[Senate Hearing 107-655]
[From the U.S. Government Publishing Office]



                                                        S. Hrg. 107-655
 
                      PARKINSON'S DISEASE RESEARCH
=======================================================================




                                HEARING

                                before a

                          SUBCOMMITTEE OF THE

            COMMITTEE ON APPROPRIATIONS UNITED STATES SENATE

                      ONE HUNDRED SEVENTH CONGRESS

                             SECOND SESSION

                               __________

                            SPECIAL HEARING

                      MAY 22, 2002--WASHINGTON, DC

                               __________

         Printed for the use of the Committee on Appropriations


 Available via the World Wide Web: http://www.access.gpo.gov/congress/
                                 senate

                                 ______




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                      COMMITTEE ON APPROPRIATIONS

                ROBERT C. BYRD, West Virginia, Chairman
DANIEL K. INOUYE, Hawaii             TED STEVENS, Alaska
ERNEST F. HOLLINGS, South Carolina   THAD COCHRAN, Mississippi
PATRICK J. LEAHY, Vermont            ARLEN SPECTER, Pennsylvania
TOM HARKIN, Iowa                     PETE V. DOMENICI, New Mexico
BARBARA A. MIKULSKI, Maryland        CHRISTOPHER S. BOND, Missouri
HARRY REID, Nevada                   MITCH McCONNELL, Kentucky
HERB KOHL, Wisconsin                 CONRAD BURNS, Montana
PATTY MURRAY, Washington             RICHARD C. SHELBY, Alabama
BYRON L. DORGAN, North Dakota        JUDD GREGG, New Hampshire
DIANNE FEINSTEIN, California         ROBERT F. BENNETT, Utah
RICHARD J. DURBIN, Illinois          BEN NIGHTHORSE CAMPBELL, Colorado
TIM JOHNSON, South Dakota            LARRY CRAIG, Idaho
MARY L. LANDRIEU, Louisiana          KAY BAILEY HUTCHISON, Texas
JACK REED, Rhode Island              MIKE DeWINE, Ohio
                  Terrence E. Sauvain, Staff Director
                 Charles Kieffer, Deputy Staff Director
               Steven J. Cortese, Minority Staff Director
            Lisa Sutherland, Minority Deputy Staff Director
                                 ------                                

 Subcommittee on Departments of Labor, Health and Human Services, and 
                    Education, and Related Agencies

                       TOM HARKIN, Iowa, Chairman
ERNEST F. HOLLINGS, South Carolina   ARLEN SPECTER, Pennsylvania
DANIEL K. INOUYE, Hawaii             THAD COCHRAN, Mississippi
HARRY REID, Nevada                   JUDD GREGG, New Hampshire
HERB KOHL, Wisconsin                 LARRY CRAIG, Idaho
PATTY MURRAY, Washington             KAY BAILEY HUTCHISON, Texas
MARY L. LANDRIEU, Louisiana          TED STEVENS, Alaska
ROBERT C. BYRD, West Virginia        MIKE DeWINE, Ohio
                           Professional Staff
                              Ellen Murray
                              Jim Sourwine
                              Mark Laisch
                            Adrienne Hallett
                              Erik Fatemi
                       Bettilou Taylor (Minority)
                        Mary Dietrich (Minority)
                    Sudip Shrikant Parikh (Minority)
                       Candice Rogers (Minority)

                         Administrative Support
                             Carole Geagley












                            C O N T E N T S

                              ----------                              
                                                                   Page

Opening statement of Senator Tom Harkin..........................     1
Opening statement of Senator Arlen Specter.......................     3
Statement of Hon. Debbie Stabenow, U.S. Senator from Michigan....     4
Opening statement of Senator Patty Murray........................     5
Statement of Hon. Paul Wellstone, U.S. Senator from Minnesota....     5
Statement of Audrey S. Penn, M.D., Acting Director, National 
  Institute of Neurological Disorders and Stroke, National 
  Institutes of Health, Department of Health and Human Services..     6
    Prepared statement...........................................     8
Statement of Dr. Ole Isacson, director, Center on 
  Neuroregeneration Research, McLean Hospital and Harvard Medical 
  School.........................................................    13
    Prepared statement...........................................    14
Statement of Joan Samuelson, founder and president, Parkinson's 
  Action Network.................................................    17
    Prepared statement...........................................    19
Statement of Don Schneider, Parkinson's patient, Clinton, IA.....    21
    Prepared statement...........................................    23
Statement of Muhammad Ali, former heavyweight boxing champion, 
  accompanied by Lonnie Ali......................................    25
    Prepared statement...........................................    27
Statement of Michael J. Fox, founder, the Michael J. Fox 
  Foundation for Parkinson's Research............................    28
    Prepared statement...........................................    31
Prepared statement of Senator Thad Cochran.......................    42
Letter from Do No Harm: The Coalition of Americans for Research 
  Ethics.........................................................    42











                      PARKINSON'S DISEASE RESEARCH

                              ----------                              


                        WEDNESDAY, MAY 22, 2002

                           U.S. Senate,    
    Subcommittee on Labor, Health and Human
     Services, and Education, and Related Agencies,
                               Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 9:42 a.m., in room SH-216, Hart 
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
    Present: Senators Harkin, Murray, and Specter.


                opening statement of senator tom harkin


    Senator Harkin. Good morning, everyone. The Senate Labor, 
Health and Human Services, and Education Appropriations 
Subcommittee will now please come to order.
    Three weeks ago, this subcommittee held a hearing on 
Alzheimer's disease, a condition that destroys the mind while 
leaving the body basically intact. Today we will discuss its 
biological opposite, Parkinson's disease, a condition that 
destroys the body while the mind stays fully aware of what is 
happening.
    This is a devastating disease, as we will hear from our 
witnesses. But a cure is finally in sight. Scientists have made 
exciting advances against Parkinson's in the past year alone, 
particularly in the areas of embryonic stem cell 
transplantation, deep brain stimulation, and possible 
environmental and chemical causes of the disease. Many 
researchers believe that Parkinson's will be cured sooner than 
any other major neurological condition, possibly within the 
decade.
    This progress would not have been possible without the 
National Institutes of Health, which supports 11 Udall Research 
Centers across the country, among many other efforts to cure 
Parkinson's. Senator Specter and I have led the effort to 
double funding for the NIH over 5 years, and I am proud to say 
we will complete that goal this year.
    I am concerned, however, by the fact that NIH funding for 
Parkinson's has not kept pace with our doubling effort. This 
has occurred despite increasingly strong language in the Labor-
HHS appropriations bills. So, I will pay close attention to 
NIH's plans for Parkinson's research in the years to come.
    We have an outstanding panel of witnesses this morning. I 
would like to give a couple special welcomes, first to Don 
Schneider, who traveled here from my home State of Iowa to tell 
us about his experience with Parkinson's. Don, I thank you and 
your wife, Rita, for being with us.
    Of course, I would like to welcome the greatest, to me the 
greatest athlete, perhaps one of the greatest human figures of 
the 20th century, Muhammad Ali.
    Muhammad, your efforts to promote peace around the world 
and to help people in need are as legendary as your victories 
in the boxing ring. I know that I was, as much as anyone in 
this room and all over the world, so thrilled when you lit the 
torch at the Olympics. It brought back so many memories.
    I think one of the great legacies, Muhammad, of your life 
and your career is you teach people never to give up. If you 
get knocked down, get up and come back again. I think that is 
the hope and I think that is the courage that you give everyone 
in this room and everyone who is afflicted with Parkinson's. We 
may have had setbacks, but we are getting up and we are coming 
back again. So, we thank you for giving us that courage and 
that leadership. We are honored to have you here today.
    I also offer my warm welcome to Michael J. Fox. You may 
know him from Spin City and Family Ties or many successful 
films. But now that he has hit the New York Times Best Seller 
List with his memoir, titled Lucky Man, he may have found his 
true calling in being an author. Again, Michael Fox, thank you 
very much.
    We are also honored and fortunate to have with us today 
three former Senators. Let's hear it for Claiborne Pell, our 
former Senator from the State of Rhode Island.
    Next to him another great Senator, Charles Mac Mathias, of 
Maryland.
    And he could not be here, but his better half and someone 
who we enjoyed being with for so many years and still do, 
Carolyn Long, wife of former Senator Russell Long.
    Brock Adams was supposed to be here. I understand he is on 
his way, and I will introduce him when he arrives.
    All four of these Senators have Parkinson's. We miss them 
greatly here in the Senate, but we are honored that you could 
be here today.
    Finally, I would recognize one other special person, Ruth 
Kirschstein. Get ready, Ruth, because we have a surprise for 
you. Dr. Kirschstein began her career at NIH in 1956. She has 
held numerous positions there including Director of the 
National Institute of General Medical Sciences, Acting Director 
of the NIH, and her current position, Deputy NIH Director.
    Ruth is a visionary and has been a tremendous leader during 
her service at NIH, playing a key role in launching the Human 
Genome Project and promoting women's health research. 
Throughout her career at NIH, there is one thing she has always 
paid particular attention to and that is the next generation of 
scientists, building up programs that encourage our best and 
brightest to enter the field of medical research.
    So, it gives me great pleasure to announce this morning 
that Senator Specter and I, along with Chairman Regula and 
Congressman Obey in the House, have inserted language in the 
upcoming supplemental appropriations bill that will rename the 
National Research Service Awards program the Ruth L. 
Kirschstein National Research Service Awards.
    Congratulations, Ruth, and thank you for your decades of 
service to our Nation. We look forward to many years of 
continued service at the NIH.
    Now I would yield to my great friend, Senator Specter, for 
his opening remarks.


               opening statement of senator arlen specter


    Senator Specter. Thank you very much, Mr. Chairman, and 
good morning, ladies and gentlemen.
    This overflow audience is a testament to the importance of 
curing Parkinson's. It is a matter which this subcommittee has 
been working on very hard for many, many years. As Senator 
Harkin outlined, we set out to double the funding for the 
National Institutes of Health. It has been moved from $13 
billion to $23 billion, and the President has recommended in 
this year's budget an additional $3.7 billion; which will more 
than reach the doubling goal--possibly exceed our goal to 
double funding.
    People ask what is next, and I say: ``Well, the next step 
is to triple the funding for NIH.''
    We are a very wealthy country with a gross national product 
in the range of $10 trillion and a Federal budget in excess of 
$2 trillion. Also, it is a matter of establishing priorities, 
and there is nothing more important than health. The increase 
in funding has given the scientists the opportunity to do 
intensive research and clinical studies. The experts who 
appeared here recently from the National Institutes of Health 
on neurological diseases thought that we may have the cure for 
Parkinson's within 5 years. It is not a guarantee, but it is an 
estimate.
    We face a very difficult challenge, ladies and gentlemen. 
Now pending before the Senate, and up for a vote in the course 
of the next several weeks, is a procedure called nuclear 
transplantation. It is commonly referred to as therapeutic 
cloning, and that is a misnomer. It is not cloning at all. 
There is an agreement against cloning to create another person, 
but when you have the procedure nuclear transplantation, it is 
accomplished by taking the DNA, for example, from a person who 
has Parkinson's so that the stem cell is consistent with that 
person and will not be rejected.
    Regrettably the House of Representatives has criminalized 
this procedure which is, to my way of thinking, an absolute 
anathema, and we have to stop that in the U.S. Senate. When we 
have had crowds, audiences overflowing in this room on 
Alzheimer's and breast cancer and heart disease and many other 
ailments, Senator Harkin and I have sounded the bugle to have 
Americans tell their Senators not to criminalize an important 
medical procedure that may conquer so many, many diseases.
    That is what we are calling on today.
    There is a great deal more that could be said, but we have 
a very distinguished group of witnesses here today. As Senator 
Harkin has noted, we are especially grateful to Muhammad Ali 
and Michael J. Fox, who, when they come here, attract a lot of 
attention because there is so much admiration for what they 
have done. And that kind of attention stimulates public 
response to our call to influence Senators to allow us to 
continue the indispensable research to cure Parkinson's and 
many other maladies.
    When The Champ took his bow, he looked pretty strong to me. 
He looked pretty resilient. I think he might still go 10 rounds 
under the proper circumstances. See, there he goes.
    When we met in the back room, he walked in with Michael J. 
Fox, and I told him not to be too tough on Michael just because 
Michael was bigger and stronger than The Champ was.
    And we thank Michael J. Fox for all that he has done. He 
has been in this room on many occasions and his efforts have 
been very instrumental in leading this subcommittee to move 
ahead with the funding for the National Institutes of Health.
    So, we have come a long way, but we have got a long way to 
go, and our work is cut out for us. Anybody within sound of our 
voices, contact your Senators. Thank you.
    Senator Harkin. Thank you very much, Senator Specter.
    Although not a member of the committee, she wanted to be 
here to recognize her perhaps most famous constituent, Senator 
Stabenow of Michigan.
STATEMENT OF HON. DEBBIE STABENOW, U.S. SENATOR FROM 
            MICHIGAN
    Senator Stabenow. Well, thank you, Mr. Chairman. I also am 
here as a family member of a grandmother who had Parkinson's 
disease and want to thank you very much for your leadership, 
Senator Harkin and Senator Specter. I am committed to do 
whatever we need to do to get the job done.
    I am very much appreciative of the opportunity, before 
leaving to go preside over the session, to help introduce our 
most famous Michiganian in the world, from Berrien Springs, 
Michigan, Muhammad Ali and Mrs. Ali. Welcome. It is a great 
pleasure. We are very, very proud that you are Michigan 
residents. There is no question that from his career in the 
ring to his global diplomatic efforts to his many charities and 
philanthropic work, Muhammad Ali has been a role model to all 
of us. We in Michigan are particularly proud of that.
    I did want to comment, though, that particularly in the 
days after September 11, when fear really threatened to divide 
all of us, I was very proud that it was Muhammad Ali who 
stepped forward and issued a call for unity and tolerance. So, 
in addition to all that you are doing, in addition to the fact 
that you are here today, I have quoted you frequently in 
saying: ``Rivers, ponds, lakes, and streams, they all have 
different names, but they all contain water. So religions have 
different names, but they all contain the truth.'' So, I want 
to thank you for those words at a time that was very critical 
for our country.
    You have fought a lot of battles in a lot of rings, and I 
know that you are here today to focus on your greatest battle, 
the fight against Parkinson's disease, one that you share with 
millions of Americans. We want you to know that for those of us 
here today, we are in the fight with you and we thank you very 
much for your heart and your strength and your courage. Thank 
you.
    Senator Harkin. Thank you very much, Debbie.
    I would recognize Senator Murray for an opening statement 
and then Senator Wellstone.


               opening statement of senator patty murray


    Senator Murray. Thank you very much, Mr. Chairman, and 
thank you to your leadership, to Senator Specter, and to all of 
the people here who are fighting for such an important cause.
    As I have shared with you before, my father had multiple 
sclerosis and from the time I was 15 until he died a few years 
ago, my mother was his caregiver. We hold the hope that so many 
thousands of Americans do for research so that other families, 
other people do not have to live through the really tough, 
tough times that I have known and my family has known. But his 
spirit carries with me.
    I share all your hopes and dreams that stem cell research 
will provide the answers for so many people. We simply cannot 
allow political decisions to jeopardize what is out there, the 
promise of hope for so many families.
    So, thank you very much, and thank you to all of our 
witnesses today.
    Senator Harkin. Thank you, Senator Murray.
    Perhaps one of our strongest voices and supporters in this 
fight against Parkinson's, my neighbor to the north, Senator 
Paul Wellstone.
STATEMENT OF HON. PAUL WELLSTONE, U.S. SENATOR FROM 
            MINNESOTA
    Senator Wellstone. Thank you. Thank you, Mr. Chairman. I am 
not a member of the committee, and it is gracious of you to let 
me make an opening statement. I will stay under an hour for my 
opening statement.
    Senator Specter has been equally gracious.
    I think the only thing to say is I want to thank you, Mr. 
Chairman, for your commitment. I want to thank the panelists, 
and of course, Mr. and Mrs. Ali and Michael J. Fox, and Joan 
Samuelson, whom I have known for so many years. But I would 
like to thank everyone else. I see Senator Pell here and I just 
want to thank all of you who are here today. Thank you for your 
courage. Milly, thank you for being here. There are so many 
heroes and heroines.
    I think the one thing I want to say is that this hearing I 
approach with a sense of history because I do not think time is 
neutral, and I think it is terribly important. I had a chance 
to help write the Mo Udall bill, and we now have the Center of 
Excellence and the focus, but we need the resources. Time is 
not neutral. And everybody is here today to make sure that we 
have that research focus and that we find the cure. It is so 
important.
    And none of this would happen except for the fact--look at 
this room, Mr. Chairman. Look at all of the men and women who 
have had the courage to tell their own stories. Joan, look how 
far this has come. But the whole point is to now have the 
resources and to have the focus and to find the cure.
    I would like to thank everybody. It is an honor to be here.
    Senator Harkin. Thank you very much.
    There is just one other person I'd like to recognize before 
I go to Dr. Penn to lead off our witnesses--someone who is 
really in the forefront of this fight, giving voice to it by 
writing a wonderful book about his wife--Mort Kondracke. Mort 
Kondracke has been a great hero.
    We also are blessed to have with us the former staff member 
of Senator Claiborne Pell, who is now the Senator from Rhode 
Island, Jack Reed. Senator Jack Reed is here with us too.
    Now we will go to our witnesses. We have all of your 
statements. They will be made a part of the record in their 
entirety. I would ask if you could summarize your statements in 
less than 10 minutes. Then we can get into some questions.
STATEMENT OF AUDREY S. PENN, M.D., ACTING DIRECTOR, 
            NATIONAL INSTITUTE OF NEUROLOGICAL 
            DISORDERS AND STROKE, NATIONAL INSTITUTES 
            OF HEALTH, DEPARTMENT OF HEALTH AND HUMAN 
            SERVICES
    Senator Harkin. Again, Dr. Penn is the Acting Director of 
the National Institute of Neurological Disorders and Stroke. 
She was named the Deputy Director of NINDS in 1995. Dr. Penn, 
welcome to the committee.
    Dr. Penn. Thank you, Mr. Chairman. I am accompanied today 
by Dr. Diane Murphy, the Program Director in neurodegeneration, 
who is right behind me.
    I would like to share with you the NIH studies and plans 
for Parkinson's disease. NIH and particularly NINDS have been 
heavily invested in supporting critical research in Parkinson's 
disease for over 3 decades. Indeed, over fiscal years 1996 to 
2001, NIH funding for Parkinson's research rose by 126 percent 
and NINDS funding by 91 percent.
    We have supported the research which delineated the 
usefulness of L-dopa, mapped the critical brain circuits 
affected by Parkinson's disease, and developed critical animal 
models. NINDS expanded these efforts by establishing the Morris 
K. Udall Centers of Excellence for Parkinson's Disease 
Research, and these centers include investigators who are 
working on almost every area identified as a priority by the 
Parkinson's Disease Research Agenda, which was developed in 
2000, in collaboration with the research and advocacy 
communities, and we revisited it last January.
    Parkinson's, as many of you know and as was said, is a 
debilitating neurodegenerative disease caused by progressive 
loss of dopamine nerve cells in the brain regions that control 
movement. Abnormal protein aggregates, which are called Lewy 
bodies, are seen in dopamine nerve cells, and cardinal clinical 
signs are tremor, rigidity, and slow movements.
    Now, Parkinson's patients need therapies that can restore 
function and replace the missing nerve cells. Although 
levodopa, which replaces lost dopamine, restores function for a 
while, 75 to 80 percent of nerve cells are already lost when 
the first signs are evident. So, we need to protect, restore, 
and replace nerve cells in the specific brain centers.
    So, important new evidence has emerged which is converging 
to shed light on how these cells are damaged. The availability 
of families with multiple members affected with Parkinson's 
allowed identification of genes, and then the defective 
proteins now known to be important to mechanisms of normal 
protein clearance and also to degeneration in Parkinson's. The 
abnormal proteins in the familial forms fold into aggregates, 
accumulate in and are toxic to dopamine nerve cells.
    There is new evidence that rotenone, a commonly used 
pesticide which produces oxidative damage, also causes these 
proteins to aggregate, Lewy body-like aggregates, and damages 
dopamine nerve cells and causes severe loss of movement in 
rodents.
    So, based on the better information on the mechanisms of 
damage, we have funded the infrastructure for design and 
testing of drugs that have the potential for protecting 
dopamine nerve cells against the causes of Parkinson's by 
slowing the degeneration, and drugs chosen on the basis of 
pilot studies will ultimately move into large clinical trials.
    In the meantime, we are evaluating available results and 
promoting the clinical trials of deep brain stimulation, a 
surgical therapy that can achieve excellent control. DBS, 
however, involves implantation of electrodes into specific deep 
brain centers, and they have to be specifically implanted. It 
can be used on both sides of the brain, and it can restore 
nearly normal motor performance.
    We have helped to design a study initiated by the Veterans 
Administration to compare best medical management with DBS in 
over 300 patients, and our funds will support the patients from 
the affiliated academic health centers to provide a larger and 
more diverse study group.
    Now, cell replacement is another strategy for therapy in 
advanced Parkinson's, and we long have supported studies of 
embryonic stem cells from rodents in these studies. 
Investigators are now reporting success in driving murine 
pluripotent ES cells toward a neural fate and even to dopamine 
nerve cells. There have been a few successful reversals of 
motor disorders in rat models of Parkinson's simply by 
implanting undifferentiated mouse ES cells.
    Fetal tissue transplantation demonstrated successful 
replacement of dopamine nerve cells in Parkinson's patients. 
There was no immune rejection, but very little impact on the 
clinical signs, and that is an absolute necessity. We must do 
that.
    Our own intramural investigators have obtained approved ES 
cell lines, and are working to direct them to become dopamine 
nerve cells before investigating implantation either into the 
animal models or ultimately into human brain.
    We are committed, within the President's stem cell policy, 
to encouraging investigators to expand these studies. Grant 
solicitations in areas such as gene therapy, stem cells, 
environmental and genetic risk factors, drug screening, and 
surgical therapies have encouraged investigators to apply their 
knowledge, and numerous new grants have been awarded.
    We recognize that the Congress and the Parkinson's 
community have concerns about the level of funding provided to 
the implementation of the research agenda in light of the 
generous NIH and institute appropriations. We have actually 
invested more in Parkinson's research than any other of our 
major disorders, except stroke. However, workshops and planning 
for others of our disorders increase with increasing 
exceptional scientific opportunities for advances. And these 
disorders include epilepsy, multiple sclerosis, brain tumors, 
amyotrophic lateral sclerosis, spinal cord injury, muscular 
dystrophy, and autism. All of these demand attention. 
Maintaining an appropriate balance among the many disorders 
within our mission continues to be a challenge.


                           prepared statement


    So, we are extremely proud of the progress our 
investigators have made in the science of Parkinson's disease, 
which is already having an impact on therapy and ultimately 
will allow the cure. With all of the institutes across NIH, and 
with the collaborations with external advisors from the 
research and voluntary communities, we are confident of 
success.
    So, thank you, Mr. Chairman. I will be pleased to answer 
any questions you have.
    [The statement follows:]
                Prepared Statement of Dr. Audrey S. Penn
    Mr. Chairman and Members of the Committee, I am Dr. Audrey Penn, 
Acting Director of the National Institute of Neurological Disorders and 
Stroke (NINDS). NINDS has a long history of supporting critical 
research in Parkinson's disease (PD), and we are currently leading the 
National Institutes of Health (NIH) effort to implement the Parkinson's 
Disease Research Agenda. We have exciting progress to report, and I am 
pleased to present some of the highlights of this work to you today.
                               background
    Parkinson's disease, as many of you are aware, is a devastating and 
debilitating neurological disorder caused by the progressive loss of 
nerve cells that control movement. These cells produce the 
neurotransmitter dopamine, and their disappearance from the brain leads 
to tremors, rigidity, and slowing of movement. Other disabling effects 
can also occur, including speech problems and, in some individuals, 
difficulties with thinking, sleep, and depression. Parkinson's affects 
more than 500,000 Americans at any given time, and its severity varies 
from person to person. For some, the disease is marked by a rapidly 
debilitating physical deterioration, while in others, the disease can 
be managed for years with available medical therapies. Most people are 
diagnosed with the disease after the age of 50, although this disorder 
is not uncommon in younger people. All of these individuals need 
treatments that can control their disease and eventually a cure, and we 
are committed to continuing an intensified and coordinated effort to 
bring research to bear on this need.
    For more than three decades, NINDS has been heavily invested in PD 
research. We have supported early studies of L-dopa, fundamental 
research on the brain circuitry affected by PD, the development of 
critical animal models, and important advances in understanding the 
genetic basis of parkinsonism. In the late 1990s, NINDS expanded these 
efforts by establishing the Morris K. Udall Centers of Excellence for 
Parkinson's Disease Research. Selected through a competitive review 
process, these Centers have proven to be a sound investment. Over the 
past several years, they have developed essential collaborations and 
have contributed to a wide range of research investigations, from the 
genetics of PD and cellular dysfunction of neurons in the disorder, to 
studies of brain circuitry, neuropathology, and preclinical testing of 
therapies.
    As requested by Congress, and in light of the numerous 
opportunities in Parkinson's research, NINDS took its commitment to 
this field one step further, by leading the development of a multi-year 
scientific research plan for PD. As part of this effort, all components 
of the PD community came together to evaluate progress, re-examine 
plans and priorities, and identify critical research needs and new 
approaches with significant promise. NIH submitted this plan, the 
Parkinson's Disease Research Agenda, to Congress in March 2000. 
Although we are all optimistic that the Agenda will serve as a useful 
road map to developing and integrating treatments for PD, it is not 
possible to predict a precise time line for major breakthroughs or a 
cure for this disorder--even in a time of great scientific progress.
    We believe that one of the most important results of developing the 
Agenda was that it highlighted the promise of many ongoing areas, as 
well as new opportunities in PD research, and the importance of 
accelerating progress in all of them simultaneously. To address these 
needs, NINDS and NIH staff have developed numerous grant and contract 
solicitations, consortia, and workshops that complement the 
investigator-initiated awards that make up the core of our grant 
programs. The number of NINDS-initiated PD research activities 
undertaken since the inception of the Agenda has far exceeded that for 
any other disease in the history of the Institute, and the number of 
NINDS staff working on PD has been expanded beyond that for other 
disorders within the Institute's mission. The scientific community has 
responded enthusiastically to these actions, and several significant 
research efforts have resulted, including the initiation of major 
clinical trials that we believe will have a significant impact on the 
treatment of Parkinson's--both in individuals who have just recently 
been diagnosed, and in those in the later stages of the disease.
                              drug therapy
    For several decades, replacement of the neurotransmitter dopamine 
has been the mainstay of PD therapy. The delivery of the dopamine 
precursor L-dopa, as well as other drugs that stimulate the brain's 
dopamine receptors, have given many people symptomatic relief, enabling 
some to continue working and enjoying recreational activities for 
several years after their diagnosis. However, these treatments can come 
at a price--their effectiveness can diminish over time; they can cause 
uncontrolled movements and other debilitating side effects; and perhaps 
most importantly, they do not stop the continuing loss of nerve cells.
    The identification of a therapy that could preserve dopamine 
neurons--a true neuroprotective agent--would be a watershed event in PD 
research. NINDS has now taken an important step towards addressing this 
urgent need, building on years of research to understand the disease at 
the molecular level. In September 2001, NINDS awarded funds to develop 
the design and infrastructure for a large trial of drug therapies 
believed to have the potential for slowing the loss of dopamine-
producing nerve cells. In order to identify the most promising 
compounds for testing, NINDS solicited recommendations from academic 
and industry researchers, as well as from members of the advocacy 
community. Many drugs were suggested for consideration, and extramural 
experts, the trial organizers, and the scientific staff of NINDS 
developed detailed, objective criteria, in order to permit an unbiased 
evaluation of all suggestions. NINDS asked the committee to use this 
approach so that the selection of compounds for further testing would 
be based solely on their scientific promise. Following the initial 
pilot studies to determine proper dosing, safety, tolerability, and any 
preliminary evidence of benefit in Parkinson's patients, the most 
appropriate compound, or compounds, will be selected to proceed into 
definitive Phase III controlled trials. These studies are expected to 
enroll approximately 3,000 subjects at 42 testing centers. The results 
from the pilot phase of the project are expected within the next two 
years, but preliminary results from the Phase III trial are not 
anticipated until approximately 2010-11. This effort represents a 
significant commitment on the part of NINDS--one that will require an 
investment of approximately $40 million.
                            surgical therapy
    Even with the promise of new and improved drug treatments for 
Parkinson's, critical attention is also being focused on surgical 
therapies, especially for advanced PD. The U.S. Food and Drug 
Administration has recently approved deep brain stimulation (DBS)--the 
passage of electrical current through electrodes that are surgically-
implanted in very specific brain regions, critical to motor control--
for the treatment of advanced Parkinson's, and interest in this option 
is growing steadily. NINDS' commitment to the exploration of DBS as a 
therapy for PD goes back several years, and includes solicitations 
targeted to several technical aspects of DBS therapy. The Institute has 
now funded a number of investigators to study many basic questions 
about DBS, and we have assembled these researchers into a consortium 
that will meet for the first time in June 2002. In addition, NINDS is 
collaborating with the Department of Veterans Affairs (VA) on the 
largest clinical trial ever of DBS to treat PD. In this study, which 
will enroll approximately 300 subjects at six VA sites and affiliated 
academic institutions, researchers will compare stimulation of one of 
two different brain regions to best medical management of Parkinson's. 
If DBS is shown to be the more effective approach, subjects on medical 
management will also receive DBS--and the effects of the two different 
stimulation strategies will be compared. The results of the trial will 
address questions of critical importance to those affected by PD now, 
and NINDS support of the academic sites in this trial will enable the 
appropriate enrollment of both women and minorities in the study.
                    cell and tissue transplantation
    For people with advanced PD, who have already lost many of their 
dopamine-producing nerve cells, replacement cell or tissue therapy is 
another promising strategy. Studies of fetal tissue transplantation 
have already demonstrated that this approach is feasible in the 
treatment of PD, and advances in stem cell biology have made this 
therapy a future possibility as well. NINDS has long supported research 
on animal embryonic stem cells and adult stem cells, and some of this 
work has demonstrated success in reversing motor impairments in animal 
models of PD. We are committed, within the criteria of the President's 
stem cell policy, to expanding these studies further, and to 
aggressively exploring the potential of human embryonic stem cells in 
treating this disorder.
         research agenda implementation and scientific advances
    These examples illustrate the types of targeted program activities 
that have already contributed to the implementation of the PD Research 
Agenda. Grant solicitations and workshops in areas such as gene 
therapy, stem cells, the cellular basis of PD, environmental and 
genetic risk factors, drug screening, and surgical therapies have 
encouraged investigators to apply their knowledge to the field of PD 
research, and numerous new grants have been awarded. Although NINDS has 
initiated a number of these activities, many other NIH Institutes and 
Centers (ICs) have also developed programs that are directly responsive 
to the needs identified in the Agenda. For example, the National 
Institute of Environmental Health Sciences (NIEHS) is currently 
developing a Consortium Centers Program, that will operate as a highly 
interactive national network engaged in research to understand the 
potential environmental influences in the causation of PD. In addition, 
multiple ICs participated in a joint exploratory grant program with 
several private PD research funding organizations.
    While the initiation of these actions has been a critical part of 
our implementation effort, we recognize that it is ultimately the 
scientific output of the Agenda that will make a difference in the 
lives of people with Parkinson's. To that end, we have progress to 
report on a number of fronts:
  --NINDS-supported stem cell researchers and their collaborators have 
        found that mouse embryonic stem cells can develop into dopamine 
        neurons in a rodent model of Parkinson's and help reverse 
        impairments in motor function. Importantly, these cells exhibit 
        their plasticity without any manipulation beyond implantation 
        into the motor control regions of the brain. This work builds 
        upon studies of the factors that can induce cells to become 
        dopaminergic neurons, conducted over many years by NINDS 
        intramural investigators and others, and it emphasizes the need 
        to pursue stem cell applications within the federal policy.
  --Although several genes that are involved in inherited forms of 
        Parkinson's disease have been identified, the influence of 
        particular genes on the more common forms of the disease is not 
        fully understood. However, researchers have now conducted 
        large-scale screening of the human genome and have identified 
        several chromosomal regions that may be involved in PD. In 
        particular, one study has identified small differences in the 
        tau gene--which codes for a protein known to play a role in 
        Alzheimer's disease and other neurodegenerative disorders--as a 
        possible susceptibility factor for Parkinson's.
  --While the influence of inherited genes on the development of PD has 
        not been completely characterized, gene therapy is emerging as 
        a promising technique for restoring function in animal models 
        of this disorder. This work took a dramatic step forward two 
        years ago, when NINDS-funded investigators found that the 
        delivery of specific growth factors to primates with a 
        parkinsonian condition, using a genetically-modified virus, 
        could have dramatic reparative effects. Now a separate group of 
        researchers has added to this armamentarium, demonstrating that 
        a different virus--engineered to deliver enzymes critical for 
        the production of L-dopa--can have similarly impressive effects 
        in a rat model of the disorder. As researchers accumulate more 
        information about the safety and efficacy of different delivery 
        systems and treatment compounds, translational research on gene 
        therapy for PD can move forward.
  --NINDS and the National Institute on Aging have supported research 
        that demonstrates exposure of rodents to the pesticide rotenone 
        can cause the development of anatomic and behavioral changes 
        that mimic those seen in PD. In addition, work supported by 
        NIEHS has shown that other agricultural compounds can also 
        produce abnormalities in cells that are similar to those 
        produced by PD. This mounting evidence strongly implicates 
        environmental toxicants in the development of PD, and along 
        with the genetic contributions to the disease, establishes a 
        framework for more extensive studies of risk factors and their 
        cellular effects.
  --Last month, intramural researchers at NINDS published a study 
        showing widespread effects of PD on the sympathetic nervous 
        system. This system controls functions such as blood pressure 
        and heart rate--those we think of as automatic. Until this work 
        was completed, researchers did not appreciate the extent to 
        which the disease damages these nerves. Individuals with PD 
        often experience symptoms such as orthostatic hypotension, or a 
        drop in blood pressure upon standing, and the loss of 
        sympathetic nerves observed in this study may help to explain 
        why this occurs.
    Despite the progress made by NIH-supported investigators, the task 
of implementing the Agenda will require our continued attention. A 
great deal of basic science research is still needed, and much of what 
is known must be moved along, so it can advance into the clinic. Our 
Institute is acutely aware of this need, and we are taking steps to 
facilitate translational studies across all areas of disease. We expect 
these plans will have a very positive impact on PD research, since many 
researchers in this community are poised to move their work into 
preclinical studies, and thus could take immediate advantage of such a 
program.
                              future plans
    The most valuable outcome of the Agenda has been its use as a 
scientific planning tool. For the past two years, we have used the 
Agenda, along with the feedback we have received from the external 
scientific community through workshops and conferences, to guide our 
efforts. Since the start of the PD Research Agenda, NINDS has organized 
four meetings on different aspects of Parkinson's, and other NIH ICs 
have supported at least six others. The January 2002 Consortium meeting 
held at the request of Congress offered an additional opportunity for 
the research, advocacy, and NIH communities to engage in specific 
discussions about evolving needs in PD research. Among a wide range of 
suggestions offered by the clinical and basic science discussants, six 
emerged as priority areas from both groups:
  --Participants encouraged NIH to strengthen translational, or bench-
        to-bedside, research. Translational projects are often quite 
        different from research grants that test straightforward 
        hypotheses about disease causation and treatment, and are at 
        varying points of development along the basic to clinical 
        research spectrum. For several months, NINDS has been 
        developing a new grant program that will attract proposals that 
        bridge basic studies with model development and preclinical 
        evaluation of therapies, and will develop a framework in which 
        these applications can compete more effectively for funding. We 
        expect this program to be initiated in early fiscal year 2003.
  --Participants also encouraged NIH to increase our understanding of 
        how PD affects the dopamine systems of the brain. For years, 
        NINDS-funded researchers and our own intramural scientists have 
        been engaged in this work, primarily through basic science 
        approaches to understanding the fundamental malfunctions in 
        dopamine neurons that lead to their degeneration. We will 
        continue to support this research, through investigator-
        initiated awards, as well as special solicitations and 
        workshops, as critical new areas of biology are identified.
  --To complement these efforts, participants recommended further 
        expansion of research beyond the dopamine systems of the brain. 
        This would include other brain systems and circuits that may be 
        affected by PD, the effects of PD throughout the body, and the 
        resulting non-motor complications of PD--which can range from 
        depression and sleep disturbances to speech problems. NINDS is 
        committed to supporting many aspects of this research, 
        including continued exploration of the damage to sympathetic 
        neurons caused by PD. An expansion of this work in all relevant 
        research areas will likely require a trans-NIH effort.
  --Despite the wide use of validated scales to assess outcomes, both 
        NINDS and PD researchers in general have recognized the need 
        for better biomarkers--biological indicators/tests of disease 
        susceptibility, progression, or response to treatment. 
        Certainly, our continued focus on the genetics of PD will lead 
        to new ways to assess individual disease risk. However, early 
        biomarkers of this risk and later markers of progression may be 
        much more difficult to develop. NINDS will continue to fund 
        improvements in imaging and other currently used techniques; 
        however, the central problem in identifying new markers is our 
        incomplete understanding of the disease process at the cellular 
        level. For example, researchers in the Alzheimer's disease 
        community understand how specific molecules are broken down in 
        affected neurons--this offers hope for finding some of these 
        molecules in the spinal fluid or blood. However, researchers 
        have not fully characterized the degradation processes that 
        take place in neurons affected by PD, and thus, we do not know 
        if evidence of these processes can be detected peripherally. 
        NINDS staff is acutely aware of these difficulties, and will 
        continue to evaluate mechanisms that can enhance and accelerate 
        this research.
  --Participants also recommended NIH support for preclinical studies 
        of gene therapy, so that this research can move forward into 
        clinical testing. We have already solicited applications on 
        this therapy, and we expect that our efforts in encouraging 
        translational research will also help in this regard. Further, 
        once clinical studies are developed, we anticipate that the 
        framework we have already developed in our clinical trials 
        program, and our enhanced communications with the FDA, will 
        facilitate the development of gene therapy approaches in PD.
  --Lastly, the group recommended that NIH support improvements in 
        animal models of PD, including small animals and non-human 
        primates. We are already deeply invested in this work, and NIH-
        funded investigators have developed new animal models of PD 
        since the start of the Agenda. However, we are committed to 
        improvements in these models, and as a first step in the 
        process, we have already engaged the extramural research 
        community in discussions of how to facilitate the sharing of 
        models that are currently available.
    In the past two years, we have been successful in using the PD 
Research Agenda to guide our support of Parkinson's research, and this 
strategy has helped us to achieve the balance of investments outlined 
in the original Agenda. NIH estimates that PD research funding will be 
approximately $199 million in fiscal year 2002 and $215 million in 
fiscal year 2003. We believe that sufficient resources will be 
available to support the PD Agenda during this period, while NIH also 
attends to its many competing priorities. We will use both the 
recommendations from the original Agenda and those identified at the 
January and subsequent consortia meetings to guide the allocation of 
our resources in different areas of PD research.
    We recognize that the Congress and the Parkinson's community have 
concerns about the level of funding that NIH has been providing for the 
implementation of the Agenda. Appropriations for NIH and its individual 
ICs have been extremely generous in past years, and Parkinson's 
research has clearly benefitted from this generosity. As a result, 
NINDS invested more of its fiscal year 2001 funds on PD research than 
on any other disorder except stroke, which has an incidence at least 
ten-fold higher than that of PD. However, workshops and planning 
efforts increasingly indicate that opportunities for research advances 
against problems such as stroke, epilepsy, multiple sclerosis, brain 
tumors, autism, spinal cord injury, muscular dystrophy and health 
disparities are abundant. Maintaining an appropriate balance among the 
many disorders within the NINDS mission is a challenge as the Institute 
moves toward the future. One hopeful note is that basic research 
applies to many disorders, and even research focused on a particular 
disease, has a bearing on many others. NINDS must capitalize on these 
synergies to most effectively carry out its mission in the coming 
years.
    In closing, we are extremely proud of the progress we have made in 
accelerating research in Parkinson's disease, and we are grateful for 
the support of the Congress in these efforts. We do not have a cure 
yet, but we are initiating clinical trials that we believe will be 
critical to improving the treatment and quality of life of individuals 
with PD; we are developing a framework so that basic research can be 
effectively translated into treatments; and we continue to invest in 
essential basic science research--the foundation for all progress in 
medical science. We are not alone in these efforts. Many other ICs at 
NIH are involved in the implementation of the PD Research Agenda, and 
several voluntary organizations have expressed an interest in further 
collaborations. We will continue to work with other ICs through the NIH 
Parkinson's Disease Coordinating Committee, and with our external 
advisors and colleagues from the research and voluntary communities 
through the Parkinson's Disease Implementation Committee. With all NIH 
ICs and voluntary organizations working together, this undertaking can 
and will be successful.
    Thank you, Mr. Chairman, for the opportunity to speak with you 
today. I would be happy to answer any questions.

    Senator Harkin. Thank you very much, Dr. Penn. We will go 
down through all the witnesses, and then we will come back for 
questions.
    Next we have Dr. Ole Isacson, Director of the Center of 
Neuroregeneration Research and the Udall Parkinson's Disease 
Research Center at McLean Hospital at Harvard Medical School. 
Dr. Isacson is now an associate professor of neurology at the 
Harvard Medical School. Dr. Isacson, welcome.
STATEMENT OF DR. OLE ISACSON, DIRECTOR, CENTER ON 
            NEUROREGENERATION RESEARCH, McLEAN HOSPITAL 
            AND HARVARD MEDICAL SCHOOL
    Dr. Isacson. I want to thank you for inviting me and for 
your leadership on this issue. First of all, I would like to 
tell you that I am also very honored to speak about the 
exciting science that is possible through the work and the 
effort at the NIH. Beyond our science, it is also a human 
effort in that there is also a wonderful team spirit on this 
where the science has reached a level where we can actually 
make an implementation of a research agenda as Dr. Penn just 
mentioned.
    With your permission, Mr. Chairman, I would like to use 
this chart to show some of the work on science that relates to 
this.
    Herein lies the problem. This is the part of the brain that 
is called the midbrain, and in this part of the region here, 
about an inch across, you have something called the substantia 
nigra. Here you have the famous dopamine cells that everybody 
talks about that die in the disease. So, we have a few million 
here among trillions of nerve cells. The process of Parkinson's 
disease affects most of the brain, but only these cells here 
seem to be vulnerable. When you lose them, you get Parkinson's 
disease.
    So, obviously from a very common sense perspective, you 
realize, as Dr. Penn mentioned, that preventing this 
degeneration, reactivating the cells, or replacing them is a 
very reasonable strategy. And I will show you in a couple of 
minutes here that that can be done.
    So, this is what we teach at Harvard. So, what I am showing 
the Senators now is a drawing of how the brain works. It is 
known as a synapse, this thing here.
    If you remember the million cells in the midbrain, each one 
of them sends about a thousand of these very microscopically 
small, less than we could ever see without a microscope, up in 
the front of the brain. They are these terminals where that 
release the dopamine. The Nobel Prize last year was awarded for 
people who understood that when you lose the dopamine here, you 
can take a drug L-dopa that gets accumulated here and sent out 
here into this brain region.
    This is a very sophisticated element, and we scientists are 
trying to restore that one, and we are using every effort we 
can, all the scientific efforts we can, to restore this unit 
here. Most of the drugs that you currently can take as a 
patient relate to the understanding of this. But there are a 
number of new opportunities in restoring the function here, 
activating this element with growth factors, for example, which 
may become a home run, or any other analogy you want to choose, 
for Parkinson's patients.
    This next shows the mechanism. As Dr. Penn mentioned, there 
are gene defects, the way the cell works, its energy metabolism 
called mitochondria, the proteins that were mentioned, the way 
they mess up the dopamine neurons and the way that leads to 
dysfunction of that particular cell. At each of these phases 
listed on this panel here, there are research advances. What we 
feel as scientists is we now need to translate those, make them 
real for the patients, and aggressively move forward to 
organize the scientific efforts.
    There are many ways to organize that. This scientific chart 
here or this strategy here shows you some of these novel 
therapeutic approaches. They include what we call biomarkers. 
We need to be able to look at the brain and see what is 
happening both during the disease process and when we try 
restorative therapies. We are trying to prevent the disease as 
I mentioned previously, trying to keep the brain working, also 
replacing the cells, and also as was mentioned previously, we 
are using stem cells. This country is very well known--I am 
actually an immigrant--all over the world for its innovation 
and attention to discovery. We need a free science to be able 
to find the necessary treatments for Parkinson's disease, both 
using stem cells, understanding gene biology, and aging.
    So, finally, to give you some evidence of that, thanks to 
the NIH Udall Center, the Udall bill, my team in Boston managed 
to translate some of these findings from stem cells into an 
experimental model of Parkinson's disease. What you see here on 
this panel is an imaging on the left side, but on the right 
side here you see implantation of mouse embryonic stem cells, 
and these stems cells differentiate into to the dopamine neuron 
that I told you was the core of the problem. So, in a prototype 
manner, we are already able to show in the laboratory that we 
have ways of obtaining the cell that dies in Parkinson's 
disease. Obviously these are prototypes, which means just like 
a new airplane or any new discovery, that we need a lot of work 
to move these things forward, and I look forward to describing 
some of the organizational methods, management that maybe can 
accomplish that.
    So, if I may wrap up here, some of these concrete 
scientific studies do not only pertain to Parkinson's disease. 
Parkinson's disease, for reasons of its scientific promise, has 
spearheaded many other discoveries. When we make breakthroughs 
for Parkinson's disease, it is very likely that we will also 
make breakthroughs for ALS, Alzheimer's disease, and spinal 
cord degeneration. So, Parkinson's disease research is a way of 
opening doors to new therapies. Therefore, I feel very 
strongly--and most scientists and doctors feel the same way--
that there is a real need to focus on this disease and do 
everything we can possibly to help and cure patients with 
Parkinson's disease.

                           PREPARED STATEMENT

    This shared purpose we also feel with you as the Government 
and giving us the opportunity to do the research.
    I would like to end my testimony there. If you have any 
further questions.
    [The statement follows:]
                 Prepared Statement of Dr. Ole Isacson
    Senator Harkin and members of the committee, I am Ole Isacson, 
Director of the Neuroregeneration Laboratory, McLean Hospital and 
Harvard Medical School, and the NIH/NINDS funded Udall Parkinson's 
Disease Research Center of Excellence. The research center I direct is 
dedicated to basic research on the prevention and treatment of 
Parkinson's disease and neurodegenerative diseases. For Parkinson's 
disease, we have developed models for new treatments with cell 
replacement and transplantation of embryonic stem cells. We have shown 
that we can reduce parkinsonism in several experimental models that I 
will describe to you. In particular, I would like to emphasize that 
over the last few years with the available Udall bill, the activities 
that these centers have created throughout the United States, and there 
are 11 of them, is considerable. The work on Parkinson's disease 
treatments and possibly cures is an achievable goal with effort placed 
in science and medicine. It is my opinion that there is an opportunity 
to increase the funding for Parkinson's disease research to reach the 
next technological level, which would include treatments. A strong 
research effort can be funded further to grow research centers and to 
grow national core facilities to provide service to smaller research 
groups across the nation and internationally to reach their scientific 
and therapeutic goals for Parkinson's disease faster. In particular, by 
building such an effort, we will increase the capacity not only for 
achieving treatments for Parkinson's disease, but there will be several 
measurable and meaningful results for the treatments of 
neurodegenerative diseases such as Alzheimer's, Huntington's and 
Amyotrophic Lateral Sclerosis (ALS; Lou Gehrig's disease), to mention a 
few, as well as spinal cord damage.
    One of the most successful drug therapies for any neurological 
disease is L-dopa for Parkinson's disease. This was made possible 
primarily through the insights of scientists and clinicians, who in the 
late 50s and early 60s used the information obtained from animal and 
pathological studies to provide patients with a treatment. My 
laboratory's approach for Parkinson's disease is based on the idea that 
the degenerated dopamine neurons can no longer provide synapses in 
which the drug (L-dopa) can be converted and released in regular 
amounts into the striatum, where dopamine receptors translate this into 
neuronal firing and activation of the striatum. L-dopa and dopamine 
analogues, while initially helpful, eventually become insufficient with 
debilitating side effects for the patient. Since this loss of efficacy 
is likely due to continued loss of synaptic control, the homeostatic 
mechanism of transmitter release, the reinnervation with synapses by 
implanted or regenerated dopamine neurons can potentially provide a 
better intervention than drugs alone. Many practical issues remain 
before it becomes a standard and reliable therapy. Hopefully, 
scientific insights about new donor cell sources, as are described 
here, their axonal integration and connections will provide patients 
with a useful therapy. Clearly, it is necessary for these scientific 
discoveries to be matched by technical developments in neurosurgery to 
achieve that translation into useful clinical practice. Rapid progress 
seen in developmental biology, molecular biology, as well as technical 
developments of neurosurgery can further accelerate achieving 
regeneration and repair for a large number of neurological patients in 
need.
    Typically, without any pharmacological treatment, a person 
afflicted with Parkinson's has a stiff posture and slightly unstable 
gait, with the arms trembling. In addition, many with Parkinson's 
disease experience emotional difficulties in dealing with the disease, 
but do not feel that their minds are otherwise affected. The 
instability in their posture, the masked face, the gait disturbance, 
the speech disturbance and the poor dexterity are very incapacitating. 
This type of patient was first described coherently by James Parkinson 
(1755-1824) in an essay ``On the Shaking Palsy'' (1817, Sherwood, Heely 
and Jones, London, England). In the United States alone, there are now 
at least a million Parkinson patients, and approximately 1-2 percent of 
persons above age 65 will get the disease. Nationwide, drug therapy 
alone costs about $6 billion per year and the cost of hospital care and 
other consequences associated with a person having Parkinson's disease 
are estimated at $25-50 billion per year.
    Like Alzheimer's disease, Parkinson's is a disease that may happen 
in younger people, but the risk increases dramatically with age. This 
is probably because many of the cellular systems in the brain are 
difficult to renew or regenerate by themselves. While there are 
trillions of nerve cells in the brain, when nerve cells start 
degenerating as we get older it becomes harder and harder for the brain 
to compensate for the loss of these cells. For instance, in Parkinson's 
disease the symptoms are caused by the selective loss of a relatively 
small population in the brain consisting of approximately 500,000 
dopaminergic cells. They are situated deep in the midbrain in a place 
called the substantia nigra, literally the black substance, caused by 
melanin seen in those neurons. In any brain that grows older, some of 
these dopaminergic neurons will dysfunction over time. The rate at 
which they die or dysfunction is individual. For certain people, whose 
rate of dopaminergic cell loss is slightly higher than normal, the 
likelihood that they will eventually lose the critical 85-90 percent of 
the cells that are needed for normal function is high. The brain 
somehow manages to compensate for a loss of about 85 percent of these 
cells, but when only a small number of functional dopamine cells or 
less remain on each side of the brain, the symptoms of Parkinson's 
disease appear. The neurotransmission that takes place at the nerve 
terminals that produce dopamine is necessary for all of us to initiate 
movements and without it, we freeze up and become unable to move.
    The pharmacological substitution therapy provided by L-dopa 
revolutionized the treatment of Parkinson's disease. The neurosurgical 
treatment (pallidotomy) now became uninteresting to many clinicians, as 
it was hoped that L-dopa was a sufficient treatment for Parkinson's 
disease, and moreover, that this type of pharmacological substitution 
would be possible for all of the other neurodegenerative diseases. It 
turned out that the solution wasn't so simple. After 5 to 10 to even 15 
years of treatment, the L-dopa became less effective, and not in the 
manner of normal drug-induced tolerance. As is now well known, the 
patients experienced severe fluctuations in the drug effect, despite 
relatively constant levels of the drug in the blood and the brain. The 
so-called ``OFF'' phenomenon describes a time when the drug somehow 
becomes ineffective for the patient. At such times, the patient freezes 
up momentarily and loses mobility. The ``ON'' times are when the drug 
works and the patient gains mobility. However, both the ``ON'' and'' 
OFF'' times may be adverse. Symptoms can fluctuate wildly with L-dopa 
treatment or analog drugs. During ``OFF'', freezing and rigidity and 
inability to initiate movement is then further compounded by side 
effects during ``ON'', such as extra, involuntary movements generated 
by the drug. These hyperactive movements and dystonia (abnormal muscle 
tension and postures) are debilitating. Given that these ``ON-OFF'' 
phenomena appear earlier and more prominently in patients with 
chemically induced Parkinsonism (such as due to MPTP toxicity), it 
seems probable that the more severe the damage to the dopamine system, 
the less likely it is that systemic drug delivery (oral administration 
of drugs, for instance) will be effective. Moreover, it is reasonable 
to assume that one of the reasons L-dopa becomes less effective is that 
it cannot be taken up by the decreased number of surviving dopaminergic 
neurons to create some form of regulated release of the transmitter.
    This has led a number of scientists to question whether 
pharmacological drug substitution therapy will be effective for the 
age-related neurodegenerative diseases. If synaptic control and 
regulated release of a single substance is needed, then we may have to 
deal with the more complex issue of trying to re-create synaptic 
networks and/or preserve them from degeneration. Since the ``ON-OFF'' 
phenomena in Parkinson's disease are so debilitating, some 
neurosurgeons and neurologists found it worthwhile to explore 
pallidotomy once again in the 1990s. More recently, electrical 
stimulation of the subthalamic nucleus (DBS) has been shown to 
alleviate some of the movement disorder of Parkinson's disease. Another 
procedure, ``thalamotomy'', surgically removes a subset of neurons in 
the thalamus that participates in the parkinsonian tremor. Like all 
experimental methods, there is the need for an extensive evaluation of 
the effects.
    In addition to the L-dopa or dopamine agonist drugs previously 
mentioned, and the neurosurgical treatment methods, there are a number 
of research efforts to prevent or treat Parkinson's disease. Some 
centers are involved in locating so-called susceptibility genes for 
Parkinson's disease. Although there seems to only be a small proportion 
of Parkinson's patients with a genetic component, certain genes may 
make it more likely to develop Parkinson's disease. If the disease is 
multifactorial, susceptibility genes may lower the threshold for 
developing the disease. Some scientists also indicate that there may be 
a heterogeneity among susceptibility genes, such that different 
genotypes may develop the same Parkinsonism. And as we have previously 
discussed, the disease is age-linked and therefore a number of 
biochemical changes occurring naturally by age may interact with the 
genes at various times. Such genetic research, in combination with new 
methods in molecular biology, may give us tools to develop preventive 
treatments.
    As previously discussed, when dopamine is so severely reduced in 
the caudate putamen that Parkinsonism appears, we can give patients a 
precursor of dopamine, L-dopa, to reverse some of the loss of dopamine 
in the brain. This was first reported by Birkmayer and Hornykiewicz 
(Wien Klin. Wochenschr. 73, 787-788, 1961). Along with the discovery 
that L-dopa substitution worked in the early phases of Parkinsonism, 
the last 35 years of neurological research has provided us with a 
number of drugs that can either mimic the action of dopamine (analogs/
agonists), block its uptake from the synapse (re-uptake blockers) and 
stimulate its release or inhibit its metabolic removal. In addition, 
other neurotransmitter-related drugs that interact with dopamine in the 
caudate and putamen have been used. The outstanding discovery that the 
precursor to dopamine (L-dopa) will provide symptomatic relief for 
patients with Parkinsonism still remains with some minor modifications, 
the major drug treatment for patients. However, the fact that this drug 
and other similar drugs lose their effectiveness over time still 
remains the major problem with Parkinson's disease. It is unclear at 
this time whether optimization of the dopamine agonist effects can 
provide an effective long-term treatment for Parkinsonism, even if new 
receptor agonists are developed. The question therefore remains whether 
it will be necessary with synaptic replacement in the striatum to 
reverse the course of advanced Parkinsonism.
    In cell culture and animal studies, it has been shown that brain-
derived neurotrophic factor (BDNF) can help dopaminergic neurons 
against toxic insults. Similar effects have been obtained by infusions 
and increased supply of glial-derived neurotrophic factors (GDNF) by 
somatic gene therapy. If research is directed towards appropriate 
delivery of such substances to patients at risk for developing 
Parkinsonism or patients with accelerated cell loss in the substantia 
nigra, it is likely that some benefits could be derived. Moreover, by 
this kind of research we may find other substances that could mimic the 
effect of trophic factors and therefore help prevent the degeneration 
in the substantia nigra and other vulnerable brain regions. It is my 
overall impression that basic neurobiological research towards 
understanding the mechanism involved in neuronal death, and of 
dopaminergic neuronal death in particular, are well-underway and very 
focused. It is likely that these studies will yield sufficient insight 
to develop new clinical therapies. A word of caution in this regard, 
though, is that while clinical trials may be initiated, it could be 
some time before they are refined so that they can be available to a 
large number of Parkinson's patients.
    The evolving science and therapies for brain disorders may develop 
in parallel with insights about the brain's own capacity for repair. In 
fact, the brain is probably the most adaptive organ at a structural 
level for continuous change and signaling, as well as morphological 
adaptation to functional demand. I am therefore convinced and very 
optimistic that new technologies and therapies can be developed through 
scientific research to cure Parkinson's disease. A national effort and 
increased funding for such work would provide the stimulus to take 
advantage of these unique opportunities at this time.

    Senator Harkin. Thank you very much, Dr. Isacson.
    Now we turn to the driving force behind almost all of this, 
Joan Samuelson, president and founder of the Parkinson's Action 
Network.
    A lawyer for many years, she was diagnosed with Parkinson's 
in 1987. Mrs. Samuelson has testified before this subcommittee 
more than 10 times, and we are proud and privileged to have you 
back again. Please proceed.
STATEMENT OF JOAN SAMUELSON, FOUNDER AND PRESIDENT, 
            PARKINSON'S ACTION NETWORK
    Ms. Samuelson. Thank you so much from the bottom of my 
heart, Mr. Chairman, Senator Specter. Your visionary leadership 
on this subject has benefitted our community of a million 
Americans with Parkinson's disease beyond measure, and giving 
us the opportunity to be heard and the work you have done to 
help our cause we are deeply grateful for beyond anything I can 
describe, and thank you so very much.
    My testimony today I see as a story of hope. It is about 
hope that is essential, and it is a story about failed hope in 
the past and hope that we hope will be able to be realized in 
the future and should be. Hope is an ingredient that, to 
someone who has been diagnosed with Parkinson's disease, is as 
essential as food to continue living.
    When you walk out of a doctor's office with a diagnosis of 
Parkinson's disease, your foundation has been taken from you 
because you are told you have a progressive, degenerative, 
chronic motor disorder that will only get worse. But there is 
wonderful medication that now will enable us miraculously to 
walk into a room and testify and drive our cars and work in the 
world and live with dignity.
    But we also are told that those cells are continuing to 
die, as Dr. Penn said, 75 to 80 percent of them are already 
gone, and that cell death and cell shutting-down is continuing 
relentlessly and that there is no solution to that right now.
    What that means is we have a disease for which we cannot 
hope that we are going to outlive the odds, that we are going 
to beat the odds because there are not any odds to beat. There 
is not such a thing as remission. There is not such a thing as 
perhaps some combination of chemo and radiation that causes us 
to be labeled a survivor and be able to march in parades with 
that label. We know that we are going to eventually become 
prisoners of our bodies, unable to move and speak and swallow 
and die before our time. And yes, Parkinson's does kill.
    So, what we have to do is cling to what is raw hope. What 
we have now, as Dr. Penn and Dr. Isacson were describing and as 
we heard in the scientific briefing at our public policy forum 
yesterday, is that our hope is now a verifiable expectation. 
Parkinson's is no longer called incurable. It is curable. What 
that means for us is that we can hope with something more 
concrete, but what we need is for that hope to be realistically 
matched with the opportunity to realize the scientific results 
from the promise that these scientists have been describing. 
And therein lies the dilemma that I want to talk about.
    My testimony needs to be, I think, a bit of a report card. 
In 1999, we had the tremendous honor, Michael and I, of 
testifying before this committee, and at that point scientific 
promise was great and on the basis of that and on the basis of 
that hearing and your leadership, the scientists in the country 
involved in Parkinson's research teamed up with the National 
Institutes of Health and created the Parkinson's Disease 
Research Agenda, an historic document that laid out a road map 
to realize that promise and that hope with a cure, with some 
curative therapy that would rescue these million Americans or 
as many of us as the science could realistically rescue with 
enough money. And so, the science was laid out and a price tag 
was put on it of $1 billion over 5 years. And the clock began 
to run.
    That research agenda was set in the year 2000, and as this 
committee knows so well and as we have come back to you and 
discussed it, it has not been funded. There are scientists that 
come to us and speak to our gatherings and describe the 
enormous promise, but their extreme frustration with the work 
that could be done that is not being done. The consequences of 
that are great and real and human.
    What it means is that we have people for whom hope is 
fading. We cannot take care of those for whom hope has died, 
and we have lost people in the 3 years since 1999 and it 
grieves us. The father of our advocacy director, Lynn Phillips 
from Mississippi, many people who are gone or who are 
completely prisoners of their bodies. And hope is fading 
terribly for people like Milly Kondracke who sits behind me.
    We should try to save Milly. It may not be possible 
scientifically, but it could. And we must try, it seems to me, 
as a country if we have that potential. And there are many 
others for whom hope is still there and it is strong, but we 
know we are in trouble.
    Three years ago I described going to see Mo Udall and that 
being my future. I am still doing well, relatively, for 16 
years post-diagnosis, and I am so deeply grateful for that, but 
I wake up every morning just about as frozen as he was when I 
went to see him. And some day that pill I take will not work, 
and that day may be soon. And I so desperately want, as every 
one of these other people in this audience and the rest of the 
million Americans, our country to make the investment that it 
must because the science is there to benefit not just us, but 
people with the other disorders that Dr. Isacson described.

                           PREPARED STATEMENT

    We know it is a difficult problem, but we believe that with 
the leadership of the Congress, working with the National 
Institutes of Health, that the money is there and that it must 
be spent because hope is real and realistic now. Given that, it 
would be a crime to let it fade.
    So, thank you for your leadership and your vision. I just 
ask that we work together on this next difficult but doable 
step. Thank you.
    [The statement follows:]
                Prepared Statement of Joan I. Samuelson
    My testimony must begin with our thanks on behalf of the entire 
Parkinson's community to this Committee, for this hearing, for the 
opportunity to be heard, and for your leadership on our behalf. We are 
deeply grateful to Chairman Harkin, Senator Specter and the members of 
the Committee to help ensure that this dreadful disease is conquered as 
soon as humanly possible.
    I also would like to recognize several members of the audience who 
have gone to great lengths to be here. First, joining us today are 
three former Senators who have Parkinson's disease, the Honorable 
Claiborne Pell (D-RI), Brock Adams (D-WA) and Charles Mathias (R-MD). 
Also joining us today is Mrs. Carolyn Long, wife of Former Senator 
Russell Long (D-LA), who also has Parkinson's. I know they share our 
message today.
    Also present are Lynn Fielder from Palo Alto, California, and her 
nine year-old daughter, Maya. Maya recently wrote Senator Harkin, 
explaining how her mother's life may depend on an increased federal 
commitment for Parkinson's research. Her letter will appear in the 
Congressional Record today. Thank you all for being here.
    I seek to persuade this Committee of three things. First, the cost 
of Parkinson's--human, financial and otherwise--is too great to endure. 
Second, it is now possible to take concrete steps to stop it. Third, 
that it requires the federal government to honor a commitment made two 
years ago, to fund development of a cure thoroughly and aggressively.
    So there are many reasons for our plea to you today. Our message 
today is one of huge human suffering, dazzling scientific promise--and 
a failure of our government to translate that promise quickly. It is 
inexpressibly sad, but true. Parkinson's is waging a war in the brains 
of the million of us diagnosed, and the several million more Baby 
Boomers and others who have pre-symptomatic dopamine cell loss. This 
war will take an unacceptable number of victims. We have weapons 
sitting in the warehouse. And--by government choice--we are meandering 
to a cure.
    This is, in a way, a progress report, given almost three years 
after our first report to this Committee in September 1999. It is a 
hard thing to do for two reasons. First, it requires that we tell tales 
of the failure of hope. That goes against every instinct of those of us 
diagnosed with a chronic progressive disorder of this magnitude: with 
such news, the only way to go on living is to keep our spirits alive, 
which requires hope--the food on which the spirit feeds. So, we believe 
the cure will come--in time for each of us.
    The brutal reality of Parkinson's degeneration, however, is that as 
more and more dopamine neurons shut down, we require more and more 
dramatic rescues, until the day when the system utterly fails to work. 
At that point, we are forced to recognize that hope is gone and give up 
our personal dream in favor of those with more time. In the three years 
since the 1999 hearing, I have watched hope fade in that way for many 
people. It is always a cruel thing to watch; sometimes it is lethal.
    Take Lynn Phillips of Mississippi. He tried every experimental 
program, including a deep brain stimulation procedure that required his 
town to throw a huge chicken fundraiser to pay for it. But finally, 
Parkinson's won: the death certificate presumably refers to 
complications secondary to his Parkinson's--but Parkinson's had so 
beaten him up that he had few defenses left.
    And take Fred Zeiss of New York City, who was forced in recent 
years to put aside his career, and in his depression put on 100 pounds. 
It was the resulting heart attack that killed him, but his family says 
it was really Parkinson's.
    Our office was hit hard this past year by Parkinson's deaths to the 
father of our Advocacy Director, John Rogers, who died last fall after 
brutal suffering; and the uncle of our Executive Director, Elisabeth 
Bresee Brittin, last winter. There are many others across the country, 
most of whom have not died, but live lives robbed of nearly every 
freedom they possess short of the freedom to think and dream. The 
stiffness and slowness of movement combine to cause the body to freeze 
up. At that point, the mind is encased as if in an iron lung, by an 
unyielding outer shell. That shell is us, though: the body is 
imprisoning itself. In those cases, it feels just about as cruel to 
watch them continue to live.
    When I was diagnosed, I decided that I would never succumb to such 
a state. I still hold a profound belief that I will be rescued in time 
to keep my livelihood, my independence and dignity. But I have to admit 
that, more frequently than three years ago, I experience episodes of 
that final stage--when the available medications work poorly at best.
    So where are we in fulfilling the desperate hope of a million 
Americans, and the approaching need of millions more? The science is 
full of promise: There is a dazzling set of cutting-edge biomedical 
approaches waiting to be applied. They include:
  --High throughput screening of possible toxic agents and therapeutic 
        compounds;
  --Gene-environment initiatives using high tech testing;
  --Applying information on proteins involved in Parkinson's genetics 
        to understand the disease process;
  --Imaging advances for earlier diagnoses before symptoms appear;
  --Neuroprotection: applying all these advances to prevent cell loss 
        in the healthy and protect those afflicted against further 
        deterioration.
    And, for the million-plus of us who need a therapeutic rescue, 
there is an equally dazzling array of new approaches:
  --Cell restoration
  --Cell replacement
  --Gene therapy
  --Viral vector technology
  --Cell line creation technology, using techniques such as stem cells
    The science of Parkinson's is at the front lines in all these 
areas. Eminent scientists are so optimistic that for years they have 
been predicting and quantifying the time remaining--highly unusual, and 
hopeful, behavior.
    But precious little concrete movement toward completion of some 
curative treatment has occurred. It is not the fault of science. It is 
a failure of government to act. This is the second piece of the report 
that it hurts to tell.
    I hasten to add that I do not fault this Subcommittee. It in 
particular has frequently expressed its concern and led initiatives 
that support Parkinson's research. In response to Congressional 
urgings, in 2000 the NIH convened a team of Parkinson's researchers who 
developed the Parkinson's Disease Research Agenda--a plan that called 
for a $1 billion additional investment in Parkinson's research over 
five years. Since the Agenda's development, the Congress--and 
especially this Committee--has urged the NIH in increasingly strong 
language to fully fund the Research Agenda. Every element for success 
seemed to be in place, including the process of ``doubling'' the NIH's 
overall budget by 2003, to ensure that a Parkinson's increase would not 
come at the expense of other disorders.
    Despite these efforts, the federal commitment for Parkinson's is 
falling far short of the Agenda's targets. While each month brings 
further progress and new discoveries that could lead to a Parkinson's 
cure, the percentage of spending on Parkinson's research has not even 
kept up with overall NIH spending. In fact, in the two years since the 
Agenda was completed, there already is a $100 million shortfall in the 
NIH's spending on Parkinson's research. The numbers create problems in 
funding that we hear constant stories about: the many grant applicants 
with great ideas and high peer review scores, but where low funding 
scores kept them below the pay line.
    At the root of the problem is an utter failure of leadership to 
implement a research agenda for Parkinson's. Despite some very hard 
working and wonderful scientists at lower levels, there has been an 
absence of vision and commitment at the top--of both the NIH and the 
key brain-related institute--which manifests in many ways. Despite huge 
opportunity for major strides in brain research, the NINDS directorship 
has been a revolving door for years. The institute's lack of focus and 
direction has discouraged good candidates. The NIH hierarchy seems to 
regard the Parkinson's Disease Research Agenda as nothing more than a 
distant aspiration rather than an operational document that must be 
funded. However, scientific directors cannot make this happen without 
budgetary and policy commitments from the top. This situation is, 
without question, having the effect of delaying a Parkinson's cure.
    For all these reasons, the road to a Parkinson's cure is a 
meandering one, with huge consequences. First and foremost, people with 
Parkinson's will suffer. That is simply not right. Americans with other 
disorders that seemed intractable--AIDS and cancer, for example--are 
alive because of the benefits of federal research investments. It 
should be Parkinson's turn. Moreover, the scientific and bio-
technological advances that result unquestionably will speed 
breakthroughs in many other disorders.
    So what is to be done? The Congress cannot allow this un-met 
promise to continue. We urge this Committee and the rest of Congress to 
use every available power to turn this around quickly. We urge the 
following:
  --That the NIH Director use his transfer authority to commit $50 
        million for Parkinson's research this year;
  --Full funding of the $197.4 million increase over the baseline year 
        for 2003, year three of the NIH's five-year Parkinson's Disease 
        Research Agenda, including significant funding of translational 
        and clinical research;
  --Complete the five-year doubling of the NIH's budget by providing 
        $3.7 billion (for a total of $27.3 billion) in fiscal year 
        2003;
  --Continue and expand the NIEHS budget, with an increase of $30 
        million in fiscal year 2003 for Parkinson's focused research;
  --Work closely with the NIH to ensure that they aggressively 
        implement the Parkinson's Disease Research Agenda.
    It is the responsibility of the federal government to seize this 
opportunity and that of Congress to ensure that they do, including that 
the NIH be responsive to Congressional report language regarding 
Parkinson's funding. That's why your leadership is critical to ensure 
that the visionary Parkinson's Disease Research Agenda is regarded as 
an operational document that must be fully funded and implemented, 
rather than merely an aspirational document that is never truly 
realized.
    We fear that we already have missed the opportunity to save some 
people by failing to fully fund the great scientific potential. But, if 
we act now, there are many others who can still be saved. With this 
Subcommittee's leadership, the future we dread will be rewritten into a 
history in which Parkinson's has been sidelined forever. That day can't 
come too fast.

    Senator Harkin. Thank you very much, Joan.
    Don Schneider lives in Clinton, Iowa. That is on the 
Mississippi River, for those of you who do not know. It is the 
same town where he was born. He worked at radio station KROS 
for most of his career, eventually rising to general manager of 
the station, and President of the Iowa Radio Network, before 
Parkinson's disease forced him to retire 3 years ago. He is 
accompanied here by his wife, Rita.
    Don, thank you for being here. As I said, your statement 
will be made a part of the record in its entirety. If you could 
just sort of sum up what you want us to know about how this has 
affected you and what you want us to do. Please proceed.
STATEMENT OF DON SCHNEIDER, PARKINSON'S PATIENT, 
            CLINTON, IA
    Mr. Schneider. Well, I would first like to say for an Iowa 
farm boy who was standing in a hayfield on Sunday, it is pretty 
overwhelming to be here in front of these bright lights and on 
this panel with these great personalities. In fact, I kind of 
feel as out of place as a faithful husband on an edition of As 
the World Turns.
    But anyway, I guess I am here to put a human face on 
Parkinson's disease, and I figure Muhammad is providing the 
pretty face, so you will just have to put up with mine.
    Fifteen years after my diagnosis, Parkinson's disease is 
continuing to slowly but surely chip away at my quality of 
life. It has forced me to leave a job I loved, placed a heavy 
financial burden on my family, and at times each day leaves me 
unable to walk, read a book, or even dress myself. For someone 
raised as an independent farm boy, I cannot express the 
frustration that accompanies this type of disability.
    As the Senator mentioned, I come from Clinton, Iowa. After 
graduating from high school, I attended radio school at Brown 
Institute in Minneapolis, and at the age of 19, started as a 
night announcer on a small radio station in Clinton, Iowa. I 
served in a number of capacities with that station, everything 
from an announcer to program director. In 1987, I purchased 
stock in the company and was named general manager.
    Professionally I was active in the Iowa Broadcasters 
Association and, as the Senator mentioned, President of the 
Iowa Radio Network. I was also active in my local community as 
every small businessman is. I was a member of the Kiwanis Club, 
helped the United Way board of directors, served on the 
Substance Abuse Council, and was part of countless fund raisers 
for many worthwhile projects in the Clinton area.
    I enjoyed working with young people. I was inducted into 
the Junior Achievement Hall of Fame for serving as an applied 
economics advisor. I coached junior football and basketball. 
Later I even took up the stripes as a high school basketball 
official.
    It was in 1988, during a high school basketball game I was 
refereeing, when I held out my hand to indicate two shots, I 
noticed an uncontrollable shaking. Well, my family had also 
begun to notice a blank stare on my face, and I was 
experiencing slowness of movement and pain in my neck. One 
visit to the clinic and I was diagnosed with Parkinson's 
disease at the age of 35. For 5 years after my diagnosis, I hid 
it from all but my family. When people asked, I would simply 
say I had a neurologic disorder. As Michael Fox put it, you do 
not want to believe this is happening to you and you certainly 
do not want anyone else to know what is happening to you. You 
worry about what they will think, how they will treat you. It 
was extremely difficult, after being someone who was always in 
charge, to be forced to depend on others to help me.
    At first, with the help of my medications, I continued 
living a relatively normal life, and as long as the medication 
was working, I could do just about anything. But eventually the 
progression of the disease and side effects of the medication 
left me no longer able to be fully functional at work, and my 
condition worsened to the point that I had to end my broadcast 
career and retire from the station in 1999.
    Today I reside in rural Clinton County with our three 
youngest children. My two older children are now finished with 
school and living on their own. Katie, 21, is serving our 
country in the U.S. Army stationed at Fort Polk, Louisiana. My 
other daughter, the oldest, Sarah, graduated from the 
University of Iowa Hospitals and Clinics and is working as a 
registered nurse in the Neurology Department.
    This is not to say that it has been easy. I can recall many 
profound sadnesses that I saw in the eyes of my family after 
the diagnosis and we all faced the uncertainty of what will 
happen in the future. I cannot deny that each day I worry about 
what the future will be like. On one hand, I know there has 
been great progress made. There are new medications that have 
become available just in the 15 years that I have had 
Parkinson's disease. But there is still no known cause and the 
possibility of being trapped with an active, alert mind in a 
body you cannot control is a fate worse than death.
    Since giving up my job, we have had to rely on my wife's 
income in an accounting firm and Social Security disability to 
get by. Fortunately, my wife makes a good living, but it has 
taken an economic toll on our family. We are facing the 
prospect of soon losing our health insurance with its 
prescription drug coverage. With a cost of over $700 a month 
for my prescriptions, this will certainly make us have to do 
with a lot less.
    I often think about all my family has been missing and had 
to give up because of my diagnosis and condition with 
Parkinson's disease, and I have tried to channel some of that 
anger into the work I have done with a local support group in 
Clinton, Iowa. Our group of over 30 families has been a great 
help to me in facing the daily struggles of Parkinson's.
    No one knows why or how I got this terrible disease. Is it 
genetic? Well, two of my great uncles did have Parkinson's 
disease, but one was on the maternal, the other on the paternal 
side. Does the environment play a role? I grew up drinking farm 
well water, but so did the rest of my family and none of them 
has Parkinson's. The bottom line seems to be we just do not 
know what causes this disease, but I am hopeful that we will 
have the answers soon.
    I am not a quitter and I refuse to give up hope. I have 
always had a love of old cars. In fact, I keep a red Corvette 
in my garage at home right now. One of my mottos that I have 
tried to use all the time, dealing with Parkinson's disease, I 
stole from a movie called The Gumball Rally. As the race in 
that movie is about to start, a driver in a Ferrari turns to 
his co-pilot, tears off the review mirror, and says, ``now the 
first rule of Italian driving--what's behind me does not 
matter.''
    I do try to keep looking ahead rather than worrying about 
what is behind me and remembering all that I have lost, trying 
to be thankful instead for my wonderful family and all that I 
have going for me.

                           PREPARED STATEMENT

    Again, I thank you, Senator Harkin, and I am especially 
proud as an Iowan of your being awarded a second Mo Udall Award 
last night for your work for fighting against Parkinson's 
disease. And as The Champ might put it, with the help of all 
these great people, I cannot see how we will not whip this 
thing sooner or later. Thank you.
    [The statement follows:]
                  Prepared Statement of Don Schneider
    Thank you, Chairman Harkin, for holding this important hearing 
today on Parkinson's research. As a fellow Iowan, I am especially 
honored to be here today to speak to you about Parkinson's disease--
both the incredible toll it takes on its victims and their families--
and the great urgency of providing the federal resources necessary to 
cure this dreadful disease.
    Fifteen years after my diagnosis, Parkinson's is continuing to 
slowly but surely chip away at my quality of life. It has forced me to 
leave a job that I loved, placed a heavy burden on my family and at 
times each day renders me unable to walk, read a book or even dress 
myself. For someone raised as an independent farm boy, I cannot express 
the frustration that accompanies this disability.
    Let me begin by giving you a little background about myself. I was 
born in Clinton, Iowa and raised on a farm in Mt. Carroll, Illinois. 
After graduating from high school, I attended radio school at Brown 
Institute in Minneapolis, Minnesota. At age 19, I went to work as a 
night announcer for KROS radio in Clinton. After serving in a number of 
capacities at the station--everything from Announcer to Program 
Director--I purchased stock in the company and was named General 
Manager in 1987. Professionally, I was active in the Iowa Broadcasters 
Association and served as President of the Iowa Radio Network. I was 
also very active in the local community--a member of the Kiwanis Club, 
helping the United Way's Board of Directors for the Clinton Substance 
Abuse Council and was involved in countless fundraisers for various 
worthwhile projects in the Clinton area. In addition, I have always 
enjoyed working with young people. I was inducted into the Junior 
Achievement Hall of Fame for serving as an Applied Economics Advisor. I 
have always had a deep love of sports, especially basketball. I tried 
to share that with youngsters by coaching junior football and 
basketball. Later, I even took up the stripes as a high school 
basketball official.
    It was in 1988, during a basketball game I was refereeing, I held 
out two fingers to indicate two shots when I noticed shaking in my left 
hand. My family had begun to notice a blank stare on my face and I 
began experiencing slowness of movement and pain in my neck. One visit 
to the clinic and I was diagnosed with Parkinson's at the age of 35. 
For five years after my diagnosis, I hid it from all but my family. 
When people asked, I simply said, ``I have a neurological condition''. 
I could relate very well to the feelings expressed by Michael J. Fox 
when he was first diagnosed with Parkinson's. You don't want to believe 
this is happening to you and you certainly don't want anyone else to 
know what is happening to you. What would they think? How would they 
treat me? It was extremely difficult after being someone that was 
always in charge to be forced to depend on others to help me.
    At first, with the help of my medications, I was able to continue 
living a relatively normal life. As long as the medicine was working, I 
could do just about anything. But eventually, progression of the 
disease and side effects of the medications left me no longer able to 
count on being fully functional at work. My condition became so 
unpredictable that I was forced to end my broadcasting career in 1999.
    Today I reside in rural Clinton with my wife, Rita, and three 
youngest children, Joseph 17, Sam 14 and Anne 10. My two oldest 
children are now finished with school and living on their own. Katie, 
21, is serving our country in the U.S. Army. She is stationed in Ft. 
Polk, Louisiana where she currently works with a mobile medical unit. 
Sarah, our oldest, recently graduated from the University of Iowa and 
is now at University Hospitals and Clinics working as a registered 
nurse in the Neurology Department--something that certainly takes on 
added significance given my condition. I am very lucky to have a 
strong, supportive family that has stood by me from the beginning.
    That's not to say it has been easy. I can still recall the profound 
sadness in the eyes of my family members and the uncertainty and sense 
of dread we all felt when word came of my diagnosis. I cannot deny that 
each day I worry about what our future will be like. On the one hand, 
great progress has been made and many new medications have become 
available in just the short time I have been affected. On the other 
hand, there is still no known cause and the possibility of being 
trapped with an alert, active mind in a body I cannot control is more 
frightening than I can describe.
    Since giving up my job, we have had to rely on my wife's income 
from her job at an accounting firm and Social Security to get by. 
Fortunately, she makes a good living, but there is no question that 
Parkinson's has taken an economic toll on our family. We are facing the 
prospect of soon losing our health insurance with prescription 
coverage. With a cost of over $700 a month for my prescription 
medication, we will certainly have to make do with a lot less. I often 
think about all that my family is missing because of Parkinson's 
Disease.
    I have tried to channel some of my anger over being diagnosed with 
Parkinson's into something positive. I started a Parkinson's support 
group in Clinton several years ago, which I still facilitate. This 
group of over thirty families has been a great help to me in facing the 
daily struggle of life with Parkinson's.
    No one knows why or how I got this terrible disease. Is it genetic? 
Two of my great uncles had Parkinson's--but one was on my maternal side 
and the other was on my paternal side. Does the environment play a 
role? I grew up drinking farm water, but so did the rest of my family 
and no one else has Parkinson's. The bottom line is we just don't know 
what causes Parkinson's. But, I am hopeful that we will have answers 
soon. Scientists have made remarkable progress and with adequate 
funding could find new treatments and even a cure in my lifetime.
    I am not a quitter and I refuse to give up hope. I have always had 
a love of old cars, and have used as a motto a line from an old car 
movie ``The Gumball Rally''. In that movie as the race is about to 
start, a driver in a Ferrari turns to his co-pilot, tears off the rear 
view mirror, and says, ``now the first rule of Italian driving--what's 
behind me does not matter''. I try to do the same. Keep looking ahead 
rather than worry about what I've lost and remember all I have to be 
thankful for--most importantly my wonderful family. I hope that by 
staying involved and active in the fight for a Parkinson's cure, I can 
make a difference in my destiny and that of the million other Americans 
suffering from this dreadful disease.
    Again, I thank you for the opportunity to be here today.

    Senator Harkin. Don, thank you again so much, again for 
putting a real human face on what this means to families.
    Now, as the most recognizable man on the planet, Muhammad 
Ali--we have already said a lot about him--certainly needs no 
introduction. He is simply the greatest of all time.
    Lonnie Ali has been married to Muhammad for 14 years and 
has coordinated all his affairs for the past decade. Among her 
many activities related to Parkinson's disease, Mrs. Ali serves 
on the board of the Michael J. Fox Foundation for Parkinson's 
Research. We welcome you both here, and Mrs. Ali, again, your 
statement will be made a part of the record and Muhammad's will 
be made a part of the record. Please proceed as you so desire.
STATEMENT OF MUHAMMAD ALI, FORMER HEAVYWEIGHT BOXING 
            CHAMPION
ACCOMPANIED BY LONNIE ALI

    Ms. Ali. Thank you, Chairman Harkin. A little correction. I 
have been married to Muhammad 16 years.
    I have to count every year.
    But thank you and the members of the subcommittee for 
inviting Muhammad and me here today for this important hearing 
on Parkinson's disease research funding. We are grateful for 
your past support and for focusing attention on this important 
topic.
    We were compelled to be here today because of the troubling 
situation we see occurring with regard to Parkinson's research, 
that may be unnecessarily delaying progress toward better 
treatments and even a cure for Parkinson's. We are here because 
Muhammad has never been one to sit back quietly and wait for 
things to happen. He is and always has been a fighter, not just 
in the ring, but with each and every cause he believes in. We 
are here today as champions of the National Institutes of 
Health research, who will not stop until we reach the gold, a 
cure for Parkinson's.
    To the world, my husband is known as an Olympic Gold Medal 
winner, the Heavyweight Champion of the World, and a man who 
has always stood up for what he believes in. No matter what the 
cause, Muhammad has always used his charm and grace and wit to 
better the world. From the antiwar movement, to the fight for 
civil rights, to his efforts to raise awareness about the 
plight of many third world countries, Muhammad has never been 
far from the center ring.
    Today, however, he is facing an opponent unlike any he has 
ever fought. Just as the million other Americans who suffer 
from Parkinson's, Muhammad is battling a relentless, 
remorseless, insidious thief. Parkinson's recognizes no titles, 
respects no achievements, nor bows to any amount of talent, 
courage, or character. Parkinson's does not discriminate. There 
is no question that Parkinson's is the fight of Muhammad's 
life.
    But Parkinson's affects more than just those who have the 
disease. As the wife, friend, and confidant of someone who 
lives with someone with Parkinson's, I can tell you that our 
entire family and our close friends have been profoundly 
impacted as well. At this time in our lives, we had expected to 
be enjoying retirement, continuing to fight for important 
causes, and most importantly, enjoying time together as a 
family. Parkinson's never stops trying to rob us of those 
dreams. Even though Muhammad keeps punching back and refuses to 
go down for the count, we are certainly not living the life we 
had envisioned.
    We often talk about how much more Muhammad would be doing 
to make the world a better place, to stand up for those who 
cannot stand up for themselves, to fight racism, and to spread 
his message of peace. There can be no doubt that Parkinson's is 
depriving not only our family, but the Nation and even the 
world of Muhammad's full contribution.
    But Muhammad is only one man. There are 1 million Americans 
suffering from Parkinson's. Imagine what those million 
Americans could be doing to better the world if not for this 
disease.
    While Muhammad and I keep up the fight on a personal level, 
scientists are fighting each and every day in laboratories 
across the country to find a cure. They tell us that 
Parkinson's is the most curable neurological disease. In fact, 
at a hearing before this subcommittee on September 28, 1999, 
Dr. J. William Langston, president of the Parkinson's Institute 
and a member of the scientific advisory board for the Michael 
J. Fox for Parkinson's Research, said: ``While science is full 
of serendipity and unexpected surprises in research, sometimes 
you hit a point where it's time to focus. I truly believe that 
we are now at a point where there is enough knowledge that it 
is a time to focus. With a focused effort, the pieces are in 
front of us, the science is there. I think we can make major 
progress towards this disease.''
    We have reached a crossroads. We know the science is there 
but the money is not. I am proud to serve as a member of the 
board of the Michael J. Fox Foundation for Parkinson's 
Research. The foundation is doing tremendous work to fund 
incredibly promising private research. Now it is time for the 
Federal Government to get into the fight for real. We must 
provide the Federal funds necessary to carry out this promising 
research. As the world's leader in biomedical research, our 
Government has a responsibility to realize the tremendous 
scientific potential and provide adequate funding.
    Two-and-a-half years ago, the NIH established the 
Parkinson's Disease Research Agenda, which called for a $1 
billion increase in Parkinson's funding. Unfortunately, the 
Parkinson's agenda is not being fully funded. In fact, there is 
a $100 million shortfall for this year alone.
    Time is of the essence. People with Parkinson's do not have 
any time to waste. This tragic underfunding may lead to missed 
opportunities for better treatments and even for a cure. 
Congress and the NIH have an opportunity to oversee effective 
treatments and possibly a cure for Parkinson's, if the 
necessary funding is made available.
    Muhammad has never been one to do anything halfway, and he 
has never settled for doing something second best in anything 
that he has done, in the ring, in his work on humanitarian 
causes, or in his personal life. We implore the NIH and 
Congress to not go halfway on the Parkinson's Research Agenda. 
The Federal Government must aim high and work hard to reach the 
goal of finding a Parkinson's cure.

                           PREPARED STATEMENT

    Our challenge to you today is to champion this research and 
to fully fund the Parkinson's Disease Research Agenda by 
committing $353.3 million for year 3. Together let us knock 
Parkinson's disease down for the count.
    Thank you very much.
    [The statement follows:]
                    Prepared Statement of Lonnie Ali
    Thank you, Chairman Harkin and Members of the Subcommittee for 
inviting Muhammad and me to be here today for this important hearing on 
Parkinson's Disease research funding. We are grateful for your past 
support and for focusing attention on this important topic.
    We were compelled to be here today because of the troubling 
situation we see occurring with regard to Parkinson's research, that 
may be unnecessarily delaying progress toward better treatments and 
even a cure for Parkinson's. We are here because Muhammad has never 
been one to sit back quietly and wait for things to happen. He is and 
always has been a fighter, not just in the ring, but with each and 
every cause he believes in. We are here today as champions of National 
Institutes of Health (NIH) research, who will not stop until we reach 
the gold--a cure for Parkinson's.
    To the world, my husband is known as an Olympic gold-medal winner, 
the Heavyweight Champion of the World and a man who has always stood up 
for what he believes in. No matter what the cause, Muhammad has used 
his charm, grace and wit to better the world. From the antiwar 
movement, to the fight for Civil Rights to his efforts to raise 
awareness about the plight of many Third World countries, Muhammad has 
never been far from the center ring.
    Today, however, he is facing an opponent unlike any he has ever 
fought. Just as the million other Americans who suffer from 
Parkinson's, Muhammad is battling a relentless, remorseless, insidious 
thief. Parkinson's recognizes no titles, respects no achievements, nor 
bows to any amount of talent, courage or character. Parkinson's does 
not discriminate. There is no question that Parkinson's is the fight of 
Muhammad's life.
    But Parkinson's affects more than just those who have the disease. 
As the wife, friend and confidant of someone with Parkinson's, I can 
tell you that our entire family, and our close friends, have been 
profoundly impacted as well. At this time in our lives, we had expected 
to be enjoying retirement, continuing to fight for important causes 
and, most importantly, enjoying time together as a family. Parkinson's 
never stops trying to rob us of those dreams. Even though Muhammad 
keeps punching back, and refuses to go down for the count, we are 
certainly not living the life we had envisioned.
    We often talk about how much more Muhammad would like to be doing 
to make the world a better place--to stand up for those who can't stand 
up for themselves, to fight racism and to spread his message of peace. 
There can be no doubt that Parkinson's is depriving not only our 
family, but the nation, and even the world, of Muhammad's full 
contribution. But Muhammad is only one man. There are one million 
Americans suffering from Parkinson's. Imagine what those million 
Americans could be doing to better the world if not for this disease.
    While Muhammad and I keep up the fight on a personal level, 
scientists are fighting each and every day in laboratories across the 
country to find a cure. They tell us that Parkinson's is the most 
curable neurological disease. In fact, at a hearing before this 
Subcommittee on September 28,1999, Dr. J. William Langston, President 
of the Parkinson's Institute and a member of the scientific advisory 
board for The Michael J. Fox Foundation for Parkinson's Research, said: 
``[W]hile science is full of serendipity and unexpected surprises in 
research, sometimes you hit a point where it's time to focus. I truly 
believe that we are now at a point where there is enough knowledge . . 
. that it's time to focus. With a focused effort, the pieces are in 
front of us, the science is there. I think we can make major progress 
towards this disease.''
    We have reached a crossroads. We know the science is there--but the 
money is not. I am proud to serve as a member of the board on The 
Michael J. Fox Foundation for Parkinson's Research. The Foundation is 
doing tremendous work to fund incredibly promising private research. 
Now it's time for the federal government to get in the fight for real. 
We must provide the federal funds necessary to carry out this promising 
research. As the world's leader in biomedical research, our government 
has a responsibility to realize the tremendous scientific potential and 
provide adequate funding.
    Two and a half years ago, the NIH established the Parkinson's 
Disease Research Agenda, which called for a $1 billion increase in 
Parkinson's research funding over five years. Unfortunately, the 
Parkinson's Agenda is not being fully funded. In fact, there is a $100 
million shortfall for this year alone.
    Time is of the essence. People with Parkinson's don't have any time 
to waste. This tragic underfunding may lead to missed opportunities for 
better treatments and even a cure. Congress and the NIH have an 
opportunity to oversee effective treatments and possibly a cure for 
Parkinson's, if the necessary funding is made available.
    Muhammad has never done anything halfway, and has never settled for 
second best in anything he has done--in the ring, in his work on 
humanitarian causes or in his personal life. We implore the NIH and 
Congress to not go halfway on the Parkinson's Research Agenda. The 
federal government must aim high and work hard to reach the goal of 
finding a Parkinson's cure.
    Our challenge to you today is to champion this research and fully 
fund the Parkinson's Disease Research Agenda by committing $353.3 
million for year three. Together, let's knock Parkinson's Disease down 
for the count.
    Thank you very much.

    Senator Harkin. Now the founder of the Michael J. Fox 
Foundation for Parkinson's Research, someone who has given us 
so much hope and encouragement and courage through his book and 
through his forming this foundation. This is Michael J. Fox's 
third appearance before this subcommittee. Mr. Fox, we welcome 
you back.
STATEMENT OF MICHAEL J. FOX, FOUNDER, THE MICHAEL J. 
            FOX FOUNDATION FOR PARKINSON'S RESEARCH
    Mr. Fox. Thank you and good morning. Mr. Chairman, Senator 
Specter, and members of the subcommittee, thank you for this 
opportunity to testify.
    Is it just me or were you sitting in different seats the 
last time I was here?
    Senator Harkin. I am constrained to say it is ``back to the 
future.''
    Mr. Fox. I apologize if that is a sore subject for some 
members of the subcommittee, but I bring it up only to make the 
point that it is a tribute to each of you that irrespective of 
the musical chairs of electoral politics and who sits in which 
seats on the dais, the subcommittee's commitment to biomedical 
research funding has remained consistent and committed. And we 
are very grateful.
    Mr. Chairman, all Iowans and all Americans can be grateful 
and proud of your leadership on issues of health, including 
your continuing efforts to make biomedical research a higher 
national priority. You and Senator Specter have spearheaded the 
historic effort that will soon succeed in doubling the budget 
for the National Institutes of Health over 5 years. The fact 
that you have done so, despite difficult budgetary time, 
changing administrations, and changes in majority control, 
underscores the notion that illness and injury truly are non-
partisan issues that need bipartisan solutions.
    I am grateful for the subcommittee's invitation but I would 
not have come back again if I did not feel I had something 
constructive to add. Although we appreciate this forum, none of 
us here today has any interest in becoming another of this 
city's self-perpetuating cottage industries.
    Back in 1999, I testified that Parkinson's research was far 
ahead of the money, that high quality and high impact projects 
are being slowed down or stalled completely by the lack of 
available support. In addition to appealing to you and to the 
NIH, it was clear that there was more that we could do 
ourselves. It did not take long to find a group of like-minded 
people and together we launched a foundation with the single 
purpose of stimulating and supporting research, strategic 
thinking, and collaborations to accelerate the cure for 
Parkinson's.
    We are committed to enabling the work of scientists, and to 
do so, we focus on the process of identifying, funding, and 
tracking research. We try to target where we can have the 
biggest impact and to employ the best methods to shorten the 
funding cycle, share the outcomes of research, and stimulate a 
coordinated effort to translate promising findings into a cure.
    Some of our programs support investigator-initiated grants, 
the bread and butter of the NIH system and an indispensable 
mechanism for supporting new ideas. But with our emphasis on 
higher-risk, higher-reward projects, we have streamlined the 
NIH model and applied some of our own innovative thinking.
    We have also enlisted scientists to identify the highest 
priority areas of research and recommend proactive steps we can 
take to move the field forward in meaningful ways. Such 
assessments have led to several specific funding initiatives, 
including a search for a conclusive diagnostic test or 
biomarker for Parkinson's, and development of a cell line 
specifically for the study and treatment of Parkinson's.
    Last fall we launched a $2.2 million initiative to develop 
cell lines with characteristics deemed relevant to Parkinson's. 
As with our other programs, the scientific response was 
overwhelming. We received applications from a veritable who's 
who of cellular biologists worldwide. The number and the 
quality of the proposals compelled us to double the program's 
budget to $4.4 million, which made it possible for us to 
support a portfolio of projects exploring all the promising 
techniques for creating cell lines from adult, fetal, and 
embryonic cells. The number and diversity of these programs 
will allow for a meaningful comparison of these exciting 
technologies.
    In our request for applications, we made it clear that we 
valued results over technique or cell source. Our program is to 
develop an effective tool to study and treat Parkinson's, not 
to support new technologies for their own sake or to pick 
favorites among emerging therapies. As any patient will tell 
you, their favorite therapy is the one that works. This is an 
obvious and logical approach if your goal is to cure a disease, 
but often the political debate can lead to arbitrary decisions 
or otherwise obscure the fact that the goal of the research is 
to treat, heal, and cure.
    I want to commend you, Senators Harkin and Specter, along 
with Senators Feinstein, Hatch, and all your other bipartisan 
colleagues, for supporting the Human Cloning Prohibition Act of 
2002, which strikes the necessary balance between development 
of potentially lifesaving research and inappropriate 
applications of this powerful technology. It is important to 
make clear that the debate is not about promoting one type of 
research over others. It is about protecting researchers from 
being demonized or criminalized so they can go about their work 
exploring new opportunities to treat illness and disease.
    Development of such promising new therapies puts us on the 
threshold of a new era of medicine. Today a neurologist may be 
able to do little more than tell you the name of the disease 
that is taking away your life, or in some cases he or she may 
be able to give you a prescription or two to ease the symptoms 
for a few years. It is not a great proposition, but there is a 
paradigm shift underway. Understanding of the brain and of 
neurological disorders is advancing at a staggering pace, 
moving from definition of the disease, to treatment, to the 
possibility of repairing the brain and restoring lost function. 
The time has come when the brain is no longer just a place for 
research, it is a place for cures.
    The NIH recognizes this shift and has taken some steps to 
respond. Unfortunately, vacant leadership positions have 
prevented the bold action we need. Our foundation has succeeded 
thus far mostly by tapping into the enormous backlog of 
promising, yet underfunded and unfunded science. We did not 
create this opportunity. We are simply responding to it with 
whatever resources we can muster. As exciting and gratifying as 
it is, seeing the possibility only increases our impatience and 
sense of frustration of what is not getting done. NIH has the 
resources and the infrastructure to do much more.
    To meet the opportunity, I encourage the new NIH Director 
to immediately fill the open NINDS Director position and to do 
so with someone committed to using all available tools, 
including the Director's discretionary budget authority. I 
believe the NIH should responsibly pursue all available 
regenerative therapies for Parkinson's and other diseases and 
adopt an aggressive, proactive Bunsen burner to bedside 
approach to creating cures not just research.
    I will shorten my comments.

                           prepared statement

    In describing our efforts, we often make analogies to great 
achievements like the moon shot. But I am here to tell you that 
administering a successful research program is not rocket 
science. It is mostly common sense and the will to get things 
done. And we are going to get this done. This subcommittee, 
this Congress, and the NIH have the opportunity to make it 
happen in time for many more people today living with 
Parkinson's.
    Thank you.
    [The statement follows:]
                  Prepared Statement of Michael J. Fox
    Mr. Chairman, Senator Specter, and members of the Subcommittee, 
thank you for this opportunity to testify.
    Is it just me, or were you sitting in different seats the last time 
I was here?
    I apologize if that is a sore subject for some members of the 
Subcommittee, but I bring it up only to make the point that it is a 
tribute to you that irrespective of the musical chairs of electoral 
politics, and who sits in which seats on the dais, this Subcommittee's 
commitment to biomedical research funding remains constant.
    Mr. Chairman, all Iowans, and indeed all Americans, should be 
grateful for your leadership on issues of health, including your 
continuing efforts to make biomedical research a higher nation 
priority. This Subcommittee--along with other individuals in this 
room--have spearheaded a historic effort that will soon succeed in 
doubling the budget for the National Institutes of Health over five 
years. You have accomplished this feat through difficult budget times, 
through changing administrations, and even through changes in majority 
control--an achievement that underscores the notion that illness and 
injury truly are non-partisan issues needing bipartisan solutions.
    I am grateful for the Subcommittee's invitation, but I would not 
have come back again if I did not feel I have something constructive to 
add. None of us here has any interest in becoming another of this 
city's self-perpetuating cottage industries. Our appeals to you are 
part of our larger effort to accelerate the cure for Parkinson's 
disease. Much progress is being made, but there is no question that a 
well-funded and coordinated effort by the federal government would 
hasten the pace. And as you have already heard, time lost to 
Parkinson's inevitably means that lives are lost as well.
    You've also heard from Dr. Isacson about the wide array of 
promising research opportunities relating to Parkinson's. He and dozens 
of other senior investigators make clear the inevitability of a 
breakthrough. Taken together, their message is unmistakable: curing 
Parkinson's is not a question of ``if''? It is a question of ``when''?
    Back in 1999, I testified that Parkinson's research was far ahead 
of the money. Joan, Dr. Bill Langston, and I all testified that high 
quality and high-impact projects were being slowed down or stalled 
completely by the lack of available support. In addition to appealing 
to you and the NIH, we saw there was more we could do ourselves. With 
their help and advice, and together with a group of like-minded people, 
we launched a foundation with the single purpose of stimulating and 
supporting research, strategic thinking, and collaborations to 
accelerate the cure for Parkinson's.
    We are lay people committed to enabling the work of scientists, and 
to do so we focus on the process of identifying, funding, and tracking 
research. We try to target where we can have the biggest impact and to 
employ the best methods to shorten the funding cycle, share the 
outcomes of research, and stimulate a coordinated effort toward the 
cure.
    Some of our programs support investigator-initiated grants--the 
bread and butter of the NIH system and an indispensable mechanism for 
supporting new ideas--but in keeping with the higher-risk, higher-
reward nature of our mission we've streamlined the NIH model and added 
our own wrinkles.
    We've also enlisted scientists to identify the highest-priority 
areas of research and recommend proactive steps we can take to move the 
field forward in meaningful ways. Such assessments have lead to several 
specific funding initiatives, including the development of a cell line 
specifically for the study and treatment of Parkinson's.
    One month after the meeting that made the recommendation we 
launched a $2.2 million initiative to develop cell lines with 
characteristics deemed relevant to Parkinson's. We received 
applications from a veritable who's who of cellular biologists 
worldwide. The number and quality of the proposals compelled us to 
double the program's budget to $4.4 million, which allowed us to 
support a portfolio of projects exploring all the promising techniques 
for creating cell lines from adult, fetal and embryonic cells. The 
number and diversity of these programs will allow for a meaningful 
comparison of these exciting technologies.
    In our request for applications we made it clear that we valued 
results over technique or cell source. Our program is to develop an 
effective tool to study and treat Parkinson's, not to support new 
technologies for their own sake or to pick favorites among emerging 
therapies--any patient will tell you that their favorite therapy is the 
one that works. This is an obvious and logical approach if your goal is 
to cure a disease, but often the political debate can lead to arbitrary 
decisions or otherwise obscure the fact that the goal of the research 
is to treat, heal, and cure.
    I want to commend you Senators Harkin and Specter, along with 
Senators Feinstein, Hatch and all your other bipartisan colleagues for 
supporting the ``Human Cloning Prohibition Act of 2002,'' which strikes 
the necessary balance between development of potentially life-saving 
research and inappropriate applications of this powerful technology. It 
is important to make clear that the debate is not about promoting one 
type of research over others, it is about protecting researchers from 
being demonized or criminalized so they can go about their work 
exploring new opportunities to treat illness and disease.
    Development of such promising new therapies puts us on the 
threshold of a new era of medicine. Today a good neurologist may be 
able to do little more than tell you the name of the disease that's 
taking away your life, or in some cases he or she may be able to give 
you a prescription or two to ease the symptoms for a few years. It's 
not a great proposition, but there is a paradigm shift underway. 
Understanding of the brain and of neurological disorders has advancing 
at a rapid pace, moving from definition of the disease to treatment to 
the possibility of repairing the brain and restore lost function.
    Not too long ago it was an anathema to think that the brain has any 
capacity to regenerate and repair itself. But in recent year many 
scientists have embraced this recently revolutionary concept and run 
with it. Dr. Isacson, for example, is so convinced in the potential of 
the science that he has named his lab the ``Neuroregeneration 
Laboratory.''
    NIH recognizes this shift and has taken some appropriate steps to 
respond. Nonetheless, they still trail behind the scientists out on the 
cutting edge--those whose experience increases our confidence that a 
cure is within reach. Our own experience shows the type of efficient 
funding process that is possible and the level of interest there is in 
doing the necessary work. All of this is tremendous progress, but it 
also increases impatience and sense of frustration over what is NOT 
getting done.
    To meet the opportunity, I encourage the new NIH Director to fill 
open NINDS Director position, and to do so with someone committed to 
using all available tools--including the Director's discretionary 
budget authority--in the fiscal year 2002 and fiscal year 2003 budgets 
to direct significantly more funding toward implementation of PD 
Research Agenda. I believe the NIH should responsibly pursue all 
available regenerative therapies for Parkinson's and other diseases, 
and to adopt and an aggressive, proactive ``Bunsen burner to bedside'' 
approach to pursuing cures, not just research.
    I want the Subcommittee to know that we in the private sector hope 
to engage in greater collaboration with NIH when tapping Parkinson's 
researchers for advisory and planning meetings. The goal is to reduce 
the number and replication of meetings and allow more time for the best 
scientists to work in their labs.
    When I first appeared before this Subcommittee I spoke about my 
experience with Parkinson's disease. I did so in very personal terms 
because that is what I know. I know my own Parkinson's, which is 
different than Muhammad's, or Joan's, or Don's, or Milly Kondracke's. 
Every person who is diagnosed with Parkinson's is given their own 
custom version of the disease--and no operating instructions, I might 
add.
    The other thing given to every person diagnosed--particularly the 
growing number of young-onset cases--is a reason to hope.
    We are told that scientists are making great progress and that with 
the proper funding there may be a cure in five or ten years. We hear 
that there is no shortage of good ideas, just a shortage of research 
money. More recently we have been told that more money is on the way. 
The heroic efforts of the grassroots advocacy community are having an 
impact and Congress is taking steps to ensure more Parkinson's research 
funding. Congress passed Parkinson's-specific legislation, asked NIH to 
develop a Parkinson's Research Agenda, and last year adopted strong 
report language urging more funding and full implementation of the 
research agenda.
    These have each been significant accomplishments, and we are all 
grateful to this Subcommittee and your colleagues in the Senate and 
House for your support. And yet despite these legislative achievements, 
support of Parkinson's research has failed to keep pace with the 
overall growth in NIH's budget, it has not meet the goals of the NIH 
Research Agenda and it falls far short of the scientific opportunity. 
Is it that this system is not designed to systematically and 
aggressively study, treat, and cure a disease? If that's true, we have 
got to reinvent the system.
    NIH has a vital roll funding basic research and supporting 
scientific explorations. But when there are opportunities to reduce 
human suffering and societal costs by curing a disease like 
Parkinson's, then I think it is appropriate for the National Institutes 
of Health to commit a fraction of it's resources to actually treating 
the nation's health. Parkinson's disease is both an individual and 
national challenge. We ought to act as surely as we act in response to 
other challenges to our health, our lives, and our society.
    I would not take this coveted time before the Subcommittee to argue 
for something than cannot be done. Our experience is evidence that it 
can. And we'll keep at it, because unlike some other reports you may 
have heard, we have yet to determine any shortage of interest in 
Parkinson's research or in high-quality, high-impact projects that 
await funding. Don't let anyone tell you that everything that can be 
done is being done or that the scientific community has reached its 
capacity for Parkinson's research.
    What's more, I believe we are at the ``tipping point'', the moment 
of critical mass when the momentum towards the cure becomes 
irresistible and the only remaining question is whether the federal 
government will be helping lead the process, or will it be trailing 
along behind?
    In describing our efforts we often make analogies to great 
achievements like the moon shot. But I am here to tell you that 
administering a successful research program is not rocket science. It 
is mostly common sense and the will to get things done. And we're going 
to get this done. This Subcommittee, the Congress, and the NIH have the 
opportunity to make it happen in time for many more people living today 
with Parkinson's.
    Thank you.

    Senator Harkin. Michael, that was a very profound 
statement. Thank you so much.
    Before I turn to Senator Specter, who would like to ask 
some questions and make a statement, we have now been joined 
also by another former U.S. Senator and former Secretary of 
Transportation in the administration of President Carter. Our 
former colleague, Senator Brock Adams of the State of 
Washington, is also here.
    Senator Specter.
    Senator Specter. Thank you very much, Mr. Chairman, for 
deferring to me. I am going to have to excuse myself in a few 
moments and wanted a chance to make a few closing comments.
    This is an unusual hearing where there is applause. 
Customarily there is tough cross examination on witnesses when 
we have to get into some of the very difficult matters. But 
there is a lot of love in this room and a lot of unity of 
purpose to try to reach a common goal, and that ought to be 
noted.
    This subcommittee will pursue these issues with great 
intensity, as we have, and we will try to see to it that there 
is full funding for Parkinson's, because it is true that the 
money is there. The funding is there and it is a matter of 
allocation. We try to depoliticize the matter by leaving it to 
the discretion to the National Institutes of Health, but we 
have a view and they do listen to us more than occasionally.
    Dr. Ruth Kirschstein is smiling. She had been acting 
Director of NIH and she is now Deputy Director. I join Senator 
Harkin in saluting you, Dr. Kirschstein, for your great service 
and the award which you have received today.
    I compliment you, Mr. Fox, on many things, but you noticed 
the role reversal up here. Senator Harkin has the gavel. I 
touch it. It is almost too hot to handle.
    Senator Harkin had been the chairman back in 1994 and I 
took over in 1995 for 6\1/2\ years. But we have had a seamless 
transition. It does not make any difference between Tom Harkin 
and Arlen Specter who the chairman is. I think we both learned 
a long time ago, if you want to get something done in 
Washington, you have to cross party lines. I know the American 
people are sick and tired of the bickering that occurs in 
Washington, which is all too frequent, but not on this 
subcommittee and not on this purpose. And we are determined to 
move ahead.
    Joan Samuelson, I know exactly what you mean with your 
comment about no time to lose. I think that is exactly right. 
You only have your health once, and there is no time to lose. A 
constituent of mine, Jim Cordy, in Pittsburgh, who suffers from 
Parkinson's carries around an hourglass, and whenever he sees 
me, he inverts it to let me know that the sands of time and the 
seconds of his life are ticking away. That is the kind of 
intensity which we appreciate and understand.
    Mr. Don Schneider, you have still got a strong voice. You 
can tell radio there. You can tell projection. We hear you. We 
hear you loud and clear.
    And thank you, Dr. Penn and Dr. Isacson, for what you have 
contributed here today.
    Muhammad Ali was in Pittsburgh not too long ago. He has 
great resiliency in responding to the bell to come out 
swinging, and with The Champ in our corner and with Mrs. Lonnie 
Ali's eloquent statement, we have our work cut out for us.
    We have special momentum from Claiborne Pell, Mac Mathias, 
Brock Adams, and Mrs. Russell Long, and really from millions 
and millions of Americans.
    I would conclude on the note which Michael J. Fox sounded 
about the pending legislation. Everyone in America is either 
afflicted with the disease, has a family member afflicted with 
the disease or knows somebody who is. If there is an 
understanding that this legislation could cripple the efforts 
to use stem cells to cure Parkinson's, Alzheimer's, heart 
disease, and cancer, et cetera, America would rise up in an 
avalanche. That is a message we are working to carry forward. 
This hearing is very, very helpful because of the focus of 
attention it has brought on this critical problem.
    So, I thank you and I give you the pledge of the 
subcommittee--I know I speak for Tom Harkin and all the 
members--that we will continue fighting, and I think we are 
going to win it. Thank you all very much.
    Senator Harkin. And though not a member of the committee, 
but again, one of the most effective and powerful voices in 
fighting Parkinson's in the entire United States Congress, 
Senator Paul Wellstone.
    Senator Wellstone. Thank you, Tom.
    You know, Arlen, I do not know that we always agree, but I 
cannot think of a word that you just uttered that I could 
disagree with. And I just would like to say to everybody here, 
those who testified, those who came, everyone, and all the 
people that your represent around the country, it is an 
absolute honor to work with you. We will all take this journey 
together, and there is no doubt in my mind that we will 
succeed. Thank you.
    Senator Harkin. Thank you very much, Paul.
    Well, since they just both gave my speeches, I will just 
refrain from giving a speech here. But I would like to ask a 
couple of questions, make a point, and then maybe ask a couple 
of questions.
    Dr. Penn, I know that you put that chart up that pointed 
out the increases in Parkinson's disease funding in the mid-
1960's that was above the annual increases at NIH.
    Dr. Penn. Sir, it is 1996 to 2001.
    Senator Harkin. 1996, 1997, 1998, 1999, and 2000.
    Dr. Penn. Right, over 5 years.
    Senator Harkin. For argumentative purposes and debate 
purposes, we can all use percentages to try to make our case. 
When people tell me that we have had this huge percentage 
increase in anything, I always ask one question. What is the 
baseline? You see, to go from 0 to 1 is an infinite percentage 
increase. So, I have got to know what the baseline is. Quite 
frankly, yes, I would agree that percentages were higher, but 
we started from a very, very low baseline.
    So, I think what we have to look at in cases like this, 
especially in biomedical and medical research, is where are you 
in the spectrum from knowing nothing to translating it into a 
cure. Where are you on that?
    It would seem to me that in this specific case of 
Parkinson's, that needle is way past the halfway mark in terms 
of knowing nothing, starting the basic research, to getting to 
the point of doing translational types of applications. Now, 
that is the point at which we have to focus not so much on 
percentages and percentage increases, but what are the requests 
out there for projects, what are we capable of doing in 
translating this research to the bedside, what are we capable 
of doing right now in moving ahead from the basic research, 
which we have passed a lot by--Dr. Isacson spoke about it--to 
really translating this into clinical trials?
    So, I am not interested in the percentage. I want to know 
how much money overall will it take to move that needle towards 
the cure from where we are right now. And that is what we are 
focused on here. What is it going to take dollar-wise, not 
percentage-wise?
    Now, I know the President's budget has $215.1 million for 
Parkinson's funding for next year. That is up from $198.8 
million from last year. That percent would be 8.2 percent. But 
again, I would like to get off the percent increase. I want to 
know what is it going to take dollar-wise. I do not know if you 
could speak to that or not, Dr. Penn.
    Dr. Penn. I couldn't possibly estimate dollar-wise. What I 
can say is that at NINDS, and with the rest of the institutes, 
we are convinced that the scientific advances have been really 
excellent, that all the investigators that came and 
participated and were involved in the Parkinson's Research 
Agenda that have put in applications that went successfully 
through rigorous peer review have been funded. We funded 80 
applications in 2 years between 2000 and 2002 on----
    Senator Harkin. 80 percent?
    Dr. Penn. 80 brand new applications. The average cost of 
these at this point is about $400,000. We have got the 
initiatives out there. We are funding the Udall centers. And 
when we had the meeting of the consortium in January of 2002 to 
look again at this agenda and where we were going, the 
investigators did not want to talk budget. They wanted to talk 
science, and they were very pleased at the fact that all the 
areas of the agenda were really moving forward. So, as I tried 
to say in my opening statement, I think we are on the verge of 
excellent control and a much better quality of life, though we 
are going to need to work on all of the things that Dr. Isacson 
mentioned to achieve a cure.
    Senator Harkin. Well, the Parkinson's Research Agenda is 
intended to answer the dollar question. I might turn to Joan on 
this and just ask you. The Parkinson's Research Agenda is 
asking for, as Mrs. Ali mentioned, $353.3 million. Again, I do 
not need you to go into great detail, but how do you arrive at 
a figure like that?
    Ms. Samuelson. Well, the scientists did it. They met and 
discussed several areas of research with great promise in 
detail. They had the experts from all the areas. And they put 
dollar amounts on it. It is interesting, because we had a 
research plan just sponsored by the Parkinson's Action Network 
before the NIH's, and it arrived at similar numbers. It was a 
matter of the scientists who are the best in the field, who 
understand what it takes to run the lab and to do the work and 
have the wish list of projects that they are not funding, 
devoting their time to figuring it out. That is the same thing 
that happened with the NIH's. It was a very deliberate, 
elaborate process with a room full of investigators who are NIH 
recipients and understand the process. It was a very sober, 
careful process that arrived at these numbers that would 
gradually add up to an increase of $1 billion over 5 years.
    Senator Harkin. So, from that, you are saying that there is 
enough in the scientific community to warrant that kind of 
spending that would be solid, good research, and I assume some 
trials within that.
    Ms. Samuelson. Absolutely.
    Senator Harkin. Dr. Penn, will we be doing some trials in 
the next year?
    Dr. Penn. Yes, we will and we have the agents. The meeting 
was yesterday on the neuroprotective agents that are 
potentially useful. Of course, they have to be studied in pilot 
trials before you put them safely into phase III trials on 
humans.
    We also are doing this trial with the Veterans 
Administration on the deep brain stimulation which I think will 
really improve control enormously. It also has the potential of 
improving the motor side effects of L-dopa, and that would be 
tremendous because L-dopa is a wonderful drug. It just causes 
all kinds of side effects.
    We have got to replace the cells, though. I will not deny 
that.
    Senator Harkin. Well, that leads us to Dr. Isacson then. 
Two things I want to ask you about. I understand that your 
center is investigating a number of different neurological 
disorders, Alzheimer's, Huntington's, ALS, Parkinson's. There 
may be others that I do not know about. Which of those do you 
believe is closest to actually having some form of a cure?
    Dr. Isacson. Oh, I think it is absolutely Parkinson's 
disease. The understanding of the underlying disease process is 
clearer in that case and also probably the treatments are going 
to be simpler in the sense that once you have the science.
    You need, however, to build capacity here in the sense that 
the Parkinson's Research Agenda that was mentioned--that is a 
scientific document that has been evaluated in terms of what 
you would need in terms of funding. But to implement that 
requires an effort. It requires innovation also in the way that 
the centers are organized. We talk now about core facilities to 
build up services for the scientific labs to move faster. There 
is a need to build capacity into the system. Even when you have 
made a scientific discovery, you need to move it forward.
    I feel that the scientists and clinicians involved in this 
effort need to work with NIH. We seem to have a good 
understanding and agreement on the pieces here, but your 
leadership on this issue and pointing out that we need to take 
a very aggressive path forward that we understand is a 
reasonable thing to do.
    Senator Harkin. Dr. Isacson, I understand also that by 
moving ahead aggressively in Parkinson's--it is my 
understanding at least from your testimony and others'--that 
may lead to other avenues of cures for other neurological 
disorders.
    Dr. Isacson. If I may comment.
    Senator Harkin. Yes, please.
    Dr. Isacson. I am glad you asked that. I am convinced that 
when we talk about treatment modalities, most of us know we can 
go to the pharmacy and we get a drug. But there are new 
modalities that will come out of what we have discovered and 
worked on in the States for a long time, for example, the 
genome project. All these knowledge bases in science are likely 
to generate new technologies, new modalities. And when we break 
open the door to new treatments for Parkinson's disease, there 
is going to be a lot of movement also for other diseases, and I 
am thinking about ALS, Huntington's disease, even spinal cord 
damage. So, I can assure you that the scientific community 
again agrees on this, that it is useful and reasonable to 
spearhead Parkinson's disease, to open up the new treatment 
modalities.
    Senator Harkin. I understand that you have had some notable 
success--and you mentioned it--in using embryonic stem cells in 
rats that were undifferentiated that you put into the brains of 
rats. You had instilled in them the Parkinson's-like disease 
and these rats have recovered. Is that so?
    Dr. Isacson. That is correct.
    Senator Harkin. Is it not so that we are about 95 percent 
like a rat?
    I do not mean we politicians. I am not saying that.
    I am saying we as humans, I think genetically. The genes. 
Do we not share about 90-some percent? I do not know what it 
is, but it is pretty close.
    Dr. Isacson. Just to be contradictory, I think that none of 
the psychology seems to overlap.
    But biologically speaking, you are right.
    Senator Harkin. Genetically speaking.
    Dr. Isacson. Genetically speaking, there is a huge overlap. 
What we learn from animals--we call them animal models--we can 
usually create models for new therapies. One can call them 
prototypes to have a more general understanding. And those 
prototypes that we build, sometimes even in fruit flies, give 
us knowledge and insight about molecular mechanisms and what I 
call the new therapeutic modalities, new technologies to help 
the patients.
    So, yes, the kind of work we have done on stem cells is 
important. It is very clear that we can obtain the cells that 
die in Parkinson's through stem cell work, and as I mentioned 
previously, I think it is absolutely necessary to have freedom 
of research typical of our country to pursue that vigorously as 
you have indicated in your bill, for example, on nuclear 
transplantation.
    Senator Harkin. Give me some idea. When do you think we 
would actually--I mean, looking ahead, if we had a robust 
increase in Parkinson's funding for the next year, take me down 
the road a little bit. I can ask Dr. Penn this or maybe even 
Joan. I will ask anyone. When do you think we might actually 
see some human clinical trials?
    Dr. Isacson. Well, my opinion, in this case, of course, is 
an opinion.
    Senator Harkin. That is all I am asking.
    Dr. Isacson. My thinking on this is that we are very close. 
There are a number of these research areas, defined in this 
Parkinson's Research Agenda by NIH, that are likely to generate 
clinical trials. As mentioned by Dr. Penn, neuroprotective 
trials for up to $500 million over the next 7 years will give 
us insight about new drugs that can prevent the cells from 
dying. We are looking also at gene therapy, sometimes 
misunderstood, but again, taking advantage of the molecular 
revolution, genome project, to look at new drugs that use 
therapeutic genes. That is likely to move into pilot clinical 
trials quite soon, maybe before 5 years.
    So, to give you an impression, I think a number of these 
efforts are moving along, as you said I think correctly, in the 
process towards what is reasonable. I always say that FDA is 
sometimes lambasted for not being responsive, but in the end we 
come there with our ideas and they look at them if they are 
safe, and then we test them. But there is a process there.
    Senator Harkin. Dr. Penn, anything else on that?
    Dr. Penn. I would say that FDA is actually a partner. We 
have talked to them about how we would move when using the 
approved ES cell lines in people because, after all, there are 
several issues there. So, they are waiting in the wings for us 
to get to that point.
    I have talked to our own major investigator in this area 
who is in our intramural program who is proceeding to, as I 
said in the statement, drive the human ES cells toward dopamine 
cells. He thinks that will take him 1 to 2 years to just do it, 
and then, of course, you have to get it into the brain safely 
and you have to fulfill the FDA guidelines. And then we could 
actually get to a pilot clinical trial in people.
    But again, science moves up and then it moves back, and you 
cannot always predict. So, I do not want to give you an exact 
date. But we fully intend to move into clinical trials with the 
approved cell lines as soon as we can.
    Senator Harkin. That brings me to Michael Fox then. What 
you have been doing with your foundation on the fast track 
funding process that your foundation has worked out with NINDS, 
can you tell us just again, Michael, how this works and what 
you have been able to do so far?
    Mr. Fox. To sum it up, basically we approach this problem--
and one of the reasons why I went through the things that we 
had done was not so much to blow our horn, but to show that 
what this really calls for I think--our proximity to the goal 
calls for really an innovative approach and to know that if we 
had--just, for example, the amount of time that it takes for an 
application for a grant, if we can trim those processes in a 
responsible way, if we can make it easier for the scientists to 
do what they need to do and just take an innovative approach to 
the way the machinery of science normally works, we can hasten 
our march toward a cure.
    So, what we were able to do was to cut down. We put out an 
RFA, request for application, for our first round of grants. I 
believe that the time frame was something like 3 months, much 
shorter. What happens then is you attract a lot of different 
researchers that might not have been able to do it otherwise 
and you widen the field of people who want to get involved and 
then you widen the talent pool.
    What had happened in our case was we were very fortunate to 
have the NIH come to us and comment on that fast track and join 
us and help us fund some of those proposals. So, it was a very 
exciting response from them and very responsible, and we were 
thrilled. For us, it really showed that there can be innovative 
partnerships and goal-oriented partnerships that make it easier 
for scientists to do the work.
    There is nothing harder for a scientist than to initiate a 
field of study and then have funding dropped out or to not know 
what they are getting into. It is not a question sometimes of a 
scientist not wanting to do the work or not having work to do, 
but he is a person too and he or she has responsibilities to 
their employees and to the lab and to their families. So, they 
need to know that they will be backed all the way and that 
things will be made to facilitate their work. These are not 
wizards in the sky. These are people doing real work. So, we 
need to appreciate that and make it easier for them.
    Senator Harkin. Dr. Penn, how do you feel the partnership 
is working?
    Dr. Penn. The partnership is working. We were very 
fortunate to be able to partner with the Michael J. Fox 
Foundation.
    And just for the record, the reviews for those innovative 
fast track grants actually occurred on September 11, and people 
finished the reviews because it was so important and did not 
try to--they could not leave town. We could not even get back 
to NIH. But it was accomplished. We have a great group.
    We have always worked with voluntary organizations to 
identify new and promising investigators, and to try to start 
up research, because those folks do have to go through peer 
review ultimately for their next grants, and we like to make it 
as straightforward and as promising for them as possible.
    Senator Harkin. Again, congratulations on the foundation 
and what you are doing with this partnership is very 
innovative. It is something I have not seen before.
    Mr. Fox. Thank you. That is what we need, though.
    Senator Harkin. We might use the model for other things 
too, you know.
    Mr. Fox. I did not have a chance to say it early but 
everybody on this panel I thank personally for the things that 
they have done. I think a lot of people bring innovative 
thinking to this problem but the problems are so real and the 
need is so real and the urgency is real. And we really feel we 
can get this done.
    Senator Harkin. Don Schneider, I have a couple of 
questions, but one I really have got to ask you. What year is 
that red Corvette?
    Mr. Schneider. 1977.
    Senator Harkin. Is that right? I had a 1977 Corvette. Well, 
we cannot take this time to talk about Corvettes.
    Mr. Schneider. I can dust it for fingerprints.
    Senator Harkin. We will do it later sometime.
    As somebody who has been very active all his life and taken 
charge and everything, it would be helpful for you to put a 
human face on things, just talk a little bit. What did you have 
to do to get ready for this morning?
    Mr. Schneider. When I get up in the morning, I cannot walk. 
My feet shuffle like they are stuck to the floor. I tremor, 
shake the whole bed, until my medications kick in. Then once my 
medications kick in, it is just like a light switch. I go from 
not being able to move to being able to do anything. That lasts 
for a couple hours, and then the next dose is due. That is my 
day.
    Senator Harkin. Mrs. Ali, how about you and how about 
Muhammad? How is his day?
    Ms. Ali. Yes, Muhammad has been quite fortunate because he 
was diagnosed with Parkinson's in 1981, so he has had it for 
over 20 years and probably had it before then. But I have seen 
the progression in the last 5 or 6 years similar to what 
everyone here has related. And Parkinson's is like every other 
disease. It is individual. It affects people in different ways.
    If you ever looked at a fight tape of Muhammad or an 
interview or a documentary, you know how he lit up the screen 
and how he loved the camera. Now you see him sitting here with 
his eyes closed. It is not because he is trying to block you 
out, it is because Parkinson's made him photophobic to light. 
His face does not love the camera like it used to.
    In fact, I think the biggest thing that Parkinson's has 
done is rob this man of his confidence which I think is just 
absolutely horrible. I think we are being deprived of a lot of 
things from this man and a lot of other people, but his day is 
not like it used to be. It is very difficult for him to move 
around. He is a prisoner in his body.
    Senator Harkin. Of all the good that you have done, 
Muhammad, around the globe, I still believe that you are one of 
the greatest ambassadors of good will this country has ever 
had. If I were President, I would be calling on you, I can tell 
you that, even with Parkinson's. I think again the courage that 
you show to people around the world who know you, this could 
have a profound effect and will have a profound effect on 
people. There are a lot of people around the globe who look 
upon you, and rightfully so, as a great hero of theirs. They 
may not have much hope for their lives, but you give them hope. 
So, I encourage you, Muhammad, keep on and just keep on 
fighting. You got it, man.
    Well, Mrs. Ali, you quoted Dr. William Langston who said 
sometimes you hit the point where it is time to focus.
    Ms. Ali. That is correct.
    Senator Harkin. And now is the time to focus.
    I thank you all for being here. I will close by just saying 
that, first, a disclaimer. We do not on this committee specify 
what NIH has to do. We are not scientists. I am not a 
scientist. I believe over my years here, though, I have 
absorbed quite a bit. I am not an expert, though. But I have 
been on this committee now 18 years, first under Lowell Weicker 
and then Lawton Chiles. Then I was chairman, then Senator 
Specter, and now I am back again as chair. Through those years, 
we have seen great progress made through NIH. It really is the 
crown jewel of the Federal Government, no doubt in my mind. And 
I am proud that Senator Specter and I were able to work 
together collaboratively to double the funding for NIH. So, I 
do not feel within my purview or Senator Specter's or anyone 
else to tell NIH put this money in this research, put this 
money in that research.
    But I am a public servant. I have to reflect what the 
public wants. That is my oath of office. I also need to 
translate to NIH what we hear here in this hearing room. Now, 
scientists are doing their job. Our job is to try to help them 
do their job, not in the way of explicitly telling them what to 
do, but our telling them here is what we are hearing from the 
public. Here is what we know on the record. Here is what 
experts from different fields have told us. And it is the 
interest of this subcommittee that funds NIH that you take this 
into consideration and look at it in your decisions on how much 
to put in funding different disease groups.
    That is why last year some people say I stepped out of 
bounds--but I do not believe so--in the language that I 
inserted in with our funding bill on Parkinson's. Year after 
year, under Senator Specter and last year under my 
chairmanship, we kept seeing that needle move more and more 
away from just the basics into actually something that needs to 
be translated. So, we wanted and I wanted specifically to put 
some very strong language in there not just to tell scientists 
what to do but to tell them here is the sum and substance of 
what we have heard here, not just me, but all the witnesses, 
the experts, the other scientists in the field are saying. And 
you need to act on this and come back and tell us what you are 
going to do.
    So, I think that is a proper role for us to play here and 
we will continue to play that role. So, I will in drafting the 
language on this bill again say to Dr. Zerhouni, who is now the 
new head of NIH, that this is what we are hearing, that the 
language I used last year was intended to let you know that 
this committee feels very strongly that we need not just a 
percentage increase, but we need to get as close as possible to 
the research agenda put forward by the Parkinson's Action 
Network. As close as possible.
    And you have my word that language will be in there this 
year.
    In our oversight hearings, we will have again Dr. Penn and 
the head of NIH down to ask what they are doing in this area, 
because I believe this is what this committee has heard from 
you and from other witnesses, that we need to move ahead 
aggressively in this area.
    So, again, I thank you all very much for being here. Joan, 
I think thank you especially for your great leadership in this 
area. You have been the driving force behind this. Actually, 
you know, Joan Samuelson probably wears about a 5 shoe or 6 
shoe, but I feel sometimes it is about a size 15 in the middle 
of my back sometimes.
    But it feels good because you are doing the right thing and 
you keep us informed and advised. You keep pushing us. And that 
is what you ought to be doing too. Keep on pushing us too.
    Dr. Penn, thank you for your leadership there.
    Muhammad Ali, Michael J. Fox, thank you so much for your 
leadership, your inspiration. You have given us all this hope 
and courage.
    Don Schneider, see you back in Clinton. We are going to 
lick this thing.

                 prepared statement and letter received

    We have received the prepared statement of Senator Thad 
Cochran and a letter from Do No Harm: The Coalition of 
Americans for Research Ethics. They will be placed in the 
hearing record.
    [The statement and letter follow:]
               Prepared Statement of Senator Thad Cochran
    Mr. Chairman, thank you for conducting this hearing on Parkinson's 
Disease research. Parkinson's Disease is a good example of how our 
efforts to increase medical research funding are making a difference.
    We began this effort in 1997 with the Morris K. Udall Parkinson's 
Disease Research Act. Since that time, there has been impressive 
progress in the effort to find a cure.
    Important areas of this research include prevention, diagnosis and 
treatment of Parkinson's. Another important development has been the 
collaboration between NIH Institutes and researchers. We must explore 
further how advances in imaging technologies can improve diagnosis and 
treatment of Parkinson's. We must also consider such areas as the link 
between environmental conditions and the disease. We can only address 
many of these issues through greater NIH research collaboration.
    I agree with a statement Michael J. Fox made several years ago that 
``this is a winnable war''. I believe, however, it is only winnable if 
we continue our investment in research. I thank the researchers and 
patients here today for keeping us focused on how this investment will 
help us win this war.
                                 ______
                                 
           Letter from Do No Harm: The Coalition of
                             Americans for Research Ethics,
                                                      May 21, 2002.
Hon. Tom Harkin,
Chairman, Subcommittee for Labor, HHS and Education,
Senate Appropriations Committee, Washington, DC.
    Dear Senator Harkin: I would like to submit this letter and 
enclosed fact sheet as a written submission for your May 22 hearing on 
Parkinson's disease. These are submitted on behalf of Do No Harm: The 
Coalition of Americans for Research Ethics, a coalition of scientists, 
researchers, bioethicists and others supporting adult stem cell and 
other research avenues to cure disease that do not rely on the creation 
and destruction of human life.
    It is important to note how predictions have changed in less than a 
year regarding the most promising avenues for Parkinson's research.
    Last summer the Parkinson's Action Network urged Congress to 
support federal funding of embryonic stem cell research, declaring: 
``We need a medical rescue and we need it now. Scientists agree it is 
possible this decade'' (PAN press release, July 17, 2001). Just a few 
months later, however, PAN testified to the President's Council on 
Bioethics that clinical benefits from this source are highly 
uncertain--and that any benefits which do ultimately arrive may take 
``another generation'' to help human patients (Statement of Elisabeth 
Breese Brittin, Transcript of the President's Council on Bioethics, 
January 18, 2002). This shift in prognosis is warranted by the very 
disappointing results thus far from the use of embryonic stem cells. 
These cells have produced some modest benefits in animal trials for 
Parkinson's disease, but also shown a disturbing tendency to form 
lethal tumors when placed in living animals. Thus they are a very long 
way from being considered safe (let alone effective) for human clinical 
trials. Use of stem cells from cloned embryos poses its own additional 
problems and risks, due to the havoc wreaked by the cloning process 
upon orderly gene expression and other factors.
    Fortunately, there is also great reason for hope regarding this 
disease. At the same time that timetables have been lengthened for 
benefits from embryonic stem cells, timetables have been moved up for 
benefits from adult stem cells and other alternatives. Recent clinical 
trials have shown an almost complete reversal of Parkinson's symptoms 
for one patient, using his own adult stem cells, and very promising 
results for several other patients using donated adult retinal cells. 
These avenues, as well as new advances in gene therapy and other 
approaches, do provide reason to hope that we can indeed speak of a 
cure for Parkinson's in this decade.
    We hope Congress will take note of these new developments, which 
provide a ``win-win'' situation for all involved in the stem cell 
debate: A clear path to new treatments and perhaps cures, without 
posing the moral and legal problems connected with embryo research and 
cloning.
            Sincerely,
                                                Gene Tarne,
                                           Communications Director.
   Treating Parkinson's With Adult Stems Cell and Other Alternatives
                               in humans
Total Reversal of Symptoms Reported
    Using adult neural stem cells, Dr. Michel Levesque, at the Cedars-
Sinai Medical Center in Los Angeles, reports a total reversal of 
symptoms in the first Parkinson's patient treated. The patient, a 57-
year old former fighter pilot, is still without symptoms three years 
after the adult neural stem cells were removed from his brain, coaxed 
into becoming dopamine-producing cells, and then reimplanted. Because 
the stem cells came from the patient, there was no need for 
immunosuppression to overcome rejection. ``I think transplantation of 
the patient's own neural stem cells and differentiated dopaminergic 
neurons is more biologically and physiologically compatible--more 
efficacious and more elegant,'' said Levesque. In addition to its use 
for Parkinson's, the technique is under study for juvenile diabetes, 
stroke, brain tumors, spinal cord injury, and other conditions.
    Reference.--Results presented April 8th, at the meeting of the 
American Association of Neurological Surgeons.
Retinal Cell Implants Improve Parkinson's
    A team at Emory University School of Medicine has shown that 
implanting retinal cells into the brains of people with advanced 
Parkinson's disease can improve motor function by almost half, 
according to a follow-up study of six patients. The team noted: ``We've 
been following these six participants for over a year, and we've found 
they've improved, on average, nearly 50 per cent in motor function.'' 
The retinal cells used were taken from deceased donors and grown in the 
lab. The team is not using immunosuppressants.
    Reference.--Result presented April 18 at the annual conference of 
the American Academy of Neurology in Denver and reported in the New 
Scientist, 18 April 2002.
    N.B.--There are no clinical treatments for Parkinson's based on 
cloning or embryonic stem cells.
                               in animals
Stimulating Adult Brain Stem Cells Decreases Parkinson's Symptoms
    Injection of growth protein into brains of Parkinson's rats caused 
their neural stem cells to grow, migrate to the site of damage, and 
begin to replace missing nerve cells. Eighty percent (80 percent) of 
the rats received a benefit from the treatment, with no tumor 
formation.
    Reference.--J. Fallon et al.; ``In vivo induction of massive 
proliferation, directed migration, and differentiation of neural cells 
in the adult mammalian brain,'' Proc. Natl. Acad. Sci. USA 97, 14686-
14691; December 19, 2000.
Progenitor Cells Reverse Severe Parkinson's Symptoms in Rats
    Researchers at Chicago's Rush University report coaxing progenitor 
cells from the brains of rats into becoming dopamine neurons to treat 
Parkinson's disease. Led by Paul Carvey, the team discovered an 
important ``shortcut'' to creating a more efficient, more reliable, and 
safer source of stem cells with the ability to turn into specific 
neurons or brain cells. This study is the first to identify the signal 
that instructs stem/progenitor cells to become dopamine neurons. The 
researchers watched the cells develop, and selected and grew cells that 
were close to becoming neurons. They then grafted the cells into brains 
of Parkinson's rats, effectively curing the animals' severe Parkinson 
symptoms. The ability to select and grow large numbers of adult stem 
cells that would become neurons also has the potential to revolutionize 
the treatment of Alzheimer's disease, multiple sclerosis and numerous 
other diseases and disorders of the brain and nervous system.
    Reference.--Results reported at the Experimental Biology Meeting in 
New Orleans, April 2002.
    N.B.--In contrast to these animal studies using adult stem cells, a 
widely publicized study showed Parkinson's rats injected with mouse 
embryonic stem cells receiving a modest benefit for just over 50 
percent of the rats, but one-fifth (20 percent) of the rats died of 
brain tumors caused by the embryonic stem cells.
    Reference.--L.M. Bjorklund et al.; ``Embryonic stem cells develop 
into functional dopaminergic neurons after transplantation in a 
Parkinson rat model,'' Proc. Natl. Acad. Sci. USA 99, 2344-2349; Feb 
19, 2002 (published online Jan 8, 2002)
Gene Therapies Treat Parkinson's in Rats, Monkeys
    The injection of two corrective genes into a specific brain region 
generated significant restoration of normal limb movement in rats with 
Parkinson's disease. Limb impairments were completely reversed in rats 
that had near-total Parkinsonian lesions on only one side of the brain, 
meaning that some of their dopamine-producing cells remained intact. 
But even in the rats with complete destruction of dopamine-producing 
cells, the delivery of gene therapy resulted in a limited amount of 
restored motor function. ``We anticipate gene therapy will offer a way 
to help patients with Parkinson's disease live many years longer free 
of disabling symptoms,'' the researchers noted.
    Reference.--D. Kirik et al.; ``Reversal of motor impairments in 
parkinsonian rats by continuous intrastriatal delivery of L-dopa using 
rAAV-mediated gene transfer,'' Proceedings of the National Academy of 
Sciences USA 99, 4708-4713; April 2, 2002.
    A Japanese research team has demonstrated delayed delivery of gene 
therapy can provide significant recovery from Parkinson's symptoms. 
Four weeks after inducing Parkinson's damage in their brains, rats were 
given an injection of a gene vector which produced a growth protein 
call ``glial cell line-derived neurotrophic factor'' (GDNF). The 
animals showed remarkably higher levels of dopamine secretion and 
significant behavioral recovery, even up to 20 weeks following the 
injection.
    Reference.-- Wang L. et al.; ``Delayed delivery of AAV-GDNF 
prevents nigral neurodegeneration and promotes functional recovery in a 
rat model of Parkinson's disease,'' Gene Therapy 9, 381-389; March 
2002.
    Treatment with three gene therapy vectors has shown behavioral 
recovery in Parkinson's monkeys. The treatment resulted in remarkable 
improvement in manual dexterity and restoration of motor functions, 
with the behavioral recovery persisting for over 10 months in one case. 
The scientists say that this triple gene therapy method may offer a 
potential therapeutic strategy for Parkinson's disease.
    Reference.--S. Muramatsu S. et al., ``Behavioral recovery in a 
primate model of Parkinson's disease by triple transduction of striatal 
cells with adeno-associated viral vectors expressing dopamine-
synthesizing enzymes,'' Human Gene Therapy 13, 345-354; February 10, 
2002.

                         CONCLUSION OF HEARING

    Senator Harkin. Thank you all very much for being here, 
that concludes our hearing.
    [Whereupon, at 11:23 a.m., Wednesday, May 22, the hearing 
was concluded, and the subcommittee was recessed, to reconvene 
subject to the call of the Chair.]

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