities that offer doctorate degrees in health sciences. This
    program increases the number of minority scientists engaged in
    biomedical research and facilitates studies on minority health. Second,
    the Institutional Development Award (IDeA) program fosters health-
    related research and increases the competitiveness of investigators at
    institutions in 23 states and Puerto Rico, which have historically low
    aggregate success rates for grant awards from the NIH. The IDeA program
    provides workforce development, research opportunities, science
    education, and extends high-speed connectivity to IDeA institutions to
    facilitate research collaborations. For example, NCRR funded the Lariat
    Project to provide six states (Alaska, Hawaii, Idaho, Montana, Nevada,
    and Wyoming) with high-speed, fiber-optic network connections. This
    project has improved not only research capacity in these states, but
    also enhanced their economic development, higher education, and
    healthcare opportunities. To ensure these underserved communities have
    access to innovative research opportunities, we are exploring ways to
    facilitate partnerships with these communities and the CTSAs.
        One of the many ways that community engagement is improving
    research is through a component of the IDeA program called IDeA
    Networks of Biomedical Research Excellence (INBRE) program. This
    program enables critical connections among different research
    institutions and facilities, as well as between mentors and students.
    For example, the Montana INBRE brought together the seven tribal
    colleges within the state to conduct collaborative research projects.
    Today, these tribal colleges, which prior to the INBRE program had not
    interacted on research projects, are working together to identify
    research areas and collaborate with other undergraduate institutions
    within Montana.
        Community engagement is synonymous with the NCRR Science Education
    Partnership Award (SEPA) program. By bringing together active
    biomedical and clinical researchers with educators, community leaders,
    and other interested organizational leaders, SEPA is stimulating public
    interest in health issues and encouraging young people to pursue
    careers in medical research. SEPA grantees currently collaborate with
    several RCMI and IDeA institutions and are beginning to make similar
    connections through CTSA community engagement activities. At Jackson
    State University, RCMI- and IDeA-funded researchers have partnered with
    the Jackson Public Schools through a SEPA grant to provide mentoring
    and research internships for students and professional development for
    teachers. Another SEPA project at the University of Utah, offers over
    100 online activities, podcasts, and virtual labs on topics ranging
    from cloning to stem cells.
        Innovative partnerships are providing the cohesion needed to ensure
    that the matrix of NCRR programs results in a maximum return on
    investment for all Americans. We are expanding our outreach efforts
    with the pharmaceutical industry, healthcare organizations and
    providers, and other Federal agencies, such as the Food and Drug
    Administration and the National Science Foundation. These collaborative
    partnerships will not only enable us to make research discoveries
    faster, but will ensure that these discoveries are quickly translated
    into improved patient care.
                                   conclusion
        Through our matrix of programs and partnerships, NCRR expects to
    fulfill its charge to transform the practice of clinical and
    translational research and in turn, improve the future of health and
    medicine. The launch of the CTSA Consortium marks an exciting time in
    the history of NIH and for our Nation. It further enhances NCRR's long-
    standing investment in basic, translational, and clinical research. Our
    innovative programs and partnerships are maximizing our research
    investment to ensure that medical advances are reaching the people who
    need them.

        Senator Harkin. Dr. Alving, thank you very much.
        Now we turn to Dr. Patricia Grady, who has served as the
    Director of the National Institute of Nursing Research since
    1995. She pursued her graduate education at the University of
    Maryland, receiving a Master's Degree from the School of
    Nursing and a Doctorate in Physiology from the School of
    Medicine. Dr. Grady's scientific focus is primarily in stroke
    research.
        Dr. Grady, welcome back to the committee.
    STATEMENT OF DR. PATRICIA A. GRADY, DIRECTOR, NATIONAL
                INSTITUTE OF NURSING RESEARCH
        Dr. Grady. Thank you, Mr. Chairman. I appreciate the
    opportunity to present to you, Senator Stevens and the staff, a
    brief description of some of the activities that are going on
    at the National Institute of Nursing Research.
        The NINR supports clinical and basic research to establish
    a scientific basis for the care of individuals across the life
    span. NINR's research has contributed to improving the health
    of the American people for more than two decades. Our 20th
    anniversary provided an opportunity to look toward the future
    and update our strategic plan which formulates innovative ways
    to address the major health challenges facing our Nation,
    including the concurrent trends of an aging population, a
    growing racial and cultural diversity, an increasing reliance
    on technology and a rising demand for nurses.
        In response to these and other challenges, you heard the
    Director of NIH call for a new kind of health care system. In
    the spirit of today's hearing I would like to briefly describe
    for you important research that is preemptive and predictive
    and how that research is shaping our vision for the future.
        The first preemptive example could have major implications
    for improving the lives of premature infants and their parents.
    Current practice during the birth of a pre-term infant is to
    clamp the umbilical cord immediately after delivery. However,
    delayed cord clamping has been shown to have certain advantages
    for the infant.
        In a recent study, NINR supported investigators compared
    the effect of immediate verses delayed umbilical cord clamping.
    The results of this simple modification were very encouraging.
    Infants in the delayed cord clamping group had nearly a ten-
    fold lower rate of late onset infection and nearly a three-fold
    lower rate of brain hemorrhage. Each of these complications
    carries a high risk of disease, disability and death.
        Another study tested the effect of a coping intervention
    for parents of pre-term infants, in which parents participated
    in a program about prematurity, infant behaviors and infant
    development. The effect of this program was dramatic. Parents
    demonstrated improved parenting behaviors and reported
    decreased stress levels. Moreover, the infants averaged 3.8
    fewer days in the Neonatal Intensive Care Unit, which
    translated to a savings of roughly $5,000 per infant.
        Developing preemptive strategies to reduce the risk factors
    for cardiovascular disease is another important research focus
    for us. A group of investigators tested a community based
    behavioral educational intervention to improve blood pressure
    management among young African American men. The intervention
    reduced blood pressure and subsequently reduced by half the
    incidence of left ventricular hypertrophy, a form of heart
    damage caused by high blood pressure.
        We've also made strides in studying and preventing medical
    errors that continue to trouble our hospitals and clinics. For
    example, surgical sponges accidentally left inside patients can
    lead to complications ranging from infection to death. NINR
    investigators demonstrated that a radio frequency
    identification tag system for surgical sponges could quickly
    and accurately detect the presence of sponges retained at
    surgery. This is just one example of the type of innovative
    research needed to reduce the adverse health effects and
    significant cost implications associated with medical errors.
        Investigators have also demonstrated a clear link between
    low nurse staffing levels and an increase risk to patients.
        Senator Harkin. What?
        Dr. Grady. Low nurse staffing levels and an increased risk
    to patients. Decreased nurse staffing levels are associated
    with increased mortality and morbidity, specifically,
    infections and other complications. These studies highlight the
    importance of the growing national nursing shortage upon the
    health of our population.
        Finally, nowhere is the need for better preventive and
    preemptive efforts greater than in the minority communities and
    in other underserved populations. Recently scientists reported
    the first randomized controlled trial of a culturally tailored
    HIV risk-reduction program for Hispanic adolescents, a program
    that was successful in reducing risky behaviors for up to 1
    year.
        Another group of scientists developed an intervention that
    reduced stress and depression in low income single mothers,
    improving their ability to care for their children. Programs
    such as these are critical for reducing health problems in
    vulnerable communities and demonstrate the progress we have
    made already.
        Let me now provide you with a few examples of new methods
    for predicting the needs of patients and for anticipating ways
    to proactively maintain quality of life for patients and their
    caregivers. One example of predictive illness management comes
    from NINR's research on the care of patients at the end of
    life. As you probably know, NINR is the lead institute at NIH
    for this important area of research.
        One of our research teams characterized the functional
    decline in patients with specific illnesses in the last year of
    life. Trajectories range from--sudden, unexpected death to
    variations in illness and recovery, to steady and irreversible
    decline. This knowledge helps caregivers to better anticipate
    the course of illness, allowing the health team to tailor
    treatment strategies and improve quality of care.
        Yet another study showed that minority patients who used
    spiritual coping are more likely to want aggressive care at the
    end of life such as life support, tube feeding or mechanical
    ventilation. Such findings can allow caregivers to better
    incorporate the culturally based needs and desires of patients
    and their families.

                               PREPARED STATEMENT

        In conclusion, NINR is strongly committed to the NIH vision
    of a healthier Nation. We are proud of the important progress
    we have made toward this goal and we look forward to continued
    successes. We stand ready to address tomorrow's challenges
    based upon our 20 years of scientific accomplishments. Thank
    you, Mr. Chairman, Senator Stevens. I'd be happy to answer any
    questions that you or the Committee might have.
        [The statement follows:]
                  Prepared Statement of Dr. Patricia A. Grady
        Mr. Chairman and Members of the Committee: I appreciate the
    opportunity to present the fiscal year 2008 President's budget request
    for the National Institute of Nursing Research (NINR). The fiscal year
    2008 budget included $137,800,000.
                                  introduction
        The mission of the NINR is to support clinical and basic research
    that establishes a scientific basis for the care of individuals across
    the lifespan--from management of patients during illness and recovery
    to the reduction of risks for disease and disability, the promotion of
    healthy lifestyles, promoting quality of life in those with chronic
    illness, and care for individuals at the end of life. NINR's research
    programs also place special emphasis on eliminating health disparities
    and on the health issues faced by the underserved.
        NINR's research has contributed to improving the health of the
    American people for more than two decades. In 2006, NINR concluded the
    year-long observance of our 20th anniversary at NIH. During that
    period, we took stock of our scientific accomplishments, recognized our
    contributions to clinical practice, and launched a newly revamped web-
    site in support of our stakeholders. We also assessed the future role
    of nursing science in addressing the major health challenges of our
    Nation: an aging population; a growing racial and cultural diversity
    and the attendant health disparities; an increasing reliance on
    technology in health care settings; and a rising demand for nurses.
    Within this context, NINR developed a new, forward-looking Strategic
    Plan.
        NINR's new 5-year Strategic Plan elucidates a unified framework for
    addressing the dynamic health care landscape. The Plan leverages key
    strengths of the NINR research community and focuses on areas of
    critical research opportunity including: Self-Management, Symptom
    Management, and Caregiving; Health Promotion and Disease Prevention;
    Research Capacity Development; Technology Integration; and End-of-Life.
    Pursuing this strategy, we seek to apply NINR's resources to the areas
    of public health which have the greatest needs, and in which NINR can
    have the greatest impact.
        Allow me to briefly describe our programs within this framework,
    highlight recent accomplishments, and share our vision for the future.
                             ninr research programs
        Self-management, Symptom Management, and Caregiving.--NINR's focus
    on the quality-of-life science continuum comprises three key research
    concepts: self-management, symptom management, and caregiving. Self-
    management science explores strategies that empower individuals to be
    more involved in their own health practices. Symptom management science
    focuses on biological and behavioral components of health and illness
    that improve the management of symptoms. Caregiving science addresses
    the quality-of-life dimensions experienced by care recipients as well
    as formal and informal caregivers across diverse health care settings.
        Improving Care of Premature Infants.--According to the Centers for
    Disease Control and Prevention (CDC), half a million preterm infants
    are born in the United States each year, carrying a significant risk of
    death and disability, and often requiring care in a neonatal intensive
    care unit (NICU). In addition, their parents endure high levels of
    stress, anxiety, and depression (Miles, 1999; Singer, 1999, Wereszczak,
    1997).
        In one study, NINR-supported investigators assessed the effect of
    ``immediate'' (7 seconds) versus ``delayed'' (32 seconds) umbilical
    cord clamping on health parameters of preterm infants. Compared to the
    immediate clamping group, infants in the delayed group had nearly a 10-
    fold lower rate of late-onset septic infection, which carries a high
    risk of morbidity and mortality (IOM, 2006), and nearly a 3-fold lower
    rate of intraventricular hemorrhage, which carries a risk of
    developmental deficits (IOM, 2006).
        Another study by NINR-supported investigators assessed the effect
    of an educational program on the psychological care needs of parents of
    preterm infants. Utilizing the Creating Opportunities for Parental
    Empowerment (COPE) educational program, parents were taught about
    prematurity, infant behaviors, and infant development. As a result,
    parents demonstrated improved parenting behaviors and reported
    decreased stress levels. Meanwhile, the infants averaged 3.8 fewer days
    in the NICU than controls, which translated to a savings of roughly
    $5,000 per infant (Melnyk, 2006).
        Taken together, these studies demonstrate the significant potential
    benefits of combining a minor modification to a medical procedure at
    virtually no cost and an educational program during the care of preterm
    infants to improve health outcomes while reducing health expenditures.
    Their adoption into standard practice, and the exploration of
    additional approaches, could result in a more robust reduction in
    prematurity-related complications in early childhood, disability,
    death, and health care costs in excess of the $2.5 billion in estimated
    potential savings through the COPE intervention alone ($5,000 savings
    per infant multiplied by the estimated 500,000 preterm infants born in
    the United States each year).
        Quality-of-life research directly impacts populations across the
    lifespan from the very early stages of life. In 2007, NINR plans to
    support research on symptom clusters in cancer and immune diseases, as
    well as biobehavioral research methods.
        Health Promotion and Disease Prevention.--Within Health Promotion
    and Disease Prevention, NINR scientists explore dimensions of behavior,
    health in community settings, patient safety, and the biological
    factors useful in ensuring long-term positive health outcomes.
        Culturally-tailored HIV/AIDS Intervention for Hispanic Youths.--
    According to the CDC, the incidence of acquired immune deficiency
    syndrome (AIDS) is up to three times higher among Latino adolescents
    than among their white counterparts (CDC, 2004). NINR-supported
    scientists tested a culturally-tailored HIV education program called
    ``Cuidate! (Take Care of Yourself)'' among Hispanic adolescents.
    Compared to controls, youths in the program were 34 percent less likely
    to report having had sexual intercourse in the past 3 months, 47
    percent less likely to report having multiple partners across the
    follow-up period, and reported more consistent use of condoms. This
    study demonstrates the benefits of a customized, population-specific
    intervention and highlights its potential to reduce health disparities
    if applied across a range of settings (Villaruel, 2006; Jemmott 1998).
        In 2007 NINR plans to support research that incorporates an in-
    depth knowledge of cultural factors into HIV prevention studies among
    young people.
        Research Capacity Development.--NINR is engaged in enhancing the
    research capacity of nursing science. NINR supports pre- and post-
    doctoral training through both individual and institutional training
    grants. NINR also supports Research Centers to establish and maintain
    hubs of research, such as the NINR Nursing Partnership Centers on
    Health Disparities, which bring together colleagues from research
    intensive institutions and minority-serving schools of nursing, with
    the goals of exploring health disparities research questions and
    training investigators from underrepresented populations.
        In 2008, NINR will support academic research enhancement
    opportunities in minority-serving institutions.
        Technology Integration.--NINR's focus on improving health care and
    quality of life encompasses the development, use, and adaptation of
    technologies. Functional technologies that assist patients and those
    that facilitate reporting of biological indicators of health and
    disease status form the framework of the technology integration
    program, including uses of technology for telemedicine, patient
    education, communication, and patient safety.
        Radiofrequency Identification (RFID) and Patient Safety.--The
    Institute of Medicine (IOM) estimates the cost of medical errors to be
    over $37 billion annually; nearly half is associated with preventable
    errors; and, up to 98,000 deaths each year are attributable to medical
    errors (IOM, 1999). Currently, certain medical errors such as the
    retention of surgical sponges within patients after surgery persist.
    NINR-supported scientists have demonstrated that a radiofrequency
    identification (RFID)-tag system for surgical sponges accurately
    detected the presence of sponges retained at the surgery site after
    wound closure was simulated. If implemented into practice, this
    approach may not only contribute to the reduction of medical errors,
    but also decrease both the time spent in the hospital as well as heath
    care expenditures.
        In 2008, NINR plans to support studies focused on stimulating
    technological strategies that improve health outcomes through the Small
    Business Innovation Research (SBIR) and Small Business Technology
    Transfer (STTR) Programs.
        End-of-Life.--The science of end-of-life explores research
    questions of this complex period for dying persons, family members, and
    both professional and informal health care providers. End-of-life
    scientists seek to understand not only biological aspects of dying, but
    also the needs of dying persons, including symptom relief, decision-
    making, advance directives, and palliative care. In addition, issues of
    culture, age, spiritual beliefs, and disease-specific considerations
    are included in research strategies.
        Chronically Critically Ill and End-of-Life Care Preferences.--
    Patients who are or may become chronically critically ill may benefit
    from having advance directives in place should they lose the ability to
    communicate their preferences. NINR-supported investigators examined
    the frequency of documentation of advance directive choices of 1,128
    patients hospitalized with a chronic critical illness. Results indicate
    that about two-thirds did not have an advance directive to document
    their care preferences, and may benefit from an educational program in
    end-of-life care and documenting their preferences.
                                   conclusion
        NINR's dedicated investigators act on their clinical experience and
    insight to develop and test innovative solutions to the major health
    challenges facing our society. Equipped with a new Strategic Plan, we
    aim to sustain the pace of nursing science discoveries in the years
    ahead by bringing together innovation and determination within a
    strategic framework to improve clinical practice and patient care. With
    20 years of research, NINR has garnered expertise for new opportunities
    to address tomorrow's challenges.Thank you, Mr. Chairman. I will be
    happy to answer any questions that the Committee might have.

        Senator Harkin. Thank you very much, Dr. Grady.
        Now we turn to Dr. John Ruffin, who is the Director of the
    National Center on Minority Health and Health Disparities. He's
    led the effort at NIH to promote minority health and reduce
    health disparities for over 15 years and oversaw the
    development of the first Comprehensive Health Disparities
    Strategic Plan at NIH.
        Dr. Ruffin, welcome to the committee. Please proceed.
    STATEMENT OF DR. JOHN RUFFIN, DIRECTOR, NATIONAL CENTER
                ON MINORITY HEALTH AND HEALTH DISPARITIES
        Dr. Ruffin. Thank you, Mr. Chairman, Senator Stevens. Today
    I'm here to give you a brief report on the progress the
    National Center on Minority Health and Health Disparities and
    the National Institutes of Health is making to promote the
    improvement of health among our Nation's racial and ethnic
    minority population. To advance research toward eliminating
    health disparities among all affected populations including the
    medically underserved, poor and rural populations.
        Senator Specter, I'm sure you will recall the hearings that
    you and others convened in the late 1990s on minority health
    and health disparities. I participated in many of those
    hearings which ultimately led to the creation of the NCMHD. The
    release of the Institute of Medicine report entitled, ``Unequal
    Treatment'', came right on the heel of the Center's creation.
    That report, you will recall, was a vivid depiction of the
    state of affairs of the health care system and health among
    this Nation's diverse population.
        Six years ago Congress established the NCMHD and gave us
    the authority to be the focal point at the National Institutes
    of Health for Minority Health and Health Disparities research.
    We took that authority seriously and have established the basis
    to fulfill our mission. There are a number of things that we
    know related to minority health and health disparities and then
    there are some unknowns that we continue to work toward
    understanding.
        For example, what we have not yet uncovered is the cause of
    health disparities. We still do not know why racial and ethnic
    minorities and poor populations across this Nation continue to
    be burdened by diseases and conditions like HIV/AIDS, cancer,
    infant mortality, mental health and stroke, for example. What
    we do know is that there are multiple factors that contribute
    to disparities in health.
        These are the types of issues that we are seeking to
    understand through our own research at the NCMHD as well as
    through the research efforts of the Institutes and Centers that
    my colleagues around the table spearhead, and other Institutes
    and Centers at NIH that are not represented here today.
        Our approach to health disparities is multi-proned. Through
    research we study the diseases, the conditions, and the issues
    to gain insight into the core of the problem. To conduct
    research we have to have the capacity, the facilities and the
    workforce to carry out the studies. We also need to have the
    community involved, not only as research subjects, but actively
    engaged in planning and conducting research, translating the
    research results and--disseminating the information back into
    the communities.
        To get at this, you, the Congress, statutorily mandated
    four initiatives that would set the framework for us to
    accomplish our goals in these areas. Those are our Centers of
    Excellence program, Research Endowment Program, Loan Repayment
    Program and the Community Based Participatory Research Program.
        If you look at figure 1 the map, which I gave to you in the
    book there, you will note that geographically our programs are
    in every State except Vermont and Delaware. So we have set the
    foundation by implementing the programs that you mandated.

    [GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

        So what difference are we making to eliminate health
    disparities using this multifaceted strategy? If you look at
    the Centers of Excellence, much of the multidisciplinary
    research that we are conducting in communities across the
    country is being carried out through the Centers of Excellence
    Program that you authorized. We have funded 76 Centers
    nationwide since 2002.
        Our research endowments have led to the establishment of
    educational and training facilities such as pharmacy and public
    health schools. We've helped approximately 17 institutions to
    build their competitive edge for health disparities research.
    In order to attract the best and the brightest to the health
    profession, we have made loan repayment awards to about 1,100
    highly qualified doctorate level health professionals. An
    estimated two-thirds of the graduates have secured academic or
    research positions.
        Imagine cutting edge biomedical research being led within
    our communities by members of the community. That's what our
    Community-Based Participatory Research Program is about. We
    launched this three-phase program in 2005. We received an
    overwhelming number of applications, approximately 180. Today
    we are supporting 25 grants under this program.
        Mr. Chairman, our portfolio at the NCMHD is small in terms
    of dollars and numbers of programs, but that does not prevent
    us from fulfilling our mission. Collaboration is a large part
    of what we do within the NIH and with other agencies including
    my colleagues represented at this table.
        Some of the initiatives within their health disparities
    portfolio that we have helped to support include: the Health
    Disparities Nursing Research Center for the National Institute
    of Nursing Research, the Bioethics Center at Tuskegee
    University with the National Center for Research Resources,
    research on autoimmune disease with the National Institute of
    Allergy and Infectious Diseases and the Vanderbilt-Meharry
    Comprehensive Cancer Center with the National Cancer Institute.
        In conclusion, the NCMHD is making progress to predict and
    preempt disease through its Centers of Excellence and Community
    Based Participatory Research Program. We're building a
    culturally, competent workforce to deliver personalized
    medicine using the loan repayment program. Our Community-Based
    Participatory Research Program also embraces a critical element
    of medicine and that is the participatory aspect.
        Overall, our contribution has heightened awareness about
    health disparities, has increased the Nation's capacity to
    conduct health disparities research, recruited, trained and
    attracted an increasing cadre of individuals to research
    careers on minority health and health disparities and
    germinated innovative and productive partnerships involving the
    community. But we have barely touched the surface. There is far
    more to be done.

                               PREPARED STATEMENT

        The success of our health disparity effort, Mr. Chairman,
    depends upon our ability to further develop and sustain good
    models that we have all established. I thank you for the
    opportunity to brief you today.
        [The statement follows:]
                     Prepared Statement of Dr. John Ruffin
        Mr. Chairman and Members of the Committee: I am pleased to present
    the President's budget request for the National Center on Minority
    Health and Health Disparities (NCMHD) for fiscal year 2008, a sum of
    $194,495,000, which represents a decrease of $895,000 over the
    comparable fiscal year 2007 appropriation.
        At the turn of the 21st century, the issue of health disparities
    was still a pervasive public health challenge. Racial and ethnic
    minority and medically underserved populations were suffering
    disproportionately from disease and death; individuals living in
    medically underserved communities in rural or urban cities were also
    experiencing similar disparities in health status and health outcomes;
    there was a national need for minority scientists in biomedical,
    clinical, behavioral, and health services research. There were very few
    racial and ethnic minorities in science, technology or engineering.
    This raised concern about the future of these fields and their
    potential to eliminate health disparities given the nation's changing
    demographics, and the projected significant increase of racial and
    ethnic minority populations.
        This depiction of health in America was a part of the impetus for
    the creation of a national Center to address minority health and health
    disparities. Recognizing the gaps and the challenges, and understanding
    the promise of biomedical research, the Congress wisely established the
    National Center on Minority Health and Health Disparities (NCMHD) on
    the premise that through research, training, dissemination of
    information, and other programs, minority health would be improved, and
    health disparities would be reduced in the short-term and eliminated in
    the long-term. The NCMHD has embraced multiple partnerships as the
    guiding principle for understanding and addressing this national health
    crisis.
        While the overall health of the American population has improved,
    sadly, health disparities have not declined. Nevertheless, within the
    past six years the investments of the NCMHD have positively impacted
    communities throughout this nation and globally. Our contributions have
    heightened awareness about the seriousness of health disparities;
    increased the nation's capacity to conduct health disparities research;
    recruited, trained and attracted an increasing cadre of individuals
    from health disparity populations to research careers on minority
    health and health disparities; and germinated novel and productive
    partnerships involving the community.
                        understanding health disparities
        The Centers of Excellence program has become a leading force for
    research into various diseases and health conditions in health
    disparity populations such as HIV/AIDS, mental illness, obesity,
    diabetes, cardiovascular disease, stroke, infant mortality, and cancer.
    Collectively, these Centers have published more than 200 articles on
    the priority diseases/conditions and issues related to minority health
    and health disparities among all racial and ethnic minority, medically
    underserved, and low-income populations. Leveraging of resources and
    expertise with other NIH Institutes and Centers and federal agencies,
    and among our grantees has fortified our capacity to conduct research
    into the most critical diseases and issues concerning disparities in
    health. Basic, clinical, social science and behavioral studies are
    examining the many factors that are believed to contribute to poor
    health in our communities. Understanding the cause of disparities in
    health is pivotal in determining and applying appropriate preventive,
    diagnostic, and treatment modalities.
        Access to health care is a major health problem that potentially
    perpetuates health disparities. Those who have more resources are
    better positioned to benefit from costly new discoveries in science and
    medicine. An estimated 45 million Americans have no health insurance,
    most of them being racial and ethnic minority, rural, and low-income
    populations. A lack of access can delay timely medical care and
    increase the effects of disease without proper treatment. A study
    examining adherence to cervical cancer screening guidelines among
    publicly housed Hispanic and African-American women, found that only 62
    percent of those sampled had received a screening for cervical cancer
    within the past year. 29 percent of the participants noted that no
    health care provider had ever notified them that they needed a
    screening test for cervical cancer. In this study, Hispanic and older
    women were far less likely to adhere to screening guidelines. The
    results prove the need for continued and increased efforts to ensure
    that medically underserved racial and ethnic minority women have access
    to cancer screening services. Understanding the complex nature of
    health disparities and the influence of socio-economic, biological,
    environmental, behavioral, and other factors, remains a research
    challenge that we must continue to examine through pioneering research.
                 training the workforce: removing the barriers
        Access to health care is a multi-pronged problem that is
    complicated by the shortage of health professionals from underserved
    communities. Racial and ethnic minorities make up only 14 percent of
    the physicians in America. The NCMHD and its partners have been working
    to diversify and strengthen the science workforce through training.
    Two-year loan repayment awards have alleviated the financial burden of
    pursuing higher education for approximately 1,100 health professionals.
    These trainees with MD, PhD, DDS, and other doctorate level science
    degrees, engage in research, health promotion, and outreach activities
    in numerous disciplines to heighten awareness and deepen our
    understanding of specific diseases and conditions, and issues in health
    disparities.
        Racial and ethnic minorities represent 64 percent of the current
    pool of NCMHD loan repayment awardees. An estimated two-thirds of the
    graduates have secured academic or research positions. The funding
    provided by loan repayments have helped to advance the careers of
    awardees and expose them to additional funding sources for their
    research activities. The program is slowly, but evidently achieving its
    mission to recruit and retain highly qualified health professionals in
    the workforce. In 2006, endowment funding supported the training of two
    Native American students completing the four-year Doctor of Pharmacy
    program at the University of Montana. This is a significant
    accomplishment because of the critical need to create permanent tenure
    track positions for Native Americans. At the University of Wisconsin at
    Madison, School of Public Health, the infrastructure established with
    NCMHD funding has helped to secure funds for a Health Disparities
    Research Scholars Training Program. This five-year training program
    will commence in Spring 2007 and it is anticipated that it will
    increase the number of researchers committed to health disparities. We
    will continue to enhance our focus on the recruitment and retention of
    individuals of health disparity populations to develop a culturally
    competent and well-trained workforce to address the burden of health
    disparities in our diverse communities.
                         creating the competitive-edge
        The quality of health among health disparity populations, and the
    delivery of health care can be improved by training a diverse workforce
    that is representative of the community being served. However, in order
    to conduct innovative research, it is essential to have the right
    capacity such as the facility, faculty, students, and training
    programs. Notable progress has been made in developing research
    capacity at more than 40 academic institutions.
        Having an endowed chair signals an institution's strength in a
    specific discipline. It is an incentive for a medical school to recruit
    and retain the most preeminent faculty in a given field, and adds
    credibility to its medical education program. Endowed chairs
    traditionally have been located at the most prestigious medical
    schools. NCMHD funding has established endowed chairs at three
    minority-serving institutions, Meharry Medical College, Morehouse
    School of Medicine, and the University of Hawaii. These endowed chairs
    are vital to building a critical mass of distinguished scientists in
    cancer, cardiovascular disease, diabetes, neuroscience, women's health,
    and Native Hawaiian health. This will place these institutions on the
    competitive edge to advance their study of minority health and health
    disparities in these fields. At Meharry, the endowed chair funds have
    helped to recruit a nationally renowned scientist to lead its Center
    for Excellence in Health Disparities Research in HIV/AIDS.
        Research capacity in terms of physical infrastructure has increased
    considerably at several institutions after obtaining NCMHD funding. In
    some instances, facilities for health disparities research did not
    exist prior to NCMHD Centers of Excellence funding. Today, Charles R.
    Drew University has space totaling 8000 square feet, New York
    University 3,900 and Claflin University 3,403 square feet dedicated to
    conducting health disparities research. As a result, these institutions
    have been able to expand their research and training activities. The
    University of South Carolina-Claflin EXPORT Center recently erected a
    Molecular Virology Laboratory at Claflin University which houses state-
    of-the-art equipment for microscopic gene cell isolation and
    examination, where HIV viral load assays for example, can now be
    studied. The University of New Mexico houses the only School of
    Medicine in the state, and endowment funds have helped to establish the
    Institute of Public Health to address chronic health issues among low
    income and racial and ethnic minority populations.
                             value of partnerships
        Our success in eliminating health disparities will ultimately
    depend on our ability to translate the lessons learned from our
    research endeavors, into usable tools and programs for the community.
    We have expanded our partnership base, and moved beyond the tradition
    of limiting partnerships to academic institutions, into domains where
    we can have the capacity to respond to health disparities in any form.
    We have continued collaborations NIH-wide, across the Department of
    Health and Human Services, and with other agencies such as the
    Department of Justice. Our efforts also have engendered unique
    partnerships between academia and the community; the community and
    local, state or federal agencies; research-intensive institutions and
    minority-serving institutions; and among NCMHD Centers of Excellence
    within a given state and state health agencies.
        In partnership with the National Institute of Environmental Health
    Services, the private sector, universities and schools, molds and other
    allergens that may trigger asthma in children are being studied post-
    Katrina. In conjunction with the DHHS Office of Minority Health we
    mobilized our Centers of Excellence to respond to emergency health
    needs in the community and offer research opportunities at NIH for
    scientists after Hurricane Katrina. Today, the community is benefiting
    from electronic medical records, and telemedicine programs that are
    being incorporated into the health care infrastructure. In Oklahoma we
    have been able to reach more than 65,000 American Indians through a
    partnership of the Oklahoma Project EXPORT Center with nine tribes. The
    power and impact of our partnerships has touched the global community
    from state to state to places like Asia, Africa, Europe and the
    Caribbean where our students and faculty engage in research training.
                               imagine the future
        We have begun to set the foundation through our research, training,
    capacity development, and outreach efforts to transform the health of
    this nation, but we have barely touched the surface. There is far more
    to be done. In three years, according to the Healthy People 2010
    report, health disparities should be eliminated. However, the recent
    Midcourse Review of the report underscores the fact that not enough has
    been done overall to demonstrate any significant decline in health
    disparities.
        Imagine a Nation where differences in health status and health
    outcomes no longer exist among populations. Imagine a nation where all
    Americans can lead a long and healthy life. Imagine a country where all
    Americans can access quality health care. Imagine physicians and health
    care professionals of all racial and ethnic backgrounds, in any
    specialty, practicing in every community across this country. Imagine
    cutting-edge biomedical research being led within our communities by
    members of the community. Imagine the discovery of solutions for
    critical diseases like diabetes, mental illness, cardiovascular
    disease, HIV/AIDS or obesity emerging from a community lab.
        At the NCMHD we are cognizant that no single entity alone can solve
    the complex problem of health disparities. The sustainability and
    success of our health disparities efforts depends on strategic
    partnerships. We will continue to expand our network to address the
    diseases and issues that are already familiar to us, and examine new
    and emerging health disparities challenges in prisons, housing
    communities, or among our men. We must also be able to respond to
    health crises as they arise. Novel and multi-faceted strategies must be
    exercised and increased at the community, national and global level if
    we are to succeed in using the power of biomedical research to
    transform the health of racial and ethnic minority and medically
    underserved populations and eliminate the scourge of health
    disparities.

                                 NCMHD PROGRAMS

        Senator Harkin. Thank you very much, Dr. Ruffin. I assume
    on this map you gave us, that CBPR, the green dot, is Community
    Based Participatory Research?
        Dr. Ruffin. That's correct, sir.
        Senator Harkin. We don't know how many are in each State.
    We just know there's something going on there, right?
        Dr. Ruffin. I think I can also tell you we've established
    25 of those programs thus far. I think I have a map that I
    might be able to share with you that shows the distribution of
    those 25 programs.
        Senator Harkin. Tell me again what's that loan repayment
    program? How does that work?
        Dr. Ruffin. The loan repayment program is where we pay back
    the loans of individuals who go into health disparities
    research. These individuals get about $35,000 a year, principal
    and interest is paid as a repayment for those individuals to go
    into health disparities research. It is modeled a lot like the
    AIDS-Loan repayment program which many of you are familiar
    with, except in this case, our loans are given to not just MDs
    but to all health professionals.
        Senator Harkin. Would that be nurses too?
        Dr. Ruffin. Nurses, dentists, individuals in clinical
    psychology, sociology, all of the medical professions are
    eligible to apply for these loan repayment programs.
        Senator Harkin. Interesting. I have to find out more about
    that.

                                    VACCINES

        Dr. Fauci, I would like to talk a little bit about
    vaccines. As you know we have provided over $6 billion to HHS
    to prepare for a flu pandemic. A lot of that money is to
    develop both egg-based and cell-based vaccine capacity in this
    country. We've been through that many times.
        But in the case of a pandemic even after spending this
    money, it will take us months to develop a vaccine that will be
    effective against the strain of flu that proves to be able to
    be transmitted from human to human. It will still take time.

                               UNIVERSAL VACCINE

        Now, I've heard a lot about this idea of a universal
    vaccine. One that would be effective against all strains of
    flu, a vaccine that could be stockpiled now, made immediately
    available at the time of a pandemic or one that could be
    routinely administered to people giving them immunity in
    advance of a pandemic in certain areas.
        I recently met with some people who were developing a DNA
    based vaccine that identifies proteins. It was very interesting
    to me--that are common to all strains of flu. And I understand
    your Institute has supported some of this work. I just need to
    know more about this. Is there this possibility that we could
    get this universal vaccine that--since we identify proteins
    that are the same in all the different flus? Is this possible?
        Dr. Fauci. It is conceptually possible. I think over time
    it will be likely.
        When you look at a flu virus the major components that we
    traditionally over the years have made vaccines against, have
    been the H and the N proteins that are on the surface. They
    stand for hemagluttinin and neuraminidase. That's the reason
    when you hear about flu--you name flus by the differences,
    H5N1, H3N2.
        Now the good news is that the body makes a really good
    immune response against the H and the N. The bad news is that
    the H and the N change from influenza to influenza. Which is
    the reason why each season, to get a perfect match, most of the
    time you have to fine tune and tweak the vaccine a bit so that
    it's a little bit different than the one you did the year
    before to get optimum and maximum protection.
        The concept that you're referring to, Mr. Chairman, is the
    idea of getting the components of the virus that don't change
    from strain to strain and season to season. Two of those
    proteins are the M2 or the matrix protein, and the NP or the
    nuclear protein. They don't seem to change from strain to
    strain. So then you--you ask the obvious question. If I was
    infected with seasonal flu 3 years ago, why am I not protected
    against the seasonal flu the next year or the year after?
        The reason is the body does not make a very robust immune
    response against the M protein and the NP. So the strategy that
    we're working on with the people that you mentioned is to get
    those proteins and put them in a very immunogenic form. So that
    the body makes a very robust immune response that would cross
    over and help protect not only against this season's flu, but
    next season's flu and the year after.
        Also, theoretically if you do it right, you could get a
    universal vaccine that would even be protective against a wide
    variation. The way we're seeing with the H5N1. Because the H5N1
    that's circulating in birds in south east Asia right now, is
    very much different from the H3N2 that we all get exposed to
    every season. So that's the concept and the strategy of a
    universal vaccine.
        The results that we're getting, preliminarily, in animal
    studies are really rather encouraging. Now you know in vaccine
    work it takes years to go from the concept to something that's
    in a bottle for people to use. But, I, myself am quite
    encouraged about that possibility.
        Senator Harkin. So you're funding research on this?
        Dr. Fauci. Oh, absolutely. We're funding research by our
    extramural grantees and contractors. We're collaborating with
    some of the pharmaceutical companies. For example Merck itself
    is working on a M2 vaccine. We're doing intramural research.
        You mentioned the DNA approach. Where you can take the gene
    of any particular protein and code it for the protein that you
    want and essentially say I'm going to inject somebody with the
    DNA. That DNA will then cause the body to express the protein
    on a cell that makes a good immune response. At the Vaccine
    Research Center under Dr. Gary Nabel, at the NIH, that's what
    we're doing with HIV. It's easily done also in influenza.

                       FUNDING INFLUENZA VACCINE RESEARCH

        Senator Harkin. Do you think we're putting enough resources
    into that on the balance of things? This is very promising.
        Dr. Fauci. It is very promising. It's very promising.
        Senator Harkin. It would be a big deal.
        Dr. Fauci. It would. It would. As you know I've always told
    you over the years you never ask a scientist if you put enough
    in. Enough is when you get the answer. We are putting a
    substantial amount. We are concerned as we all are with--when
    we have a flat budget will we be able to take advantage of some
    of the opportunities that would arise. So we have to be very
    careful in our prioritization. But we're putting substantial
    resources into it.

                        VACCINES AND AUTOIMMUNE DISEASE

        Senator Harkin. Two other things. I just want to ask one
    about vaccines and I want to ask about allergies.
        Children get a lot of vaccines by the time they're three
    years old. I've heard estimates ranging from 18 to almost 30.
    Having a new grandchild myself last year, their parents are
    looking at all the shots that this kid is supposed to get by
    the time they're, well, 1 and then by 2. It was pretty darn
    close to 30.
        I've heard a lot of concerns. That, you know--while each of
    these vaccines are very good in terms of saving lives, building
    immunity that maybe collectively, putting them all together
    could lead to autoimmune diseases later in life. I've heard a
    lot of this, read about it. So, again, I want to know, what
    kind of research is being--done on that aspect of all of these
    together effecting autoimmune diseases later in life?
        Dr. Fauci. It's obviously a good question because it is a
    matter of concern to some people. There have been studies done
    looking at retrospective data of children who get vaccinated as
    to whether or not there's this propensity to autoimmunity.
        The basis of that concern, I think is the basis of why you
    really do want to vaccinate people because in people who have a
    genetic predisposition to autoimmunity, it is often triggered
    by an infection. We know that, for example with certain of the
    autoimmune diseases like lupus and rheumatoid arthritis and
    things like that.
        So the question is mimicking the infection by a vaccine
    going to induce autoimmunity. The answer is in studies that
    have been pretty carefully done, no. But, importantly, the
    infection itself is a much more potent potential inducer of
    autoimmunity than is the vaccine that you give to somebody to
    prevent the infection.
        So if we didn't vaccinate people and they actually got
    these infections that would be an even worse scenario. So if
    you're asking me, I can give the example: I have three children
    and they've gotten all the vaccinations. I feel very, very
    comfortable with having my children vaccinated with the menu of
    vaccines that are all recommended.
        So, the concern is understandable. The research in the
    studies that have been done to see if there is a connection
    have all indicated that there is not.

                                 FOOD ALLERGIES

        Senator Harkin. One last thing, allergies. A friend of mine
    in Iowa--we're just talking about kids and our kids, grandkids.
    It turned out that their little boy had developed severe food
    allergies.
        You and I have talked about this before in previous
    hearings. Three hundred percent increase in the number of
    pediatric food allergy cases over the past 10 years. That's
    alarming.
        Dr. Fauci. Yes.
        Senator Harkin. What's going on? You know, what is
    happening out there?
        Dr. Fauci. To be honest with you, we don't know. There are
    some theories about that, but food allergy is something that we
    have now, we have had for some time. But even most recently
    based on the data you're talking about, are taking it very,
    very seriously.
        Not only is food allergies--and certainly the recognition
    of and probably the reality of, more than just the recognition
    of are increasing. Not quite sure why that has occurred. I'm
    certain that there are factors that are not fully appreciated
    by us right now. But the thing that worries us is that some of
    these food allergies are more than just trivial. You can
    actually get anaphylaxis. One of the important ones, for
    example, is--is peanut allergies is really, really tough.

                           PEANUT ALLERGIES IN CHINA

        Senator Harkin. I've heard. Now tell me if I'm wrong on
    this. Have you ever heard this about kids in China eating a lot
    of peanuts there. But they don't get peanut allergies. But we
    get peanut allergies here. Have you ever heard such a thing?
        You haven't heard that one?
        Dr. Fauci. I haven't heard that but I thought you were
    going to say that the Chinese were putting something in it that
    is toxic.
        Senator Harkin. No, it's just that China grows a lot of
    peanuts, like ours. The kids eat a lot of peanuts. But they
    have nowhere near the peanut allergies we have in this country.
    I was operating under the assumption that was factual data. I
    don't know.
        Dr. Fauci. I've not heard this.
        Senator Harkin. Look into that.
        Dr. Fauci. I certainly will. I certainly will.

                          RESOURCES FOR FOOD ALLERGIES

        Senator Harkin. But--again, with the 300 percent increase
    do we have enough resources going into that? It's our resources
    again.
        Dr. Fauci. It's the same answer to the question. We are
    doing a substantial amount. We could do more. Definitely.
        Senator Harkin. I'm told that NIH hosted an expert panel on
    food allergies in the spring of 2006. Last year. The
    participants developed a proposed road map to guide future
    research. But it has been a year now and I understand the road
    map still hasn't been approved. Give me an update on that,
    would you?
        Dr. Fauci. We met with that group in my conference room
    about 3 months ago. We walked away from that with them. They
    are quite satisfied with the portfolio that we've put together.
    With regard to a strategic plan that's almost a logistic thing,
    about getting a plan and a plan approved through the Department
    and what have you.
        But the research that we're doing right now on food
    allergy, we've developed a very good relationship with the
    constituency groups on that. I have a lot of responses to that
    meeting that were very favorable.
        Senator Harkin. Well, alright. I just wondered what was
    happening there. I just--you can jump in anytime, just jump in
    if you have some things you want to cover. Go ahead.

                    COORDINATION WITH DEPARTMENT OF DEFENSE

        Senator Stevens. Tony, what about coordinating what you're
    doing with the other agencies? We're putting a lot of money in
    defense for investigation dealing with substances that might be
    used by terrorists for instance. Are you working with them too?
        Dr. Fauci. Yeah. There is a rather excellent coordination,
    Senator Stevens, between ourselves, the Department of Homeland
    Security and the Department of Defense. In fact, we feel very
    good about that. We were doing that--we've developed a good
    relationship with them.
        Even antedating bio-defense because a lot of the things
    that they have done for force protection, malaria, and things
    like that, we have worked very closely with them. When the bio-
    defense issue arose following 9/11, we, in fact, strengthened
    our interaction with them. With the new Department of Homeland
    Security, we're even coordinating very nicely with them.

                  BIOLOGICAL, RADIOLOGICAL, OR CHEMICAL ATTACK

        Senator Stevens. That was going to be my next question
    because it just seems with the world wide impact of the
    terrorist movements that they're going to turn to substances
    one of these days. Are we prepared for that?
        Dr. Fauci. We are not totally prepared. I would be
    misleading you if I told you we're totally prepared for any
    biological, radiological, or chemical attack that we have. But
    since 2002, we have built up a rather robust research and
    development portfolio and have made some significant advances.
        Obviously, you never know where, when or if a terrorist is
    going to strike in a biological, radiological, chemical way.
    But we have countermeasures now that we didn't have before. We
    were completely vulnerable to a smallpox attack. We had 18
    million doses of smallpox vaccine in our reserve. Right now we
    have over 400 million. That's happened just over the past
    couple of years.
        Senator Stevens. That was my next follow up because it
    seems to me that we're doing a lot of research and prevention,
    but what about reaction to such events when they take place.
    That seems to be the area that we could be most effective.
        Dr. Fauci. Right.
        Senator Stevens. We can't immunize everybody against
    anything.
        Dr. Fauci. Sure.
        Senator Stevens. But we can get prepared for specific
    problems that might arise. Are we doing that?
        Dr. Fauci. We are. We are, Senator. I'll give you two
    examples that are actually very important examples.
        You talk about treatment. We've never had any treatment for
    smallpox or pox viruses. There is a drug that we've helped
    develop with a pharmaceutical company called ST-246 which is
    very effective in an animal model against smallpox. You may
    have read in the newspaper about a military person who was
    getting vaccinated for smallpox with vacinea didn't fully
    realize that his child had eczema. When you expose the wound of
    a smallpox inoculation to a child with eczema, they can get an
    eczema vaccinatum which is a very terrible disease.
        The child did get it accidentally, and doctors tried
    everything with the child and we brought this drug in. They
    treated the patient with the drug and the child has made a very
    remarkable recovery. So that's a--N equals one in medicine that
    doesn't mean anything, but this, I think, is an important
    indication that we now have an important drug.
        We also have some antitoxins that we didn't have, for
    example against anthrax. We've developed the first Ebola
    vaccine that, I think is a very important advance.
        Senator Stevens. What about post exposure to nuclear. I
    heard the other day about something that would reduce the after
    effects of nuclear exposure.
        Dr. Fauci. Right.
        Senator Stevens. Is that really an accomplished fact.
        Dr. Fauci. What we are doing and we've had to partner with
    our colleagues from the cancer community, with the National
    Cancer Institute is to develop better versions of the drugs
    that are used on patients following a radiation to rescue bone
    marrow. For example, to allow the bone marrow to regenerate in
    a much more rapid and efficient way than it would to wait for
    it to normally respond. That's the main nuke-rad counter
    measure that we have.
        Senator Stevens. Are we stockpiling that?
        Dr. Fauci. Yes, we are. We have that in the National
    Strategic Stockpile.

                                  NCI FUNDING

        Senator Stevens. Dr. Niederhuber, if I may? I was really--
    you know we doubled the research money for you in one period
    that Connie Mack and bipartisan effort. We did that over one
    period. I think it was a little less than 10 years. Are we
    going to look at a necessity to double it again in the next
    decade?
        Dr. Niederhuber. Well, living as we have for the past 3-4
    years with a less than inflation budget has certainly taken its
    toll on the programs. If you calculate that up it's about a 12
    percent decrease from where we might want to be at this point.
        Senator Stevens. Well, since you had 125 percent increase
    in the past years before that. Where do you think you'd stand
    if we hadn't done it?
        Dr. Niederhuber. Oh, I think we would be much worse off in
    the country as a whole. I think the increase that Congress, in
    its wisdom, legislated and appropriated did a great job in this
    country in building up research infrastructure that was
    lagging. We built about $16 billion worth of new research space
    at our Research Universities across the country. I think that
    was badly needed.
        Having come recently from the academic community we had
    some real pent up needs in the academic community. We were able
    to increase our faculties where we needed to in the biomedical
    research arena. So I think this was all, Senator Stevens, very
    needed.
        The issue I think for us, as a country, has been that when
    you build up you need to keep moving with inflation in order to
    maintain what you've built. I think that's the issue that we
    are facing.

                              GENERATIONAL CANCER

        Senator Stevens. That's reasonable, I think.
        Let me ask you a personal question. I had three generations
    of pancreas--pancreatic cancer ahead of me and I got prostate
    cancer. Now someone told me the other day that in all
    likelihood I had the same cancer. Is that possible that it
    migrated to my predecessors but didn't migrate for me?
        Dr. Niederhuber. Well, I don't think I would look at it
    quite that way, having been involved with managing and
    operating on patients with pancreatic cancer for most of my
    career, I think these are two separate diseases. They each have
    specific risk factors. I could share that with you.
        Senator Stevens. I just want to know what to tell my sons.
        Dr. Niederhuber. Well, I think the thing to tell your sons
    is that we're working hard to better understand the risk. What
    I was going to say that actually in July of this year our
    Center of Excellence in the National Cancer Institute focused
    on trying to understand risk in populations and risk for
    developing different cancers. We've just finished a whole
    genome scanning project in prostate and in breast and this July
    we'll launch one specifically in pancreatic cancer. So it's
    relevant to your question, Senator.
        Senator Stevens. Well, let me know will you?
        Dr. Niederhuber. I certainly will.
        Senator Stevens. What do I tell them--follow their
    grandfather, their great grandfather?
        Dr. Niederhuber. Live healthy, exercise, eat well.

             ATTRACTING STUDENTS TO SCIENCE AND TECHNOLOGY CAREERS

        Senator Stevens. Which one should they be careful of?
    Anyway, let me ask you, Ms. Alving.
        Are you familiar with Norm Augustine's report titled:
    ``Rising Above the Gathering Storm'', which discuses the
    problem of having enough students turning to the study of
    science and technology?
        Dr. Alving. Yes, Senator. We're very aware of this at NIH.
        Senator Stevens. But what are all of you doing about that?
    All of you have basic money, research money. I understand what
    you're doing Dr. Ruffin. That's very good.
        We do the same thing by the way. We pay some of our staff
    who have high loans, before they migrate out to where they get
    paid more. So we have a little bit of a fund here. We can sort
    of entice them to stay a year or two longer. But are you doing
    anything about the concepts of trying to attract students into
    the areas so that you're not the last of the breed in terms of
    scientists who are studying these things for us?
        Dr. Alving. Yes we are, Senator. I would say that NCRR is
    working very diligently on this. The other Institutes and
    Centers are working on this, as well, because across NIH we
    recognize this as a very large challenge. We also recognize----
        Senator Stevens. Let me interrupt you. Do you have
    internships for people in college to attract them so they'd be
    interested to go to graduate school? Do you reach out to
    people?
        Dr. Alving. Absolutely. For example, let's look at the IDeA
    program that I mentioned earlier. I personally visited Montana
    this last year and I saw how the investigators at the more
    research intensive universities are reaching out to the tribal
    colleges. So there are now research projects underway at the
    tribal colleges. The tribal students can go to the University
    of Montana and really envision research careers.
        I remember one young man told his father he was going into
    biomedical research. He was Native American. His father said
    well, that's not what we do. But he said yes, this is what I do
    want to do.
        So we are reaching out to students, I would say, of all
    ages, because to really attract students into research and into
    biomedical careers, you really have to get them at a very young
    age. In one of our SEPA programs, our Science Education
    Partnership Awards, one of our very fine investigators has
    developed a bus in Boston that actually is well equipped as a
    laboratory. It's even visited the NIH campus.
        The bus goes throughout Boston. So it goes into the
    underserved areas. Students can get onto this bus, which is a
    traveling mobile lab, and learn about DNA and learn some of the
    simple experiments. In fact, I think this has been really
    replicated throughout many of the States.
        So we're really attacking this, I think, at multiple
    levels. We're reaching out to the Hispanic community as well.
    And many of our very well funded researchers have very active
    programs where they serve as mentors and bring high school
    students into their labs. It's probably still not enough, but
    we're all very aware.
        Senator Stevens. If this Nation has a problem--the problem
    is the downward trend of our students who seek graduate
    education in science, technology, and engineering, which are
    very difficult areas of study. We've got to find some way to
    move out and give them incentives to continue.

                               CONGENITAL DEFECTS

        I know I'm using my time. Dr. Grady, I just recently came
    about in connection with a relative. The problem of a defective
    heart valve which came from, they tell me, from what you
    mentioned, a problem at birth. Now what my question to you is
    have we any way to check this as people grow older? Whether
    they do have those defects that develop because of improper
    handling at birth?
        Dr. Grady. There are a number of tests that are now
    available where we can through imaging and other diagnostic
    tests tell very early on in children if there is a
    developmental defect.
        Senator Stevens. I'm talking about this person's almost 60.
    He was just determined--to have blood clots going to the brain.
    Suddenly they find out that was--escaped through some valves
    that have been defective since child--since birth. Now I--and
    he's had exams. He's been in the service. Why doesn't--why
    won't that show up on exams?
        Dr. Grady. Well, it turns out that many of us have
    problems, birth defects, congenital defects that we are really
    unaware of. Sometimes we die without being aware of them. But
    now that the life expectancy of the average American is longer,
    many of these things which would not have surfaced before are
    now surfacing.
        Senator Stevens. But how can we--can we discover them?
        Dr. Grady. Up until recently the imaging technology and the
    other technologies that we had were not able to. But we now
    have imaging technologies which have a very high resolution.
    You can tell things are happening in tissue that are structural
    and even metabolic disorders much earlier in life.
        Senator Stevens. Those valves could be discovered with the
    proper test?
        Dr. Grady. Yes. Very likely they could have been.
        Senator Stevens. Are we developing any indications that
    would lead people to take those tests?
        Dr. Grady. Actually there is a move on for people to do
    screening, whole body scans, et cetera and much higher
    technological screening early on in life. Some of these things,
    as we're all aware of, are not covered by insurance so people
    opt not to do them. But I think the technology is now becoming
    available and people's awareness that they should screen for
    things and that they should have check ups early is much
    higher. So hopefully, we'll be catching these earlier.
        Senator Stevens. We saw something that both the government
    and the insurers are not going to pay the cost of scans,
    particularly full body scans.
        Dr. Grady. That is currently the situation. There is a
    great deal of discussion, whether or not they should be
    available and for what particular conditions they would be most
    helpful.

                               MEDICAL SCREENING

        Senator Stevens. This is very disturbing. This person is
    now blind, partially. He's got tunnel vision because of those
    clots and had no idea that that existed. I was told it could
    have been diagnosed at any time prior to that if he had had the
    proper exposure to the scans. But I don't know how.
        We've got all these systems. I don't know how we can get so
    that subjective to the people who need help, know that need
    help. Is that part of any of the studies we're making? How do
    we find out who needs this help?
        Dr. Grady. It is a problem in that we are trying to inform
    people. But we also have difficulty getting people to come in
    for screening exams which we know are helpful: mammography,
    breast cancer screening, and there are a number of other
    screenings that people do not necessarily take advantage of.
        We are studying--we're funding a number of studies however,
    that look at what it takes to get people incentivized to come
    in for screening. We have some very interesting information
    related to, you mentioned relatives, related to mothers and
    daughters. Daughters being more tuned into health prevention,
    getting mothers to come in, senior citizens and younger people,
    et cetera. So we're working on a number of techniques to
    incentivize people to come in for screening.
        Senator Stevens. I was told last week that there is now a
    system where you can go and have your--what your gene chain set
    out. They can compare that to the types of illnesses that come
    from these genes that you are determined to have and they can
    then give you a prediction on what you're going to suffer. I
    said why don't we all get that? They said, well, it's cost.
    That it's not available to the average income person today. Are
    we going to get to where we can get that for the average
    person?
        Dr. Grady. Well, it is true that it is not covered by
    insurance but also--we're not quite there yet where these tests
    are 100 percent accurate.
        For some things such as stroke, we have developed and
    identified risk factors. We can weigh each one and there's a
    whole scale where you plug in your blood pressure, your age, et
    cetera. Then you can alter--what if your blood pressure came
    down a certain amount and you get a score which you can then
    program. If I alter my diet, if I lower my blood pressure, if I
    exercise more, that will reduce my chance of getting a stroke
    by x percent or so many points. So I think we are moving in
    that direction in some areas, but we're really not there yet.
        Senator Stevens. Maybe some of us don't want to know that's
    the problem.
        Senator Harkin. Do you have thoughts on what Senator
    Stevens just asked?
        Dr. Niederhuber. I was just going to comment that we--all
    of the Institute Directors were at a conference all day on
    Friday at the NIH and during that day we were talking about
    some of the latest technology coming online to do rapid
    sequencing. I believe, you can correct me, colleagues, if I'm
    wrong, but I believe the quote was that, ``with this new
    technology today we can sequence half of our genome in 3 days
    at about $3,000.''
        So you can see how quickly within the next few years we
    will be approaching our goal of being able to sequence the
    entire genome of you as a patient within 3 or 4 hours for
    $1,000.
        Senator Stevens. Would it be cost effective for us to do
    that publicly?
        Dr. Niederhuber. Well, that's a very good question,
    Senator. I think that we all recognize in the science community
    that this information, this alphabet if you will, is the base
    of the information. We know that we have a lot more work to do
    in taking that code, if you will and understanding what that
    code means in terms of the proteins that our cells produce.
        The changes in those proteins as they're produced and how
    they relate to what makes you function and you as an individual
    and your diseases and me, as an individual and my diseases. So
    we have a lot to build on. But that is like the periodic table
    of chemistry, if you will. It is the information based upon
    which we will gain this kind of knowledge and this kind of
    understanding of the disease. It's a step, but a very important
    step.

                                    GENOMICS

        Dr. Fauci. Can I add we should be careful though not to
    think that if you--if we, even if we get it inexpensively that
    if you get your genome and you look at your sequence, you're
    going to know exactly what's going to happen to you. That's--
    most diseases are multigenic. They rely a lot on interaction
    between the genetic factors and the environment.
        So although you could get some probabilities there's still
    going to be the need for the broad, healthy things you need to
    do no matter what your genome is. So we spoke about that also.
        Senator Stevens. I said it was the last question. But I
    forgot this one.

                                  END OF LIFE

        Dr. Grady, you gave us this chart, tracking patient
    disability in the last year of life identifies opportunities to
    tailor interventions. We were told last year that in the last 2
    years of the person's life they would probably spend as much
    money for health care as they've spent in all previous years.
    Are you suggesting here that there's some way to alter that?
        Dr. Grady. Your statement is true. What we are suggesting
    is that these are trends. So it's a very large population study
    but it gives parameters within which you can better be able to
    predict what a course of illness may be like. That doesn't mean
    it will necessarily be that way for each individual person, but
    it gives you parameters.
        So it gives you a sense of what one could expect and
    hopefully to be able to better plan. It's an imperfect system
    when translated to single individuals but it does give the
    patient, the family, and the health care team some idea.
        Senator Stevens. Are you suggesting you think science can
    tell us when a disease is really terminal no matter what
    happens?
        Dr. Grady. We're still not there yet. It's very difficult.
    You can, as we all know, predict within some time frames. But
    still individuals are very different from person to person. So
    you have guidelines, but I would not be offering a finite
    timeline.
        Senator Harkin. Well, I want to pick up a little bit of
    what Senator Stevens just said this end of life care. I just
    wrote it down here. It's got to be more rational, caring and
    cost effective.
        A lot of it is just irrational. The way it's administered.
    I don't know if it's more caring for a person to--to do
    expensive operations or anything like that knowing full well
    that the end of life is coming anyway than it is to just give
    him palliative care. Address yourself to that too.
        Most--our health care system is not very good when it comes
    to palliative care--and then so a lot of people stay in acute
    care until they die. It just costs a fortune.
        Dr. Grady. It's very complicated, Senator, both Senators.
    What we found out so far--we've just scratched the surface.
        What we've found out so far however that is disturbing is
    that some of the things that we could do we are not doing
    consistently. For example, pain management. We know a great
    deal about pain management and our ability to handle pain in
    these stages of life. Yet, we find great disagreement between
    what the health team advises, what the patient says they want
    and what the family says that they think the patient wants.
        So whether it's an intensive care unit setting or a hospice
    setting or chronic care setting, we find great disagreement.
    This is all within the therapeutic window of pain medication
    that could be administered that would be safe to administer. So
    that's one thing we know.
        The other thing we have found is that--that many patients
    do not have advanced directives. They haven't really thought
    ahead. They haven't talked with their family, but even if they
    have many of the systems that we have are required. They
    basically are not allowed to withhold treatment, even if that
    is the patient's request.
        So if in an emergency the ambulances are called or
    anything, it doesn't usually matter in practice if the person
    says no advanced measures.
        Senator Harkin. What would you think about that? I've never
    talked to Senator Stevens about this but this idea of having
    advance directives? People don't. They just don't think about
    it. Maybe when people get on Medicare that ought to be a part
    of when you qualify for Medicare that you ought to have a
    requirement that you have some kind of advance directive.
        Dr. Grady. Well if the person would have an opportunity to
    do that it would at least allow them to think about it. It
    would give the family some sense of where they should go and
    some guidance. It turns out the other studies we've done that
    look at the caregivers of terminal patients that the largest
    stress for them is reported to be that they didn't know what
    their family member wanted. They had to make a decision really
    acting in the dark by their report. That they felt was, by
    their report, almost as stressful as seeing the disability.
        Senator Stevens. But is that partly related to the
    liability factor of the caregiver in case another person--
    family member says you could have saved them and you didn't.
        Dr. Grady. There seems to be a great deal of anxiety about
    that.
        Senator Stevens. Well, I think, Senator Harkin is right. I
    think we ought to try to do something. I witnessed my first
    father-in-law after he had brought back to life. He was a
    minister and a grand man. He was in his mid 90s. I never heard
    him swear in his life, but he swore at the doctor that brought
    him back to life. He died about 2 months later and I think that
    is a very unfortunate thing. He did not have a directive. But
    there ought to be something to deal. Maybe we could tie to
    Medicare.
        Senator Harkin. I've thought about that. I hear this all
    the time. There is a liability problem there. People don't
    think about it. Families don't know what to do.
        Senator Stevens. I see my friend is here. I'm late for
    another appointment. So thank you very much, Senator.
        Senator Harkin. Thank you, Senator Stevens.
        I want to follow up on one thing and that's on the nursing
    shortage.
        Dr. Grady. Yes.

                                NURSING SHORTAGE

        Senator Harkin. We had a hearing on global health a few
    weeks ago. We talked about the brain drain and other countries.
        What's happening in other countries is a lot of their
    nurses especially in health care professionals are getting
    their degrees and that kind of thing. Then they come here,
    better paying jobs. We have a shortage of nurses here now so we
    started looking into this.
        Well then, what did we find out? There's a shortage of
    nurses in this country. There's a demand for nurses. American
    Schools of Nursing last year turned away 42,866 qualified
    applications for baccalaureate and graduate programs due to a
    shortage of nurse faculty.
        Dr. Grady. That is correct.
        Senator Harkin. Now, we're in a real problem here.
        Dr. Grady. We are.

                             TRAINING NURSE FACULTY

        Senator Harkin. We need more nurse faculty. But if we don't
    have the slots for them, it seems to me pretty soon, they're
    going to start retiring and we're going to have fewer and
    fewer. I don't know.
        Your Institute supports a lot of nurse faculty through
    research grants. So what role does your Institute play in
    increasing the number of nurses trained here in America,
    especially teaching nurses, faculty--teaching nurses? I don't
    mean just nurses that are out in the community, but I mean
    teaching.
        Dr. Grady. Senator Harkin, those are the nurses that we
    support in our training line. We have 7 percent of our budget
    devoted to training.
        Senator Harkin. 7?
        Dr. Grady. Yes, 7 percent, which is twice the NIH average.
    So we're dedicating a reasonable chunk of our budget to
    training. The people that we train are those individuals who
    become the teaching faculty. We train them to do research, but
    that's what faculty do on campuses of Schools of Nursing across
    our country.
        So we have designed a number of programs to try to get
    these students in early. We work with the K through 12
    programs. We work with the other graduates to encourage them to
    get doctorates. We also have what we call fast track programs
    so that they come into the baccalaureate program, come out with
    their Ph.D. without stopping.
        Senator Harkin. Thank you. What if you were advising us? If
    you could say here's what we're going to do. What would we do
    say; give us 3, 5 years. What would a 5-year plan look like to
    get more teaching faculty in this country?
        Dr. Grady. I think the 5-year plan would have some loan
    repayment, but I think that looking at loan repayment or
    service repayment. For example and this dates back to the older
    days, but we used to, if people had supported education that
    they would not have to pay back the loans, but they would pay
    back in service, teaching at schools as faculty, et cetera. I
    think maybe something of that sort.
        Incentives to get people into the field earlier, I think
    there is a real sense and this is partly what we're working on
    internally is people are expected to get their advanced
    education but they're expected to work along the way because it
    is clinical profession. So we are trying to help design
    programs so that that is not necessary.
        Believe it or not, many States require, in order to teach
    in a School of Nursing, that you have to have a Masters in
    Nursing and not just get your Bachelor's and then go on to a
    Ph.D. So there are a number of issues that we're working on.
    But it is safe to say that that the demand over the next 10
    years is going up in excess of 20 percent. We're only supplying
    another 6 percent.
        So we need programs that are attractive. We need programs
    to help retention. We have programs to help get people in but
    we need to figure out how to retain them. I think we need also
    to work on the quality of life issues such as loan repayment.
        Senator Harkin. Well, we need some advice. I mean if you
    turn away 42,000 last year. I assume the same will happen this
    year, maybe more.
        Dr. Grady. Yes. We are, as you had identified very
    astutely, expecting an increased retirement. It turns out that
    faculty in Schools of Nursing tend to retire earlier than
    later, 62 versus 65 or so on. So we really are getting a crunch
    from several directions. So we're hard pressed to try to design
    as many programs as possible to get people in and to make the
    field as attractive so that they will stay in.

                                NURSING RE-ENTRY

        Senator Harkin. Let me ask you this. I was amazed to
    discover in my State of Iowa a few years ago that there are a
    lot of nurses in my State, and I'm sure it must be true in
    other States. They went to nursing school. They became an RN.
    They were an RN for a while. They got married, started having
    families. They got out of nursing, raised their families. Kids
    are grown. They may not have been in nursing for 15, 18, 20
    years. I was amazed to find out how many there were in my
    State.
        So I began asking a few of them once I found out. In
    meeting people you never knew they were nurses. You meet them
    in other walks of life and find out they were a nurse. Would
    they ever think about going back into it. And they said, Oh,
    yes. But you know I don't, you know, have the wherewithal. It
    costs money to get retrained, go back to school. You know we're
    now in our late 30s, 40s. You know, yeah, if I had the ability
    or had the financial resources and stuff.
        I just wonder if there's an untapped pool out there of
    nurses who may be in their late 30s, early 40s that would get
    back in if they had the wherewithal to do so.
        Dr. Grady. I believe there is, Senator. We've been talking
    with some of the schools about a re-entry program and with the
    AACN about re-entry programs. That is precisely what you're
    describing. To get people to come back in, if they have
    incentives.
        You know it probably would not take a great deal of
    incentive. But to get people to think about it and to try to
    figure out some creative ways to get people back into the
    field. It is a wasted resource. Basically if people would like
    to come back to work, they have the background. I think it's an
    untapped resource.
        Senator Harkin. We ought to look--we ought to just see if
    there's some suggestions out there.
        Dr. Grady. I'd love to--we'd love to work on this, with
    you.

                SUPPORT FOR WOMEN PURSUING PROFESSIONAL CAREERS

        Dr. Alving. The reason I'm nodding my head is that if you
    look at medical schools now, about 50 percent of the students
    in medical schools are women. We have a very big problem in
    this country in that there's very little support, child care
    support for example, for women who are trying to pursue
    professional careers. So this pertains to veterinarians, of
    whom 80 percent of the students are women, nurses and now
    physicians.
        So I think we're going to have to think about some sort of
    ability to provide resources, child care, for those
    professional women. These nurses might not even drop out. They
    might stay in if they felt that their families and their
    children could have the appropriate type of child care.
        Other countries have organized centers where they can, you
    know, provide day care. So that's another component of it. But
    I do support re-entry. I would also support it if they could
    only drop back to half time and not drop out, because once you
    drop out it's harder to re-enter. You lose confidence and
    that's a little bit more difficult.
        Senator Harkin. Interesting concept. I'm justified that the
    programs--programs for specified for certain groups like
    nurses. That's interesting.
        Dr. Ruffin. Senator Harkin, I think one of the areas too
    where we need to pay more attention is to our 2 year
    institutions around the country. This is an untapped resource
    to a great extent. I think that the attitude as it relates to 2
    year colleges around the country has changed.
        It used to be that the thinking was that individuals would
    go to the 2 year institutions to sort of bone up for the 4 year
    experience. That attitude is totally gone. We have great
    instructors now at these 2 year schools and good students at
    these 2 year institutions.
        The problem is we're not bridging them. They're not
    transitioning to the 4 year institutions. We need more bridging
    programs that we can tap that vast resource of individuals who
    are at these 2 year institutions and begin to bridge them into
    our 4 year institutions in those challenging programs like
    nursing.
        That's one of the areas that I think we need to concentrate
    on. It is a place where we need to visit that we haven't put
    much attention on.
        Senator Harkin. Very good. Dr. Niederhuber, let me ask you
    before I just turn to Senator Cochran.
        I just wanted to ask you about clinical trials. Flat
    budgets for NCI over the past few years have taken a toll on
    clinical trials. When we finalized the fiscal year 2007 budget
    earlier this year, NCI was asking the cooperative groups that
    run cancer trials to trim their cost by 10 percent and reduce
    the number of open slots for patients by 3,000. Are those
    figures still accurate? I mean we did put some more money, as
    you know, in.
        Dr. Niederhuber. When we were trying to guess what that
    2007 appropriation might be we were forced to ask everyone to
    do a worst case scenario. So they did work on a 10 percent cut.
    We actually, just the past few days, have been meeting together
    at NCI to put in place our funding program for the cooperative
    groups that are the bulk of the grants that support clinical
    trials research across the country, as you know.
        It looks like it's going to be closer to a 5 percent
    decrease from last year. But that still translates into a
    decreased number of trials that will be open and a decreased
    number of patients that will go on trials as you understand.
        One of the difficulties with this uncertainty in the budget
    for the clinical trials aspect of research, it's complicated to
    explain, but part of the support goes for infrastructure, bio-
    statistics and just the infrastructure people that have to be
    there. Another part of the budget is a bit of a guess in that
    we set aside resources that pay on a per patient basis. So as a
    patient goes on trial, that capitation gets allocated to cover
    part of those costs. It doesn't in any way cover the cost of a
    patient going on clinical trial. We're lucky in most trials if
    we come even close to 50 percent of the cost.
        So, the problem the community at large is facing across the
    academic universities is not knowing exactly how that budget is
    going to grow or stay flat over the next few years. They have
    to be very careful on deciding to start a trial, get it up, and
    get it in place. That takes time and commitment. Not knowing
    for sure if the dollars are going to be there to support that
    trial in the second, third, and fourth years.
        One of the things we do not want to do is to have to stop a
    trial in the middle. That would be a disaster. We just wouldn't
    want to do that. So I think that what I am seeing is that my
    community is being a little cautious in the number of trials
    they're willing to open up and willing to start because they
    can't predict down the road 2008, 2009, and 2010, what the
    resource flow is going to be.
        Do you follow that? It's a complex issue. It's hard to
    explain a little bit until you get your hands into it.
        Senator Harkin. But you can assure that this 10 percent cut
    is no longer valid because of the----
        Dr. Niederhuber. It's not going to be that much in 2007.
    It's going to be closer to 5 percent.
        Senator Harkin. We need some kind of--I'll have to think
    about that a second. I have a question about pancreatic cancer,
    but I wanted to turn first to Senator Cochran.
        Senator Cochran. Mr. Chairman, thank you very much for
    convening this hearing.
        It is good to meet with the heads of the different
    Departments at NIH where you're undertaking very important
    research. We appreciate the hard work that all of you are
    doing.
        We want to be sure that the budget request is as generous
    as it can be as well as the appropriations that follow. That
    when we approve a budget for this next fiscal year it reflects
    our genuine concern about doing the best we can do in
    developing research programs that will give us answers to
    problems relating to health and disease, infectious diseases,
    all the gamut of subjects that the Institute is working to help
    us understand.

                   PANDEMIC FLU AND OTHER INFECTIOUS DISEASES

        I noticed that in Dr. Fauci's National Institute of Allergy
    and Infectious Diseases, you're doing a good bit of work in
    Avian flu and some other areas of that kind. I wonder what
    progress, if you can tell us is being made in coming up with
    new ways of dealing with some of those challenges of infectious
    diseases.
        Dr. Fauci. Well we have a very extensive portfolio in
    emerging and re-emerging infectious diseases, as you know. That
    is a major component of what we do. You mentioned pandemic flu
    and the concern that we have now because of the activity that
    is going on with bird flu particularly in south east Asia.
        What's happened over the last year since I testified before
    the committee is some significant advances in that regard. We
    tend to link, Senator Cochran, our preparedness for seasonal
    influenza with that of pandemic. We feel as a group that we
    don't prepare well enough for seasonal flu. We have not
    advanced the vaccine technology for seasonal flu. The shots
    that you and I get every year that everyone else gets every
    year or should get every year, we haven't advanced that
    technology to the 21st century. We really need and we are not
    only re-looking at it but really transforming it.
        For example, we make influenza vaccines now by growing them
    in eggs and then harvesting the virus in a very antiquated
    process which has great restrictions on scalability and the
    amount you can make. We've invested a lot of money to get the
    more up to date, 21st century methodologies for vaccine, either
    growing it in cells or doing recombinant DNA technology. We've
    made some significant advances in that regard.
        I mentioned before you came in that the pre-pandemic
    influenza vaccine for H5N1 that we tested over the past couple
    of years has now been approved by the FDA as a licensed
    vaccine. What we need to do and are doing rather successfully
    is applying, for example, the technology of adjuvants, which is
    a substance which enhances the body's response to a vaccine so
    you can get away with a much lower dose and can scale up
    rapidly.
        So I would report to you today that the work on emerging
    infections in general but in particular with regard to your
    question about pandemic flu is coming along very well.

                               HEALTH DISPARITIES

        Senator Cochran. That's very encouraging. We appreciate the
    good work that you're doing. I noticed in one of my staff memos
    here that a recent report indicated that one of our counties in
    Mississippi has the highest mortality rate from breast cancer
    in the Nation. That stopped me. It's twice the national average
    in Madison County, Mississippi.
        I wonder, we've talked about disparities. I think this
    might be something that the Research Centers in Minority
    Institutions program may be involved in. Dr. Alving, I think
    you'd know about that and can contribute something to our
    knowledge about what progress we're making at the National
    Center on Minority Health and Health Disparities.
        Dr. Alving. At the National Center for Research Resources
    we fund the RCMIs, or the Research Centers in Minority
    Institutions. We also work with Dr. Ruffin of the National
    Center on Minority Health and Health Disparities. I think also
    at the NCI there is a very big program in minority centers in
    cancer outreach.
        I would wonder if there isn't a multi-factorial reason for
    this high mortality. The first question would be is it due to
    lack of screening. Second we would want to know that if there
    are women who have increased breast density which can also
    affect the screening results or the mammography. But I would
    really wonder about access to care and preventive measures.
        As you know, the NHLBI funds the Jackson Heart Study in
    Mississippi, which is not only an observational study, but is
    dealing with ways of getting the participants used to the idea
    of preventive care and screening. We and the Research Centers
    in Minority Institutions are setting up a translational
    research network, with Jackson State as the data coordinating
    center, where we can do improved outreach and clinical trials
    in minority populations and also work collaboratively with my
    colleagues here at the table.
        Senator Cochran. Let me ask Dr. Ruffin to comment on that
    too.
        Dr. Ruffin. Senator Cochran, I think that first of all what
    I would like to do is really congratulate the people in the
    State of Mississippi, if you're looking for an example of
    partnerships.
        I just believe that whatever the disease area happens to be
    whether it's heart disease in the case of what we're doing with
    NHLBI or whether it's breast cancer or any of the other
    studies, whether we're talking about just getting the
    communities to participate in a clinical trial, I think there's
    a model in Mississippi that ought to be emulated. That is the
    ability of the institutions in the State of Mississippi to come
    together and work together.
        We've got programs at the Center that are working. The one
    that you're referring to, the Center for Health Disparities in
    the State of Mississippi has brought all of the institutions
    there together. The University of Mississippi Medical Center,
    Tougaloo College, Jackson State and many other institutions
    come together to work on these issues. So I believe that
    irrespective of which disease we're talking about, because
    health disparities is a very complex issue, it deals with a
    whole plethora of different disease areas and you have so many
    experts there who are working on various aspects of this issue.
        I think that by bringing these individuals together and
    everybody working together and understanding where their
    various strengths and weaknesses are, we're going to get an
    answer to a number of very important questions here.
        Senator Cochran. Well, that's very encouraging and we
    appreciate your hard work and efforts in that regard. Now, you
    mentioned, was it Dr. Niederhuber or Dr. Fauci, did you have a
    role--do you have a role in this specifically?

                           INFORMATION DISSEMINATION

        Dr. Niederhuber. Dr. Niederhuber. Dr. N. is easier.
        Senator, we as you might imagine at the Cancer Institute
    track very carefully the hot spots, if you will. We color them
    red. I don't know if that's significant politically or not but
    we know where those hot spots are for various cancers. Some of
    those areas are industrial; others are what you would call
    rural.
        Appalachia, if you go down through Appalachia we have very
    high incidence of certain kinds of especially female associated
    cancers. It's a multiple factorial problem. There's not one
    simple fix to this. Part of it has to do with education. Some
    of it has to do with socioeconomic status of those communities.
        We look also very carefully at the environment and whether
    there are environmental relationships that we can pin to risk.
    We look at the genetic changes in the population to see whether
    there's a relationship with the genetic background or inherited
    genetic patterns in those communities that relate to this risk
    as well.
        We're looking at all aspects of it. It's a very complicated
    issue. Certainly an awful lot of it though has to do with
    education and an opportunity or access to science, to care.
        As I mentioned in my opening statement before you arrived,
    Senator, we're launching in the next few days actually, 10
    pilot centers across the country that are specifically targeted
    at rural communities. Not universities, but in community
    environments around community hospitals and probably about 100
    to 250 bed facilities. The purpose of those pilots is to try to
    learn as much as we can about what we're going to need to do to
    bring the latest of our science, the latest of our discoveries
    directly to those people.
        We know that 85 percent of patients with cancer get the
    care for their cancer in the community where they live. They
    don't leave the community. They don't travel to M.D. Anderson
    in Houston or to Memorial Sloane Kettering or to Duke
    University or wherever. They stay right at home for a variety
    of reasons. Part of it has to do with age and the dependency on
    the family for support and care. That's just what's happening
    in this country.
        We have to understand that better. We have to understand
    how we're going to get our science, our discovery to people
    where they live.
        Senator Cochran. It's very interesting. Well, we thank you
    for the good work that you're doing. We appreciate your being
    here at the hearing. We look forward to continuing a close
    relationship with you as we go through the mark-up process.
    Thank you.

                             CANCER SPORE'S PROGRAM

        Senator Harkin. Thank you, Senator Cochran. As I said, Dr.
    Niederhuber, pancreatic cancer, number four killer among
    cancers. Once it strikes, very little hope. Senator Stevens had
    talked a little bit about that. It's one of the few cancers for
    which mortality rates are virtually the same today as they were
    30 years ago. So that makes the work of the three pancreatic
    cancer SPOREs so important, the Specialized Programs of
    Excellence.
        Dr. Niederhuber. Absolutely.
        Senator Harkin. I understand that NCI is considering
    changes to the SPORE program that could have a significant
    impact on pancreatic SPOREs. Could you tell me about your plans
    in that area?
        Dr. Niederhuber. Actually, I think that the changes that we
    have been making, Senator, have actually strengthened the
    program. We have been working very hard to keep as much
    resources, financial resources into this program as we have had
    in the past. So we've been scraping to do that.
        When I came onboard I looked at some of the struggles and
    some of the problems. Having come from the academic community
    and having been Cancer Center Director and knowing a little bit
    from the outside about the issues that this SPORE program has
    and how difficult it is to bring the basic scientist together
    with the clinical scientist. It's not an easy accomplishment
    for any university to build one of these programs, one of these
    collaborative efforts.
        So I began working directly with the currently funded
    leadership of the SPORE program across all of the diseases.
    Some of the things that we decided to do together,
    collectively, was one to have them come in separately.
        Senator Harkin. Individualized.
        Dr. Niederhuber. We would have the lung cancer programs all
    coming in at the same time but then not being able to come back
    in for 2 or 3 years for funding. That didn't make a lot of
    sense to any of us. So we've changed that structure around.
    We've put in place three separate times a year when anybody who
    comes together and creates a SPORE program in breast or
    prostate or pancreatic cancer. They have the resources to put
    into this and to compete for one of these grants. They can come
    in September/October or January/February or in the springtime.
        They also now have the opportunity, if the study section
    who reviews that application doesn't give it quite the score to
    get funding, a score level, they then have the opportunity to
    immediately respond to that, revise their application and come
    right back in. That was not something that existed before.
        I met with the SPORE PIs about 3 weeks ago at the American
    Association of Cancer Research meeting in Los Angeles, since
    they were mostly all there. We had a special opportunity for
    them to come and sit with me. I reviewed with them the funding
    plan we have put in place so that they could understand the
    resources and how the resources were being distributed. They
    could see the same detail that I have.
        I think they really appreciated that. It was the first time
    that anybody had been that open and shared with them the
    details of funding. We talked about the future. We talked about
    some innovative things that we might do with the program that
    might further enhance the SPORE program.
        So I think we have a very collegial working relationship
    with the research community that's committed to putting these
    grants together and to keeping them going. The goal is the best
    science.
        Senator Harkin. I understand but again I think there's some
    concern that the pancreatic cancer SPOREs will get squeezed
    out.
        Dr. Niederhuber. No. You're talking to a person who's spent
    his whole life doing pancreatic cancer surgery. So, I'm very
    committed to being sure we continue that.

                               PANCREATIC CANCER

        Senator Harkin. One last thing.
        Dr. Niederhuber. I'm hopeful that there will be other
    Institutions that will feel they have the resources, academic,
    and intellectual resources, to come in. If we get another good
    application that number is not frozen at three, we'll fund the
    best we can get.
        Senator Harkin. Ok. One last thing. Pancreatic cancer is so
    bad because there's no early detection.
        Dr. Niederhuber. Correct.
        Senator Harkin. Once you've found out and we all assume
    we've all had friends die of it. I just had one recently within
    the last couple of years who was my back seat guy when I flew
    in the Navy. Literally within, probably, 9 months he was dead.
        Dr. Niederhuber. Six months to a year.
        Senator Harkin. I've had others say the same thing. By the
    time you detect it, it's too late. What kind of hope can you
    give us? What kind of research is going on for some kind of
    early detection, methodology for pancreatic cancer?
        Dr. Niederhuber. If you remember in my opening presentation
    I highlighted that. Our genome-wide scanning that we are doing
    to look at large cohorts of patients to determine what genetic
    changes may be present in their genome, in their code of DNA,
    what changes they may carry with them that predict. For example
    we studied breast first, then prostate. We've learned quite a
    bit from that.
        We've had, I think, over the past 3 months, six papers I
    believe it is. Don't quote me for sure on that number. But I
    think it's six papers in Nature which is one of the leading
    journals as a result of that work in both prostate and breast.
    So in July of this year we will begin the same kind of study in
    pancreatic cancer.
        I am a person very interested in pancreatic cancer. I'm
    very excited about that because I think that's the first step
    in getting the kind of background information we need in terms
    of what changes may exist in your genome that says you've got a
    greater risk over your lifetime of developing this kind of
    cancer. It's a huge step for me, I think, in what we need to
    know. It will be a great foundation to build on. I hope that
    out of that we will get some clues of what kind of, we call
    them biomarkers, to look for in this particular cancer.

                                  TUBERCULOSIS

        Senator Harkin. Thank you very much. Dr. Fauci, I'm hearing
    more and more about drug resistant tuberculosis. I just had a
    question on it this weekend from someone. How big is the threat
    and how prepared are we to deal with it?
        Dr. Fauci. It's a growing threat, Mr. Chairman that we're
    concerned about. As you know, TB is a very, very important
    global problem. One third of the world's population is infected
    with tuberculosis, not sick with it, but infected with it.
        Senator Harkin. One-third of the world's population is
    infected with tuberculosis.
        Dr. Fauci. One-third of the world's population is infected
    with tuberculosis, right. We get about 8 million new cases a
    year with 1.3 to 1.6 million deaths. Twenty percent of all of
    the tuberculosis active cases are multiple drug resistant. It
    means that it's resistant to the standard drugs that we use.
    But we do have alternative drugs. Ten percent of that 20
    percent have what we call extensively drug resistant
    tuberculosis or XDR as it's referred to. It's a growing
    problem.
        We are ratcheting up very aggressively our tuberculosis
    portfolio to address the issue of drug resistance. We just, as
    I mentioned earlier, put together a strategic plan that I
    presented to my National Advisory Council this morning. Then we
    will be formalizing that plan. It is a real serious problem.
        It was first brought to the attention of the scientific
    community from about 54 cases that were identified in South
    Africa, of which an astounding 52 died. That's a very, very
    high rate. The reason it is likely because they were also co-
    infected with HIV. It isn't just confined to people with HIV.
        But when you say extensively drug resistant you mean that
    the standard INH and rifampicin, the drugs that you usually
    give. It's resistant to them. It's resistant to the
    fluoroquinilones and it's resistant to at least one injectable
    third-tier tuberculosis drug like amikasin and drugs like that.
    So it's a very serious problem.
        In some cases it is completely non-curable. So we have to
    work really fast to get other drugs into the pipeline. But
    importantly to make the right diagnosis because you get drug
    resistant TB by not properly treating regular TB, and you don't
    properly treat it because you don't diagnose it early enough.
    Then when you do, people don't come back for follow-up because
    they start to feel better right away. So we need to have a good
    screening process and a very sensitive diagnostic. All of that
    is part of our strategic plan that I was talking about a moment
    ago.

           MULTIPLE DRUG RESISTANT AND EXTENSIVELY DRUG RESISTANT TB

        Senator Harkin. I think most people would be alarmed to
    find out tuberculosis which we thought was in the Dark Ages has
    come back so strongly. I had not known that 1 out of 3, 30
    percent. That's alarming.
        From the figures that you gave me it's about--you say about
    20 percent are multiple drug resistant.
        Dr. Fauci. Ten percent of that 20 percent are extensive.
        Senator Harkin. So 2 percent are resistant to anything.
        Dr. Fauci. Right. Exactly.
        Senator Harkin. Is that in just a certain area of the
    world? Is that confined to a certain area?
        Dr. Fauci. Thirty-seven countries now have extensively drug
    resistant tuberculosis. There are a few cases we have in the
    United States that have been taken care of and contained. The
    problem is very serious in southern Africa. Interestingly we
    have a considerable number of cases in the Eastern European
    bloc countries and even in Korea. But there are 37 countries
    worldwide that have extensively drug resistant tuberculosis.
    That's reported.
        But given the fact that most of that one-third of the
    world's population is in the developing world in areas in Asia
    and India and China and in Africa. That's where you don't
    likely get the medical care to get the diagnosis to get it
    treated. So it's a problem that's probably underestimated. So
    I'm telling you it's 20 percent and then there's 10 percent of
    20. It's probably an underestimate as to what's really going
    on. It's a serious problem.
        Senator Harkin. Is it highly transmissible?
        Dr. Fauci. Well, it's transmissible like any tuberculosis.
    You need close continued contact and it's aerosolized droplets
    that contain the tuberculosis bacillus.
        Senator Harkin. Anthrax.
        Dr. Fauci. Yes.
        Senator Harkin. Recent estimates have said we need to be
    prepared for an anthrax attack. HHS has stockpiled anthrax
    vaccine and antibiotics. The problem with antibiotics is that
    they have to be administered shortly after any kind of attack
    or event. I've heard that there are other therapeutics that
    could target the toxins released by the anthrax bacteria and
    therefore could be effective even after the onset of symptoms.
        Dr. Fauci. Correct.

                       ANTHRAX ANTIBIOTICS AND ANTI-TOXIN

        Senator Harkin. Tell me more about that.
        Dr. Fauci. Sure. We started a program right at the point of
    a few months after the anthrax attacks here in our capital. One
    of the concerns we had is that we have very, very good
    antibiotics for anthrax. In fact, the clinical trial was done
    among Senate and House staff when they were given Ciprofloxacin
    following known exposure.
        In fact it's very interesting. Some of you may not know
    that when they did blood test screening of antibodies that many
    of the people who just did perfectly well because they took
    Ciprofloxacin or doxycycline. Actually you have proof that they
    were exposed, which means that if they did not take the
    antibiotic they very likely would have gotten sick. So the
    people who took the antibiotics did the really, the right thing
    about taking the antibiotics. I say that because we have good
    antibiotics.
        But what we are concerned about is, remember, several of
    the postal workers here in the city who were misdiagnosed
    initially. Then when they finally had the right diagnosis and
    were put on Ciprofloxacin, they were so advanced in the disease
    that the circulating anthrax toxin was the thing that killed
    them as opposed to the replicating anthrax bacillus.
        So, what we've done and we've been rather successful at it
    is to develop antibodies against the toxin itself. So if you
    have the antibiotic, prevents the replication of the bacteria,
    but the anti-toxin neutralizes the circulating toxin which is
    the thing that actually caused the death of several of those
    people. So we do have it. Some of it is already in the
    stockpile and we're working on even better ones.
        Senator Harkin. I was not aware of that.
        Dr. Fauci. Yeah, yeah, it's true.
        Senator Harkin. You actually have it in the stockpile now.
        Dr. Fauci. We have an order for it through Bioshield.
        Senator Harkin. Again this would be effective even after I
    become symptomatic--after the symptoms arise. You could target
    that? You say you're working on others, you mean there's----
        Dr. Fauci. There are multiple--there are three major toxins
    and we have antibodies to all of them. One of the ones, the
    lethal toxins that are the ones that we're most concerned
    about. We have now molecular biological techniques where we're
    trying to make monoclonal antibodies against. Monoclonal
    antibodies in anybody you actually code and manufacture to make
    only the response against a particular toxin you're worried
    about.
        Senator Harkin. How certain are you? I mean, what's the
    success rate if you had 100 people who became symptomatic with
    anthrax and you gave them this vaccine? What's the survival
    rate?
        Dr. Fauci. It depends when you get it. I have to tell you
    being an infectious disease person and having taken care of a
    lot of people who have advanced septicemia and shock. Once a
    person goes into the toxic septicemia of endotoxic or other
    types of shock the salvage rate of those individuals is very
    low.
        So I think even with an anti-toxin, if given early enough,
    before you have a lot amount of accumulated toxin, it would
    probably increase the salvage rate and decrease the morbidity
    and mortality significantly. I can't put a number on it for you
    because the clinical trial has not been done. So it would be
    folly for me to say, oh it's a 90 percent, 80 percent. We just
    don't know. We just don't know.
        Senator Harkin. How soon?
        Dr. Fauci. I hope we never have to test it.
        Senator Harkin. How will you know? How will you ever know?
        Dr. Fauci. We'll know when we have another attack.
        Senator Harkin. That's about the only way.
        Dr. Fauci. We have animal models which have worked very,
    very well in the animal models. But again we always be
    careful--if you tell me based on the animal model would I
    project that it would be a success I would say yes. But I have
    to be very cautious because there's a big leap between a
    successful animal model and what works in the human.

                               CANCER STEM CELLS

        Senator Harkin. I've got to go but a couple of things I
    wanted to cover. Cancer stem cells. There's an idea that within
    a tumor there are cancer stem cells are really the driving
    force. That if we could just figure out how to get to those
    stem cells and target those that we would have a better success
    rate in curing cancer. What can you tell me about that?
        Dr. Niederhuber. Well, it's a very exciting area of
    research. It is not a totally new concept. It's really an old
    concept. But it has come back in just the past few years.
        An example, Senator Harkin, a year ago at the AACR, the big
    national research meeting, there were maybe 20, 25 papers. This
    year there were over 225 papers at the meeting. So it just
    shows you how the community has become excited and interested
    in this concept.
        So we know that within our tissues, the normal tissues of
    our body there are cells that are responsible for regenerating
    those tissues. Let's take the lining of the intestine, the
    colon, for example. We know that there are what we call tissue
    stem cells that have a certain division property that allows
    them to regenerate that lining of the colon.
        So the concept is that the genetic changes that occur that
    lead to a cancer may have to occur in those cells, in those
    tissue stem cells, in order for the cancer to become a
    significant lesion--to have the property or potential for
    invasion and the potential for spread. In the tumor the bulk of
    the tumor cells don't carry that kind of genetic imprint.
        It's like thinking of the cell as an orchestra. Some of the
    instruments that give that orchestra in that cell the
    properties of being stem like in character are in a
    subpopulation of the tumor, maybe 1 percent, maybe as much as 2
    percent of the tumor. The bulk of the cells in the tumor don't
    have that set of instruments playing at that particular moment.
        We think we're doing a good job of getting rid of the bulk
    of the tumor but what gets left behind is that one percent of
    cells that can lie quiescent in the tissues of the body for a
    number of years. Those of us who practice oncology over the
    years have been always puzzled by seeing a patient with breast
    cancer seemingly cured 15 years or so later coming back with
    the disease seemingly everywhere. It may be part of the
    explanation of this.
        So without question we need to learn more about these
    cells. We need to learn what gives them resistance to the
    therapies that we use. We know that they have certain
    properties that can pump drugs that get into the cell
    immediately back out of the cell. So there are a lot of things
    that are--that make them more difficult to target. Maybe we
    haven't been specifically targeting them in the ways that we
    need to.
        Some of the new research is showing pathways that are
    unique to those cells. That is, signal pathways within the cell
    and potential ways to target them that are unique. So I think
    you'll see over the next few years a lot more research going on
    that is trying to get at that population of cells, better
    characterizing it and better targeting it for therapy.

                       NATIONAL PRIMATE RESEARCH CENTERS

        Senator Harkin. Thank you very much. I have a couple of
    last questions for Dr. Alving. This subcommittee has been very
    supportive of the primate centers. We included report language
    in a lot of our past bills, so I was disappointed to see in
    your budget request that your plans cut the funding for the
    centers by $1.7 million for a total of $72.3 million. What's
    the reason for that cut in the primate centers?
        Dr. Alving. This was in the congressional justification
    estimate and now the fiscal year 2007 joint resolution, which
    was a higher change from the CJ. But what we have had to do and
    what we are doing throughout the NCRR is to look at where we
    can best put our resources.
        We are actively working with the primate centers to better
    manage the consortium. We're saying that they need to work
    together as a consortium in managing their animal facilities
    and in managing the breeding of the animals. We're very
    supportive of the work and they also are working with the
    CTSAs. So if we have improved funding we will be able to put
    more money into that program.
        Senator Harkin. Your budget request cut that funding.
        Dr. Alving. This was according to the amount of money that
    we had allocated as we went across the budget. We will put this
    money back in. We also are committed----
        Senator Harkin. So, if we--I mean, excuse me for
    interrupting. So if we do better than the President's budget
    will you put that money back in?
        Dr. Alving. Yes. Yes, we will.
        Senator Harkin. Ok.
        Dr. Alving. But also realize, Mr. Chairman, that we are
    working on building up our CTSAs and that's another challenge
    in NCRR. As we are building the primate centers, we'll be
    working with the CTSAs. For example, two of our CTSA awardee
    institutions, Oregon and UC Davis have primate centers. Those
    primate centers are working in that consortium as well.
        But we are very supportive of the primate centers. They're
    doing excellent work. I visited four out of eight of them. We
    want to work with them as a consortium to support them.

                           GCRC TRANSITION INTO CTSA

        Senator Harkin. Ok. Well we'll try to put some more money
    in there for it. It's not that big. One last question on the
    CTSAs. As you say you're building them up, but what happens to
    the General Clinical Research Centers? I guess they're going to
    be folded into them or something like that?
        Dr. Alving. There will be a transition into the Clinical
    and Translational Science Awards. For example, of the first 12
    CTSA awards that were provided, 16 General Clinical Research
    Centers were included. Those have become part of the CTSAs.
        We're also emphasizing pediatrics in the CTSAs. For
    example, at the University at Pennsylvania, two General
    Clinical Research Centers were folded into that CTSA award, one
    from the Children's Hospital of Pennsylvania, one from the
    University of Pennsylvania. Now they are absolutely working
    together.
        Senator Harkin. So you can assure me there will be no
    diminution of training researchers the next generation in
    translation and clinical research because of this new
    structure.
        Dr. Alving. What we're really building is the training of
    the clinical researchers because the GCRC program never
    included training. So this is a big component of the new CTSAs.
        Senator Harkin. Thank you. Any last things from anyone else
    that I didn't touch on or that you wanted to express yourself
    on before I gavel this closed here? I thought it was a very
    good hearing. I think we got a lot out and a lot of good
    information.
        Again, I thank you all very much for your leadership in all
    these various areas. I just hope that we can get a little bit
    better budget than what the President requested. We will. We'll
    get better than what the President requested. And now we're
    looking ahead to see how we can repair some of the damage of
    the last few years. The 12 percent or 13 percent that we've
    come down in NIH over the last 4 or 5 years and we've got to
    get it back up again. But that's our problem. We'll see if we
    can do better on that.
        So with that, thank you very much. We have one more group
    from NIH and we haven't scheduled a hearing but I assume it
    won't be this week and it won't be next week because we're not
    here. So it will be sometime in June we'll have the last set of
    hearings.

                         ADDITIONAL COMMITTEE QUESTIONS

        So I thank you very much and we will keep the record open
    for any questions that other Senators who weren't here today
    have for you that they might submit in writing.
        [The following questions were not asked at the hearing, but
    were submitted to the Department for response subsequent to the
    hearing:]
                   Questions Submitted by Senator Tom Harkin
                         food allergies and anaphylaxis
        Question. Dr. Fauci, children who have had atopic dermatitis, also
    known as eczema, are more likely to have severe food allergies and
    asthma. Has the NIAID considered the possibility of funding a
    complementary initiative, perhaps in coordination with the NHLBI, on
    atopic dermatitis as it relates to asthma and food allergy?
        Answer. The National Institute of Allergy and Infectious Diseases
    (NIAID) is committed to supporting research to better understand the
    relationship of atopic dermatitis (AD) to asthma and other allergic
    diseases, particularly food allergy. At this time, the NIAID is
    supporting several studies in this area. The Consortium of Food Allergy
    Research is conducting an observational study of the development and
    loss of tolerance to foods in a cohort of 400 children, ages three to
    twelve months, at a high risk of developing food allergies, including
    children with AD. The study will correlate biological markers and
    immunologic changes associated with the development of peanut allergy
    and the resolution of allergies to egg and cow's milk, and evaluate
    genetic and environmental influences on these food allergies.
        Another NIAID-sponsored program, the Immune Tolerance Network, is
    conducting two clinical trials related to food allergy and AD. The
    first will determine whether feeding a peanut-containing snack to young
    children at risk of developing peanut allergy will prevent development
    of this allergy. The subjects are children between 4 and 10 months of
    age with AD and/or allergy and they will be followed until they reach 5
    years of age. The second clinical trial is enrolling children with AD
    who are between the ages of 18 and 30 months and at high risk for
    developing allergies. This trial will determine whether oral
    administration of cat, grass, and house dust mite allergens will
    prevent the development of allergy to these and other allergens and
    asthma in these children.
        The NIAID Inner-City Asthma Consortium is conducting the Urban
    Environment and Childhood Asthma (URECA) observational study, which
    will assess antibodies to milk, egg white, and peanut in infants at
    risk for developing allergic diseases, including asthma, allergic
    rhinitis, and AD. The study will look for a correlation between food
    allergies and the onset of asthma later in life.
        Lastly, the NIAID currently collaborates with NHLBI on two
    initiatives related to asthma. One of these, Immune System Development
    and the Genesis of Asthma, includes a grant which studies the
    relationship of AD to asthma.
        Question. What plans does NIAID have to encourage research
    applications on anaphylaxis? Has the NIAID considered the need for
    clinical studies of emergency room treatment for anaphylaxis?
        Answer. To address the problem of anaphylaxis, the NIAID is
    pursuing two major approaches: expanding support for research on the
    causes, treatment, and prevention of allergic diseases, including food
    allergies and food-allergy-induced anaphylaxis; and supporting national
    and international conferences that will disseminate new knowledge and
    promote a more cohesive approach to the diagnosis, prevention, and
    clinical management of anaphylaxis.
    Expanding research
      --The Report of the NIH Expert Panel on Food Allergy Research
            discussed food-induced anaphylaxis in detail and emphasized the
            need to study the pathogenesis of severe food allergy.
      --The NIAID-funded Consortium of Food Allergy Research is conducting
            an observational study of the natural history of food allergy,
            which is expected to provide new information about severe
            allergic reactions and anaphylaxis. In addition, the Consortium
            is conducting a clinical trial focused on severe food allergy,
            which will use increasing oral doses of egg to treat patients
            with severe egg allergies.
      --The NIAID has just announced a new initiative, Exploratory
            Investigations in Food Allergy, which encourages studies on
            severe life-threatening food allergy.
    Supporting national and international conferences
      --The NIAID, in partnership with the Food Allergy and Anaphylaxis
            Network (FAAN), a patient advocacy group, convened meetings in
            2004 and 2005 to establish clinical criteria to identify cases
            of anaphylaxis with high precision, review evidence on the most
            appropriate clinical management of anaphylaxis, and outline
            research needs in this area. Participants included experts and
            representatives from professional, governmental, and lay
            organizations. The proceedings of these symposia were published
            in the March 2005 and February 2006 issues of the Journal of
            Allergy and Clinical Immunology.
        The NIH Expert Panel on Food Allergy Research considered the need
    for clinical studies of emergency room treatment for anaphylaxis and
    presented its recommendations as part of its report.
        Question. Does NIAID make information available to health
    professionals about the best approaches to treating food allergy?
        Answer. The Consortium of Food Allergy Research was initiated in
    2005 to develop new approaches to treat and prevent food allergies. As
    such, one of the goals of the Consortium is the development,
    implementation, and dissemination of educational programs for children,
    their parents, and pediatric health care workers. In addition, the
    Consortium supports preclinical research, observational studies, and
    immune-based clinical trials for treatment or prevention of food
    allergies.
        To ensure that the information on diagnosis, prevention and
    management of anaphylaxis is developed and widely disseminated to the
    medical community, NIAID, in collaboration with FAAN and the American
    Academy of Allergy, Asthma and Immunology, is organizing a series of
    meetings. These are scheduled to begin in July 2007 and will develop
    evidence-based guidelines for the diagnosis and management of food
    allergy, including anaphylaxis.
                            tobacco-related research
        Question. Dr. Niederhuber, in March, you told NCI's Board of
    Scientific Advisors that the Tobacco Control Research Branch has been
    cut by $6.5 million between fiscal year 2004 and fiscal year 2007. Are
    those numbers still correct? If so, can you tell us how cutting back on
    this type of research will affect our ability to prevent tobacco-
    related cancers?
        Answer. The Tobacco Control Research Branch (TCRB) budget was $19.2
    million in fiscal year 2004. We are still in the process of making
    final funding decisions, but the current estimate for fiscal year 2007
    is $12.7 million, which is a reduction of $6.5 million from fiscal year
    2004. Part of the reduction during the period between fiscal year 2004
    and fiscal year 2007 was due to the expiration of some tobacco control
    research initiatives. However, additionally, the period following the
    doubling of the NIH budget has resulted in very difficult choices in
    terms of setting priorities and implementing funding decisions. The NCI
    Executive Committee and advisory boards have worked diligently to
    conduct strategic priority setting and decision making related to the
    scientifically appropriate distribution of resources. In order to
    pursue new and emerging opportunities in cancer research, we must make
    choices about which programs and research initiatives come to an end.
        In terms of planning for the future, scientists in TCRB are
    currently working on several new research concepts in response to the
    2006 NIH State of the Science Conference, ``Tobacco Use: Prevention,
    Cessation and Control,'' and other priority setting reports. NCI will
    use these concepts to develop and redirect initiatives in tobacco
    control research in the future.
        NCI's research efforts in the prevention and control of tobacco use
    are premised on three fundamental facts: all tobacco products are
    hazardous; there is no safe level of tobacco use or ETS exposure; and
    the only proven way to reduce the burden of disease and death due to
    tobacco products is to prevent their use and to assist those who use
    tobacco products to quit. Further progress in reducing tobacco use is
    an important challenge facing the public health, medical, and policy
    communities.
        The Tobacco Control Research Branch (TCRB) maintains a diverse
    portfolio of research and dissemination activities. Most noteworthy are
    the following:
      --Transdisciplinary Tobacco Use Research Centers (TTURC). The TTURCs
            are a collaboration between NCI, NIDA, and NIAAA to study
            tobacco use control and addiction research spanning diverse
            areas ranging from molecular biology, genetics, neuroscience,
            and epidemiology to imaging, primary care, behavioral science,
            communication, health policy, biostatistics, economics, and
            marketing. Collaborative research across disciplinary
            boundaries permits scientific exploration of the complex and
            interactive determinants of tobacco use.
      --Testing Tobacco Products Promoted to Reduce Harm is a program which
            funds multidisciplinary research on the interplay of behavior,
            chemistry, toxicology, and biology to determine the cancer risk
            potential of reduced-exposure tobacco products.
      --Smokefree.gov is a state-of-the-art Web site developed by NCI in
            collaboration with the Centers for Disease Control and
            Prevention (CDC) and the American Cancer Society (ACS). It
            offers science-based tools and support to help smokers quit.
            Smokefree.gov complements the National Quitline Network that
            has established a new state-supported national telephone number
            so smokers in every state have access to information and
            proactive smoking cessation counseling.
      --The Health Disparities Network is a unique endeavor to understand
            and address tobacco-related health disparities by advancing
            science, translating scientific knowledge into practice, and
            informing public health policy. In partnership with the
            Pennsylvania State University, core scientific activities are
            focused on methodology, treatment/cessation, prevention,
            translation/community, and policy. The formation of the network
            fills a void by establishing a mechanism to bring together an
            ethnically diverse group of researchers representing different
            disciplines and interests to answer multiple questions related
            to the research agenda in health disparities and explore
            optimal mechanisms for translating research into practical and
            effective community strategies.
                                minority health
        Question. Dr. Ruffin, if the Subcommittee were able to provide
    additional funding for the Center over the President's budget request,
    what would be your top priority for how to spend it (e.g., health
    disparities research vs. research capacity-building and
    infrastructure), and why? Please be as specific as possible.
        Answer. The fiscal year 2008 President's Budget request of $194.5
    million will support NCMHD's highest priority research activities.
    However, if the NCMHD were to receive any additional funding over the
    President's budget request, those funds would go towards research
    capacity-building specifically in the area of training. Having a strong
    and culturally diverse workforce is vital to the ability of NCMHD to
    fulfill its mission to improve minority health and eliminate health
    disparities. NCMHD would place additional emphasis on recruitment and
    retention at every level of the pipeline.
        First, NCMHD would strengthen the retention component of the NCMHD
    Loan Repayment Program in order to keep more individuals from health
    disparity populations interested and involved in health disparities
    research, as well as attract young investigators from these populations
    to the biomedical research field in general.
        Second, NCMHD would be to further develop the capacity of our
    Centers of Excellence to enhance their capability in conducting
    research into the multi-factorial issues associated with health
    disparities. The research efforts of these Centers contribute
    significantly in enhancing the nation's understanding of health
    disparities, and offer the training and professional research
    environment required for the workforce to study minority health and
    health disparities issues.
                                 food allergies
        Question. Dr. Fauci, during the hearing, you indicated that the
    ``roadmap'' which was developed by the leading food allergy researchers
    and experts in immunology after they met in March 2006 is still in the
    process of being approved. When will it likely be released?
        Answer. In March 2006, the National Institute of Allergy and
    Infectious Diseases (NIAID), on behalf of the Secretary of the
    Department of Health and Human Services, convened the NIH Expert Panel
    on Food Allergy. The Expert Panel met to review current basic and
    clinical research on food allergies and develop recommendations for
    enhancing and coordinating research activities concerning food
    allergies. The recommendations have now been posted on the NIAID
    website at http://www3.niaid.nih.gov/healthscience/healthtopics/
    foodAllergy/ReportFoodAllergy.htm.
                                     ______

                Questions Submitted by Senator Daniel K. Inouye
                          native hawaiians and cancer
        Question. Dr. Niederhuber, Native Hawaiians have a much higher
    mortality rate from cancer than other residents of the State. What
    efforts has the National Cancer Institute taken to understand cancer in
    Native Hawaiians?
        Answer. The National Cancer Institute (NCI) continues to support
    research to find the causes of cancer health disparities and to develop
    effective ways to improve cancer outcomes for Native Hawaiians. Among
    these continued efforts are: enhancing surveillance of Native Hawaiian
    populations to document the extent of cancer health disparities and
    monitor progress in improving cancer outcomes in these communities;
    empowering Native Hawaiian communities to participate in setting cancer
    research goals and priorities; assuring access to community-based
    health care that is culturally and linguistically appropriate;
    supporting infrastructure for Native Hawaiian communities that promotes
    cancer awareness, supporting research education and training in cancer
    prevention and control research by Native Hawaiian researchers, and
    supporting the development of evidence-based information and
    interventions to improve cancer outcomes in Native Hawaiian
    communities.
    Community Networks Program
        Two of NCI's Community Networks Programs continue to address Native
    Hawaiian populations: 'Imi Hale--Native Hawaiian Cancer Network, and
    WINCART: Weaving an Islander Network for Cancer Awareness, Research and
    Training. These five-year grants, engage in cancer education,
    community-based participatory research and training targeted
    specifically to the Native Hawaiian population.
        The Native Hawaiian Cancer Network, 'Imi Hale, is located in
    Honolulu, Hawaii and collaborates with key partners at the community,
    state, and national levels to provide support systems and expertise to:
    (1) provide a core organizational infrastructure; (2) increase
    utilization of proven interventions to reduce disparities; (3) increase
    the number of Native Hawaiians participating in community-based
    research to reduce cancer health disparities through recruitment,
    training, and mentorship; (4) promote research that focuses on the
    spectrum of issues relevant to cancer health disparities, with an
    emphasis on developing interventions that can be used in and by Native
    Hawaiian communities; and (5) provide evidence-based information on
    reducing cancer health disparities to decision and policy makers at the
    community, local, state, and Federal levels.
                                    wincart
        WINCART aims to: (1) identify multilevel barriers to cancer control
    among Pacific Islanders; (2) improve access to and utilization of
    existing cancer prevention and control services for these communities;
    (3) conduct community-based participatory research; (4) increase the
    number of Pacific Islander researchers through training, mentorship,
    and research projects; (5) sustain community-based education, training,
    and research activity through government and organizational
    collaborations; and (6) disseminate research to aid in the reduction of
    health disparities among Pacific Islander communities. Research
    activities focus on obesity, tobacco, cancer screening, survivorship,
    and recruitment of Pacific Islanders into clinical trials. The Network
    works with the NCI-supported Cancer Information Service to develop
    culturally and linguistically appropriate educational materials.
        nci surveillance of cancer health in native hawaiian populations
        NCI continues to strengthen the Surveillance Epidemiology and End
    Results (SEER) Program which has expanded its surveillance coverage and
    activities to capture 70 percent of Native Hawaiians and Pacific
    Islanders in the surveillance network. These include cancer
    surveillance, behavioral risk factor surveillance, health information
    and health services data, and epidemiologic data. This expansion is
    critical to uncovering the extent of the cancer problem and monitoring
    progress in eliminating cancer disparities in Native Hawaiian and
    Pacific Islander communities.
                    cancer in pacific island subpopulations
        The NCI also recognizes the dramatic disparities found in many
    Pacific Island subpopulations, including rural Native Hawaiian
    populations. Through the Minority Institution/Cancer Center Partnership
    Program, NCI supports a research partnership between the University of
    Guam, and the Hawaii Cancer Research Center to address the cancer
    research needs of Guam and adjoining Islands.
        Through the Cancer Information Service, NCI supports efforts to
    provide NCI products, resources and services, including promotion of
    the Clinical Trials Education Series and clinical trials to individual
    hospitals in Hawaii approved through the American College of Surgeons
    Commission on Cancer (ACoS). In addition, CIS provides professional
    training in cancer and cancer clinical trials throughout Hawaii, raises
    awareness among Kauai Community College (KC) nursing students about
    cancer clinical trials, and promotes access and dissemination of NCI
    cancer clinical trials resources. These efforts have improved screening
    rates among Hawaii's medically underserved populations.
                                    nursing
        Question. Dr. Grady, could you discuss the funding rates of the
    NINR compared to other institutes at the NIH? What percentage of
    nursing studies are co-funded with other institutes? What are your
    impressions of co-funded studies?
        Answer. NINR, like the rest of NIH, calculates success rates by
    dividing the number of research project grant (RPG) applications
    selected for funding in a given fiscal year by the total number of RPG
    applications reviewed during that year. In fiscal year 2006, NINR had a
    success rate of 18 percent, slightly lower than the overall rate of 20
    percent for NIH as a whole. NINR has historically had success rates
    lower than the NIH average; however, success rates can and do fluctuate
    from one year to another based on both the number of applications
    received and the overall NINR budget. In fiscal year 2006, NINR chose
    to devote about 72 percent of its budget to the support of RPGs.
        In fiscal year 2006, approximately 7 percent of NINR-supported
    research grants were co-funded by one or more of the other NIH
    Institutes and Centers (ICs). However, co-funding is only one aspect of
    NINR's overall collaborative effort across NIH. In today's increasingly
    complex, interdisciplinary research environment, NINR views trans-NIH
    collaborations as an important part of its research mission. In
    addition to co-funding research, other such efforts include: co-
    sponsoring new research initiatives with other ICs, leading the NIH
    effort in end-of-life research, and maintaining leadership roles in
    trans-NIH activities such as the NIH Pain Consortium, Public Trust
    Initiative, and Roadmap. Greater collaboration with other ICs increases
    both the visibility of nurse scientists in the greater research
    community and trans-NIH awareness of research areas traditionally
    associated with nursing science, such as symptom management and disease
    prevention. Interdisciplinary collaborations also provide our own
    investigators with opportunities to expand the breadth of their work
    into areas of research not previously associated with nursing science.
                           niaid and native hawaiians
        Question. Dr. Fauci, in your testimony, you indicate that
    autoimmune diseases, allergic diseases, asthma and other immune-
    mediated diseases are significant causes of chronic disease and
    disability in the United States and throughout the world. With respect
    to asthma and lower respiratory disease, Native Hawaiian adults have a
    much higher prevalence of asthma compared to other adults in Hawaii--71
    percent higher than the total State prevalence. How can the NIAID
    contribute to a greater understanding of the asthma among Native
    Hawaiians?
        Answer. Native Hawaiians, along with other minority U.S.
    populations, have higher asthma prevalence. A recent Centers for
    Disease Control and Prevention report indicates that the prevalence of
    asthma in children in Hawaii, is among the highest in the Nation. The
    National Institute of Allergy and Infectious Diseases (NIAID) welcomes
    research grant applications focusing on the causes of increased asthma
    prevalence and morbidity. While the NIAID is not currently supporting
    research that investigates asthma in Native Hawaiians, the Institute is
    actively supporting research in other groups who have high asthma
    prevalence and morbidity.
        One of the Institute's initiatives is the Inner City Asthma
    Consortium (ICAC), which aims to identify the causes for increased
    asthma prevalence and morbidity and develop effective management
    approaches in urban, minority children populations.
        Additionally, the NIAID and the National Heart, Lung, and Blood
    Institute (NHLBI) co-sponsor the ``Immune System Development and the
    Genesis of Asthma'' program, which supports research on changes in
    immune function that occur early in life and lead to the development of
    asthma.
        Information gained from these studies will enhance our
    understanding of the mechanisms of increased asthma in specific
    populations. We hope that this understanding can be extended to Native
    Hawaiians and can lead to measures of prevention and therapy that will
    ameliorate this significant health problem.
                                  dengue fever
        Question. Dr. Fauci, in 2001, Hawaii experienced an outbreak of
    dengue fever that lasted 8 months, in which over 1,500 people
    experienced severe sickness. Worldwide, dengue fever kills
    approximately 25,000 each year, and it is estimated that there are
    between 50 million and 100 million cases of dengue fever illness each
    year. Given the impact of this disease on my constituents, what efforts
    has the NIAID taken towards vaccine development?
        Answer. The National Institute of Allergy and Infectious Diseases
    (NIAID) is currently supporting several research projects to develop a
    safe and effective vaccine against dengue fever. Development of a
    dengue vaccine is challenging because of several factors, chiefly, the
    requirement that a dengue vaccine be tetravalent, that is,
    simultaneously protective against all four dengue serotypes.
    Researchers at the NIAID have developed components of a tetravalent
    dengue vaccine that are undergoing clinical testing. Other efforts to
    develop a vaccine against dengue fever include support of the following
    research projects:
      --Preclinical and clinical development of a recombinant subunit
            vaccine against the 4 dengue serotypes (Hawaii Biotech, Inc.,
            Aiea, HI): Additional formulation studies and toxicology
            testing are currently ongoing in preparation for a Phase I
            clinical trial planned for 2008.
      --Preclinical development of live attenuated vaccine against the 4
            dengue serotypes (InViragen, LLC., Mount Horeb, WI): Extensive
            safety and efficacy testing is currently being conducted in
            different animal models in preparation for a Phase I clinical
            trial.
      --Development of a microneedle array system for delivery of a DNA
            tetravalent dengue vaccine in the skin (Cyto Pulse Sciences,
            Glen Burnie, MD): This vaccine is currently being tested for
            immunogenicity in different animal models, and the microneedle
            array will be tested in human volunteers for safety.
      --Development of dengue virus replicon system to measure dengue virus
            neutralizing antibodies in the serum (Integral Molecular,
            Philadelphia, PA): This assay will be evaluated using serum
            samples of patients who are hospitalized with dengue fever in
            Nicaragua.
      --Recombinant envelope protein domain III as a candidate subunit
            dengue vaccine (University of Texas Medical Branch, Galveston,
            TX): The long-term goal of this project is the development of a
            candidate subunit vaccine that induces neutralizing antibodies
            for all four flaviviruses that cause dengue fever.
        Question. When may we expect to have an effective product?
        Answer. The candidate vaccines listed previously are moving through
    the product development pipeline. However, the challenges facing the
    development of a safe and effective vaccine are still significant. The
    timeline for a vaccine product to be manufactured for use in the United
    States depends upon a manufacturer successfully completing late-stage
    clinical trials, including a Phase IV population effectiveness trial
    and submitting the results to the Food and Drug Administration for
    licensure. This can be a lengthy process and can extend several years
    after clinical trials have been completed.
        Question. Which other States may be affected in the near future?
        Answer. According to the Centers for Disease Control and Prevention
    (CDC), there is a small risk for dengue outbreaks in the continental
    United States. However, the epidemic in Hawaii in 2001 serves as a
    reminder that many states in the United States are susceptible to
    dengue epidemics. In particular, states in southern and southeastern
    United States, where the Aedes aegypti mosquito is found, are at risk
    for dengue transmission and sporadic outbreaks (http://www.cdc.gov/
    ncidod/dvbid/dengue/index.htm).
        Question. What impact, if any, could global warming have on the
    spread of dengue-carrying mosquitoes?
        Answer. Environmental events, such as climate shifts, weather
    changes, and deforestation, can affect infectious diseases,
    particularly vector-borne diseases such as dengue virus. High
    temperatures, in combination with favorable rainfall patterns, could
    prolong the disease transmission season in places where the virus
    already exists or expand the ranges of the mosquito vectors to places
    where the disease is not usually found, such as Hawaii and the southern
    region of the continental United States.
                             terrorism preparedness
        Question. Dr. Fauci, the NIAID has been assigned the responsibility
    to coordinate research to develop countermeasures against a range of
    radiological and chemical threats. You describe how the Centers for
    Medical Countermeasures against Radiation coordinate activities with
    interagency partners, including the Department of Defense, Department
    of Energy, and Department of Homeland Security. Could you describe
    ongoing research of medications that would provide protection against
    radiation in the event of a small nuclear weapon or a dirty bomb?
        Answer. The National Institute of Allergy and Infectious Diseases
    (NIAID) is currently evaluating multiple compounds, including many
    drugs that are licensed for other indications, for use as
    countermeasures to combat the effects of an incident involving release
    of radioactive material. This research is part of the NIAID radiation
    and nuclear countermeasures program, which is guided by the NIH
    Strategic Plan and Research Agenda for Medical Countermeasures Against
    Radiological and Nuclear Threats.
        Examples of specific NIAID-supported research initiatives include:
      --Research on all elements of radiation injury and the development of
            products that can be licensed and included in the Strategic
            National Stockpile.
      --Programs to screen candidate compounds for use as radiation
            countermeasures. These programs have tested 40,000 compounds
            and identified 52 for further evaluation.
      --Development of improved forms of the chelating agent
            diethylenetriaminepentaacetic acid (DTPA). A chelating agent is
            a compound that binds to a radionuclide and facilitates and
            accelerates its elimination from the body.
      --Research on 29 candidate drugs that exhibit activity against a
            broad range of radionuclides that might be used in radiological
            dispersion devices or ``dirty bombs'', including several that
            currently lack effective treatment approaches, such as
            Strontium 90 and Cobalt 60.
        Research to develop medical countermeasures to treat radiation
    injury remains in the early stages of development; significant research
    and pre-clinical testing is needed before we will have candidate
    products developed to treat radiation injury that can move forward for
    licensure.
                                     ______

                  Question Submitted by Senator Arlen Specter
                                 ovarian cancer
        Question. Dr. Niederhuber, as you are aware, there is currently no
    early detection method for ovarian cancer. Because of this, more than
    75 percent of women diagnosed with ovarian cancer die within five years
    of being diagnosed. If we were to find these cancers early, the
    mortality rate falls dramatically to about 15 percent. And, ovarian
    cancer is not alone; similar statements could be made for pancreatic
    cancer. Please share NCI's strategy for fiscal year 2008 regarding
    early detection research, such as biomarkers, for cancers like ovarian
    and pancreatic, where the incidence numbers are smaller than, say,
    breast or prostate cancer, but the mortality rates are much higher.
        Answer. NCI launched the Pancreatic Cancer Cohort Consortium
    (PanScan), which is conducting whole genome scans of common genetic
    variants in 1,200 pancreatic cancer cases and 1,200 controls from 12
    cohorts to identify markers of susceptibility to pancreatic cancer. The
    promising genetic variants (single nucleotide polymorphisms (SNPs)
    identified will be validated by testing data from participants in a
    pancreatic cancer case-control consortium. It is anticipated that SNPs
    that are highly likely to be markers for genetic variants related to
    pancreatic cancer risk will emerge from this analysis as they have in
    similar studies on prostate and breast cancers, and lead to further
    studies of gene-gene and gene-environment interactions with pancreatic
    cancer risk factors. It is hoped that the PanScan will lead to
    identification of not only susceptibility genes but early markers for
    disease. This would be particularly useful for pancreatic cancer which
    is usually diagnosed at an advanced stage.
        There are also several projects being conducted on ovarian and
    pancreatic cancer in NCI's Early Detection Research Network (EDRN).
    Scientists are conducting research to enhance early detection of
    ovarian cancer. EDRN plans to screen serum DNA from larger cohorts of
    early ovarian cancer patients and controls collected by the EDRN- and
    SPORE-funded clinical centers for validating the optimized panel of
    genes for early detection and risk assessment. There are also a number
    of similar studies to discover biomarkers for the early detection of
    pancreatic cancer.
        NCI launched a unique program in September 2006, the NCI's Clinical
    Proteomic Technologies Initiative (CPTI). CPTI represents a highly-
    organized approach to apply proteomic technologies and data resources
    to support the discovery of biomarkers for the early detection of
    cancer and to monitor therapeutic outcomes. CPTI will advance the field
    of clinical cancer proteomics through the development of an integrative
    team framework that networks multiple research laboratories to permit
    large-scale, real-time exchange and application of existing and newly
    developed protein measurement technologies, biological resources, and
    data dissemination. Efforts will include refining and standardizing
    technologies, reagents, methods, and analytic platforms in order to
    ensure reliable and reproducible identification, quantification, and
    validation of proteins from complex biological mixtures; and evaluating
    new technological approaches to identify proteins that occur during
    cancer development.
        In December 2005, leaders from NCI and the National Human Genome
    Research Institute (NHGRI) launched The Cancer Genome Atlas (TCGA)
    Pilot Project, a comprehensive effort to accelerate understanding the
    molecular basis of cancer, and was the result of a ``blue-ribbon''
    committee of the nation's leading scientists. Cancer includes more than
    200 different diseases, each with a set of genetic changes that results
    in uncontrolled cell growth. The purpose of the Cancer Genome Atlas
    pilot is to test the feasibility of completely sequencing and
    cataloging the full range of genetic defects in 3 tumor types--brain
    (glioblastoma), lung and ovarian cancers, leading the way to a better
    understanding of all cancers.

                              SUBCOMMITTEE RECESS

        Senator Harkin. Thank you all very much. The subcommittee
    will stand in recess.
        [Whereupon, at 4:10 p.m., Monday, May 21, the subcommittee
    was recessed, to reconvene at 10 a.m., Friday, June 22.]