[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

                              ----------                              


                         FRIDAY, JUNE 22, 2007

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 10 a.m., in room SD-116, Dirksen 
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
    Present: Senators Harkin, Reed, Specter, and Cochran.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF RUTH L. KIRSCHSTEIN, M.D., ACTING 
            DIRECTOR, NATIONAL CENTER FOR COMPLEMENTARY 
            AND ALTERNATIVE MEDICINE

                OPENING STATEMENT OF SENATOR TOM HARKIN

    Senator Harkin. The Subcommittee on Labor, Health and Human 
Services will come to order. This is the last of our six 
hearings we have had on the National Institute of Health. We 
have heard from 18 Institutes so far, today we will hear from 
five more. The National Center for Complementary and 
Alternative Medicine, the National Institute of Dental and 
Craniofacial Research, the National Institute of Environmental 
Health Sciences, the National Eye Institute, and the National 
Institute of Child Health and Human Development.
    I want you all to know, I've really enjoyed the informality 
of these hearings. This is just like we've had all of the other 
ones, actually. When I first came on this committee in 1985, 
Senator Weicker, had sort of established this process of having 
these kinds of hearings. I thought they were very informative, 
and this is the way we have done it. I kept thinking, up until 
the mid-1990's I wanted to re-institute, reinstate that again.
    I found that these hour and a half or 2 hour hearings that 
we have had, for me, it's like being in class again. I get to 
learn a lot of things I didn't know about, and it's extremely 
informative, not just for me, but for our staffs on both sides, 
and people right here. I think we get a little bit more in-
depth knowledge of what each of the Institutes are doing, what 
we're looking ahead for, and I think it gives us a better idea 
of, perhaps, where our allocations of money ought to be going. 
So, it has been great to get into little bit more in depth than 
we have had.
    I just want to say a few words about the fiscal year 2008 
budget that we marked up yesterday, by the way. We proposed a 
$1 billion increase for NIH. This will allow NIH, for the first 
time since fiscal year 2005, to plan on increasing the average 
cost of new grants by 3 percent. I know that's not big, but 
it's better than what we have had, and it will provide the 
full-blown committed level for non-competing grants for the 
first time.
    We also increased the common fund by 10 percent. We've set 
aside the full amount to continue the National Children's 
Study, and provided additional support for young investigators. 
I know Senator Specter and I both wish we could have done more 
for NIH, and who knows, when it goes to conference, maybe we 
will even do more. We don't know, but we'll do as much as 
possible.
    I want to thank both Senator Specter and Senator Cochran 
for their support of NIH, and for this proposal that we have, 
that we passed yesterday in full committee.
    With that, I will yield to my colleague, and good friend, 
Senator Specter.

               OPENING STATEMENT OF SENATOR ARLEN SPECTER

    Senator Specter. Thank you very much, Mr. Chairman. Thank 
you, ladies and gentlemen for coming in today. The work of this 
subcommittee is well known, and our vigorous advocacy for NIH, 
and is even better known for our success in raising the funding 
level through the efforts of Senator Harkin, Senator Cochran 
and others on this committee.
    When I take a look at the complementary alternative 
medicine line, my recollection is it was $7 billion before my 
wife told me how important it was. I shared that information 
with Senator Harkin. We have talked about the change of the 
gavel being seamless--it doesn't matter who is there. Senator 
Cochran has been a member of this subcommittee longer than 
either of us has--and as chairman and ranking member of the 
full committee, and has given tremendous support to these 
efforts.
    I wanted to come by to send my personal greetings to you. I 
regret that I have commitments in Pennsylvania today. Friday is 
the day when we try to take care of the home front, except 
Senator Harkin who works 7 days a week, so he schedules 
hearings on Friday morning. You can shoot a canon through the 
Senate and the House today and have no risk of hitting anybody. 
Except for Senator Harkin and Senator Cochran. So, I'm going to 
excuse myself, but my staff will stay and report to me of the 
preceding, and I will be following it very closely.
    Senator Harkin. Thank you very much, Senator Specter, have 
a good weekend.
    Senator Cochran, did you have a statement?

                   STATEMENT OF SENATOR THAD COCHRAN

    Senator Cochran. Mr. Chairman, I'm pleased to join you and 
Senator Specter to welcome our panel of witnesses to the 
committee today. We appreciate the opportunity to continue our 
review of the fiscal year 2008 budget request for the National 
Institutes of Health.
    Today, we have five representatives of different Institutes 
conducting research to talk about their requests for the coming 
year, and we appreciate the participation of this panel in 
hearing and discussing with us your plans for the coming year.
    The National Center for Complementary and Alternative 
Medicine has provided, for the last 7 years, a foundation of 
scientific research in the emerging area of alternative 
medicine and therapy. Dr. Stephen Straus served as the 
Institute's first Director. We convey our condolences to the 
NIH family for the recent loss of Dr. Straus. A great deal was 
accomplished under his leadership to further our understanding 
of alternative therapies, and their role in integrating 
medicine.
    Also, the role that dental health plays in ones overall 
well being has received more attention recently. The death of a 
12-year-old child in Maryland due to a dental infection raised 
awareness of the importance of good dental care. I am co-
sponsoring legislation--the Children's Dental Health 
Improvement Act of 2007--with Senators Bingaman and Cardin, 
which seeks to provide disadvantaged children with better 
access to dental services. The work being done by the National 
Institute of Dental and Craniofacial Research is important to 
improving dental health for all Americans.
    We're learning that a number of conditions afflicting our 
population are connected to environmental factors. It's 
important that we extend our resources from simply treating 
existing diseases, to identifying ways to prevent them. As we 
learn more about the impact the environment has on different 
disease processes, we're better positioned to identify 
prevention measures. The work in this area through the National 
Institute of Environmental Health Sciences is very important, 
and I look forward to hearing about recent advances in this 
research.
    In my State of Mississippi, diabetes is a very challenging 
situation, presents a very challenging situation. There's been 
a big increase in the prevalence, and this causes many 
complications to the health of our citizens. What was once 
thought to be an adult disease is occurring now more often in 
children, as we see numbers of overweight and obese young 
people increase. Progress in this area is very important to me. 
We have more diabetes as a percentage of our State's population 
than any other State in the union. So, progress in this area 
could help a significant number of people.
    I'm not going to go through the list and talk about every 
Institute that is represented here today, but issues like 
infant mortality, the National Children's Study being done at 
NIH through the National Institute of Child Health are 
uncovering disparities which need our attention, and your 
suggestions as to what we can do about this in terms of 
national policy and funding priorities.
    Dr. Zerhouni has testified before this committee on a 
number of occasions, in March, he talked about the medical 
advances resulting from NIH-supported research, and we are 
aware of the importance of our continuing to be generous in the 
appropriation of funds for these activities--translating basic 
science, knowledge into improved and lifesaving therapies is 
very challenging, but it is very important as we work to 
improve the work being done by our Federal Government agencies. 
I appreciate the hard work all of you are turning in, and your 
dedication to ensuring that NIH is successful in these 
important areas of inquiry.
    Thank you, Mr. Chairman.
    Senator Harkin. Thank you, Senator Cochran.
    Let's just go from left to right. I would like to ask each 
of you, all of your statements will be made a part of the 
record in their entirety. I would just like to ask if each of 
you would just please speak for five to seven minutes, and 
we'll just go from left to right, then we'll just open it up 
for kind of general discussion at that point in time.
    First I will introduce Dr. Ruth Kirschstein who I don't 
really need to introduce very much, I'll do it anyway. She has 
served as Acting Director of NCCAM since August 2006. I want to 
join with Senator Cochran in expressing my condolences on Dr. 
Straus' passing. He fought that brain cancer for a long time, 
it kept coming back, and right up until the end, just did an 
outstanding job of leading that Institute.
    But, Dr. Kirschstein's career at NIH spans 33 years. In 
1974, became the first woman to serve as the Institute 
Director, head of the NIGMS, and her positions also included a 
2-year period as Acting Director of all of NIH, and I remember 
we worked together at that time. In 2002, I had the great 
pleasure of surprising her by re-naming the National Research 
Service Awards, as the Ruth L. Kirschstein National Research 
Service Awards.
    Dr. Kirschstein, welcome back, as we have for so many 
years, back to the committee, and please proceed as you so 
desire.

              SUMMARY STATEMENT OF DR. RUTH L. KIRSCHSTEIN

    Dr. Kirschstein. Thank you, Mr. Chairman, Senator Cochran, 
and Senator Reed. I want to thank you also for providing us 
with the opportunity today to discuss NCCAM's vision for the 
future, and to tell you how much we at NIH are grateful for 
your ongoing support, and thank you for your efforts on behalf 
of the health of the American public. Today as Senator Harkin 
has said, I'm here as the Acting Director of the National 
Center for Complementary and Alternative Medicine. I'm 
delighted to be back, and to see you once again.
    I have some material from NCCAM, which I want to provide to 
you, I think some of you have a strategic plan, but just in 
case, since NCCAM was established by Congress, thanks to your 
vision, Mr. Chairman, the Center has built a global scientific 
research enterprise, for the study of complementary and 
alternative medicine.
    The progress that has been made in understanding the 
scientific basis of CAM is greatly attributable, as you said, 
to the leadership of Dr. Stephen Straus, NCCAM's founding 
Director. And I want to thank you and your staff for your 
kindness in postponing the hearing on the day of his funeral, 
and to thank the staff for attending the funeral.

                          INTEGRATIVE MEDICINE

    Today, we know that many Americans are using CAM modalities 
in an effort to promote health and well-being, and to preempt 
disease, and that it is driven largely by consumer demand for 
complementary and alternative medicine. Integrative medicine is 
rapidly becoming the major force-shaping healthcare in the 
United States.
    Integrative medicine makes use of both conventional and 
complementary therapies to address all aspects of health and 
wellness. In addition, we know well, that better communication 
between patients and their medical practitioners is absolutely 
vital to ensure well-coordinated, comprehensive and safe care.
    In NCCAM's pursuit of rigorous science to understand 
complementary and alternative medicine, is the foundation that 
will build the evidence to facilitate the adoption of 
integrative medicine in our society. Our efforts to study and 
understand CAM continue to grow, and in the past year we have 
launched three new activities, a new program to assess the 
potential of community-based, primary care research networks, 
which will increase our knowledge about the efficacy and the 
cost-effectiveness of CAM modalities, as well as the safety of 
the approaches.
    We're also studying the mechanism of action underlying 
manipulative and body-based practices, such as chiropractic. 
We're developing innovative tools and technologies to study the 
biologically based aspects of mind body intervention.
    Our overall strategy is to support a diverse portfolio of 
basic translational and clinical studies. The study of 
acupuncture is an example of this approach. Clinical studies 
have demonstrated the potential of acupuncture for a number of 
conditions, such as osteoarthritis, and the basic and 
translational research using state-of-the-art neuroimaging 
technology has now elucidated mechanisms of brain function that 
have direct relevance to pain relief.
    Advances of similar importance are beginning to emerge in 
other areas. In the last year alone, NCCAM supported-research 
has demonstrated the potential of CAM for addressing a number 
of conditions, and I would like to give you a few examples.
    The spice turmeric, which has long been important as a 
component of Ayurvedic medicine, is being used in the treatment 
of many inflammatory disorders. Preliminary evidence shows that 
turmeric contains specific compounds that may have anti-
arthritic activity. This suggests potential ways in which 
turmeric may be used, and could yield insights into the 
mechanisms of arthritic disease.
    In another example, we have supported studies of the herb 
Ginkgo Biloba. This is a popular dietary supplement that is 
purported to promote brain health. Our studies in animal models 
of Alzheimer's disease have found that ginkgo reduces both the 
formation of the specific brain abnormalities that are also 
seen in humans, as well as preventing the paralysis seen in 
these animals.
    These studies of animal models are very important, and will 
serve as leadership into the hypothesis that is now being 
tested in a large clinical trial of Ginkgo--the prevention of 
dementia. This trial is supported, not only by NCCAM, but by a 
number of the other institutes.
    A very recently recognized clinical trial which you have 
referenced in your folders relates to Tai Chi, which is a 
traditional Chinese form of exercise. This modality may help 
older adults avoid getting shingles by increasing their 
immunity to the varicellis osta virus, and enhancing the body's 
immune response to the vaccine.
    Shingles, you know, affects the nerves, and causes pain and 
blistering in adults. There is a picture (Figure 1) of that in 
your folders. Shingles is caused by the same virus that causes 
Chicken Pox in children. Tai Chi combines aerobic activity, 
relaxation and meditation, and the combination of the shingles 
vaccine and Tai Chi out does the vaccine alone. This study was 
supported by the National Institute on Aging and NCCAM.



                           RESEARCH TRAINING

    But in addition, Senator Harkin alluded to the importance 
of research training. NCCAM mandate to train the next 
generation of CAM researchers. This must involve collaborations 
between CAM practitioners, and experienced scientists, and it's 
absolutely fundamental to our approach to research training and 
career development.
    Since its inception, NCCAM has increased the percentage of 
funds committed to research, training and career development 
from 1.3 percent in 1999, to 8.3 percent in fiscal year 2006.

                                OUTREACH

    Now, the other, and third, component of our mission, is to 
provide authoritative, evidence-based information on CAM. We 
have a growing communications program that distributes 
information in English and Spanish, and in both print and 
electronic form, and includes CAM on PubMed, which is a 
database developed in partnership with the National Library of 
Medicine. It indexes more than 470,000 articles related to CAM.
    We have an online continuing education program that offers 
information on a variety of topics, to help professionals and 
to the public. In addition, this year, we have a new patient 
provider educational initiative to encourage communication 
between patients and physicians about CAM use. The program, 
which is outlined in two pieces of paper in your folder 
(exhibits A&B), is called, ``Time to Talk,'' to ensure 
physicians talk to their patients, and that patients talk to 
their physicians about the use of CAM. It will ensure safety 
and integrated health care. We look forward to building on 
NCCAM's foundation of scientific accomplishments in 2008. We 
will include new activities, such as the partnership with the 
Centers for Disease Control and Prevention to support the first 
national, population-based survey, assessing CAM use among the 
United States' pediatric population. This survey will help to 
fill an important information gap, and help NCCAM to set 
additional priorities.





    Finally, we are also launching a new initiative to examine 
the potential influence of genetic variation on the likelihood 
of response to selected CAM interventions.
    With these, and other studies, NCCAM will continue to 
provide leadership in the research area.

                           PREPARED STATEMENT

    Thank you, Mr. Chairman. I thank Senator Specter, Senator 
Cochran, and Senator Reed for your continued support. I would 
be pleased to answer any questions.
    [The statement follows:]

             Prepared Statement of Dr. Ruth L. Kirschstein

    Mr. Chairman and members of the committee: I am pleased to be here 
to present the President's fiscal year 2008 budget request of 
$121,268,000 for the National Center for Complementary and Alternative 
Medicine (NCCAM).
    In the 7 years since it was established, NCCAM has built a global 
enterprise of scientific excellence and leadership in research on 
complementary and alternative medicine (CAM). NCCAM-supported studies, 
carried out at more than 260 institutions, encompass the wide range of 
CAM practices and have resulted in more than 1,500 scientific papers 
published in peer-reviewed journals. The progress that has been made by 
the research community in understanding the scientific basis of CAM is, 
in large part, attributable to the leadership of Stephen E. Straus, 
M.D., NCCAM's director from 1999 to 2006. Under his leadership, CAM 
research has been established as a legitimate field of scientific 
inquiry that is laying the scientific foundation for the emerging 
discipline of integrative medicine.
    This effort continues. In the past year, NCCAM has launched studies 
to: (1) develop innovative tools and technology for studying 
biologically based and mind-body interventions; (2) assess the 
potential of community-based primary care research networks to increase 
scientific knowledge about the safety, efficacy, and cost effectiveness 
of CAM; and (3) increase scientific understanding of the mechanisms 
underlying manipulative and body-based practices.

            NCCAM'S ROLE AND THE CHANGING NATURE OF MEDICINE

    Large numbers of American health care consumers are using CAM 
modalities in an effort to preempt disease and disability or promote 
health and a sense of well-being. Despite the relative paucity of 
information about the effectiveness and safety of these uses, Americans 
are de facto personalizing medicine through approaches that often 
require their active ongoing participation in a diverse variety of 
health practices and behavior change approaches.
    Driven largely by consumer demand for CAM, integrative medicine--
which can be defined as a health care approach that makes use of all 
appropriate evidence-based disciplines, therapies, and health care 
professionals to achieve optimal health and healing--is rapidly 
becoming a major force shaping health care systems in the United States 
and around the world. At the same time, studies continue to show that 
open communication between conventional medical practitioners and their 
patients about CAM use is uncommon. Such communication is vital to 
ensure well-coordinated, comprehensive, and safe care.
    The ultimate goal of NCCAM is to inform, through science, the 
discipline of integrative medicine. Thus, NCCAM's mission is to support 
rigorous research intended to fill the CAM knowledge gap; train CAM 
researchers; and disseminate authoritative information regarding CAM to 
the public (only one in three of whom consult their physicians about 
their CAM use), and to physicians and other health care professionals 
who rarely ask patients about CAM use.

           BUILDING THE EVIDENCE BASE OF INTEGRATIVE MEDICINE

    Because CAM interventions are widely used by the public, NCCAM 
supports a diverse portfolio of basic, translational, and clinical 
studies. The benefits of this strategy are well illustrated by the 
example of acupuncture. Clinical trials supported by NCCAM have 
documented the efficacy and safety of this widely used CAM practice in 
many but not all conditions studied. More recently, basic and 
translational research employing state-of-the-art neuroimaging 
technology has led to important insights into the mechanisms of action 
for acupuncture's effects, and has elucidated mechanisms of brain 
function that will have direct relevance to other approaches to pain 
relief.
    Advances of similar importance are emerging in other areas of CAM 
research. As is the case with acupuncture, clinical and preclinical 
information fills gaps in knowledge about a number of CAM practices and 
builds a fuller understanding of what CAM can offer. Whether a study's 
result is positive or negative, we expand our knowledge not only about 
the tested therapy, but also learn more about the condition it is 
supposed to treat. Several examples from the past year illustrate this 
point further:
  --Arthritis.--As the U.S. population ages, the need for better, 
        safer, and more effective treatments for arthritis increases. 
        Through basic studies, NCCAM-supported investigators determined 
        that extracts of the spice turmeric, an important component of 
        Ayurvedic medicine that is used in the treatment of a number of 
        inflammatory disorders, contains specific compounds with anti-
        arthritic activity, as well as others that can inhibit this 
        activity. This research suggests the need for further 
        investigation of the potential of turmeric, points toward ways 
        in which its use might be optimized, and yields insight into 
        the mechanisms of arthritic disease.
  --Neurodegenerative Diseases.--Ginkgo biloba is a dietary supplement 
        widely used for its purported beneficial effects on brain 
        function. NCCAM-funded investigators studying it in an animal 
        model of Alzheimer's disease found that it reduces both the 
        formation of the specific brain abnormalities seen in humans, 
        and the resulting paralysis seen in the animals. These 
        experiments lend support to the hypothesis that Ginkgo biloba 
        may be useful in slowing the progression of Alzheimer's 
        disease. That hypothesis is being tested in a large clinical 
        trial of Ginkgo biloba for the prevention of dementia, 
        supported by NCCAM and several other NIH Institutes.
  --Yoga for Chronic Low Back Pain.--Chronic low back pain is prevalent 
        and has few treatment options. NCCAM supported researchers have 
        concluded a randomized clinical trial studying the 
        effectiveness of yoga, exercise, or a self help book in 
        improving back function and decreasing chronic low back pain. 
        The results of the trial demonstrated that yoga was more 
        effective and produced longer-lasting pain relief than exercise 
        or the self-help book.
  --Menopause and Black Cohosh.--Given concerns about the use of 
        hormone replacement therapy to treat symptoms of menopause, 
        many women have turned to the dietary supplement black cohosh 
        for relief, although evidence supporting this approach has been 
        scant. In 2006, a clinical trial supported by the National 
        Institute on Aging and NCCAM failed to show relief of 
        menopause-associated symptoms by treatments containing black 
        cohosh. Two other large clinical trials of black cohosh 
        continue.

            TRAINING THE NEXT GENERATION OF CAM RESEARCHERS

    The rigorous basic, translational, and clinical research required 
to understand integrative medicine must involve collaborations between 
CAM practitioners and experienced scientists. This multidisciplinary 
approach is the fundamental tenet of NCCAM's strategy in support of 
research training and career development. Since its inception, the 
Center has increased the percentage of funds committed to research 
training and career development--from 1.3 percent in fiscal year 1999 
to 8.3 percent in fiscal year 2006--to support research training, 
career development, and educational opportunities. Recipients of CAM 
doctoral degrees are now among those eligible for National Research 
Service Awards, as well as for the NIH-wide loan repayment program.

                  DELIVERING AUTHORITATIVE INFORMATION

    NCCAM is recognized as a source of authoritative, evidence-based 
information on CAM. Information on CAM treatments, herbs and dietary 
supplements, advice for consumers, research results, and clinical 
trials are available in English and Spanish in print and electronic 
form. In 2006, NCCAM's website, cited by Prevention magazine for ``Best 
Alternative Medical Information,'' had more than 2.6 million visitors. 
CAM on PubMed, a database developed in partnership with the National 
Library of Medicine, now indexes more than 467,000 articles related to 
CAM. NCCAM's online continuing education program offers information on 
a variety of topics to the public and health professionals. Of 
particular note is a new patient/provider education initiative--``Time 
to Talk''--that encourages informed and open communication between 
patients and physicians about CAM use, to ensure safe, integrated, 
personalized and participatory care.

                             GOING FORWARD

    NCCAM will build on the foundation of scientific accomplishment and 
leadership that it has established during its first 7 years. Specific 
new activities planned for fiscal year 2008 include the following:
  --Working in partnership with the Centers for Disease Control and 
        Prevention, NCCAM will support the first national, population-
        based survey assessing CAM use among the U.S. pediatric 
        population. This study will fill an important information gap 
        in knowledge of CAM use in children and help NCCAM and the 
        broader scientific community in establishing pediatric CAM 
        research priorities.
  --A new initiative will examine the potential influence of genetic 
        variation on the likelihood of response to selected CAM 
        interventions. This phenomenon, an important factor in the 
        variation observed in responsiveness to conventional medicine, 
        will be examined through linking new basic research to ongoing 
        clinical trials, maximizing the value of the investment in 
        both.
  --A multidisciplinary workshop will bring together scientists from a 
        broad range of the physical, social, and biological sciences to 
        explore novel methodologies for clinical research of complex 
        CAM approaches that make up whole medical systems.
    Through these and other activities, NCCAM will continue to provide 
leadership in establishing the emerging discipline of integrative 
medicine. Thank you, Mr. Chairman. I would be pleased to answer any 
questions that the committee may have.

    Senator Harkin. Thank you very much. That last point, I 
want to follow up on in open questions on this.
    Now we'll move to Dr. Lawrence Tabak, who became Director 
of the National Institute of Dental and Craniofacial Research 
in 2000, received his D.D.S. in dentistry from Cornell, his 
Ph.D. in Biology from Sunni at Buffalo. He's also one of the 
co-chairs of an effort to promote inter-disciplinary team 
science at NIH.
    Dr. Tabak, welcome.

STATEMENT OF DR. LAWRENCE A TABAK, D.D.S, Ph.D., 
            DIRECTOR, NATIONAL INSTITUTE OF DENTAL AND 
            CRANIOFACIAL RESEARCH
    Dr. Tabak. Thank you, Mr. Chairman. I would like to thank 
you, Senator Cochran, and Senator Reed, for providing us with 
the opportunity to discuss our vision for the future, and of 
course, I want to thank each of you for your steadfast support 
of the National Institutes of Health.
    This morning I would like to discuss the NIDCR strategies 
to address the many complex diseases and conditions that fall 
within the mission of our Institute. I hope you have these 
materials. If not, I would just give them to you.
    As you can see, in the first figure, Figure 1, that I 
provided, complex diseases are those resulting--if I could 
refer you to Figure 1 of the handout that I've provided to you, 
complex diseases and conditions are those that result from an 
interplay between and among one's genes and environment, 
infectious agents and behavior, societal issues and the 
unknown.



                        EARLY CHILDHOODD CARIES

    One good example of a complex disease is early childhood 
caries, and if I could refer you to the next figure, Figure 2, 
you can see that in this condition, primary teeth can be 
decayed down to the gum line. This is a condition that is found 
disproportionately amongst underrepresented minority children. 



    NIDCR supports a research centers program to reduce oral 
health disparities, and we presently have 5 centers based 
around the country. What is unique about these centers is that 
they are embedded within their communities. What is needed to 
overcome conditions such as early childhood caries, are 
inexpensive, simple and culturally acceptable interventions.
    One such example is the use of a fluoride varnish, which 
has been worked on in a study conducted by the center at the 
University of California, San Francisco. What they have shown 
is that this approach can be highly effective in preventing 
early childhood caries in the very young, and in children at 
greatest risk.

                  SMOKING, GENETICS, AND CLEFT PALATE

    If I can refer you to the next figure, Figure 3--gene-
environment interactions, are typified by recent studies, which 
are summarized in this figure, conducted by NIDCR-supported 
investigators at the University of Iowa, together with 
colleagues at NIEHS. This work showed that babies of European 
ancestry--up to 25 percent of them, and up to 60 percent of 
babies of Asian history lack a gene. That is important in 
detoxification of cigarette smoke. If a pregnant woman smokes 
15 cigarettes a day, and lacks this important factor, the 
chances of her baby clefting increases 20-fold.



                              CHRONIC PAIN

    NIDCR scientists at the University of North Carolina are 
slowly unraveling the genetic basis of chronic pain by studying 
patients with temporomandibular muscle and joint disorder. If I 
can refer you to Figure 4, differences in susceptibility to 
pain correlate with the levels of a particular enzyme, the so-
called COMT enzyme. On the left-hand portion of this figure, 
you see individuals who have low pain sensitivity and very high 
levels of this enzyme. Then at the far end, those which have 
the highest pain sensitivity have very low levels of this 
enzyme. This makes sense because this enzyme is involved in the 
transmission of pain and this enzyme is involved in breaking 
down the transmitters of pain. So, if you have large levels of 
this enzyme, you are less susceptible to painful activity.




    What's very, very important about this is, for the first 
time we're beginning to understand the true biological basis 
for diseases and conditions, such as TMJ, which heretofore had 
proved very enigmatic. We now understand the real biological 
basis for these diseases and conditions. By unraveling the 
molecular basis, we have an opportunity for early detection and 
diagnosis, as well as potential interventions in the future.

                              ORAL CANCER

    If I can refer you to the next figure please, Figure 5. You 
see an example of an oral cancer. Oral cancer kills. The best 
hope is to detect cancer at its earliest stage. NIDCR has 
invested in a comprehensive tool kit of complimentary 
diagnostic approaches that will lead to bio-markers with both 
diagnostic and predictive value. An exciting advance in bio-
markers research has been the use of saliva as a diagnostic 
fluid. 



                          SALIVARY DIAGNOSTICS

    If I can refer you to the final figure, figure 6. On the 
left you see a lab on a chip, which currently is the size of a 
U.S. dime. This lab on a chip can already analyze multiple 
markers simultaneously, including the genetic signatures that 
are associated with oral cancers. What we have done is married 
the expertise of bioengineers with the knowledge of oral 
biologists and what is in saliva to create this program. 
Ultimately we will be able to use saliva to measure a wide 
range of bio-markers. It doesn't take too much imagination to 
see that if we can shrink the size of that lab on a chip from 
the size of a U.S. dime down to the size of a pinpoint, we 
would have the opportunity to place that device in the mouth, 
so that we could have the opportunity for real-time 
surveillance, constantly. Of course, this is the ultimate goal 
with this program.



                           PREPARED STATEMENT

    I appreciate the opportunity to tell you about these few 
exciting new approaches to address the many complex diseases 
and conditions that affect oral, dental, and craniofacial 
tissues. This is a time of tremendous scientific opportunity 
for oral health research, and of course, I would be pleased to 
answer any questions that you have.
    Thank you.
    [The statement follows:]

              Prepared Statement of Dr. Lawrence A. Tabak

    Mr. Chairman and members of the committee: I am pleased to present 
the President's budget request for the National Institute of Dental and 
Craniofacial Research (NIDCR) of the National Institutes of Health 
(NIH). The fiscal year 2008 budget request for NIDCR is $389,722,000.

   FACING THE FUTURE: INTEGRATIVE APPROACHES TO ADVANCE PUBLIC HEALTH

    Innovation has long been the great engine of progress in American 
life, including the tremendous progress made in improving the Nation's 
oral health over the last half century. From the tube of fluoridated 
toothpaste in the medicine cabinet to the high-resolution digital X-ray 
unit in the dentist's office, scientific innovations have helped more 
people than ever keep their teeth for a lifetime.
    The Nation's oral and craniofacial researchers stand on the 
threshold of even greater innovations to improve the lives of millions 
of Americans. No longer must they attempt to understand health and 
disease one gene and protein at a time. Today, they can click the 
computer mouse on their desks and call up vast databases of biological 
information. In essence, thousands of pieces to the biological puzzle 
are now on the table. If we meet the challenge to integrate the 
pieces--intentionally blurring in the process the lines that have 
defined the traditional research disciplines--great progress can be 
made in understanding the molecular underpinnings of oral and 
craniofacial health and disease. This year, I would like to offer a few 
of the many examples of how integrative science will lead to greater 
innovation. I'd also like to highlight how this innovation ultimately 
will lead to more personalized dentistry and medicine in which 
treatment can be tailored to a patient's specific disease and 
healthcare needs.

              CRANIOFACIAL CONSTRUCTION AND RECONSTRUCTION

    The human face has been celebrated in art and literature since time 
immemorial and rightfully so. It is among the body's most distinctive 
structures and, is also one of the most developmentally complex 
structures of nature. Tremendous progress has been made in recent years 
in unraveling the genetic programs that are activated in the embryo to 
produce the face and the skull. Similar progress has been made in 
pinpointing which genes can go awry to produce a cleft lip and/or 
palate.
    But much work remains. We must decipher the developmental programs 
that give rise to the various craniofacial tissues, hard and soft. By 
knowing how the craniofacial complex is assembled, it will be possible 
to better reassemble tissues that are damaged, either at birth or due 
to injury later in life. Exciting research is under way to explore the 
viability of regenerating damaged bone, teeth, and soft tissues with 
stem cells, novel biomaterials, and growth-promoting proteins. NIDCR-
supported researchers recently reported success using stem cells to 
engineer a replacement root/periodontal complex that could support a 
porcelain crown and provide normal tooth function in studies with mini 
pigs. Other investigators are well on the way to creating a replacement 
gum tissue that can be produced in sufficient quantity to repair large 
oral defects.
    The developmental programs will be helpful not only in treating 
craniofacial abnormalities but in preventing them. This year, for 
example, a team of NIDCR grantees determined that women who smoke 
during pregnancy and carry a fetus whose DNA lacks both copies of a 
gene involved in detoxifying cigarette smoke substantially increase 
their baby's chances of being born with a cleft lip and/or palate. 
About a quarter of babies of European ancestry and possibly up to 60 
percent of those of Asian ancestry lack both copies of this gene. This 
finding reinforces in a concrete, personal way the public health 
message that women, especially those who are pregnant, should not 
smoke.

                          HEAD AND NECK CANCER

    The NIDCR also has made a major investment in promoting integrative 
approaches to head and neck cancer. Our intent is to move beyond the 
current imprecise clinical definitions of these tumors, which are 
generally based on their appearance and patterns under a microscope. We 
need to examine the genetic hard drives of these tumors' cells to 
understand their abnormal and often deadly behaviors. This work already 
is taking place. NIDCR scientists have compiled comprehensive profiles 
of proteins expressed in some head and neck cancers. This information 
should help in developing true biomarkers with diagnostic and 
prognostic value.
    NIDCR-supported scientists are also developing new and exciting 
visualization tools and approaches to improve diagnosis of oral cancer. 
One such tool being tested is called the VELscope. It is a simple 
hand-held device that emits a cone of blue light into the mouth, which 
excites various molecules within the tissue, causing the tissue to 
absorb the light's energy and re-emit it as visible fluorescence. 
Because changes in the natural fluorescence of healthy tissue generally 
are different from those indicative of developing tumor cells, the 
VELscope allows dentists to observe telltale differences.
    In a recent follow-up study, the scientists reported that the 
VELscope performed extremely well in accurately and rapidly 
delineating the real borders between tumor and healthy oral tissue 
during biopsies in the clinic. Intriguingly, 19 of the 20 examined 
tumors in the study had fluorescence changes that extended in at least 
one direction beyond the clinically visible tumor. These extensions, 
which are undetectable to the unaided eye and thus would likely not be 
excised, extended up to an inch beyond the visible lesion. Leaving 
these abnormal cells in the mouth increases the chance of other tumors 
arising over time. The instrument was developed as one component of an 
integrative approach to oral cancer detection and treatment that 
combines cytology, molecular biology, and staining to improve early 
detection. This finding and others will allow practitioners to gain a 
better molecular characterization of developing tumors, providing the 
intellectual basis for more personalized treatment and a future in 
which fewer people will undergo disfiguring surgery to fight the 
disease and/or die from these cancers.

                          SALIVARY DIAGNOSTICS

    Other diagnostic tools are under development as well. The NIDCR is 
a national leader in development of the use of saliva as a diagnostic 
fluid. Several Institute grantees are working to develop tiny automated 
machines, which can rapidly and precisely perform many diagnostic 
functions that previously required painful needle sticks. One group 
recently fabricated the first disposable, low-cost, miniaturized 
diagnostic platform that can process small amounts of saliva, amplify 
its DNA and detect the levels of genetic sequences of interest. Work is 
proceeding to ultimately create a fully functional hand-held instrument 
for everyday use to detect conditions ranging from oral cancer to 
cardiovascular disease to AIDS.

              TEMPOROMANDIBULAR MUSCLE AND JOINT DISORDERS

    Integrative approaches are proving productive in our ongoing 
efforts to understand temporomandibular muscle and joint disorders, or 
TMJDs. Previously, NIDCR-supported scientists found that different sets 
of common sequence variations in the COMT gene correlate with low, 
moderate, and high susceptibility to chronic pain. This finding makes 
good biological sense. The COMT gene encodes an enzyme that helps to 
inactivate nerve signaling compounds and stop the transmission of an 
unpleasant sensation. The scientists recently showed that each of these 
sets of sequence variations changes the resulting structure of the 
corresponding messenger RNA. When a gene is expressed, it is copied 
into messenger RNA which, like an order form, contains the information 
to produce a specific protein. The scientists determined that the 
genetic variations that correlate with high sensitivity to pain produce 
messenger RNA with long, rigid loops in their structure, which reduces 
the rate of COMT protein synthesis and thus slows the nerve's ability 
to turn off an unpleasant sensory signal. The likely result: those with 
the ``sensitive'' variations will personally experience the sensation 
of pain longer and possibly more intensely.
    Such findings are particularly exciting because these studies could 
not have been conducted just a generation ago. Not enough was known 
about the basic mechanisms of pain. But as more of the biochemical 
pieces to the puzzle are found in the years ahead, great progress in 
controlling pain will be possible, and the NIDCR will help in leading 
the way for all those battling chronic pain conditions, including 
TMJDs, to find relief through a more accurate diagnosis and more 
personalized care.

        DENTAL DISPARITIES: RIGOROUS SCIENCE, PRACTICAL RESULTS

    It now has been 7 years since the U.S. Surgeon General issued the 
report Oral Health in America. As many will recall, that report pulled 
together for the first time the stark statistics of the Nation's 
``silent epidemic'' of tooth decay and other oral diseases among its 
minority and underserved populations. The reasons for these disparities 
are complex, but two facts were indisputable in the report: Many oral 
diseases are either preventable or easily controlled, and new 
strategies are needed to ensure that all Americans are aware of and 
ultimately benefit from the latest research advances.
    To meet this need, the Institute established five Centers for 
Research to Reduce Oral Health Disparities in 2001. This approach 
allows scientists to assemble multi-disciplinary research teams that 
lend a greater wealth of expertise to understand and address the 
complex elements underlying oral health disparities at the community 
level. Building on the knowledge and evidence amassed by the initial 
health disparities centers, the Institute has begun preparations to re-
compete its center grants with a specific public health aim. That aim 
is to assemble a more seamless investigative team structure that can 
take a well-defined clinical issue and with the participation of a 
community-based population, test the effectiveness of promising 
interventions on a wider scale. This approach holds considerable 
promise to yield rigorous science, participatory research with those in 
underserved communities, and a significant reduction in oral health 
disparities.

                    PRACTICE-BASED RESEARCH NETWORKS

    The Institute awarded grants in early 2005 that established three 
regional practice-based research networks, or PBRNs. Their mission is 
to create networks of practicing dentists and dental hygienists with 
their patient populations to participate in clinical studies on a 
variety of pressing everyday issues in oral healthcare. In 2006, the 
PBRNs were enlisted to investigate an important emerging health issue. 
Millions of Americans currently take a type of drug called 
bisphosphonates, typically to ease cancer-related pain or to prevent 
osteoporosis. But recent reports indicate that newly formulated 
bisphosphonates can cause in some people a debilitating thinning of the 
jawbone called osteonecrosis. What remains unclear is the prevalence of 
this unwanted side effect and, more importantly, who precisely is at 
risk. A few years ago, NIDCR would have lacked the clinical 
infrastructure in place to investigate these and other related 
questions. The PBRNs have changed the equation. The NIDCR has rapidly 
organized the needed studies to investigate the problem and will 
provide in the near future more meaningful data for the millions of 
Americans at risk.
    Traditional research approaches have produced extraordinary 
benefits to the Nation's public health. But we now face a new 
scientific frontier, and new possibilities confront our researchers. 
These opportunities require novel approaches that fall under the rubric 
of integrative science. From this coordinated approach to science, the 
biological complexity before us will give way to simplicity and once 
unimaginable public health advances in which personalized health and 
medicine become a reality.

    Senator Harkin. Thank you very much, Dr. Tabak.
    Next, we will turn to Dr. David Schwartz, Director of the 
National Institute of Environmental Health Sciences. He has 
been Director since 2005, earned his M.D. from the University 
of California, San Diego, and his Ph.D. degree from Harvard 
School of Public Health. But most importantly of all, he spent 
the better part of 12 years at the University of Iowa. Is that 
about right?
    Dr. Schwartz. Very formative years.
    Senator Harkin. His own research focuses on environmental 
lung diseases. Dr. Schwartz, welcome to the committee.

STATEMENT OF DR. DAVID SCHWARTZ, M.D., DIRECTOR, 
            NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH 
            AND SCIENCES
    Dr. Schwartz. Thank you very much, Mr. Chairman, Senator 
Cochran, and Senator Reed. It's a pleasure to be here, thank 
you for providing us the opportunity to discuss our collective 
vision for the future of medical research.
    I do have a handout that may be of help to the members of 
the committee.
    Just by way of introduction, NIEHS protects the Nation's 
health by understanding the role of the environment, in terms 
of the development and also the distribution of disease in 
society. Our view is, understanding the causes of disease will 
provide the types of insights that are absolutely necessary to 
preventing disease in society. That's the focus of the 
Institute. The work of NIEHS in the past has improved the 
average length and quality of life by looking at disease 
etiology, and also prevention of exposures that are relevant to 
disease etiology.
    If you look at the second page of the handout, Figure 1, I 
will give you two examples of work that has been done in the 
past at NIEHS that exemplifies this approach. The two examples 
focus on air pollution and lead exposure. NIEHS funded a very 
important study called ``The Six City'' study, that focused on 
air pollution and identified air pollution as a major cause of 
morbidity and mortality, especially as related to heart and 
lung disease.




    In the graph on the left-hand panel, the letters on the 
graph refer to the six different cities that the study was done 
in. You can see very clearly, as you move from left to right, 
that the level of air pollution increases, and the mortality, 
and also the morbidity, from lung and heart disease increases.
    As a result of this very compelling research, new standards 
were adopted by the EPA under the Clean Air Act, which changed 
the standards in the United States for air pollution. As a 
result, there have been marked decreases in the level of air 
pollution, but marked improvements in morbidity and mortality 
related to air pollution exposure.
    The second example is an example of collaborative work 
between NIEHS and the National Institute of Children's Health 
and Human Development. On the right-hand side, the second 
figure on the second page shows a very striking relationship 
between the concentration of lead in the blood of children, and 
IQ. The higher the lead levels, the lower the IQ. This research 
resulted in the elimination of lead in gasoline, and 
subsequently resulted in improvements--substantial decreases--
in the concentration of lead in the blood of children around 
the United States.

                             STRATEGIC PLAN

    If you look at the next page of the handout, figure 2, 
between 2005 and 2006, shortly after my arrival at NIEHS, we 
developed a strategic plan, and our strategic plan lays out a 
very clear vision--to prevent disease and improve human health 
by using environmental sciences to understand human biology and 
human disease. Embedded in this plan, we have several 
challenges that face us, that keep us focused on our mission--
our mission focusing on specific exposures and diseases that 
are relevant to those specific exposures.




    If you look at page four of the handout, Figure 3, we have 
developed 7 specific goals that help keep us on track in terms 
of the development of research priorities at NIEHS that are 
consistent with our strategic plan. So, although we've made a 
lot of progress in each one of these goals, and we've 
implemented programs in each one of these goals, I just want to 
tell you about three distinct programs.



               HEAD-OFF ENVIRONMENTAL ASTHMA IN LOUISIANA

    The first program is called the HEAL Program. It stands for 
Head-off Environmental Asthma in Louisiana, and it's based on 
in fact that children moving back to New Orleans are at very 
high risk for the development of asthma, as a result of 
exposure to a contaminated environment--the molds and the 
bacteria that have overgrown many of the environments in New 
Orleans as a result of Hurricane Katrina.
    This is a collaborative project, and it's a community-based 
project. The community is very, very involved in this project, 
and the Department of Public Health is very involved in this 
project, as is Tulane University. It's a collaboration between 
NIEHS and the National Center on Minority Health and Health 
Disparities, and also the Merck Childhood Asthma Network. It 
represents a public/private partnership, in addition to a 
collaboration within NIH. Again, the project is focused on an 
intervention program, and studying that intervention program to 
see if we could reduce the burden of airway disease in these 
children that are at very, very high risk of developing and 
exacerbating their underlying airway disease.

                    TRAINING AND CAREER DEVELOPMENT

    The second area of development that I want to highlight is 
in training and career development. We've revitalized our 
training--in fact, our training programs now go all the way 
from high school through college, including training for 
foreign scientists. The training reaches out to minority 
students, as well as physicians-scientists--two very important 
groups that are underrepresented in the NIEHS portfolio--and 
also focuses on new investigators to help them develop a focus 
in environmental sciences and have an opportunity for research 
in environmental sciences.

                        EXPOSURE BIOLOGY PROGRAM

    The third area I want to highlight is the development of 
personalized measures of exposure, very similar to what Dr. 
Tabak was talking about, in terms of these miniaturized 
exposure measurements and biological response indicators, that 
are very important in terms of identifying how much someone has 
been exposed to, and how biologically responsive someone is to 
that exposure.
    If you look at the next page of the handout, Figure 4, you 
can see that we've developed a program called the Exposure 
Biology Program that is part of the Genes, Environment, and 
Health Initiative. This new initiative is supported by all 
institutes across the NIH, and is led by me and Francis Collins 
and at NHGRI. The overall goal of the Exposure Biology Program 
is to develop personalized sensors of exposure, and also, 
biological response indicators. Step back for a second, and 
consider how we're able to precisely measure genetic variation 
across the human genome and how crude our tools are to measure 
individual differences in terms of environmental exposures--and 
you realize very quickly that this program is essential to be 
able to look at the interaction between genes and environment, 
in terms of the risk of developing disease. After all, for the 
foreseeable future, our main way of preventing disease will be 
to intervene in the environment, not to intervene genetically.




    So, it's essential that we understand this relationship 
between genes and environment, as a way of understanding risks 
related to human health. Outgrowths of the Exposure Biology 
Program might include specialized wrist bands or smart shirts 
that could alert a person, or a physician, to an exposure that 
could be detrimental to an individual's health.

                             OPPORTUNITIES

    If you turn to the last page of the handout, Figure 5, as 
we look forward, we're focused on three main opportunities. 
First, as I mentioned, through the Exposure Biology Program, 
we're developing these personalized measures of exposure and 
response indicators.



    Second, we're focusing on a number of new research programs 
on complex diseases, such as asthma and neurodegenerative 
diseases and arthritis, that are caused by both genetic and 
environmental factors. We believe very strongly that the 
environment will be very helpful in identifying the genes that 
are important in terms of the risk of developing disease.
    The third aspect that we're focused on is populations that 
are exposed to high concentrations of toxins, such as arsenic, 
or high concentrations of air pollution, so that we can reduce 
the burden of disease in these populations and improve health.

                           PREPARED STATEMENT

    So, I want to thank you for your attention. I look forward 
to your questions, and I would yield to my colleagues, and look 
forward to the informal discussion that we will have following 
everyone's formal presentation.
    [The statement follows:]

                Prepared Statement of Dr. David Schwartz

                              INTRODUCTION

    Lives saved by environmental health research can be counted in 
millions. By the Environmental Protection Agency's (EPA) estimates on 
air pollution alone, the Nation's commitment to cleaner air will 
prevent 23,000 premature American deaths; 1,700,000 new asthma attacks 
or aggravation of chronic asthma; 67,000 new cases of acute and chronic 
bronchitis; 22,000 respiratory-related hospital admissions; and 42,000 
cardiovascular hospital admissions (EPA 410-R-99-001) by the year 2010. 
The commitment to new air standards arose from NIEHS-supported research 
on air pollution such as the Six-Cities Study which revealed important 
associations between air pollution and mortality from respiratory and 
cardiovascular disease.
    Air pollution is only one example of the public health impact of 
environmental health research. Studies on adverse effects of lead, much 
of it funded by NIEHS, revealed lead-associated decrements in the IQ 
scores of young children, as well as increased tendencies by affected 
children to aggressive behaviors. It was these types of neurobehavioral 
problems that led the Nation to ban sources of lead contamination, a 
move that has led to a 78 percent decrease in average blood lead levels 
in this country (JAMA, 272:284-91 (1994)) and a corresponding 
improvement in the health of our children. Further NIEHS-supported 
research involving adults found that long-term exposure to lead is 
associated with an increased risk of high blood pressure 
(hypertension), kidney problems and cataracts. Reduced lead levels in 
the environment are expected to translate in the future into a 
decreased incidence of hypertension, kidney failure, and cataracts 
among the elderly.
    NIEHS-supported researchers have made other recent discoveries with 
high potential for public health impact. Some examples include 
identification of a novel biological mechanism that controls airway 
tone and could be targeted for the treatment of asthma; discovery of 
important mechanistic linkages between exposure to inhaled particulate 
matter and cardiovascular disease; new insight into regulatory 
mechanisms within the brain that affect learning and memory; and 
identification of the structural basis of errors in DNA synthesis that 
may result from environmental stress and have profound effects on a 
variety of human diseases, including cancer.
    As these examples illustrate, environmental health science can 
exponentially return its investments on improvements in a wide spectrum 
of diseases and disabilities. Operating on multiple molecular and 
cellular pathways, environmental agents can track these complex 
molecular pathways that lead to chronic diseases such as cancer, birth 
defects, hypertension, and neurological disorders. Because 
environmental agents often operate early in the disease process, they 
can be useful for identifying very early events in disease, suggesting 
ways to diagnose and remedy diseases before they progress. The 
challenge now is to develop techniques needed to assess environmental 
exposures as they operate at the level of individual health. This will 
require the development of sensitive devices that can assess the 
environmental exposures to which individuals are exposed in their daily 
lives. Ideally, these small, specialized, wearable sensors would 
measure environmental exposures, as well as the actual biological 
changes that arise as early markers of response in environmental 
agents. Such devices would allow scientists and physicians to access 
the more dynamic, real-world exposures of the American population and 
would provide information that could be useful to identify very early 
events in disease, suggesting ways to diagnose and remedy diseases 
before they progress.
    Many of NIEHS' recent achievements have been possible because of 
powerful tools used to study events at the genetic and molecular level 
that would have been impossible ten years ago. With so many promising 
avenues to explore, NIEHS developed a new strategic plan, New Frontiers 
in Environmental Health Sciences and Human Health (www.niehs.nih.gov/
external/plan2006/home.htm) that focuses on three major challenges and 
seven specific goals to prevent disease and improve human health by 
using environmental sciences to understand human biology and human 
disease. Steps to implement the Strategic Plan have led to research in 
exposure biology (personalized measures of exposure), epigenetics 
(inheritance not based on the sequence of DNA), comparative genomics 
(use of model systems to understand the biological effects of 
environmental exposures), translational research (integrating basic and 
applied sciences to understand the effect of the environment on human 
health), and focused training and career development programs to expand 
the workforce in environmental sciences. Our success will be measured 
in the disease and suffering that we are able to prevent.

                        EXPOSURE BIOLOGY PROGRAM

    The Exposure Biology Program, a component of the larger Genes, 
Health and Environment Initiative at the National Institutes of Health 
(NIH), was created to develop tools to precisely measure the exposure 
to chemical/biologics, dietary changes, physical activity, psychosocial 
stress, and addictive substances and subsequently assess the effect of 
these exposures on human health. This program will produce non-invasive 
tools that can be used to track exposures critical to human health. 
While new technology will be developed, this program will also borrow 
and re-engineer tools from other fields that have focused on measuring 
various component of the environment. Possibilities include the use of 
molecularly imprinted polymers that show promise in identifying 
antibodies, enzymes, and animal tissues or cells; small labs-on-a-chip 
that can be made through recent advances in silicon and glass 
micromachining; and the use of nanoparticles in biomolecular sensors. 
These technologies would be combined with new techniques to assess co-
modifiers of response such as diet and physical activity. As these 
technologies are incorporated into large-scale epidemiological studies, 
much of the background ``noise'' obscuring our ability to identify 
environmental components of disease will be reduced. Furthermore, the 
program is soliciting researchers to develop these new tools in ways 
that can also provide insight into the molecular underpinnings of 
disease response, thus identifying therapeutic targets for 
intervention.
    One exciting outgrowth of this project will be in the area of 
personalized and participatory medicine. The sensor technologies 
developed through the Exposure Biology Program are envisioned to be 
small, portable devices that can measure actual exposures to 
environmental agents, as well as monitor diet, physical activity, heart 
rate and respiration. An example would be a device that could alert an 
individual with asthma to dangerous air pollution levels. Another 
example would be a device that could determine harmful pesticide levels 
and cross-reference this information with an individual's own genetic 
risk profile for neurodegenerative diseases like Parkinson's disease. 
Alternatively, data derived from such sensor devices could be used by 
physicians to tailor treatment and prevention strategies based on 
actual exposure risks. The strategies could range from altering the 
environment or modifying behavior through disease risk education to 
selecting pharmaceutical treatments that would more accurately target 
the underlying molecular changes resulting from environmental 
exposures.

                EPIGENETICS--BEYOND THE SEQUENCE OF DNA

    The field of epigenetics is uniquely related to environmental 
health sciences. Epigenetics refers to a modification of gene 
expression that does not involve a change in gene sequence; rather, a 
sometimes slight modification of DNA or its associated proteins or 
sugars that can dramatically change gene function, sometimes into 
subsequent generations. Almost all known factors causing epigenetic 
change are from the environment, diet, or supplements. Epigenetic 
mechanisms are being linked to multiple illnesses, including cancer, 
cognitive dysfunction, and respiratory, cardiovascular, reproductive, 
autoimmune, and neurobehavioral diseases.
    Recently, NIEHS developed a program in epigenetics that supports 
research to understand how the epigenome is affected by environmental 
exposures and how this ultimately affects human health. This field is 
particularly promising in identifying how early life exposures can 
generate disease outcomes later in life. One purpose of this program is 
to identify critical windows of susceptibility to epigenetic changes, 
particularly during pregnancy, early life, and puberty. The fruits of 
this research will help us develop biomarkers of early exposure, as 
well as identifying possible therapeutic strategies to prevent disease 
later in life.

                  CLINICAL AND TRANSLATIONAL RESEARCH

    In the summer of 2007, NIEHS will complete construction of its 
first clinical research unit that will be used to study how human 
subjects respond to a variety of environmental stressors. This facility 
will foster integrated, interdisciplinary research opportunities 
between our basic and clinical scientists to speed the translation of 
knowledge from bench to bedside. NIEHS' Office of Translational 
Research is also focusing on taking discoveries from our basic and 
population-based studies and translating them into research findings 
that have direct relevance to human health and disease. New integrative 
research programs are designed to promote an interdisciplinary approach 
to focus environmental sciences on important human health conditions. 
Two examples are the extramural DISCOVER (Disease Investigation through 
Specialized Clinically Oriented Ventures in Environmental Research) 
Program and the intramural Director's Challenge. The approach being 
taken in these programs is to closely integrate basic, mechanistically 
driven laboratory research directly with patient-oriented research to 
speed the translation of the environmental health sciences into 
clinical and public health applications. Awards made under both the 
intramural program and the DISCOVER Centers will be for multi-project, 
interdisciplinary programs to understand the etiology, pathogenesis, 
prognosis, and epidemiology of disease processes such as respiratory 
diseases, cancer, or neurodegenerative diseases.

                    WORKFORCE TO MEET NEW CHALLENGES

    The much greater complexity of research techniques and the new 
focus on human health and disease requires a new, specialized 
workforce. The new environmental health workforce must be increasingly 
collaborative and must have skills to work across multiple research 
disciplines. NIEHS is refashioning its training program in order to 
produce researchers with the skill sets needed in the future. For 
promising high school and college students, the Short Term Educational 
Experiences for Research (STEER) program provides needed support for 
attracting and developing this next generation of environmental health 
scientists. NIEHS and NHGRI developed a collaborative training program 
for pre- and post-doctoral students in environmental genetics. The 
Outstanding New Environmental Scientists Award (ONES) program is a new 
way to recruit talented young independent researchers into 
environmental health science research. These programs complement 
existing training programs and, in concert, will help develop a 
workforce that can meet the many demands of environmental health 
research.

                                SUMMARY

    The opportunities within environmental health sciences are greater 
than ever. New programs initiated this past year will produce a more 
sophisticated understanding of the environmental components of disease, 
as well as a better knowledge of how individuals vary in their response 
to exposures. This information will enhance our ability to develop 
personalized approaches that can decipher an individual's actual 
exposures, their individual risks for adverse effects from these 
exposures, and ultimately lead to a customized strategy for reducing 
these risks and circumventing undesirable health outcomes. This more 
extensive understanding of environment-disease associations will, in 
the aggregate, lead to improved intervention and therapeutic strategies 
that can lessen the disease burden of our citizens. I would be happy to 
answer your questions.

    Senator Harkin. Thank you very much, Dr. Schwartz.
    Now, we'll turn to Dr. Paul Sieving. He became Director of 
the National Eye Institute in 2001, received his M.D. and a 
Ph.D. in biomedical engineering from the University of Illinois 
and conducted research focused on retinal conditions, such as 
retinitis pigmentosa.
    Dr. Sieving, welcome to the committee.

STATEMENT OF DR. PAUL A. SIEVING, M.D., Ph.D., 
            DIRECTOR, NATIONAL EYE INSTITUTE
    Dr. Sieving. Thank you, Senator Harkin and congratulations 
on saying retinitis pigmentosa. That's a big word as are many 
of the words we use in medicine, but these words have very 
important implications for disease and health of the American 
people. As Director of the National Eye Institute, it's my 
privilege to tell you, to report to you today on some of the 
remarkable advances that are happening in vision research.
    We are at a precipice in medicine as I've heard my 
colleagues also report, where we're really able now to move 
from basic research into the phase of improving health. In my 
case, the eye health of the American people. It's a very 
exciting time. With the support of the United States Congress 
our vision scientists are developing treatments to prevent 
vision loss and, even more remarkably, in some cases to 
partially restore sight for some common eye diseases, including 
age related macular degeneration that affects the older age 
population. Conditions that affect children, such as amblyopia, 
start in childhood, but the vision loss can persist for a 
lifetime.
    I think all of us can understand and appreciate that the 
loss of sight really affects people in a fundamental way. It 
threatens independence. It is socially isolating, we can't look 
at one another. It affects the quality of life. The number of 
the eye diseases that we suffer actually increase with age. 
They strike later in life. As the American people live longer 
and the baby boom generation ages, unfortunately, we can expect 
an increasing prevalence and incidence of some of these 
conditions that are related to aging.

                    AGE-RELATED MACULAR DEGENERATION

    I would like to focus my comments on one storyline of 
remarkable success involving age-related macular degeneration 
or AMD. This is a condition in which central vision is 
affected. You look at the person sitting across from you and 
his or her face dissolves into a blur. It's difficult to see 
the face of a friend. It's difficult to read a book. Obviously 
driving a car, that privilege is lost. Even simple things, such 
as cooking, those simple tasks become very difficult.
    But, the last 2 years have been a watershed time for AMD, 
both in terms of new treatments, remarkable new treatments and 
genetic factors that are now coming online. Over the past 2 
years, attention to a particular molecule called vascular 
endothelial growth factor, just about as big a word as 
retinitis pigmentosa. Vascular endothelial growth factor or 
VEGF is a molecule that was pursued quite vigorously by the 
cancer research community for many years. It turns out that 
abnormal blood vessel growth is also involved in one of the 
severe forms of age-related macular degeneration, causing 
abrupt loss of central vision. Now, over the past 2 years, an 
anti-molecule, anti-VEGF, administered to the eye, injected 
into the eye, literally, can stabilize the vision. In some 
cases, even improve reading ability somewhat.
    Senator Cochran, you mentioned the incidence of diabetes in 
your State. Diabetes is a problem of blood vessels that also 
involves the blood vessels in the eye, as you alluded to, and 
causes a condition called diabetic retinopathy, a blood vessel 
problem in the eye. So, this same molecule, the VEGF molecule 
is involved and anti-VEGF therapy is now being tried for 
diabetic retinopathy. We can hope that that will be successful. 
But, we need to intervene at an earlier course of disease.
    I would like to go over some old ground that I have 
presented here to this committee previously, called the Age-
Related Eye Disease Study, in which prevention was the focus. 
This was an NEI sponsored study. It ran for 7 years. It focused 
on the daily use of antioxidant vitamins and minerals.
    After work, hard experimental work with some 4,000 
individual subjects, participants, it was found that this 
approach delayed the onset to serious vision loss and advanced 
macular degeneration, delayed that by about 25 percent. That is 
a remarkable success. So, that if this dietary intervention 
could be fully utilized by the American people who need 
treatment, we could anticipate over the next 5 years, it would 
rescue the vision of some 300,000 people. In that study, the 
AREDS study, is now in a second phase of AREDS2, testing other 
dietary components, such as DHA or omega-3 fish oils.
    But, let's move back even one step further. So far we've 
talked about treatments and prevention, but we can actually go 
right to the root causes of AMD by looking at the genetic 
factors that predispose us, literally sitting around this 
table, to have AMD in later ages. Now, we have suspected for 
many years that genetic factors play a role in developing AMD 
and just 2 years ago, in April 2005, 26 months ago, the NEI-
supported researchers identified the first gene that 
predisposes to developing AMD in a large population. One gene, 
first time in history, a remarkable event. In the intervening 
26 months, four additional genes have been found. So now, there 
are five genetic risk factors that are contributing, we 
believe, about 75 percent of the risk for those of us around 
the table to ultimately develop AMD.
    These genes are also surprising in their molecular theme, 
their biological theme. They're in the immune system of the 
body, the complment cascade. The first factor was complment 
factor H. Another gene was complment factor B. These are 
components that operate normally in the body's immune defense 
against microbial infections. The way we think about it is, 
it's suboptimal control of this very vigorous defense system in 
the body. A normally protected pathway in which suboptimal 
control leads to chronic inflammation of the tissues of the 
retina and ultimately causes AMD to develop.
    This gives us then the first handle on something that, in 
fact, we can take to the American people from this very basic 
genetic study. That is the recognition that the environmental 
factors, as my colleague next to me has just mentioned, and 
lifestyle factors play on this genetic background to further 
increase the risk of us developing AMD.

                                EYEGENE

    This, my mentioning of these four or five genes for AMD are 
just part of the genetic story that is now rapidly evolving. 
There are some 450 genes that have been found to cause eye 
disease. These diseases include cataracts, glaucoma, 
strabismus, retinal disorders, corneal opacities, eye motility 
problems. With this wealth of genetic information, the Eye 
Institute, over the past 2 years, has a developed a 
collaborative national network of research laboratories to 
support genetic testing.
    We are calling this eyeGENE. You can go to Google and type 
in ``NIH eyeGENE'' and come up with a few pages on it. It is a 
consortium of 20 universities across the country that 
participates actively, with oversight, and setting directions 
to make available genetic information, both to research, to 
move the research along to appropriate conclusions. At the same 
time, as a corollary to provide genetic direct information to 
families. The research group is really quite excited about 
that. We will have a centralized registry for research data 
mining. We will have a secure blood collection for research, a 
research repository. EyeGENE is now receiving samples from 
physicians across the country.
    So, what I have given you is what I think is a very 
exciting story of treatment for macular degeneration, genes for 
macular generation, the ability to provide information to all 
of us before we are, literally, patients. So that, perhaps, we 
can avoid becoming a patient for these conditions. I think this 
is in the tradition, as I'm hearing, already down the table of 
real opportunities for personalized and certainly, ultimately, 
participatory medicine. The first time in history, I think, we 
are really making tremendous progress. So, it is a rich and 
rewarding opportunity for us to move forward.

                           PREPARED STATEMENT

    With that, thank you for the opportunity to testify. And, I 
will certainly be pleased to answer questions.
    [The statement follows:]

               Prepared Statement of Dr. Paul A. Sieving

    Mr. Chairman and members of the committee: I am pleased to present 
the fiscal year 2008 President's budget request for the National Eye 
Institute (NEI). The fiscal year 2008 budget includes $667,820,000 in 
the President's request.
    As the Director of the NEI, it is my privilege to report on the 
many research opportunities that exist to reduce the burden of eye 
disease.

                    AGE-RELATED MACULAR DEGENERATION

    The loss of sight affects us in fundamental ways, threatening 
independence, mobility and quality of life. Most eye diseases strike 
later in life. Thus, as life expectancy has increased and the baby boom 
generation ages, more Americans are becoming susceptible to vision loss 
and blindness. One such disease, age-related macular degeneration 
(AMD), is the leading cause of legal blindness. Based on published 
study data, 8 million older-age Americans are at high risk to develop 
advanced AMD. AMD causes a progressive loss of central vision, making 
it difficult to read, recognize faces, drive a car, or perform even 
simple tasks that require hand-eye coordination.

                          ANGIOGENESIS AND AMD

    Angiogenesis is the term used to describe the growth of new blood 
vessels. Angiogenesis plays a crucial role in the normal development 
and maturation of tissues. It also plays a role in many diseases, 
including eye diseases such as diabetic retinopathy, retinopathy of 
prematurity and advanced AMD. In advanced AMD, new blood vessels grow 
abnormally beneath the retina. These abnormal blood vessels leak blood 
and fluid, producing scarring and severe vision loss.
    NEI-supported researchers have established that a protein called 
vascular endothelial growth factor (VEGF) plays an important role in 
triggering angiogenesis in AMD and diabetic retinopathy. Thus, VEGF is 
an important target for drug development. Two anti-VEGF therapies have 
recently been approved by the FDA for the treatment of AMD. More 
recently, NEI-supported researchers have found that in animal models, 
combination therapies that control diverse elements of angiogenesis can 
completely inhibit some forms of abnormal blood vessel growth. Anti-
VEGF therapies are also being evaluated in clinical trials for diabetic 
retinopathy. NEI and NIH have invested considerable resources in 
understanding and controlling angiogenesis. That investment is already 
paying handsome dividends.

                       DISEASE MECHANISMS IN AMD

    Another critical area in developing treatments of AMD is to 
identify the causes and mechanisms of the disease early in its 
pathology. Researchers have long held that AMD can result from the 
confluence of genetic predisposition and chronic exposure to 
environmental risk factors, such as diet and smoking. In this scenario, 
a gene or genes contain subtle variations that hamper cellular function 
but may not necessarily cause disease directly. However, years of 
cumulative environmental insult can further strain the underlying 
genetic predisposition and trigger disease.
    On the genetic side of the equation, NEI-supported investigators 
have identified common variations in four genes that are associated 
with AMD and may account for 75 percent of the risk of developing AMD. 
Two of these genes--complement factor H (CFH) and complement factor B 
(BF)--contain instructions to encode proteins that help regulate the 
body's immune defense against microbial infections. This defense, 
called the complement system, provokes inflammation, a common response 
to foreign pathogens. It is thought that certain variations in these 
genes result in sub-optimal control of the complement system and cause 
chronic inflammation. Chronic inflammation may damage tissues of the 
retina and could lead to AMD.
    Chronic inflammation is thought to play a role in many other common 
diseases beyond the eye, such as Alzheimer's disease, Parkinson's 
disease, multiple sclerosis, kidney disease, stroke, and 
atherosclerosis. Although the cells, tissues, and molecular events in 
these diseases are diverse, they may share some common disease 
mechanisms that present an opportunity to cross pollinate findings from 
diverse research areas.
    The genetic discovery of the possible role of inflammation and the 
immune system in AMD is a watershed moment. We have now uncovered a 
possible central disease mechanism that may lead to a better 
understanding of this major disease and the development of therapies 
that prevent vision loss. We now hold the possibility to learn an 
individual's risk vulnerability well before the disease is detectable 
clinically, and to intervene effectively, thereby preempting the 
disease process at its early stages.

                      PUBLIC HEALTH AND PREVENTION

    Another critical and fruitful area of research is the development 
of public health strategies to prevent or delay AMD. Several 
epidemiologic studies, published in the 1990s, found evidence to 
suggest that diets rich in leafy green vegetables, which contain 
antioxidants, might be associated with a reduced risk of AMD. To 
leverage these findings, the NEI initiated a large, multi-center 
prospective study and clinical trial called the Age-Related Eye Disease 
Study (AREDS). Data from the AREDS study, published in 2001, found that 
over a 5-year period, a daily formulation of antioxidant vitamins and 
minerals (vitamins C, E, beta-carotene and zinc with copper) delayed 
the onset of advanced AMD by 25 percent.
    An estimated 8 million older-age Americans are at high risk to 
develop advanced AMD and vision loss. Of these 8 million, 1.3 million 
will develop advanced AMD within 5 years. However, now with the 
successful AREDS treatment, 300,000 of these individuals could be 
rescued from severe vision loss associated with advanced AMD over a 5-
year period. This simple and relatively inexpensive dietary 
intervention offers to the American public a valuable intervention to 
prevent severe vision loss and to reduce the need for more aggressive 
and expensive therapies.
    On the heels of this success, the NEI launched AREDS2. One of the 
primary objectives of AREDS2 is to determine whether oral 
supplementation with lutein and zeaxanthin and/or omega-3 long-chain 
polyunsaturated fatty acids will further decrease the progression to 
advanced AMD or formation of cataract. Previous NIH-funded studies have 
found high concentrations of these nutrients in the macula of the eye. 
Moreover, several studies have found an inverse relationship between 
dietary intake of these compounds and AMD. AREDS2 could result in a 
more effective but still inexpensive treatment regimen to prevent 
severe vision loss.

                            GENOMIC MEDICINE

    AMD research is but one example of genomic medicine, the effort to 
diagnose and treat patients at the molecular level. Over the past 15 
years, NEI-supported researchers have identified more than 450 genes 
that are involved in various eye and vision diseases. Considerable 
progress has been made in understanding the resultant disease 
mechanisms, and treatments are now beginning to emerge. As genomic 
medicine progresses, we must grapple with the obvious opportunity and 
challenge of genotyping individuals with eye disease and delivering 
therapies that are specifically tailored to the individual patient. 
This personalized approach to medicine is vital to improving the health 
of all Americans.
    The NEI initiated eyeGENE to address this issue. EyeGENE is an 
organized national network of research laboratories to support genetic 
testing for individuals with eye diseases. As testing services are not 
routinely available, the diagnostic information from eyeGENE will 
directly benefit such patients and families. The initiative will 
significantly aid vision research through a centralized registry that 
can be used to locate individuals who may wish to participate in 
clinical trials for new therapies. eyeGENE fills a critical research 
need that will advance the field. It includes a secure research blood 
collection and a centralized research repository of disease phenotype 
features which coupled to genes that cause disease will allow for the 
creation of the large datasets necessary to identify novel genetic risk 
factors and other epidemiologic questions. Programs like eyeGENE will 
drive genomic research and become the necessary fabric for individuals 
to benefit from advances in genomic medicine.

                          ADDITIONAL ADVANCES

    Recently, a number of developments have added further excitement to 
the field of vision research. The NEI is supporting projects that 
address the possible restoration of vision in blinding retinal 
degenerative diseases by building on recent advances in cell 
transplantation and precursor cell biology, including the use of bone 
marrow stem cell transplantation, and on ``re-engineering'' the 
production of light-sensitive proteins in retinal neurons.
    Research will continue in efforts to control angiogenesis in a 
number of eye diseases, and will include the conduct of clinical trials 
in this area. In support of this research is the Diabetic Retinopathy 
Clinical Research Network (DRCR.net). This collaborative network, 
supported by the NEI, is dedicated to facilitating multicenter clinical 
research on diabetic retinopathy, diabetic macular edema and associated 
conditions. The DRCR.net supports the identification, design, and 
implementation of multicenter clinical research initiatives focused on 
diabetes-induced retinal disorders. Principal emphasis is placed on 
clinical trials, but epidemiologic outcomes and other research may be 
supported as well. The DRCR.net was formed in September 2002 and 
currently includes more than 150 participating sites (offices) with 
more than 500 eye care providers throughout the United States. The 
success of this new model for bringing improved treatments for diabetic 
retinopathy more rapidly to patients is dependent upon the active 
participation of clinical research centers across the United States, as 
well as the participation of the patients they treat.
    Program plans for fiscal year 2008 include pursuing the research 
finding of several genes involved in Leber's Hereditary Optic 
Neuropathy, a genetic disease that frequently results in a substantial 
loss of central vision. The development of animal models carrying these 
mutations could lead to successful gene-based therapy for this disease. 
Research will also pursue remarkable new findings about how the 
activity of certain brain cells allows us to perceive a stable view of 
our surroundings despite constant head and eye movements, as 
highlighted in NEI's strategic plan. This research will help us to 
understand better the neural control of eye movements and associated 
disorders, and may have applicability in other sensory systems.

    Senator Harkin. Thank you Dr. Sieving.
    Now, we'll end with Dr. Duane Alexander, served as the 
Director of the National Institute of Child Health and Human 
Development since 1986. As I understand, you were there since 
1968, is that right?
    Dr. Alexander. That's right.
    Senator Harkin. Received his M.D. from Johns Hopkins 
University, some research specializes in developmental 
disabilities. Welcome, again, back to the committee. Dr. 
Alexander, please proceed.

STATEMENT OF DR. DUANE F. ALEXANDER, M.D., DIRECTOR, 
            NATIONAL INSTITUTE OF CHILD HEALTH AND 
            HUMAN DEVELOPMENT
    Dr. Alexander. Thank you, Mr. Chairman. I'd like to join 
with my colleagues in thanking you and the committee members 
for holding this hearing, and for your many years of strong 
support for the NIH that's allowed us to do what we've 
accomplished.
    Since the National Institute of Child Health and Human 
Development was established nearly 45 years ago, our scientists 
have made discoveries that have improved the health and well 
being of children and adults.
    For example, our research has contributed largely to the 
Nation's 70 percent reduction in infant mortality rate over 
that span of time, and 93 percent reduction in transmission 
rate from mother to child of the AIDS virus, the near 
elimination of five major causes of mental retardation, 
successful treatments for infertility, an effective 
intervention for reducing a major cause of premature birth, and 
many other benefits.
    Our current research agenda builds on its past discoveries, 
addresses some of our country's and the world's most crucial 
health needs, and moves us closer to predicting or pre-empting 
diseases and conditions such as infertility, birth defects, 
disability from limb loss and infant mortality from premature 
birth.

                         FERTILITY PRESERVATION

    One area of our current focus is fertility preservation for 
women facing cancer treatment. The chemotherapy and radiation 
used to treat cancer can irreparably damage the body's 
reproductive tissues, and render both men and women infertile.
    Males may have the pre-treatment option of storing their 
frozen sperm for later use, but no comparable option currently 
exists for women. Eggs seldom survive the freezing and 
subsequent thawing process required for storage. However, our 
scientists are developing new techniques to protect the egg 
during the freezing, thawing and maturation process. When a 
woman who has had chemotherapy or radiation is ready to start a 
family, these follicles can be thawed and then cultured. The 
resulting eggs could be fertilized, and implanted in the uterus 
to establish a pregnancy.

                         PREVENTING DISABILITY

    Preventing disability by newborn screening is another 
current emphasis for the Institute. It allows us to predict 
whether an infant has one of hundreds, literally, of genetic or 
metabolic disorders by testing a single drop of a newborn's 
blood, and treating the condition as soon as it's identified, 
preempting the infant's early death, or a lifetime of mental 
retardation or physical disability.
    The screening and treatment, developed in large part 
through NICHD research, now is provided universally in the 
United States, but only for a few disorders.
    One such disorder is congenital hypothyroidism. It occurs 
once about 3,000 births, affecting 1,300 children every year in 
the United States. Without treatment, the child with congenital 
hypothyroidism will suffer irreparable brain damage within 
months, and require a lifetime of special care.
    However, as a result of our research, children with 
congenital hypothyroidism are now routinely identified at birth 
and given treatment immediately. One thyroxin pill daily spares 
them from the brain damage that would otherwise result, thus 
eliminating congenital hypothyroidism as a significant cause of 
mental impairment. The cost of treatment is just a few pennies 
a day. The lifetime amount of dollar savings is about $140 
million a year, and the human suffering prevented is priceless.

                           NEWBORN SCREENING

    An NICHD initiative to develop the technology to markedly 
expand newborn screening to hundreds of conditions is being 
funded in fiscal year 2007, and will expand in 2008 by 
establishing a national network to pilot test these new 
successful treatments. This is a card (Exhibit A) that they use 
in New York State newborn screening program. Each State runs 
its own program, and determines which conditions it screens 
for. You can tell from what's listed here that we have moved in 
just the last year from a system which screened for 3 to 5 
conditions only, to where a majority of States are now using 
tandem mass spectrometry to screen for 30 disorders, and we're 
working with other technology developments using micro array 
chips, luminex beads, or others to markedly expand this to 
literally hundreds of genetic disorders, immunodeficiency 
diseases, muscular dystrophies, and other conditions.



                       NECROTIZING ENTEROCOLITIS

    Another cause of infant mortalitym, that NICHD is attacking 
is necrotizing enterocolitis (NEC). We have made major advances 
against other causes like respirator, distress syndrome, severe 
jaundice, meningitis or sudden infant death syndrome, but NEC 
is a continuing problem. In 40 years, we've really made little 
progress against this condition. It causes death or disability 
by destroying the intestines of premature infants, and it 
attacks about one-tenth of all infants under 1,500 grams.
    Our efforts have identified some potential treatments. One 
is epidermal growth factor, which in mice and rats is highly 
protective against NEC. Another human study, has demonstrated 
that interleukin-10 in breast milk is highly protective.
    These and other potential treatments for NEC are going to 
be tested in a special initiative, launched by NICHD, about to 
be published, and funded in 2008.

                         MEDICAL REHABILITATION

    As our country's armed forces return from stations abroad, 
and as the Nation's population continues to age, increased 
attention is needed on medical rehabilitation, to prevent 
immobility and dependence. Among the initiatives in the NICHD 
portfolio is developing mechanical limbs that allow for better 
comfort at the socket and improved mobility. Advances in this 
area can be particularly helpful to veterans who have lost 
limbs in combat.
    One exciting new finding from this research is a new type 
of prosthetic arm, that connects in a way that allows the 
amputee to use it simply by thought--thinking about using the 
arm stimulates the chest muscles that are tied into it to 
contract with relative ease, and move the arm with greater 
speed and precision.
    Researchers hope to use similar technology to restore 
natural movement and sensation to the limbs of individuals 
paralyzed by injury or stroke.

                           PREPARED STATEMENT

    Mr. Chairman, committee members, I would like to thank you 
again for your continued support of our research, as we try to 
understand disease, and improve the health and well-being of 
men, women, children and future generations. I'll be pleased to 
answer any questions.
    [The statement follows:]

              Prepared Statement of Dr. Duane F. Alexander

    Mr. Chairman and members of the committee: I am pleased to present 
the fiscal year 2008 President's budget request for the National 
Institute of Child Health and Human Development (NICHD). The fiscal 
year 2008 budget includes $1,264,946,000.
    With continuous support from this committee, the NICHD has made 
significant discoveries that have improved the health and well-being of 
children and adults. For instance, in the 45 years since the NICHD was 
founded, our research has been largely responsible for a decline in 
infant mortality of more than 70 percent, a 93 percent reduction in the 
rate of mother-to-child transmission of the AIDS virus, the elimination 
of five major causes of mental retardation, successful treatments for 
infertility, an effective intervention for reducing a major cause of 
premature birth, and many other benefits. Our scientists around the 
country are grateful to this committee for providing the opportunity to 
pursue research in these areas.
    The Institute's research agenda builds on the discoveries from the 
last decade, addresses some of our country's and the world's most 
critical health needs, and moves us closer to major breakthroughs 
against diseases and conditions such as infertility, birth defects, 
infections, limb loss, premature birth, and maternal death.

         PRESERVING FERTILITY FOR WOMEN FACING CANCER TREATMENT

    The chemotherapy and radiation used to treat cancer can irreparably 
damage the body's reproductive tissues and render men and women 
infertile. Males may have the pre-treatment option of storing their 
frozen sperm for later use, but no comparable option currently exists 
for women. Eggs seldom survive the freezing and subsequent thawing 
processes required for storage. Currently, the only option for women 
facing the prospect of such infertility is in vitro fertilization and 
long-term storage of the embryos, which tolerate freezing. However, 
this option is not always suitable. Young women with cancer may be 
forced to forego having their own children in order to receive life-
saving treatment. The NICHD's new Fertility Preservation Research 
Program seeks to develop treatments to preserve fertility among 
patients with cancer or environmental risks for infertility. Building 
on current research, such as using a gelatin mixture to surround the 
follicle containing the egg, our scientists will be developing new 
techniques to protect the egg during the freezing, thawing, and 
maturation process. The goal is to allow a small section of the ovary 
to be removed and frozen for later use. When the woman is ready to 
start a family, the frozen follicles could be thawed and then cultured. 
The resulting eggs could be fertilized and implanted in the uterus to 
establish a pregnancy.

          PROTECTING OUR CHILDREN AS WE TREAT THEIR ILLNESSES

    The Best Pharmaceuticals for Children Act (BPCA)--enacted by 
Congress to increase information about the safety, usefulness, and 
dosage of medications for infants and children--is an important part of 
the nation's ongoing effort to assure that our treatments for children 
do not harm them. As we have learned, children's immature body systems 
and metabolic rates make pediatric clinical trials essential for 
studying the impact of widely prescribed drugs on children and infants. 
Within its work on the BPCA, the NICHD, in consultation with the Food 
and Drug Administration, identifies and prioritizes drugs for pediatric 
clinical study. The NICHD collaborates with manufacturers and academia 
in designing and implementing preclinical and clinical studies of drugs 
that are widely used or integral to the care of children with specific 
medical conditions. Currently 29 studies are under way evaluating drugs 
to provide information for labeling to guide pediatric use.

           PREVENTING DISABILITIES THROUGH NEWBORN SCREENING

    Imagine being able to know if an infant has one of hundreds of 
genetic or metabolic disorders by testing a single drop of a newborn's 
blood. Imagine being able to treat the condition as soon as it is 
identified, sparing that infant an early death or a lifetime of mental 
retardation or physical disability. This screening and treatment, 
developed in large part through NICHD research, now is provided 
universally in the United States for a few such disorders. For example, 
the National Newborn Screening and Genetic Research Center reports that 
congenital hypothyroidism (CH) occurs once in every 3,000 births, 
affecting 1,300 children each year in the United States. Without 
treatment, an infant with CH will suffer irreparable brain damage 
within months and require a lifetime of special care. Because an NICHD 
grantee developed a screening test for the disorder in the 1970s, 
children with CH are now routinely identified at birth and treatment 
begins immediately. One thyroxine pill daily spares them from the brain 
damage that would otherwise result, thus eliminating CH as a 
significant cause of mental impairment. The cost of treatment: a few 
pennies a day; the lifetime net dollar savings: $140 million each year; 
the human suffering prevented: priceless.
    Currently, the number of conditions for which newborns are screened 
varies widely from state to state. The March of Dimes notes that nearly 
all of the 4.1 million American infants born each year undergo 
screening for some disorders, and about 5,000 are diagnosed with an 
abnormality. Treatments exist for the conditions for which we now 
screen, as well as for others for which screening is not yet possible. 
To remedy this situation, the NICHD is funding a series of contracts to 
develop gene-based technologies that can identify hundreds of rare 
genetic disorders in a single test. In addition, the Institute will 
fund new projects to spur research on new treatments for potentially 
screenable disorders. Examples of conditions in these categories are 
Spinal Muscular Atrophy, the leading genetic cause of infant death, and 
Fragile X Syndrome, the leading inherited cause of mental retardation. 
Expanded efforts in fiscal year 2008 will include creating a multi-site 
newborn screening translational research network to test the most 
promising new screening technologies and experimental treatments in 
collaboration with state newborn screening programs.

            REDUCING ANOTHER CAUSE OF INFANT MORTALITY: NEC

    Through research led by the NICHD, one cause of infant mortality 
after another has yielded to treatments based on new discoveries. 
Respiratory distress syndrome, severe jaundice, meningitis, and Sudden 
Infant Death Syndrome cause far fewer deaths today. One remaining 
problem is necrotizing enterocolitis (NEC). This condition affects 10 
to 12 percent of infants weighing less than three pounds, and about 30 
percent of those affected will not survive. NEC attacks and destroys 
their intestines. Unfortunately, its incidence and mortality rate have 
not changed in 40 years. Now, new NICHD studies give hope that 
prevention or effective treatment can become a reality. One study in 
mice demonstrated that epidermal growth factor, administered orally, 
was highly protective against NEC. Another study, in humans, 
demonstrated protection against NEC from interleukin--in breast milk. 
These and other potential therapies will be tested in a new NICHD 
initiative on NEC to be launched in fiscal year 2008.

                    DEVELOPING IMPROVED PROSTHETICS

    As the country's Armed Forces return from stations abroad, and as 
the nation's population continues to age, increased attention is needed 
on medical rehabilitation. The Institute's National Center for Medical 
Rehabilitation Research is a leader in such efforts and provides a 
Federal focal point for research in this important field. Among the 
initiatives in the Center's portfolio is developing mechanical limbs 
that allow for better comfort and mobility. Advances in this area can 
be particularly helpful to veterans who have lost limbs in combat. One 
exciting new finding from this research: an amputee can move and have 
functional use of a prototype prosthetic arm simply by thought. 
Thinking about moving the arm stimulates the chest muscles to contract. 
Microprocessors in the arm read the nerve signals sent by the chest 
muscles, and movement flows with relative ease and greater speed and 
precision. Researchers hope to use similar technology to restore 
natural movement and sensation to the limbs of individuals paralyzed by 
injury or stroke.

              HELPING DEVELOPING NATIONS OVERCOME DISEASE

    Every 30 seconds, malaria takes the life of a child somewhere in 
the world. The mosquito-borne disease kills more than one million 
people each year and severely sickens millions more in developing 
countries, crippling economic growth. It is one of the world's leading 
health concerns. Researchers at the NICHD's Laboratory of Developmental 
and Molecular Immunity--in partnership with researchers in the Malaria 
Vaccine Development Branch of the National Institute of Allergy and 
Infectious Diseases, and the Biotechnology Unit of the National 
Institute of Diabetes and Digestive and Kidney Diseases--may have a 
solution.
    These researchers have developed an experimental vaccine that stops 
the spread of malaria, mosquito by mosquito. The vaccine eliminates the 
parasite responsible for malaria from the digestive tract of a malaria-
carrying mosquito after it has fed on the blood of a vaccinated 
individual. Future bites from this mosquito then no longer transmit the 
disease. If it is proven safe and effective, the vaccine could free 
entire geographic regions from this destructive disease.
    The NICHD's research investments to improve health in developing 
nations go beyond laboratory benches. The Institute supports the Global 
Network for Women's and Children's Health Research, an initiative 
devoted to addressing the leading causes of illness and death in 
pregnant women and their infants in developing countries. This year one 
network study, a randomized double blind clinical trial conducted by 
birth attendants in rural India, demonstrated that giving women a 
single dose of misoprostol, a uterine muscle constrictor, just after 
delivery nearly eliminated the incidence of severe post-partum 
hemorrhage, a leading cause of maternal mortality in developing 
countries worldwide. India immediately took action to make misoprostol 
treatment available as standard care throughout the country, and other 
nations are doing the same. This one simple and cost effective 
intervention will save the lives of millions of women throughout the 
developing world.
    Mr. Chairman and members of the committee, I would like to thank 
you for your continued support of the Institute's research as we strive 
to understand disease and improve the health and well-being of men, 
women, children, and future generations in the United States and around 
the world. I will be pleased to answer any questions.

    Senator Harkin. Dr. Alexander, thank you very much.
    It's hard to know where to begin, but thank you all very 
much for excellent testimony. Very pointed, very to the point. 
We might as well start where we started with Dr. Kirschstein.

           RESPONSE TO COMPLEMENTARY AND ALTERNATIVE MEDICINE

    I'm very interested in what you mentioned about looking at 
genetic variations, and I want you to just tell me a little bit 
more about that, because it seems to me, every time we talk 
about people who have had an experience with a complementary or 
alternative medicine approach, were over the counter or 
something like that. Sometimes it seems to work for some 
people, and it doesn't for others. So, why does it work for 
some, and not for others? So, maybe there is some genetic 
variation there that allows for something to be done, and is 
therapeutic, but on the other hand, for someone else it isn't. 
Is that what you're looking at?
    Dr. Kirschstein. That's what we plan to look at. We know 
that that's true, also, for the use of more conventional drugs. 
We know that the people respond differently to drugs, and that 
there are times when the dose has to be cut, or they actually 
have to substitute one drug for another. We don't have that 
knowledge about these complementary materials, particularly the 
biologically based ones that people have been using on their 
own that they can purchase in various stores. This is what we 
want to take a look at, now that we know so much about the 
sequencing of the genome and the variation as to what could be 
happening. We're going to launch studies to that effect. We 
have not started as yet.

  NATIONAL ADVISORY COUNCIL ON COMPLEMENTARY AND ALTERNATIVE MEDICINE

    Senator Harkin. I see. I just want to cover one other thing 
with you, Dr. Kirschstein, and that is the structure of the 
advisory council.
    Dr. Kirschstein. Yes, sir?
    Senator Harkin. Here's the law that set it up.
    First of all, you know we had it first as the Office of 
Alternative Medicine, and then we changed it to NCCAM, and when 
we changed it to NCCAM in 1998, many people were disappointed 
in how the structure of the advisory panels had been set up 
previous to that. So, we wrote into law certain guidelines, put 
it right into the law. Of the 18 appointed members, 12 shall be 
selected from among the leading representatives of the Health 
and Scientific Disciplines, relative to the activities of the 
NCCAM. Particularly, representatives of the health and 
scientific disciplines in the area of complementary and 
alternative medicine members shall be practitioners licensed in 
one or more of the major systems with which the Center is 
involved.
    Then it says, ``Six shall be appointed by the Secretary 
from the general public and shall include leaders in the fields 
of public policy, law, health policy, economics, and 
management. Three of the six shall represent the interests of 
individual consumers of complementary and alterative 
medicine.''
    I understand that earlier this week you named six new 
members to the advisory Council. I've had concerns about this 
going clear back to 1991. As you know, as I said, I just read 
to you that 50 percent of the Council's non-staff members 
should be licensed CAM practitioners. Three, as I mentioned, 
from the consumer population. I don't believe that statute has 
always been met, and I want to ask you, where do we stand now 
with these additions to the panel? If you don't know that, you 
can respond to me later on.
    Dr. Kirschstein. I will expand on the question for the 
record.
    [The information follows:]

  National Advisory Council on Complementary and Alternative Medicine

    Question. The statute for the National Center for Complementary and 
Alternative Medicine (NCCAM) stipulates that at least half of the 
members of NCCAM's Advisory Council, who are not ex officio members, 
shall include practitioners licensed in one or more of the major 
systems with which the Center is concerned, and at least three 
individuals representing the interests of individual consumers of 
complementary and alternative medicine. How close is NCCAM coming to 
meeting the law?
    Answer. There are several factors that influence the composition of 
NCCAM's National Advisory Council:
  --NCCCAM's mission encompasses a diverse body of research. The scope 
        of NCCAM's research includes all organ systems and medical/
        scientific disciplines, as well as a range of CAM modalities 
        and practices within the four major CAM domains or systems 
        (manipulative and body-based practices, biologically based 
        practices, energy medicine and mind-body medicine) as well as 
        the whole medical systems of which they are a part. The 
        collective expertise of NCCAM's Advisory Council, which is 
        responsible for second-level peer review of the grant 
        applications that NCCAM receives, must reflect this diversity.
  --Regulation of and licensure to practice any medical or CAM 
        discipline is within the purview of the states, and 
        requirements vary widely. For example:
    --All states license chiropractors.
    --All states license medical doctors and most include within the 
            medical licensure standards degrees obtained from schools 
            of osteopathy.
    --Most states have some form of licensure for practitioners of 
            acupuncture and/or oriental medicine and practitioners of 
            massage therapy.
    --A large majority of states do not have any specific form of 
            licensure for practitioners of naturopathy or homeopathy.
    --Specific licensure does not exist in any state for many of the 
            CAM disciplines involved in research grant applications 
            reviewed by NCCAM's Advisory Council. Of these disciplines, 
            many can be legally practiced for health care purposes by 
            or under the auspices of licensed medical providers, such 
            as allopathic physicians, doctors of osteopathy, or 
            licensed mental health care professionals, and always 
            within the legal framework and limitations of their 
            licensed discipline.
    Table 1, attached, lists the current NCCAM Advisory Council 
members, their areas of CAM and/or medical/scientific expertise, and 
their research and professional interests relevant to their service on 
the council. The table illustrates how the composition of the Advisory 
Council reflects the need to simultaneously address relevant statutory 
requirements, and to ensure appropriate scientific and CAM expertise 
needed to carry out its charge.
    The terms of four Council members listed in Table 1 (Calabrese, 
Ezzo, Manyam, and Pickar) expire in 2007. Those members are slated to 
be replaced by six individuals whose appointments are in the final 
stages of completion. Table 2 lists the areas of CAM, medical/
scientific expertise, and the research and professional interests 
relevant to the Advisory Council for the pending new members.
    NCCAM will continue to assure that it has an appropriately 
qualified and balanced Advisory Council, as required by statute, that 
permits the Center to support the highest quality of scientific 
investigation of CAM, such as the examples highlighted in my testimony 
before the Subcommittee.

                           TABLE 1.--NATIONAL ADVISORY COUNCIL FOR COMPLEMENTARY AND ALTERNATIVE MEDICINE--MEMBERSHIP, EXPERTISE, AND RESEARCH/PROFESSIONAL INTERESTS
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
         Member degree(s)                      Institution location                   CAM expertise          Medical/scientific expertise       Professional/research interests and activities
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Lori Alvord, MD \1\ \2\...........  Dartmouth Medical School, Hanover, NH.....  Native American Medicine.  Surgery.........................  Integrative medicine.
                                                                                                                                             Health services research on patterns of care for
                                                                                                                                              Native Americans.
Stephen Barnes, Ph.D.\1\..........  U Alabama at Birmingham, AL...............  Botanicals/natural         Biochemistry....................  Botanical research.
                                                                                 products.                 Pharmacology....................  Research on diseases of aging and chronic disease
                                                                                Pharmacognosy............  Toxicology                         prevention.
Carl Calabrese, ND, MPH \2\ \3\...  National College of Natural Medicine,       Naturopathy..............  Clinical research...............  Clinical research on CAM natural products.
                                     Portland, OR.
Sheldon Cohen, Ph.D.\1\...........  Carnegie Mellon, U Pittsburgh, PA.........  .........................  Psychology......................  Role of stress, coping, and social support in
                                                                                                           Mind-body medicine..............   health and weal-being.
                                                                                                           Psychosomatics                    Psychoneuroimmunology.
Fabio Cominelli, MD, Ph.D.\1\.....  U Virginia, Charlottesville, VA...........  Gastroenterology.........  Inflammatory bowel diseases
                                                                                Cell biology.............  Mucosal immunology
Silvia Corvera, MD................  U Massachusetts Medical School, Worcester,  .........................  Endocrinology...................  Type II diabetes and metabolic syndrome.
                                     MA.
Jeaneette Ezzo, Ph.D., MsT, MPH     James P. Swyers Enterprises, Takoma Park,   Massage therapy..........  Epidemiology....................  Systematic reviews evaluating CAM evidence base.
 \2\ \3\.                            MD.                                                                   Biostatistics...................  Health policy--breast cancer advocacy.
Joan Fox, Ph.D....................  Case Western Reserve, University,           Reiki....................  Cell biology....................  Cardiovascular disease; mechanisms of action of
                                     Cleveland, OH.                                                                                           mind-body practices affecting cardiovascular
                                                                                                                                              disease.
Marjorie Gass, MD \1\ \2\.........  U. Cincinnati, Cincinnati, OH.............  .........................  Obstetrics and Gynecology.......  Women's health.
                                                                                                                                             Osteoporosis, menopause.
Ted Kaptchuk, OMD, LAc............  Harvard Medical School, Osher Institute,    Asian medicine...........  ................................  Acupuncture.
                                     Boston, MA.                                Acupuncture..............                                    Clinical and basic research on the placebo effect
                                                                                                                                              and its implications for practice and research
                                                                                                                                              methodology.
Bala Manyam, MD \3\...............  Hindu University of America Odessa, FL....  Ayurveda.................  Neurology.......................  Research on movement disorders.
                                                                                                                                             Ayurvedic herbal medicine approaches to Alzheimer's
                                                                                                                                              disease.
Joel Pickar, DC, Ph.D.\2\ \3\.....  Palmer College of Chiropractic, Davenport,  Chiropractic.............  Physiology......................  Neurophysiology of chiropractic manipulation.
                                     IA.
Bruce Redman, DO..................  U of Michigan, Ann Arbor, MI..............  Osteopathy...............  Clinical trials.................  Immunotherapeutic approaches to treatment of
                                                                                                                                              cancer.
Danny Shen, Ph.D..................  University of Washington Seattle, WA......  .........................  Pharmacokinetics................  Herb-drug interactions.
                                                                                                           Pharmacology
                                                                                                           Toxicology
Frank Torti, MD, MPH \1\..........  Wake Forest U School of Medicine Winston    .........................  Oncology........................  Cancer biology.
                                     Salem, NC.                                                                                              Antioxidants and cytokines.
Stephanie Vogel, Ph.D.............  U of Maryland Baltimore, MD...............  .........................  Immunology......................  Mechanisms of immune defense.
                                                                                                           Microbiology
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ The appointment of these six individuals was announced on June 21, 2007.
\2\ Public member.
\3\ Terms expire in 2007.


     TABLE 2.--NATIONAL ADVISORY COUNCIL FOR COMPLEMENTARY AND ALTERNATIVE MEDICINE--EXPERTISE AND RESEARCH/
                              PROFESSIONAL INTERESTS OF MEMBERS PENDING APPOINTMENT
----------------------------------------------------------------------------------------------------------------
                                            Medical/scientific           Professional/research interests and
Pending          CAM expertise                  expertise                            activities
----------------------------------------------------------------------------------------------------------------
  1 \1\Naturopathy                   ...........................  Integrative oncology.
                                                                  Cancer Prevention.
                                                                  Public policy.
  2 \1\Osteopathy                    ...........................  Osteopathic practitioner.
  3 \1\Chiropractic                  Clinical trials............  Research on CAM treatments for low back
                                                                   pain, neck pain, asthma, infantile colic,
                                                                   and headache.
      4Acupuncture                   Psychiatry.................  Practice of acupuncture.
  5 \1\Qi Gong                       Biochemistry...............  Cell biology.
       Tai Chi                       Biophysics.................  Research on mechanisms of action of qigong
                                     Cell biology...............   and acupuncture.
                                                                  Teaching of Oriental Medicine.
      6                              Internal medicine..........  Cardiovascular Disease.
                                     Cardiology.................  Epidemiology of cardiovascular disease in
                                     Epidemiology...............   African Americans.
                                                                  Epidemiology and preventive medicine.
----------------------------------------------------------------------------------------------------------------
       \1\ Public member.

    Dr. Kirschstein. I do know we have tried very hard to 
fulfill the law. We submit two names for each spot on the 
advisary council. We have been in discussion with the people 
who have worked on this, and we are always working to improve 
the submissions for the advisory council.
    On the other hand, we need a very balanced advisory 
council, because we need individuals who can take a look at 
things like the genetic variation studies that we will be 
setting up. So, this is a challenge to us, and we're going to 
work hard to meet it.
    Senator Harkin. I appreciate that, Dr. Kirschstein, could 
you please get to my staff within the next week or so, the 
rundown of the members, the six that have been appointed, I 
want to know how close we've come to meeting the law?
    Dr. Kirschstein. Yes, sir, I will do that.
    Senator Harkin. I'm still concerned about that.
    Dr. Kirschstein. I will work with you on it.
    Senator Harkin. I appreciate that. It's something, as you 
know, I've been hot on this for a long time.
    Dr. Kirschstein. Yes.

                     CAM AND INFLAMMATION RESEARCH

    Senator Harkin. I don't mean to let up on it.
    It's interesting that you mentioned in your written 
statement--I read it last night--but you mentioned something 
about the use of turmeric as an anti-inflammatory thing. Is 
that investigation ongoing right now?
    Dr. Kirschstein. Yes, sir. It is an investigation ongoing 
right now, and some preliminary data have indicated that it has 
anti-inflammatory effects, and possibly anti-arthritic effects, 
therefore we are planning to expand those studies.
    Senator Harkin. I've always asked a lot of doctors--if you 
look at my hands and look at my two little fingers, there's 
little bumps on the last thing of that digit--do you know what 
that's called?
    Dr. Kirschstein. I have one called----
    Senator Harkin. What's that called?
    Dr. Kirschstein. Osteoarthritis.
    Senator Harkin. What is that called? Aheberden's nodes, but 
it's only because it comes to the little fingers and the 
thumbs, basically where it affects--there was a Scottish doctor 
that found this, and it's prevalent among people from that area 
of the world--Scotland, Ireland, it happens to be where my 
ancestors come from. But, a very painful, arthritic conditions.
    It's interesting, because you know, I've been interested in 
complementary and alternative medicine for a long time. I was 
in Iowa last fall in the campaign and what do you do during the 
campaign? You shake a lot of hands. Well, these can be very 
painful, can you imagine shaking hands with this? It was so 
painful, I couldn't even stand to shake hands.
    I just happened at that time to have dinner with a couple 
of doctor friends of mine, brothers, Dr. Neil Sahai and his 
brother Sabash, they're from India. They have a medical 
practice in Webster City, Iowa, and they invited me over for 
dinner, great family. Their mother was there, and the best 
Indian food I've ever had in my life. So, I went there for 
dinner, just as a social thing, I know them. I was complaining 
about my hands hurting. I had arthritis in my fingers, and Neil 
Sahai, Dr. Sahai said, ``Well, I think I may have something to 
help you from India, we've got this, something called 
turmeric.''
    Well, I'd kind of heard of that as a spice before, and so 
he asked me to take two of these every day for a month, and 
just see if it had any effect, and I didn't change any other 
thing I did in my life. I changed nothing in terms of my eating 
habits or sleep, basically went on as I've been going, except I 
started taking this turmeric every day, and after about 30 some 
days or something, I just had no problem, and I have no more 
pain left in my hands at all. I take turmeric every day now. 
Now, is that the reason for it? I don't know. All I can tell 
you, I didn't change anything else. It's interesting, when I 
read your testimony last night I thought, ``Oh my gosh,'' I 
thought maybe it was just mental stuff with me, I didn't know 
what was going on. It was amazing, I had to have that happen.
    Dr. Kirschstein. Maybe next year or the year after, the 
permanent Director of NCCAM will be able to tell you the 
answer.
    Senator Harkin. Well, it's just interesting that you're 
interested in that, and looking at it. Anyway, I didn't mean to 
get into my own health thing or anything like that.
    Well, I have a lot more questions, but Senator Cochran, I 
would yield to you for another 5 or 10 minutes, and then I'll 
come back.
    Senator Cochran. Mr. Chairman, one thing that could have 
helped your hand is you quit running for President, you don't 
have to shake as many hands.

                       NATURAL RESEARCH PRODUCTS

    Senator Harkin. That's a good point.
    Senator Cochran. I think it's very interesting, to hear the 
testimony this morning. I've enjoyed the opportunity to hear 
your remarks about the different areas of inquiry the National 
Institutes of Health is engaged in, and your areas of 
expertise.
    I remember, too, in connection with dietary supplements, 
there's a growing popularity among American people in these 
kinds of things, and at our University of Mississippi, there's 
a natural products center that has been established, and it's 
been working now for some time, exploring health beneficial 
uses of natural products.
    It all started, frankly, with an idea someone had for 
undertaking marijuana research, and it's the only place in the 
country that I know about where the Government actually 
encourages the growing of marijuana, and testing and analysis, 
and trying to figure out what the medicinal properties might be 
that can be useful, and that has expanded now to include a lot 
of other areas of inquiry. It's become an international center 
for research and exchange of information, and we're very proud 
to host that in our State in Mississippi.
    I just wonder if the National Institute has had any 
connection or correspondence, communication with people down 
there who are working in these areas.
    Dr. Kirschstein, do you know of any connection or exchange 
of information?
    Dr. Kirschstein. We have a great deal of contact with the 
people down there, indeed we support research at the University 
of Mississippi on natural products botanical center, and we 
just--there was recently a meeting there which we helped 
support, so we're very active in that area, sir.

                     CAM AND PEDIATRIC POPULATIONS

    Senator Cochran. I know that one area of interest is in 
alternative medicine for children. I know I grew up in a family 
that didn't believe in taking medicine. My mother always said, 
``If you eat right, you don't have to take medicine, you'll be 
healthy.'' If you exercise and do all of these right things. Of 
course I've learned later that it's probably the genetic 
properties we were born with have an awful lot to do with good 
health, too, and disposition towards disease and illness.
    How important is it for us to concentrate on education in 
these areas of factual information that could be helpful, at 
least, to reducing anxieties, contributing to unnecessary use 
of medicines, if we can change the mindset by just improving 
the level of knowledge and understanding and appreciation of 
what the facts are? What really does matter in good health, for 
children, particularly?
    Dr. Kirschstein. It's extremely important. Dr. Alexander, 
of course, can expand on this. But one of the reasons we are 
doing this survey with the CDC is to determine how extensive 
the use of complementary and alternative practices is in 
children. We know that their parents are using a great deal of 
this, and therefore some of them, of course, are giving similar 
treatments or modalities to their children. We really don't 
have good follow up on that, and we need to begin to do some 
research, being very mindful that the child is not just a 
little adult--there are differences between children and 
adults. We must be sure that we are protecting our children at 
the same time, and that we know what we're giving them.
    The other part about education is that what we know, 
Senator Cochran, is that people, consumers, of complementary 
medicines and alternative medicines, when going to the regular 
practitioner, their doctors do not tell them that they are 
using the alternative or complementary products, and vice 
versa. The doctors do not ask them. As a result, the 
communication about all of the materials that an individual is 
using does not get transmitted. That is why we have started 
these new campaigns--education in this field, just like in all 
medical fields--is very important.

                             PRETERM BIRTHS

    Senator Cochran. Thank you. I know, Dr. Alexander mentioned 
in his testimony the problem of premature births. I think the 
statistics that we have show that this has increased by 30 
percent, just in the last 20 years. That is a substantial 
number, it's now the leading cause of newborn death. What 
factors, do you think, are the cause, or can be attributed to 
the pre-term births? What do we do in terms of national policy 
or education to improve on these numbers?
    Dr. Alexander. This is a real puzzle to us, Senator 
Cochran, because there's no question about these statistics. 
The change, the increase in premature birth is real. It's also 
accompanied by an increase in low birth weight, not 
unexpectedly.
    After many years in which this declined, it has now started 
to go up again, and the trend has persisted in spite of our 
efforts to reverse it. So, people talk about a variety of 
things that may be contributing to it. One of the first things 
people talk about is the increased prevalence of assisted 
reproductive technology--invitro fertilization, and other 
efforts to assist people who are infertile to have children. 
For a variety of reasons--sometimes because multiple fetus 
pregnancy is established--two, three, four, fetuses--all of 
which tend to increase the likelihood of prematurity. We have 
now, 1 to 2 percent of our population born as a consequence of 
assisted reproductive technology. So, as that has increased, 
the likelihood of prematurity has increased. What we're trying 
to do here with the obstetric community is encourage, when 
people do IVF, only to put one embryo back, and to establish a 
pregnancy with a single embryo, rather than two, three, four, 
five, as has been done in the past to increase the likelihood 
of establishing the pregnancy. That is one tactic.
    In addition to that, there probably is a factor of 
increased efforts to save very, very low birth weight babies, 
so that babies that might have been classified previously as 
still births, now are classified as live births, and are 
entered as babies who are live births, and thus contribute to 
infant mortality, whereas previously they would have been 
considered stillbirths because they were so small, that no 
efforts were made to help them start breathing or start a heart 
rate. That is another factor.
    But, there are others that we just don't understand. We're 
in the process of working with the Office of the Surgeon 
General to put together a report on prematurity that was called 
for by the Preemie Act that the last Congress passed. So, we're 
involved in that, and we hope through our very intense 
examination of that, which follows on the work of an Institute 
of Medicine committee focusing on prematurity, we will learn 
some more useful routes to pursue to try to get at this 
question of what is causing the increase, and what can we do to 
reverse it?
    Senator Cochran. Thank you. Thank you, Mr. Chairman.
    Senator Harkin. Thank you, Senator Cochran.

                TEMPOROMANDIBULAR JOINT/MUSCLE DISORDERS

    Dr. Tabak, I think you and I talked about this a long time 
ago. That included report language, for many years, on TMJ, and 
you mentioned it briefly. We discussed it several years ago 
again. Very briefly, could you tell what advances have been 
made recently in the area of TMJ? On the muscle and joint 
disorders? Are you doing some research on regenerating damaged 
bone and tissue, but just again, give me a couple of minutes on 
that.
    Dr. Tabak. Surely, and thank you for the question.
    We've actually done quite a bit in this area. The most 
important thing is that we are now attracting researchers with 
different talent sets to study this enigmatic set of diseases 
and conditions. We have finally been able to attract 
geneticists, neurologists, neuroscientists, individuals who are 
able to look at the entire system, as opposed to the very 
specific joint.
    By bringing in these additional people with their 
expertise, we're beginning to get a much more balanced view of 
this complex, and probably heterogeneous, set of diseases and 
conditions. The work that you alluded to, work related to 
replacement of diseased joints, is ongoing. We have a very 
extensive bioengineering program, which makes use of advanced 
material development. The materials are not stagnant, they are 
typically impregnated with so-called growth factors, similar to 
those that Dr. Sieving spoke to you. These growth factors can 
help inform the surrounding cells as to what they should be 
doing to facilitate regeneration and regrowth. So, we're really 
looking at this at all levels.
    A final point that I will make is that we recently funded a 
longitudinal study at the University of North Carolina termed 
OPERA, which is looking at individuals before they even develop 
symptoms of temporomandibular joint/muscle disorders. What 
we're doing in this prospective longitudinal study is 
collecting a large amount of data--including biological 
samples--so that as the individuals within the cohort begin to 
develop symptoms and evidence of disease, we will have already 
banked materials. Once and for all we can begin to get insight 
into the very earliest stages of the disease, so that we can 
begin to pick out those people in the community who are most at 
risk. I think that's going to be a very important adjunct.
    We have programs to look at the very earliest stages of the 
disease. We have programs looking at the disease as it 
currently exists, and then we have the programs at the end 
stages, where we are recreating the joint for those individuals 
who have had extensive joint destruction.
    Senator Harkin. Very good, I'll keep on top of this. We've 
been on it for several years, and I'm really interested in, 
again, pushing this ahead and advancing the early detection of 
that, and intervention on that program.

                                 AUTISM

    Dr. Schwartz, let's talk a little bit about autism. You 
didn't really cover that in your testimony, but we just had a 
hearing on that, and it was the first hearing we've had on this 
committee just looking at autism.
    Anyway, you look at it, autism is almost epidemic right 
now. The increases over the last 2 years have been phenomenal, 
and the number of kids diagnosed with autism. Again, we're 
looking at things like, we know the earlier you get to it, 
there are certain interventional-type programs you can do that 
can lessen the effects of autism later on.
    But, still, kids have autism. We don't know whether it's 
genetic or environmental, and it seems to be, in taking with 
CDC, maybe it's some genetic, maybe some environmental. Maybe 
the two feed off of each other. I'm wondering, what are you 
doing in your Department, what are you doing, looking at any 
environmental aspects of autism? Any correlative types of 
things that deal with autism and the environment?
    Dr. Schwartz. I agree with you entirely. I think a very 
important area of health research in the United States, with 
the changing patterns of disease. It looks like environment is 
playing an important role in terms of increasing the risk of 
developing disease, the patterns of disease, the severity of 
disease, or the type of disease that children are presenting 
with. Because we recognize that, we have been working in a very 
focused way to address this issue of autism. In fact, we've 
increased our funding from 2006 to 2007 from $1.8 million to 
$3.5 million in the area of autism.
    We have a new study that we are funding at the University 
of California in Davis, UC Davis.
    Senator Harkin. Just stop right there a second. Okay, tell 
me again, how much you're spending this year, on autism?
    Dr. Schwartz. In 2007, $3.5 million.
    Senator Harkin. That's all you're spending on looking at 
environmental aspects of autism? Is that what you're saying?
    Dr. Schwartz. That's correct.
    Senator Harkin. Out of $637 million?
    Dr. Schwartz. That's correct. As I said, we have doubled 
the amount from 2006 to 2007.
    Senator Harkin. Okay, but I'm just wondering why we haven't 
been doing more before that. I'm always interested when people 
tell me they've doubled, or something's gone up by 100 percent, 
I always try to remember, and remind people that zero to 1 is 
an infinite increase. So, it depends on where you're starting 
from.
    Dr. Schwartz. In the climate of a flat budget, we have 
increased the investment in this area, because we recognize the 
importance of this. So, let me just tell you the things we're 
doing, and that we're planning to do, because I think it really 
gets at your questions which are, what will our investment be 
over the next several years, and how seriously do we take this 
disorder?

                            AUTISM RESEARCH

    In terms of the $3.5 million, we just initiated a very 
large, prospective study of children at risk of developing 
autism to try to identify the factors that pre-date the 
development of autism to understand the biological signals, and 
also the genetic factors, as well as the environmental 
exposures, that are related to the development of autism.
    That's one thing. The second thing is that we're working 
with the Centers for Disease Control to make their panel of 
exposure measurements, which constitutes about 150 biological 
exposure measurements, available to these long-term 
epidemiological studies to try to understand whether pesticides 
in the blood, or solvents, or metals in the blood are related 
to the risk of developing autism in these populations that have 
already been established.
    The third thing that we have done is we recently helped 
develop a conference with the Institute of Medicine focusing on 
the environment and autism. Dr. Alexander was involved in that 
conference. Dr. Insel, Director of the National Institute of 
Mental Health, was also involved in that conference, and we 
identified several areas of potential collaborative activities 
in the area of autism that we want to pursue further. So, we're 
currently in discussions with the National Institute of Mental 
Health--one other thing, we are newly supporting this year are 
the Autism Centers of Excellence. One of those Centers will be 
supported by NIEHS. That will be in the 2008 budget, so that is 
not counted in the $3.5 million.
    Now, one of the areas we're developing in collaboration 
with the National Institute of Mental Health is to take our 
Environmental Health Science Centers and when they are co-
localized with the Autism Centers of Excellence, we will 
provide extra support for those two areas of expertise, to 
collaborate effectively on how the environment is affecting 
autism.
    Senator Harkin. Okay. In a recent issue of Discover 
Magazine, I think there was a cover story on autism, yes, and 
it had an interesting map. This was of the State of Texas, and 
it had a map of the State of Texas, like three maps. One showed 
the number of reported cases of autism in young children. I 
think it was, maybe, 10 years ago. I could be off on that, but 
some time ago. The next map showed the use of, by county by 
county, it was a map of the counties of Texas. I think it was 
EPA data showing the amount of, levels of, I don't know if they 
were carcinogenic, but of different compounds in the 
environment that was, sort of, toxic. It had a lot to do with, 
I think, petrochemicals. It had a lot to do with pesticides, 
herbicides, a whole panoply of things, a whole bunch of things.
    Then, the next map showed the increase in the rate of 
autism. You overlay that map and it is just amazing. It's just 
about the same. So again, this is your department, right?
    Dr. Schwartz. That is correct.
    Senator Harkin. It seems to me that you really ought to be 
really pushing the envelope on this to try to find these kind 
of patterns and getting more scientists involved and getting 
more grants. I don't know what the rate or what the kind of 
proposals that are coming in that actually get through the peer 
review process. I would be interested in knowing what 
percentage or how many of the peer reviewed client proposals 
that come through, requests that come through to study the 
environmental aspect of the impact on autism. How many of those 
are being granted?
    Dr. Schwartz. A great question.
    Senator Harkin. Is it 15, is it 20?
    Dr. Schwartz. We can provide that information to you.
    [The information follows:]

               Success of NIEHS Autism Grant Applications

    The NIEHS received eight research applications for projects 
focusing on autism in fiscal year 2006. Three of the proposals, or 37.5 
percent, were funded. This percentage is substantially higher than the 
success rate of the overall NIEHS portfolio and demonstrates the 
Institute's commitment to autism research as a program priority.

    Dr. Schwartz. It is more than 20 percent. It's probably 30 
or 40 percent. I think we are looking at this as a challenge 
and also an opportunity for the field of environmental 
sciences.

                               THIMEROSAL

    Senator Harkin. Are you looking, there was for some time 
this thought that Thimerosal was a leading cause. Medical 
professionals and researchers said that that's not the case. 
CDC basically testified that they did not think there was a 
correlation there, but there's other thoughts that it's the 
amount of vaccinations that are given to kids before the age of 
2. Now, it's like 25 or 26 or something like that.
    Do you know, Dr. Alexander?

                             IMMUNIZATIONS

    Dr. Alexander. If you add all the diseases together and the 
number of immunizations you get for each one of them, that's 
about the right ballpark.
    Senator Harkin. Somewhere between 20 and 30. I know my 
grandson, they're just wrestling with that right now, but this 
is something relatively new. I mean new in the last 20 years or 
so. We never did that before.
    Dr. Alexander. But, there's been no thimerosal in any of 
these vaccines for the last 5 years.
    Senator Harkin. Not the thimerosal, I'm just saying maybe 
it's the number of these and the cumulative effect it has. As 
you said, these are not just little adults. Everything is 
different in a baby and you're talking about giving between 20 
and 30 immunizations between, before they're 2-years-of-age. 
There's some thought that maybe just the accumulation of that 
may have some affect on autism.

                       NATIONAL CHILDREN'S STUDY

    Now again, I don't know and I don't know if any research is 
being done into that either through you or through you.
    Dr. Alexander. Let me tell you something that is about to 
be done. It's a payoff benefit from the National Children's 
Study that you made reference to earlier. NIEHS and EPA and CDC 
are joined with the NICHD and many other institutes in the 
planning for this study. One of the things that will be looked 
at as a key outcome is autism. With a prevalence of six per 
thousand, we will have 600 kids and 99,000 controls. So, we 
will have information on these children including DNA from both 
parents and the child and siblings, we will have prenatal 
exposures of the mom to a large number of environmental factors 
and toxins and substances and so forth. We will be sampling the 
child from birth with umbilical cord blood etc. and we will be 
following the environment that the child lives in, measuring 
environmental exposures. We will measure the vaccinations and 
immunizations the child gets, the whole course of their medical 
history.
    Senator Harkin. Are you talking about the children study?
    Dr. Alexander. Yes.
    Senator Harkin. That longitudinal study?
    Dr. Alexander. Right, and that will be providing us with 
this information that there is no other source to get. It will 
all be obtained prospectively and we'll be able to analyze, not 
just one thing at a time, but we'll be able to analyze gene-
environment interactions, the interactions between different 
environmental exposures and each other, and we will be able to 
look at that in relationship to family history.
    You made reference earlier with Dr. Kirschstein as to 
whether there were genetic variations and susceptibility to 
things, this is one of the things we'll be able to look at in 
the National Children's Study with validity, because it's 
collected prospectively, and we have a large sample size of 
100,000 children 200,000 parents.
    Senator Harkin. Okay, since we're on that--as you know, 
I've been a strong supporter of that, and we put the money in 
this year to continue that again. Where are we on this 
children's study? How far along are we in terms of identifying, 
fitting that 100,000 pool?

                             NCS STUDY PLAN

    Dr. Alexander. Okay, with the funding that you provided 
this year, the $69 million that you added to the appropriations 
for 2007, we will be recruiting the first one-third of the 105 
sites around the country who will be conducting the study. 
Those will be funded by September 30. That is $32 million of 
the funds that you provided. The 7 Vanguard centers that have 
been funded for the last year and a half to start some of the 
piloting for this study will be funded with about $20 million 
this year to markedly expand their efforts and get them ready, 
so that they can start to actually enroll subjects for the 
study, for the pilot phase by July 2008.
    The following year, another third of the sites will be 
added, then the following year, another third. So, we will be 
actually starting the actual recruitment of the full study 
cohort in 2009, with a pilot cohort from the Vanguard sites in 
July 2008. We also will be using the funds to set up the sample 
repository center, the laboratories that are going to be doing 
the analyses, the informatics and data collections systems, all 
of which will be electronic, so that those funds are going to 
be put to good use in 2007.
    Senator Harkin. Well, that is encouraging, and we need to 
move ahead as aggressively as possible, and I would like to 
know from you if the funding levels are adequate to move it as 
aggressively as possible? I know these things--some of these 
things take time, and no amount of money can move some of these 
things, because you just have to set up the structures, and 
have to identify the people and that kind of thing. But I would 
like to know whether or not we can move more aggressively on 
that.

                            AUTISM RESEARCH

    But I want to make the point that we shouldn't, Dr. 
Schwartz, that we--both Dr. Alexander--that we shouldn't have 
to just wait 10 or 15 or 20 years to get data and information 
from the children's study.
    Dr. Alexander. We will have all of the kids with autism 
diagnosed by age 3, so we don't have to wait 15 years. We'll be 
doing those analyses as quickly as we can have the data 
available.
    Dr. Schwartz. That is precisely why we're funding focused 
studies on the environment and autism today.
    Senator Harkin. Yes, that's my point, we can't just wait.
    Dr. Schwartz. We initiated a cohort study in October 2006--
that's $1.5 million each year to support a study that focuses 
on children at very high risk of autism, and looks at 
environmental causes of autism in relation to the development 
of the disorder.
    Senator Harkin. When you say environmental, that also might 
include immunizations?
    Dr. Schwartz. Absolutely, absolutely. Also thimerosal.
    Senator Harkin. But we don't use thimerosal any longer.
    Dr. Schwartz. So we do have studies. The thimerosal 
question is not completely a moot issue, and we have studies 
that are looking at the relationship between mercury and brain 
damage in primates and in animal models, and we're still in the 
process of doing that research.
    Senator Harkin. I thought it was a well-known fact that 
mercury in the bloodstream does affect the brain.
    Dr. Schwartz. It does affect the brain. The question is, 
does it affect the brain in terms of the risk of developing 
autism.
    Senator Harkin. I don't know the answer to that question, 
obviously. Okay, I just, again, need to keep--I want you to 
keep us up to speed, and keep my staff up to speed on what your 
Institute is doing in this area of autism.
    Dr. Schwartz. We can provide you that information.
    [The information follows:]

                         NIEHS Autism Research

    NIEHS is actively investigating possible environmental factors in 
autism risk, including studies of gene-environment interaction. These 
are some of the projects being funded:
  --The NIEHS Center for Children's Environmental Health and Disease 
        Prevention Research at the University of California (UC) Davis 
        is building on its earlier finding of immune dysfunction in 
        autism and is currently focusing on the interplay of immune, 
        genetic and environmental factors in autism susceptibility.
  --NIEHS is expanding support for continuation of enrollment in 
        another large, ongoing study at UC-Davis (CHARGE) to provide 
        the ability to detect gene-environment interactions in distinct 
        subgroups of children.
  --An epigenetic study of genes implicated in autism and their 
        interactions with neurotoxicants is also being conducted at UC-
        Davis.
  --NIEHS is funding a promising project at Johns Hopkins to develop a 
        sensitive biomarker for the immunotoxic effects of mercury (and 
        use it to compare families with and without autism).
  --NIEHS helped to plan and conduct the recent Institute of Medicine 
        workshop on Autism and the Environment: Challenges and 
        Opportunities for Research to examine the most promising 
        scientific opportunities for improving the understanding of 
        potential environmental factors in autism.
  --The NIEHS is contributing funding for the Autism Centers of 
        Excellence. Some funds are being committed in fiscal year 2007, 
        and a larger investment is planned for fiscal year 2008.
  --NIEHS plans to fund a new 5-year prospective cohort study of 
        pregnancies at high risk for autism beginning in fiscal year 
        2008.
  --NIEHS is a contributor to the National Database for Autism Research 
        (NDAR). The initial phase is focused on developing a clinical 
        module which will serve as a data repository for the ACE 
        investigators. The plan is ultimately to expand the NDAR to 
        other investigators and other types of autism research beyond 
        clinical research. NIEHS contributed $250,000 in fiscal year 
        2006.

                            ASTHMA RESEARCH

    Senator Harkin. Asthma--more and more kids getting asthma, 
it's amazing. But tracking with autism, what is going on? Why 
are so many kids getting asthma today, what's happening?
    Dr. Schwartz. Asthma is a classic example of a disease that 
is clearly increasing in prevalence, and our genetics are not 
changing to alter the risk of developing the disease, so the 
environment is contributing substantially to the risk of 
developing asthma. Environments like the environment in New 
Orleans, environments that are heavily contaminated with micro-
organisms, are risky, environments for the development of 
airway inflammation. That is one of the reasons that we're 
studying that population very carefully, to try to identify 
ways in which we can intervene to decrease the risk of asthma.
    Senator Harkin. I can't tell you how many people I've 
talked to in the last several years that come up to me and, in 
different settings, and have said, ``You know, I've never had 
allergies before I came to Washington, DC.'' That, a lot of 
people say that. There's something happening around here, I 
don't know what it is.
    Dr. Schwartz. There's a very interesting process that's 
occurring. There's definitely an interaction between airway 
inflammation that is caused by environmental pollutants, and 
the risk of developing allergic responses in the body. We're 
spending $40 million a year on our asthma portfolio. So, this 
is something we're actively engaged in to try to understand how 
these air pollutants are altering----
    Senator Harkin. When you say asthma, that's allergies also, 
right?
    Dr. Schwartz. There is a non-allergic form of asthma as 
well. Individuals who work in the hog industry can develop 
asthma caused by microbial contamination alone without any 
allergic response. They develop the same exact symptoms and 
signs of asthma that someone who has allergic asthma.

                        HEALTH EFFECTS OF NOISE

    Senator Harkin. One other area I want to cover with you, 
Dr. Schwartz, before I leave you here is, you didn't cover it 
in your thing, and I want to know if your Institute covers 
this--noise. Noise, the environmental aspects of noise, and 
what it is doing to kids today, and all of us. The noise levels 
we're subjected to all of the time, whether it's jet aircraft, 
automobile noise, just the noise around, is phenomenal. Kids 
with those plugs in their ears, listening to their iPods, and 
you don't know what volume you've got them cranked up to, but I 
suspect the volume--the more the volume gets cranked up, the 
more they lose their hearing. They keep cranking it up all of 
the time. So, talk to me about what your Institute is doing in 
looking at the environmental aspects of noise, and its effect. 
Its behavioral effect, not just the effect on loss of hearing, 
maybe neurobiological types of effects it might have on an 
individual, are you looking at that?
    Dr. Schwartz. We have a relatively small portfolio in terms 
of noise, and the portfolio that we have in relation to noise 
relates to occupational or excessive environmental exposures to 
noise.
    The Dr. Battey's institute.
    Senator Harkin. The National Institute on Deafness.
    Dr. Schwartz. They're looking at the pathophysiologic 
effects of noise.
    Senator Harkin. That's what he's looking at. I'm just 
talking about the environmental aspects, and how that impacts. 
Are you coordinating with them on that?
    Dr. Schwartz. Any time we have an opportunity to, we do. I 
don't know the specifics, and I can get that specific 
information back to you, in terms of what studies are being 
supported by NIEHS, and what studies are coordinated with the 
other institutes. I just don't have that information for you.
    Senator Harkin. Well, give us some information on what 
you're looking at in terms of noise, and what kind of research 
you're doing in terms of the effect of noise on our bodies, on 
our physiological things, and what happens with behavioral 
aspects of noise.
    Again, I read these articles in Science magazine, I read 
about certain thoughts that a lot of this noise is causing 
people to behave in odd ways. Maybe altering brain patterns and 
brain waves. I don't know. I'm just saying there's some bits 
and pieces, some research in different places going on about 
this, and I don't know who, among all of your institutes out 
there, covers this. If it's not you--I don't know if it's Dr. 
Battey or not. I would like to find out that answer. But it 
seems to me it is an environmental aspect.
    Dr. Schwartz. I'll get you that information.
    [The information follows:]

            Research on the Health Effects of Noise Exposure

    Environmental noise is certainly a ubiquitous exposure and one that 
is understudied. A recent review \1\ of the published literature 
underscores the difficulty of conducting this research. Both active 
coping strategies employed by noise-exposed people as well as 
subconscious physiological adaptation to noise complicate the ability 
to perform good studies. Furthermore, clinical expression of these 
stress reactions in the form of symptoms can take many years to occur. 
In reviewing the existing work, the authors state that:
---------------------------------------------------------------------------
    \1\ Stansfeld SA, Matheson MP, 2003. Noise pollution: non-auditory 
effects on health. British Medical Bulletin 68: 243-257.

    ``The evidence for effects of environmental noise on health is 
strongest for annoyance, sleep and cognitive performance in adults and 
children. Occupational noise exposure also shows some association with 
raised blood pressure. . . . The effects of noise are strongest for 
those outcomes that, like annoyance, can be classified under `quality 
---------------------------------------------------------------------------
of life' rather than illness.''

    That said, the authors also recognize that ``the interaction 
between people, noise and ill-health is a complex one,'' and that 
further study is needed. It may be that adaptation to noise carries its 
own health costs, or that noise can combine with other physiological or 
chemical stressors to lead to greater health impacts than noise 
exposure alone.
    NIEHS has funded research in the past on effects of noise (with or 
without concomitant ototoxic chemical exposure) on hearing loss. 
Current research applications on noise exposure resulting in hearing 
loss are typically assigned to the National Institute on Deafness and 
Other Communication Disorders. NIEHS has also funded research looking 
at effects of noise-induced stress on intestinal disease and presence 
of reactive oxygen species in rats. No specific noise-related 
solicitations are planned in the current budget, but investigator-
initiated grants would be welcomed and carefully considered. In 
addition, noise is an exposure category proposed for study in the 
National Children's Study, for which NIEHS has been a contributor of 
both funding and expertise through the planning phase.

    Senator Harkin. I'd like to kind of know who's looking over 
that.

                     AGE-RELATED EYE DISEASE STUDY

    Dr. Sieving, you mentioned the AREDS Study. It showed that 
certain supplements, beta-carotene, Vitamin C, and E, and Zinc 
can slow the progression of AMD, macular degeneration. Well, 
okay, so that's useful once a person has been diagnosed with 
AMD, is that right? But how about before? Is there any evidence 
that these can help prevent a person from getting AMD in the 
first place? Also, direct yourself to the use of lutein, I 
don't know if you mentioned that or not, but is there not some 
scientific evidence that lutein acts as a preventative, or is 
there not?
    Dr. Sieving. Those are very interesting questions. As you 
have stated, the first AREDS study explored anti-oxidants, 
principally, Vitamins A, C, E, and some minerals. The design of 
the study--when you don't know what the answer will be, you 
have to design a question that will get you the first phase of 
it, and the first phase of the answer was to look at the 
conversion from early stage AMD to later stage AMD, and it was 
found that these factors--anti-oxidants--were effective in 
slowing, retarding that progression.
    Senator Harkin. When you said delay, by 25 percent, delay 
for how long? 1 year? 2 months? 5 years?
    Dr. Sieving. That would be the perspective you and I would 
have as the person taking it, in terms of delaying, or 
decreasing the conversion from one State to another. That is a 
population statement. So it is slowing the conversion rate. The 
actual delay in time is the more difficult question to get at.
    Senator Harkin. You're saying the 25 percent of the 
population had a delayed onset?
    Dr. Sieving. That's correct, yes.
    Senator Harkin. I still don't know how much of a delayed 
onset, or did it just vary?
    Dr. Sieving. The slope, as you look at time. The proportion 
of individuals who went on to develop AMD over this 5-year 
interval was about a 25 percent reduction. So, one can think in 
terms of years of putting off the conversion for some 
individuals. The study was not sensitive at the level of 
asking, is it going to help people who have not yet been 
identified or diagnosed with some early stage of AMD.
    Senator Harkin. Now, are these helpful in preventing, how 
about lutein?
    Dr. Sieving. The question of lutein is the subject of the 
next phase of this called AREDS 2. It's lutein, zeaxanthin and 
the fish oil, omega-3 fatty acid or fish oil, DHA. So, we hope 
that we will have an answer in a few years on your question of 
lutein.
    [The information follows:]

                            Lutein Research

    NCCAM has funded an exploratory study at the Johns Hopkins 
University to investigate the effects of lutein, an antioxidant that is 
part of the carotenoid family, to address retinitis pigmentosa, which 
is an eye disease that causes loss of night vision and peripheral 
vision, and, possibly blindness. Currently, NCCAM has no ongoing 
research on lutein.

    Dr. Sieving. There is the expectation, at least, in part of 
the practicing community of physicians, ophthalmologists, that 
lutein is beneficial in retarding the conversion to active 
vision loss from advanced AMD, and that's the reason for doing 
the study.
    Senator Harkin. Dr. Kirschstein, do you know if NCCAM is 
doing anything in that area?
    Dr. Kirschstein. I do not know. I will check on it, but I 
don't think so. I think Dr. Sieving, the Office of Dietary 
Supplements may also be doing some things, and of course, 
anything that they fund, would be in conjuction with NCCAM, or 
other ICS. They do not have the authority to fund grants.

                              GENE THERAPY

    Senator Harkin. Good point. Well, and also--I understand 
that more dogs have joined Lancelot.
    Dr. Sieving. Nearly 50.
    Senator Harkin. Nearly every year, I keep hearing they're 
now going to move into primates. And then I heard recently they 
were actually going to start doing this gene therapy in humans, 
where are we?
    Dr. Sieving. Well, I'm pleased to tell you, on the 
international world scale, we have crossed your threshold of 
moving it to people. There are four groups internationally, two 
in this country, one in France, one in England, considering the 
question of whether gene delivery into people will restore 
vision, will do something beneficial for vision. And the first 
of the groups to accomplish this is in London at the Institute 
of Ophthalmology. A scientist by the name of Robin Ali, who, I 
think it would now it would be 3 months ago, had done the 
injections of this gene construct called RPE 65, in two 
individuals to my knowledge. Looking forward in future attempts 
over the next 2 months, we can expect similar experiments to be 
done in Senator Specter's home State at the University of 
Pennsylvania. That study has been funded by the American people 
through the NIH National Eye Institute, and we will have a 
second opportunity to see whether there is benefit to doing 
this gene therapy in people.
    Senator Harkin. So again, just to make sure I understand 
this, a couple of people have already been, already agreed to 
undergo this gene therapy in London? This year you will have 
some more people who will be willing to undergo this, here in 
the United States?
    Dr. Sieving. That is correct. Just for the others around 
the table, the condition that is being treated is a form, a 
genetic form, of childhood blindness. In this case, the absence 
of an enzyme, genetic absence of an enzyme called RPE 65, the 
lack of that enzyme prevents the retina from responding to 
light, and hence, the individual has no vision, and is blind. 
When that was done in Lancelot, who you met, that dog has this 
RPE 65 deficiency, and by injecting the gene construct into 
that dog, the dog can now nearly play Frisbee with you, and can 
certainly walk the halls of Congress and look at you. That is 
an extremely exciting possibility.
    As I think about opportunities to move forward on an 
experimental basis, on gene delivery as a concept in medicine, 
this is a designer circumstance to try.
    Senator Harkin. So, the first humans in the United States 
will be at the University of Pennsylvania, is that what you 
said?
    Dr. Sieving. Yes, it's a consortium between Pennsylvania 
and Florida.
    Senator Harkin. How many, do we know?
    Dr. Sieving. It will be a handful. The question the first 
time through is, one can think of this on two planes, one can 
think of the people who could potentially benefit, we hope they 
do, and it will be a small number. On the other side, this will 
be a big advance, like a moon shot to get a person to the 
moon--this is a big advance for the concepts and the validity 
of gene therapy, if these experiments are successful.
    So, we're hoping.
    Senator Harkin. So, will this be publicized? I mean, I 
would be interested in finding out how soon after a person--and 
I don't even know the process, how many injections they have to 
have?
    Dr. Sieving. One.
    Senator Harkin. Just one? Just one? I thought it was a 
pattern you had to go through.
    Dr. Sieving. No, the delivery of genetic material is 
courtesy of a virus, an adenor virus. Once that virus 
introduces the gene into the cell, it persists there. In the 
case of Lancelot, Lancelot had one injection, now some 5 years 
ago, and this dog is still seeing. So, it would be one 
injection.
    Senator Harkin. How soon after that injection would we know 
whether or not it worked?
    Dr. Sieving. Well, in the mouse, the biology in the mouse 
says that within 60 days or fewer, the transfer of the gene 
into the cell and the activity in the cell can make this 
protein. So, it should be short order, it should be on the 
order of weeks to months.
    Senator Harkin. But you don't know when this is going to 
happen.
    Dr. Sieving. We have a good idea of when it will happen.
    Senator Harkin. Is it this summer?
    Dr. Sieving. We expect this summer. Obviously, for 
something like this, we are helping to take a close and careful 
look at the safety, getting the trial started, and the first 
outcome of the study will be announced as a safety outcome. If, 
in fact, the individual recovered some form of vision, that 
would be a bonus, and quite a delightful bonus.
    Senator Harkin. That's very informative. I appreciate that. 
We will be following that.
    Dr. Sieving. We will keep you informed, obviously.
    Senator Harkin. We'll follow that very closely.

                             READING FIRST

    Dr. Alexander, I know time is running out, and I have to 
leave here in a few minutes, but I just wanted to go over one 
thing with you.
    NICHD's involvement in a program called Reading First, a 
lot of congressional interest in this area. Education's 
Inspector General found the Department officials mismanaged the 
program, steered school contracts to publishers they favored 
away from others, flagrantly ignored Federal laws on 
maintaining local and State control of school curricula. Not 
me, that's the Inspector General of the Department of Education 
said that, and we've been looking into it.
    As to be expected, the Education Inspector General focused 
mainly on the activities of the Education Department employees, 
but a former NICHD researcher named Reid Lyon also played a 
huge role in how Reading First was implemented. Lyon, a reading 
specialist, was the Chief of the Child Development and Behavior 
Branch under you. According to one news article, he said he 
spent more than half of his time between 2002 and 2004 on 
Reading First. E-mail showed that he frequently advised the 
Reading First Director Mr. Chris Doherty on how to run the 
program. He wasn't simply offering general advice, there were 
detailed discussions about how particular districts were using 
Reading First grants. We also know that Dr. Lyon wrote on 
numerous occasions to Margaret Spellings, the current Secretary 
of Education when she was Domestic Policy Advisor at the White 
House on this program.
    Now, again, I can understand that an NIH researcher who's 
an expert on reading might occasionally be called upon by the 
Department of Education to offer some expert advice when 
they're called upon. But, I don't expect someone like that to 
spend more than half of his time trying to advise another 
agency on how to run their programs, it doesn't smell right, 
there's something wrong there.
    Now, again, I know that Dr. Lyon is no longer there, he now 
works for a for-profit education company. That's fine, if he 
wants to be an advocate for that, that's what he should be. So, 
I would hope that the Chief of the Child Development and 
Behavior branch would have other things to do than like this.
    So now, again, we have a replacement coming up. Has that 
replacement been named yet?
    Dr. Alexander. Yes.
    Senator Harkin. Oh, you do have a replacement?
    Dr. Alexander. For Dr. Lyon, as chief of that branch? Yes. 
Dr. Peggy McCardle. She's been in there as branch chief for 
almost 2 years.
    Senator Harkin. Two years? I didn't know that. Is this 
person spending more time, spending half his time on Reading 
First?

                         READING FIRST SCIENCE

    Dr. Alexander. No, I think she's spending virtually no time 
on it. Dr. Lyon's time when he was involved with this, was when 
he was on detail to the White House, and was not in charge of 
the branch. Basically, that was turned over to Dr. McCardle on 
an acting basis. I have no direct knowledge on what Dr. Lyon's 
interactions were, specifically. I know that he was called upon 
frequently by the Reading First program, and the Department of 
Education in other areas as well, for advice on the scientific 
basis for different types of approaches to reading instruction. 
The legislation related to Reading First required that the 
programs have demonstrated efficacy in a scientific fashion, of 
their effectiveness in being able to result in children 
learning to read in an effective way.
    Much of the question that came to Dr. Lyon, in my 
understanding, was in terms of whether programs that were 
proposed for use in Reading First were, in fact, scientifically 
validated, research-based programs, and the advice that he 
provided was evaluating the quality of the science that was 
done in evaluating those programs. Sometimes it was very weak 
science, weak to none. Other programs have been very thoroughly 
and rigorously evaluated, and to my knowledge, and what we 
really have the authority and authorization to do, was to 
provide information and advice as to the scientific validity of 
these programs. How rigorously have they been evaluated for 
their effectiveness as a teaching method? That was a 
requirement in order for them to be funded as part of Reading 
First.
    So, that was the nature of the interaction, to my 
knowledge.
    Senator Harkin. Well, I know that, because I was very much 
involved in writing that law.
    Dr. Alexander. You were, indeed.
    Senator Harkin. In the other hat I wear on the other 
committee, and I had been following this very closely with my 
staff, and a number of these programs in a certain State were 
scientifically valid, they were passed, the scientific reviews 
and all of that. But a funding pattern emerged, that when these 
programs were evaluated and it all came down, that they had to 
use this one program, this one certain program, all of these 
things seemed to trace back, in many ways, to Dr. Lyon.
    I thought that was an odd situation, that someone from NIH 
would be so heavily involved in trying to choose one over the 
other, when they were basically scientifically validated, and 
saying, ``Well, yeah, they may be scientifically valid, they 
may all meet the scientific requirements, but this one is 
best.'' That is not--that was never, that should never have 
been his job.
    That's sort of water over the dam, but I just, again, I 
hope that we don't go through that again. It was kind of 
disturbing to me to see that that had happened, and that is why 
I asked the question about the new replacement, which I didn't 
know was there, and how much they were spending. Like I said, I 
don't mind if they're called upon for expert advice, I mean, 
that's fine--that is what they should be doing. But it seemed 
like he went overboard in being involved in how this was being 
run.

                        SPINAL MUSCULAR ATROPHY

    The last thing I wanted to cover with you is SMA. As you 
know, I've been very much involved with this ever since I first 
learned its leading genetic cause of death in small kids, and 
then how much we were looking at it, and you and I talked about 
this before, on SMA, and I've talked to Dr. Landis about it, 
also. I talked about this with Dr. Landis just a few weeks ago, 
there's some breakthrough work that NINDS is doing in this 
area.
    But, you have funded, as I understand, two small grants on 
SMA in the past few years. Since it is a leading genetic cause 
of death to infants and toddlers, I think I would have expected 
that NICHD would take a larger role than it has thus far, so 
I'm just wondering, where are you in SMA research in the coming 
year?
    Dr. Alexander. Well, last year, we funded four grants, or 
parts of four grants, focusing largely on improving newborn 
screening, and developing the capability for doing newborn 
screening for the disorder, and we additionally funded two 
grants that came in, in response to our program announcement 
for developing new therapeutic approaches to disorders that 
could potentially be diagnosed by newborn screening.
    The best progress we have to report is that in one of the 
grants, Dr. Tom Pryor at Ohio State has, in fact, developed a 
very successful approach to newborn screening for SMA. With the 
technology that he has, he's gotten samples from the filter 
paper blood spots like I just handed out to you, several 
hundred with SMA, several hundred carriers, and several hundred 
normals. They have 100 percent success in diagnosing every case 
of SMA, 100 percent success in identifying every carrier, 100 
percent success in determining unaffected individuals.
    He's also developed a methodology for incorporating this 
onto the luminex-bead system, which is one of the systems we're 
testing for new applicability. The SMA community is so excited 
and enthusiastic about this, that they've actually petitioned 
the Secretary's Advisory Committee on screening of infants and 
children for genetic disorders for inclusion of this in newborn 
screening regimens.
    So, we are very excited about this approach, we think this 
is probably going to be the one that can be incorporated, it 
can be done in a very cost-effective way, and that we will have 
the newborn screening, and as the SMA advocacy groups point 
out, all of the evidence is that it is essential to begin 
treatment at birth, or as close to birth as possible. Because 
the moms protect the fetus during development, these babies are 
pretty much okay at birth. If we can get the treatment to them, 
and have an effective treatment, that is going to be key.
    We also have two grants that are working on new treatment 
methodologies for this. There are two different approaches--one 
is to increase the production of a protein that doesn't work 
very well, another is to try and skip a codon, that is, 
blocking the formation of the normal proteins, so that we 
produce more normal protein. We're testing both of these, and 
we're hopeful that we're going to have, not just the prenatal 
diagnosis methodology, but a treatment methodology as well. 
That is where we are.
    Senator Harkin. That's good. That is good news. So that is 
what is going to be happening in the future.
    Dr. Alexander. Yes, we will continue with that.
    Senator Harkin. Now, I can't leave that without--one thing 
leads to another, don't you know? I learned about SMA and I get 
to learning about causes, and I meet with families, well then I 
start thinking about Fragile X Syndrome also, which is another 
one. Now I find out that's a leading cause of mental 
retardation, genetic cause of retardation. So, then I'm 
wondering, where are you going in that?

                   NEW APPROACH TO NEWBORN SCREENING

    Dr. Alexander. Similar story, we're working on newborn 
screening. We funded a grant several years ago, to develop and 
evaluate newborn screening for this condition, with the support 
of parents and advocacy groups. The test that we thought was 
going to work, didn't, another one that we thought was going to 
work didn't, we're now on a third approach to the newborn 
screening. This one looks like it's going to work, but we're 
still in the final testing for that. That is the essential 
component for that grant, in order to be able to diagnose this 
in newborns.
    In terms of therapy, we're farther away from that than we 
are, probably, with SMA. Although different approaches are 
being tried, we have nothing that looks real promising right 
now. But, the parent and advocacy groups still say we want to 
diagnose this in newborns, if at all possible, because we would 
like to be able to plan for these children, we'd like to 
intervene as early as possible with ancillary kinds of 
treatments, and we would like to know for our family planning 
purposes whether we have this problem, because these kids are 
often not diagnosed until 3, 4, 5, 6 years of age, and there's 
often another child born by then.
    Senator Harkin. Doesn't that, doesn't that gene just go 
through one parent or the other?
    Dr. Alexander. Yes, the mother.
    Senator Harkin. Okay, that's good information, that's good 
information. Okay, any last things before we all get out of 
here and go to lunch, or something like that? I want to thank 
all of you for coming down, it's been a good session. As I 
said, I always learn a lot of things at this, it's like being 
in class again.
    So, I thank you very much. Thanks for all of your 
leadership, Dr. Alexander. Thanks for the SMA work you're 
doing, we appreciate that. You're going to get back to me on 
some of this stuff.

                     ADDITIONAL COMMITTEE QUESTION

    There will be an additional question which will be 
submitted for your response in the record.
    [The following question was not asked at the hearing, but 
was submitted to the Department for response subsequent to the 
hearing:]

                Question Submitted by Senator Tom Harkin

                             DOWN SYNDROME

    Question. An estimated 350,000 Americans have Down syndrome. Yet 
the fiscal year 2008 proposed budget calls for spending just $13 
million on research concerning this condition--down 43 percent from the 
fiscal year 2003 level of $23 million. Why has funding for Down 
syndrome research declined so dramatically?
    Answer. The senator's funding figures for NIH-supported research on 
Down syndrome are correct. Although NICHD has the scientific lead on 
this issue, a number of other Institutes and Centers also contribute 
resources to address this condition. However, due to the competitive 
nature of the peer review process, the number of successful 
applications proposing research on Down syndrome has decreased, and 
thus funding contributed by ICs to such research has decreased.
    However, research on Down syndrome is an important part of NIH's 
research portfolio. In fact, to facilitate research on Down syndrome 
across the NIH, NICHD took the lead in pulling together a working group 
of these ICs in 2006. NICHD, NINDS and NIA form the steering committee 
for the group, which has been meeting regularly with the goal of 
producing a NIH research plan for Down syndrome in the fall of 2007. In 
addition to compiling the NIH-funded research in this area, literature 
reviews are being conducted so that new research is complementary and 
not duplicative. The working group sponsored two major scientific 
meetings, in March 2007 and July 2007, to get input from that 
community, as well as from national constituency organizations 
representing individuals with Down syndrome and their families. Input 
on the plan, which will address strategies for basic and clinical 
research on the genetics of Down syndrome, its developmental 
consequences, and its impact on cognition and synaptic function, will 
be actively sought prior to its publication.

                         CONCLUSION OF HEARINGS

    Senator Harkin. So, thank you all very much, that concludes 
our hearings.
    [Whereupon, at 12:07 p.m., Friday, June 22, the hearings 
were concluded, and the subcommittee was recessed, to reconvene 
subject to the call of the Chair.]
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