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[Senate Hearing 107-87]
[From the U.S. Government Publishing Office]

                                                         S. Hrg. 107-87

                             BLOOD CANCERS

=======================================================================

                                HEARING

                                before a

                          SUBCOMMITTEE OF THE

            COMMITTEE ON APPROPRIATIONS UNITED STATES SENATE

                      ONE HUNDRED SEVENTH CONGRESS

                             FIRST SESSION

                               __________

                            SPECIAL HEARING

                     JUNE 21, 2001--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 \1\

                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
                                     LARRY CRAIG, Idaho
                                     KAY BAILEY HUTCHISON, Texas
                                     JON KYL, Arizona
                     Terry Sauvain, Staff Director
                 Charles Kieffer, Deputy Staff Director
               Steven J. Cortese, Minority Staff Director
                                 ------                                

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

TOM HARKIN, Iowa                     ARLEN SPECTER, Pennsylvania
ERNEST F. HOLLINGS, South Carolina   THAD COCHRAN, Mississippi
DANIEL K. INOUYE, Hawaii             JUDD GREGG, New Hampshire
HARRY REID, Nevada                   LARRY CRAIG, Idaho
HERB KOHL, Wisconsin                 KAY BAILEY HUTCHISON, Texas
PATTY MURRAY, Washington             TED STEVENS, Alaska
DIANNE FEINSTEIN, California         JON KYL, Arizona
ROBERT C. BYRD, West Virginia
  (Ex officio)
                           Professional Staff
                              Ellen Murray
                              Jim Sourwine
                              Mark Laisch
                            Adrienne Hallett
                              Erik Fatemi
                               Adam Gluck
                       Bettilou Taylor (Minority)
                        Mary Dietrich (Minority)

                         Administrative Support
                             Carole Geagley
                       Correy Diviney (Minority)

    \1\ Committee and subcommittee memberships--June 6, 2001 to July 
10, 2001. Senate committee and subcommittee assignments reverted to 
that which had been in existence at the conclusion of the 106th 
Congress.

    Note.--From January 3 to January 20, 2001 the Democrats held the 
majority, thanks to the deciding vote of outgoing Democratic Vice 
President Al Gore. Senator Thomas A. Daschle became majority leader at 
that time. Starting January 20, 2001, the incoming Republican Vice 
President Richard Cheney held the deciding vote, giving the majority to 
the Republicans. Senator Trent Lott resumed his position as majority 
leader. On May 24, 2001, Senator James Jeffords of Vermont announced 
his switch from Republican to Independent status, effective June 6, 
2001. Jeffords announced that he would caucus with the Democrats, 
changing control of the evenly divided Senate from the Republicans to 
the Democrats. Senator Thomas A. Daschle became majority leader once 
again on June 6, 2001.

                            C O N T E N T S

                              ----------                              
                                                                   Page
Opening statement of Senator Tom Harkin..........................     1
Statement of Richard Klausner, M.D., Director, National Cancer 
  Institute, National Institutes of Health, Department of Health 
  and Human Services.............................................     3
New therapies....................................................     4
Prepared statement of Richard Klausner                                5
What are leukemia, lymphoma, and multiple myeloma?...............     5
Moving toward a new understanding of LLM.........................     6
Causes, risk factors, and epidemiology of LLM....................     7
New strategies for treatment of LLM..............................     8
Statement of Senator Arlen Specter...............................    12
Statement of Senator Kay Bailey Hutchison........................    14
Statement of Senator Patty Murray................................    15
Statement of Senator Barbara A. Mikulski.........................    21
Statement of Sandra J. Horning, M.D., Stanford University School 
  of Medicine....................................................    21
    Prepared statement...........................................    23
A Lymphoma primer................................................    24
Lymphoma subtypes................................................    24
Current treatment options and treatment advances.................    24
Challenges for clinical research in lymphoma.....................    25
Role of industry in clinical research............................    25
Research recommendations of the LLM-PRG..........................    26
Recommendations for congressional action.........................    26
Statement of Larry Lucchino, President and CEO, San Diego Padres.    27
    Prepared statement...........................................    28
Treatment for non-Hodgkin's lymphoma.............................    29
Advances in lymphoma research....................................    29
Convening of a blue ribbon panel.................................    29
Action on the recommendations....................................    30
Statement of Miles S. Pendleton, Jr..............................    30
    Prepared statement...........................................    32
Statement of Hagop M. Kantarjian, M.D., Chairman, Leukemia 
  Department, M.D. Anderson Cancer Center........................    35
    Prepared statement...........................................    36
Background.......................................................    36
Current status and progress in leukemias.........................    36
What are targeted therapies......................................    37
Future hopes, expectations and needs.............................    37
A brief glimpse at the leukemia program at M.D. Anderson Cancer 
  Center.........................................................    37
Statement of Senator Ted Stevens.................................    37
Statement of Geraldine Ferraro, former Member of Congress from 
  New York.......................................................    42
    Prepared statement...........................................    46
Statement of Kathryn E. Giusti, President, Multiple Myeloma 
  Research Foundation............................................    49
    Prepared statement...........................................    50
Statement of Kenneth C. Anderson, M.D., Professor of Medicine, 
  Harvard Medical School.........................................    51
    Prepared statement...........................................    53
Statement of John W. Holaday, Ph.D., Chairman and CEO, Entremed, 
  Inc............................................................    55
    Prepared statement...........................................    56
Prepared statement of Beverly S. Mitchell, M.D., President, 
  American Society of Hematology.................................    60
Prepared statement of Howard B. Urnovitz, Ph.D., Scientific 
  Director, Chronic Illness Research Foundation and Chief Science 
  Officer, Chronix Biomedi- 
  cal............................................................    62
Prepared statement of Mrs. Rafael Mora...........................    62

 
                             BLOOD CANCERS

                              ----------                              

                        THURSDAY, JUNE 21, 2001

                           U.S. Senate,    
    Subcommittee on Labor, Health and Human
     Services, and Education, and Related Agencies,
                               Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 9:35 a.m., in room SD-124, Dirksen 
Senate Office Building, Hon. Tom Harkin presiding.
    Present: Senators Harkin, Murray, Specter, Stevens, and 
Hutchison.
    Also present: Senator Mikulski.

                opening statement of senator tom harkin

    Senator Harkin. Good morning and welcome to today's 
subcommittee hearing on blood cancers.
    Before I begin, my staff has informed me we have about 300 
people lined up in the hallway outside. This was the only 
hearing room that we could obtain today, and as you know, it is 
very cramped for space. So, if I could ask everyone to please 
have a seat. If we have extra spaces, we will be able to let 
some more people in.
    Also, I would like to ask for your indulgence. If you are 
here on a panel and you are here to listen to a certain panel, 
if after that panel is finished, if you would be so kind as to 
perhaps remove yourself from the room and let others come in. 
There are a lot of people out there who would like to come in 
and participate in this hearing. So, I would just ask if you 
could do that, I know there are a lot of people out there who 
would really appreciate it, and I would appreciate that.
    This is my first hearing as chairman since 1994, and I 
would like to start first by thanking Senator Specter for the 
tremendous work he has done over the past 6 years.
    Right now there is a vote on the Senate floor. I think it 
started at 9:30. I will make my opening statement and proceed, 
and then as soon as Senator Specter shows up, I will leave to 
go vote and then he will chair the hearing.
    But even in his absence, I want to say that he and I have 
switched back and forth between chairman and ranking member 
since 1989, and we have been partners every step of the way.
    I remember back in the early days when everyone thought we 
were crazy for wanting to double the NIH budget within 5 years. 
Now we are halfway to that goal, thanks in large part to our 
bipartisan teamwork.
    Senator Specter and I have also worked together on 
education, worker rights, stem cell research, and many other 
important issues. That is not going to change just because I am 
the chairman now and he is the ranking member. He will continue 
to be a leader on the subcommittee and I will continue to seek 
his advice and support and friendship for years to come.
    So, I publicly want to applaud Senator Specter for his 
leadership on this committee and for working so closely with me 
over the years.
    Today's hearing is on the important subject of blood 
cancers: leukemia, lymphoma, and multiple myeloma.
    Seeing everyone gathered here this morning and the 300 out 
in the hall reminds me how far we have come since the days when 
people were afraid to even say the word ``cancer.'' Today we 
are not only discussing these diseases openly, but we are 
celebrating some remarkable advances in fighting them.
    Just last month, the FDA approved what is perhaps the most 
promising cancer drug ever developed. This drug called Gleevec 
was given to 54 patients with chronic myeloid leukemia. In 53 
of those patients, the disease basically disappeared. A year 
later, 51 had a normal blood count.
    One reason this is so exciting is it is the first FDA-
approved drug that directly turns off the signal of a protein 
known to cause cancer. Many researchers believe it marks a new 
era in the war against this disease.
    We are also learning more about the use of thalidomide in 
treating multiple myeloma. Those of us who remember the 
devastating birth defects caused by thalidomide in the 1950's 
might find it hard to believe that the drug could stave off 
cancer, but that does seem to be the case.
    Much work remains to be done. That is one reason why the 
members of this subcommittee are fighting so hard to raise the 
funding for the NIH, to find better treatments and cures for 
diseases like leukemia, lymphoma, and multiple myeloma.
    We are fortunate to have a distinguished panel of guests 
with us this morning to discuss blood cancers. I would like to 
personally extend a special welcome to Dr. Sandra Horning, 
Professor of Medicine at Stanford University School of 
Medicine. Dr. Horning is a native of Creston, Iowa, right in my 
back yard, and she earned her B.A. and M.D. from the University 
of Iowa. So, I am particularly proud of the work that she is 
doing on lymphoma.
    I also want to thank Geraldine Ferraro, a long-time friend 
and coworker of mine in the House of Representatives, a leader 
in my party, and I think a leader for a lot of us throughout 
the Nation. I want to thank her for being here this morning. 
Ms. Ferraro has been a trailblazer her whole life; first, of 
course, in Government and politics, and now as an advocate for 
medical research. All of us were saddened to learn about her 
multiple myeloma, but we are grateful that she has decided to 
speak out about her experiences.
    I want to recognize some other Iowans who are here today: 
Scott Smith of WOI TV, Catherine Rhoda, a patient advocate, and 
her husband John, Dr. George Weiner, a researcher at the 
University of Iowa. And I want to thank all of you for making 
the trip to Washington to be with us this morning.

STATEMENT OF RICHARD KLAUSNER, M.D., DIRECTOR, NATIONAL 
            CANCER INSTITUTE, NATIONAL INSTITUTES OF 
            HEALTH, DEPARTMENT OF HEALTH AND HUMAN 
            SERVICES

    Senator Harkin. We will first start off with a long-time 
friend and a great leader in our battle against cancer. Dr. 
Richard Klausner was appointed Director for the NCI in 1995. 
Previously he served as Chief of the Cell Biology and 
Metabolism Branch of the National Institute of Child Health and 
Human Development. He began his career at NIH in 1979 after 
post-graduate work at Harvard. He received his undergraduate 
degree from Yale and his medical degree from Duke University.
    Dr. Klausner, I personally want to thank you for your 
tremendous leadership at the National Cancer Institute and for 
all of your willingness to keep us briefed and up to date on 
everything. Welcome again this morning, and please proceed.
    Dr. Klausner. Thank you, Mr. Chairman. I want to thank you 
and the committee for holding this hearing on leukemia, 
lymphoma, and myeloma. These are a very complex and extremely 
diverse set of dozens of different diseases whose overall 
burden is immense. Currently there are about 700,000 Americans 
alive who have received the diagnosis of one of the three 
classes of diseases. One hundred thousand new cases will be 
diagnosed this year, and 60,000 Americans will succumb to one 
of these diseases this year.
    These diseases have long been at the forefront of oncology, 
or cancer research, in terms of basic science, clinical 
research and application, and progress in these diseases 
mirrors the ups and downs, the highs and lows of the history of 
cancer research. For some diseases, we can now achieve 80 to 90 
percent cure rates whereas, in others, the ability to effect 
cure is rare.
    What I want to do briefly this morning is show you some of 
the directions where we are going, as you and I have talked 
about quite a lot over the last 5 or 6 years. But before I do 
that, let me just describe a little bit of what these diseases 
are. As you said, these are diseases of the cells that make up 
the immune and the blood systems.
    All of these cells arise from a multi-potential stem cell 
that goes through a very complex, specific pattern of changing, 
of development, to differentiating so that they become the 
dozens of specialized cells of the immune and blood systems.
    This is important because each different disease is defined 
by two things: one, what type of specialized cell this cancer 
arises in; and two, the type of DNA or genetic alteration that 
results in that type of cell going from a normal cell to a 
cancer cell.
    Now, critical to the theme of how we are going to approach 
successful prevention and treatment of these diseases, for all 
cancers, is to understand their causes and to better define 
them. I have some posters here to illustrate. These diseases 
really are many different diseases. Often we misclassify these 
diseases by giving them the same name. This is a problem. We 
need to be able to move to precise and definitive ways of 
defining and diagnosing each cancer, knowing what is wrong in 
each of them, and then targeting our therapy to what is wrong.
    Let me show you one example in lymphoma. I know this may be 
a little hard to read, but there is one particular type of 
lymphoma called diffuse large cell lymphoma. We have developed 
therapies, combination chemotherapy, that will cure about 45 
percent of patients. The question is why 45 percent? One 
possibility is that this is not one disease. And as I have 
presented to this committee before, advances in technology, 
genomics, and molecular biology have allowed us to rethink our 
fundamental approach to classification of these diseases.
    On this first poster is some very new information that 
shows when we use a new technology called DNA chips, which we 
have talked about before, this single disease, a disease that 
we had a single name for just a year ago, is at least two 
diseases. Perhaps most strikingly, when we now look at the 
ability to cure patients with these two diseases, we can see 
that one type of disease can be cured over 80 percent of the 
time and the other type of disease can rarely be cured. This is 
the type of change in our approach that is going to guide how 
we are going to develop new therapies.
    Now let me briefly run through a few of these new therapies 
and a few of our new approaches.

                             NEW THERAPIES

    Senator Harkin described this new drug Gleevec that targets 
the molecular machine responsible for a particular form or 
leukemia, chronic myelogenous leukemia. It is also present in 
some other cancers. This is a drug that stops or shuts off the 
molecular machine that causes this cancer. As Senator Harkin 
said, over 90 percent of patients with CML treated with this 
single oral drug have gone into complete and sustained 
remission.
    On the next poster we can see an example of targeting the 
immune system itself against some of these diseases. This 
represents a study being done in Bethesda at the National 
Cancer Institute that has found a particular molecular target 
that is present on particular forms of leukemia, in this case a 
type of leukemia called hairy cell leukemia. This has led to 
the creation of a new molecular drug that has the specificity 
of an antibody and which is linked to a very toxic compound 
from a bacteria. This toxin, a single molecule of which gets 
into a cell, is sufficient to kill the cell, and this is now 
being used against hairy cell leukemia. In the original 
results, in patients for whom all other treatments had failed, 
over 90 percent have gone into complete and sustained 
remission.
    The next example is another immunologic approach where we 
are learning how to actually raise vaccines to vaccinate an 
individual against their own cancer. This looks particularly 
promising in these sorts of malignancies. In this case, in a 
trial headed again by an NCI investigator, Dr. Kwak, looking at 
a type of lymphoma for which we have no definitive treatment, 
what he has seen is about 85 percent of patients in whom an 
immune response can be raised against their cancers go into 
complete and sustained remission, something we have never seen 
before. This remission is not only a complete clinical 
remission, but we cannot even detect with our most sensitive 
molecular measures that any of the disease is there.
    As we heard before, myeloma has been an extremely difficult 
disease to make progress against. But recently an old drug, 
thalidomide, an infamous drug from a generation ago, was 
recognized to inhibit blood vessel formation, and in fact, this 
is the first drug that is showing some significant and 
encouraging responses in about 30 percent of patients with 
myeloma. There is a lot more to do.
    Let me just finish by describing how we are going about 
making sure that we make the right decisions about what to do.

                           PREPARED STATEMENT

    We recently finished a 9-month process with the leukemia, 
lymphoma, and myeloma community, including researchers, 
clinicians, patients, and advocacy groups, to create a 
strategic plan outlining what we need to do, what we need to 
know, what barriers we need to overcome to create a more 
definitive and successful research program against these 
diseases. This is called a PRG, or Progress Review Group. It 
has been a marvelous partnership among the entire community. We 
have now received this report, and over the next year will be 
working with the community to very aggressively implement the 
many recommendations. There is an enormous amount to be done, 
but I think there are few areas of cancer where the progress in 
science has as much possibility for rapid application than in 
this diverse set of diseases.
    So, I appreciate your attention to these diseases and for 
having this hearing.
    [The statement follows:]

                 Prepared Statement of Richard Klausner

    Good morning. I am Richard Klausner, M.D., Director of the National 
Cancer Institute. Thank you, Chairman Harkin, Senator Specter, and 
distinguished Members of the Subcommittee for inviting me to speak with 
you about research on hematologic cancers.
    Despite advances in diagnosis and treatment and improvements in 
patient survival, hematologic cancers continue to have a significant 
impact on the lives of Americans. Right now, almost 700,000 Americans 
are living with leukemia, lymphoma, or myeloma (LLM), and an estimated 
100,000 new cases occur each year. Although mortality has declined and 
5-year survival rates have increased among adults and children with 
certain forms of these diseases, an estimated 60,000 Americans will die 
of them in 2001. For all forms of leukemia, the five-year survival rate 
is only 46 percent, for non-Hodgkin's lymphoma it is 54.2 percent, and 
for multiple myeloma it is only 28 percent. Despite the significant 
decline in the death rate for children with leukemia, this disease 
still causes more deaths in children in the United States than any 
other disease. Furthermore, the death rates for non-Hodgkin's lymphoma 
and multiple myeloma are increasing at a time when death rates for 
other cancers are dropping. Since the 1970's, incidence rates for non-
Hodgkin's lymphoma have nearly doubled, although during the 1990's the 
rate of increase appeared to slow. Hematologic cancers strike 
individuals of all ages, from children to the elderly; men and women; 
and all races.

           WHAT ARE LEUKEMIA, LYMPHOMA, AND MULTIPLE MYELOMA?

    To understand these diseases, we must first understand the normal 
development of the cells they affect. Hematopoiesis is the process by 
which blood cells form and mature. All the different types of blood 
cells arise in the bone marrow from a common pluripotent hematopoietic 
stem cell, and undergo a series of developmental steps to differentiate 
into mature cells and assume specific roles in the body. New, immature 
blood cells may stay in the marrow to mature or may travel to other 
parts of the body to mature. Normally, blood cells are produced in an 
orderly, controlled way, as the body needs them. Some circulate 
throughout our bodies via blood vessels and lymph vessels. Some reside 
in the lymphatic tissues that are primarily concentrated in lymph 
nodes, thymus, spleen, and in most of our major organ systems.
    Leukemia, lymphoma, and multiple myeloma are all cancers of the 
blood-forming organs, or hematopoietic neoplasms. They arise due to 
errors in the genetic information of an immature blood cell. As a 
consequence of these errors, the cell's development is arrested so that 
it does not mature further, but is instead replicated over and over 
again, resulting in a proliferation of abnormal blood cells. Nearly 
every stage of the hematopoietic process can give rise to a distinct 
type of cancer.
    Historically, scientists and physicians have classified these 
diseases by their locations in the body, the appearance of affected 
cells under the microscope, and the natural progression of the 
diseases. In leukemia, the cancerous cells are discovered circulating 
in the blood and bone marrow, while in lymphoma, the cells tend to 
aggregate and form masses, or tumors, in lymphatic tissues. Myeloma is 
a tumor of the bone marrow, and involves a specific subset of white 
blood cells that produce a distinctive protein.
    Leukemia can arise in either of two main groups of white blood cell 
types--lymphocytes or myelocytes. Either type of leukemia can be acute, 
a rapidly progressing form of the disease in which the affected cells 
are very immature and unable to serve their proper purpose, or chronic, 
which progresses more slowly and is distinguished by cells that are 
relatively well differentiated but still function poorly. Lymphoma 
involves lymphocytes and can also be subclassified. Non-Hodgkin's 
lymphoma (NHL) is the more prevalent form of the disease. Among non-
Hodgkin's lymphomas, indolent disease progresses slowly and exhibits 
well-differentiated lymphocytes, while the more aggressive forms are 
characterized by lymphocytes with far less differentiation. Hodgkin's 
disease, which is less common than NHL and has different clinical and 
epidemiological features, has historically been distinguished from NHL 
by the presence of distinctive cells called Reed-Sternberg cells.
    Leukemias, lymphomas, and myelomas share some common features, but 
there are major differences among them--and there are similarities and 
differences within each disease group. These cancers actually represent 
a large number of diseases that vary significantly in their causes, 
molecular profiles, and natural progression. In the past decade we have 
a experienced a revolution in the field of molecular biology that has 
brought new tools that are helping us refine cancer classification in 
terms of the molecular changes that distinguish a normal cell from a 
cancerous one, and draw differences between cancerous cells of 
different types.
    This is an area of research rich in scientific promise, and the NCI 
has issued the Director's Challenge: Toward a Molecular Classification 
of Tumors, in which investigators are creating comprehensive molecular 
profiles of tumors using DNA, RNA, or protein-based technologies. These 
profiles will be used to define more informative, and clinically 
predictive, molecular classification schemes for human cancers.

                MOVING TOWARD A NEW UNDERSTANDING OF LLM

    A major NCI initiative, the Cancer Genome Anatomy Project (CGAP), 
has resulted in the cataloging of tens of thousands of human and mouse 
genes. The CGAP database is a unique resource that allows scientists to 
develop tools to perform large-scale genomic analyses to characterize 
tumors genetically. This genetic characterization can help explain why 
patients diagnosed with the same cancer differ dramatically in their 
responses to treatment. For example, a collaboration of scientists 
(including NCI scientists) genetically analyzed diffuse large B-cell 
lymphoma, an aggressive cancer that is the most common type of non-
Hodgkin's lymphoma. For 40 percent of patients with this diagnosis, 
standard multi-agent chemotherapy is curative. A compelling clinical 
problem is to understand why the remaining 60 percent of patients 
succumb to this disease despite chemotherapy. Reasoning that the 
varying therapeutic responses of patients with diffuse large B-cell 
lymphoma are due to undefined molecular differences in their tumors, 
researchers used DNA microarray technology to define the gene 
expression profiles of diffuse large B-cell lymphoma samples on a 
genomic scale. This new technology is capable of measuring the activity 
of tens of thousands of genes at the same time, thus creating a 
molecular portrait of the cells being studied.
    For this study, the CGAP was used to create a specialized DNA 
microarray, the Lymphochip, which is enriched in genes that function in 
normal and malignant lymphocytes. Lymphochip microarray analysis of 
gene expression in diffuse large B-cell lymphoma samples revealed that 
this single diagnosis actually combines two distinct diseases that 
differ in the expression of hundreds of genes. The two types of diffuse 
large B-cell lymphoma that were discovered each resemble a different 
type of normal B lymphocyte, suggesting that these cancers have 
distinct cellular origins. Clinically, patients with these two types of 
diffuse large B-cell lymphoma had strikingly different responses to 
chemotherapy. Patients with one lymphoma subtype, termed germinal 
center B-like diffuse large B-cell lymphoma, had a favorable prognosis: 
75 percent of these patients were cured by chemotherapy. Patients with 
the other lymphoma subtype, termed activated B-like diffuse large B-
cell lymphoma, had a poor response to chemotherapy with less than one 
quarter of these patients achieving a long-term remission. This study 
provides a clear demonstration that genomic-scale gene expression 
analysis can define clinically important subtypes of human cancer.
    This powerful new technology is now being used to study many 
different types of cancers, including leukemia and multiple myeloma, in 
an attempt to identify disease subgroups. For example, a new project, 
``Molecular Taxonomy of Pediatric and Adult Acute Leukemia,'' will 
attempt to correlate the expression pattern of over 30,000 genes with 
treatment outcome and with cytogenetic abnormalities for both acute 
lymphocytic leukemia and acute myeloid leukemia. In the future, such 
gene expression profiling of cancer cells will be used to guide 
patients towards therapies that are tailored for their particular 
diseases.

             CAUSES, RISK FACTORS, AND EPIDEMIOLOGY OF LLM

    Our understanding of the causes of these diseases is extremely 
limited, perhaps in part due to extreme heterogeneity of the diseases 
and the inadequacy of the traditional classification schemes to 
adequately address this heterogeneity. As our knowledge base about 
molecular subtypes grows, we hope that we will be better able to 
understand the relationships between causative factors and the 
development of LLM.
Leukemia
    The leukemias are very heterogeneous, with patterns of occurrence 
differing by age, sex, and racial and ethnic group. For example, 
highest incidence of acute lymphoblastic leukemia (ALL) is in children, 
ages 2-4, while chronic lymphocytic leukemia (CLL) is rare before age 
30, and has the highest incidence among the elderly. Chronic myeloid 
leukemia (CML) has a higher incidence among African-Americans than 
Caucasians, while the incidence of CLL is highest among Caucasians and 
extremely rare in Asians.
    The causes of leukemia in children and adults are largely unknown, 
but increased or decreased risks for developing leukemia have been 
associated with several factors. In an ongoing, collaborative follow-up 
study with Japanese investigators, NCI scientists have found strong 
evidence of radiation-induced risks for the acute leukemias and CML 
among Japanese atomic bomb survivors. NCI investigators and others have 
shown that radiotherapy and chemotherapy for a wide variety of diseases 
have been linked with moderately increased risks of acute myeloid 
leukemia (AML), although the benefits of treatment far outweigh the 
risks.
    Occupational exposures to ionizing radiation and certain chemicals 
such as benzene have also been linked with increased risk of acute 
leukemia. NCI is conducting an epidemiologic study of workers in China 
exposed to benzene at levels lower than previously studied, to 
characterize leukemia rates and to determine mechanisms of action and 
factors affecting carcinogenicity of benzene. In addition, cigarette 
smoking has been associated with modest increases in acute leukemia but 
the evidence is not yet conclusive.
    The first known human retrovirus, T-lymphotropic virus type 1 
(HTLV-1), discovered at NCI in 1981, is the primary cause of adult 
leukemia and lymphoma arising from lymphocytes known as T cells. 
Certain genetic conditions can increase the risk for acute leukemia, 
including Li-Fraumeni syndrome, Down's syndrome, Bloom's syndrome and 
several other rare conditions.
Lymphoma
    NCI investigators have recently reported on investigations of 
lymphoma incidence trends. Over the last ten years, researchers have 
studied the histologic types of lymphoma that are on the rise; 
illnesses, including other cancers, associated with lymphoma; 
occupational groups that may be at increased risks; and the role of 
genetic susceptibility. Recent research has identified several possible 
candidates for increasing risk including pesticides, organochlorine 
compounds, solvents, drinking water nitrates, and hair dyes. We are now 
evaluating whether these common exposures are contributing to the rise 
in NHL among some populations and investigating other hypothesized risk 
factors such as infectious agents, medical conditions, medical 
treatments, and genetic factors.
    There has been considerable research on the association between 
infectious agents and cancer. Helicobacter pylori is a bacterium 
associated with a particular rare type of lymphoma, mucosa-associated 
lymphoid tissue (MALT) lymphoma that arises in the stomach. Both 
Hodgkin's disease and non-Hodgkin's lymphoma, particularly some of the 
more aggressive forms, occur with increased frequency among adults and 
children infected with the human immunodeficiency virus (HIV), the 
virus that causes AIDS. In HIV-infected patients, about one-half of all 
lymphomas involving a type of lymphocytes called B cells are associated 
with the Epstein-Barr virus, including virtually all primary central 
nervous system lymphomas in patients with AIDS. A new Program 
Announcement, in collaboration with National Institute for Dental and 
Craniofacial Research, is being issued to stimulate research on viruses 
associated with the development of lymphomas among persons who are 
infected with HIV. The AIDS-Cancer Cohort is studying men infected with 
HIV to examine interactions with various environmental exposures that 
may contribute to the excess risk of lymphoma. Information from this 
project may be of value beyond the setting of HIV, as it may yield more 
fundamental biologic understanding of the interplay of viruses and 
chemicals in the development of lymphoma. A rare type of lymphoma, 
called Primary Effusion Lymphoma, which arises in the lining of the 
lung, heart or abdomen, is tightly linked to, and probably caused by, 
the Kaposi's sarcoma herpes virus (KSHV). People who have both HIV and 
KSHV are at particularly high risk. Because viruses similar to KSHV are 
known to cause lymphoma in animals, efforts are in progress to identify 
new, lymphoma-related viruses in people.
    NCI scientists are conducting very large epidemiologic studies 
addressing the relationship between the environment and lymphoma 
development. In a population-based case-control study of non-Hodgkin's 
lymphoma, NCI investigators, collaborating with the Centers for Disease 
Control and Prevention (CDC), assessed exposures to pesticides, 
solvents, and other factors using computer-assisted personal 
interviews, residential carpet dust samples, drinking water samples, 
and blood samples. Analysis continues, as investigators extract DNA 
from blood or saliva samples to assess the interaction between genetic 
variations and environmental risk factors.
    The Agricultural Health Study (AHS) is following 90,000 healthy 
farmers and their family members in Iowa and North Carolina in an 
effort to measure their risks of developing lymphoma and leukemia. NCI 
and National Institute of Environmental Health Sciences launched the 
AHS in 1993 after previous NCI research implicated occupational 
exposures to pesticides in the development of lymphoma. The study 
assesses the risks of other cancers and diseases, as well.
    A new initiative called Interlymph, coordinated by NCI and 
involving investigators in Europe and Australia, features a pooled and 
simultaneous analysis of thirteen case-control epidemiologic studies of 
non-Hodgkin's lymphoma. The international consortium of collaborators 
will examine pathology, infectious agents, family history data, genetic 
factors, and methodologies needed to accurately assess possible links 
with the development of lymphoma.
Multiple Myeloma
    The median age for diagnosis of multiple myeloma is 71 years of 
age. The incidence of multiple myeloma is much higher in blacks than 
whites, and is higher among males. Similar to incidence rates, the 
death rates are higher among males than females and higher among blacks 
than whites. This is one of the few cancer sites in which the survival 
rate is higher for blacks than for whites. The causes of multiple 
myeloma and the reasons for the racial disparity in incidence are 
unclear.
    Some studies have suggested the role of ionizing radiation, certain 
organic solvents and chemicals, as well as employment in farming and 
agricultural occupations. In recent studies, genetic factors, low 
socioeconomic status (SES), and obesity have been implicated. Recent 
attention has also focused on viruses and other infectious agents, but 
their role in the etiology of myeloma remains unclear. There is growing 
evidence that certain cytokines and chromosomal abnormalities may be 
involved in the pathogenesis of multiple myeloma. These laboratory-
based genetic measures need to be incorporated into future 
epidemiologic studies to better understand the complex relationships 
between genetic and environmental factors in the development of this 
disease.
    In a recent study, NCI investigators found that low SES, whether 
measured by occupation-based SES, income, or education, may account for 
about half of the excess incidence observed among blacks. Low SES may 
be a surrogate for a set of negative environmental characteristics, 
such as poor housing, dangerous jobs, lack of access to medical care, 
poor nutrition, and exposure to infectious agents, all of which may 
have a role in this disease.
    The rarity of this cancer makes it difficult to adequately 
investigate in a single study, so that collaborative efforts involving 
a variety of hematopoietic malignancies are being pursued.

                  NEW STRATEGIES FOR TREATMENT OF LLM

    Therapeutic research in the treatment of patients with hematologic 
malignancies has made enormous progress over the past 50 years, and the 
NCI has shepherded this important work. Many years ago, NCI established 
the National Service Center to enable basic scientists to design and 
test chemical agents for evidence of anti-tumor activity. In addition 
to pioneering cancer drug screening, the NCI funded an entire 
preclinical drug discovery and development program. The NCI has 
continuously supported investigators to pursue all phases of clinical 
evaluation of products emanating from their own discovery and 
developmental efforts, and interacts with the pharmaceutical industry 
and academic institutions to explore their novel agents.
    In the last decade, there has been an enormous investment in 
defining molecularly targeted agents in cancer chemotherapy. Recently 
we have seen some inspiring success stories, all of them direct results 
of this new approach. The first evidence of a consistent gene mutation 
associated with a particular cancer was provided about 40 years ago by 
the recognition of the Philadelphia chromosome, an abnormally small 
chromosome 22, in chronic myeloid leukemia (CML). Some years later, 
researchers noted that while chromosome 22 was shortened, chromosome 9 
was lengthened in CML patients, which suggested that the pieces of each 
chromosome were exchanged, or translocated. This observation was 
followed by the identification of a unique fusion gene, called bcr-abl, 
resulting from the translocation, and the eventual development 5 years 
ago of one of the first oncogene-targeted drugs, STI571 or Gleevec. 
This compound, which was recently approved by the United States Food 
and Drug Administration (FDA), is directed at the bcr-abl gene product, 
which is expressed in about 95 percent of CML patients, and in some 
patients with other types of cancers. Gleevec has shown remarkable 
promise in the treatment of chronic-phase CML, and NCI is partnering 
with Novartis, the drug manufacturer, to facilitate a profusion of 
clinical trials evaluating Gleevec in other cancers, including 
Philadelphia chromosome-positive ALL in adults and children. Additional 
trials are assessing the potential benefits of combining Gleevec with 
other chemotherapeutic agents. Molecular analyses of other types of 
leukemia have now produced the identification of more than 100 
additional oncogene targets that may be accessible to similar drug 
development strategies.
    Monoclonal antibodies are showing great promise in the treatment 
LLM. Among them, Rituximab, which was originally approved by the FDA in 
1997 for the treatment of non-Hodgkin's lymphoma (NHL), is an antibody 
directed at a cell surface antigen expressed on B lymphocytes and has 
been shown to be effective against many types of B cell malignancies. 
Currently, for both children and adults, rituximab is under study in 
combination with other therapies, including other monoclonal 
antibodies, attempting to attack multiple targets on a single cell 
type.
    In addition, NCI-sponsored studies are evaluating several new 
antibodies. Generally, leukemias, lymphomas, and multiple myelomas are 
derived from cells of the immune system and therefore frequently 
express antigens that are present on normal immune cells such as B-
cells or T-cells. Since these proteins are not present on other human 
cells and are not present on the stem cells that give rise to normal B-
cells and the T-cells, the antigens are excellent targets for cancer 
therapy. NCI researchers have devised a cancer treatment strategy that 
kills cells containing B-cell or T-cell specific antigens. When this 
occurs the normal cells are regenerated, but the cancer cells are not. 
One strategy is to fuse the portions of antibodies that bind to CD22 (a 
B-cell antigen) or CD25 (a T-cell antigen) to a potent bacterial toxin 
termed Pseudomonas exotoxin A. The genetically modified toxin then 
specifically binds to and kills cells expressing CD22 or CD25. Since 
many lymphomas and leukemias express CD22 or CD25, these tumor cells 
are killed.
    A promising ongoing NCI study is using this approach to combat B-
cell malignancies. The antigen CD22 is expressed on about 70 percent of 
lymphomas and leukemias. A recombinant immunotoxin termed BL22 has been 
designed and produced to kill tumor cells expressing CD22, and patients 
with hairy cell leukemia, chronic lymphocytic leukemia (CLL), and some 
lymphomas have been treated in a Phase I trial. Remarkable anti-tumor 
activity has been observed in patients with hairy cell leukemia. 
Several patients with CLL have responded as well. Enrollment into this 
trial is continuing, and once the maximum tolerated dose is 
established, Phase II trials in hairy cell leukemia, CLL, and lymphomas 
(in a post-transplant setting) will be opened for enrollment.
    Other antibodies under investigation are coupled to other potent 
anti-tumor substances, like radioactive molecules or anti-tumor 
antibiotics, and have the potential advantage of being able to deliver 
this tumor killing substance directly to the tumor site, where they 
attack antigen-positive tumor cells that other therapeutic agents might 
not penetrate well.
    Anti-cancer vaccines are a high priority research area for NCI. 
Unlike conventional vaccines, which are used to prevent illness, the 
anti-cancer vaccines represent a therapeutic approach, which seeks to 
strengthen the body's natural defenses against diseases, such as 
cancer, that have already developed. Vaccine therapy for lymphomas has 
shown considerable promise. Results of a recently completed lymphoma 
vaccine study conducted by NCI researchers have shown that there is a 
clear anti-tumor effect in a small group of patients who were 
vaccinated over the course of five years. On the basis of these 
promising results, NCI has launched a large-scale, multi-institutional, 
randomized, phase III clinical trial, to definitively test the 
experimental vaccine, which is custom-made from patients' own tumors.
    Immunotherapeutic approaches for treatment of multiple myeloma are 
also being evaluated. Investigators are examining the potential for 
immunization strategies in which a normal donor is vaccinated with the 
myeloma protein. The normal donor forms antibodies, called idiotype 
antibodies, and these are used to treat the patient. Preclinical 
studies of idiotype immunization demonstrate that this approach can 
induce an immune response that prevents tumor relapse or progression in 
myeloma models. Additional studies are determining the feasibility of 
inducing an active immune response against myeloma-specific antigens, 
such as MUC-1 and DF3.
    The NCI is involved in the development of a large number of new 
therapeutic agents with a wide array of unique mechanisms of action. We 
now know that cancer arises from the disruption of fundamental cell 
processes. Basic research findings have identified a plethora of 
potential therapeutic targets for further exploitation. There is an 
ever-lengthening list of promising agents that affect cell cycle 
regulation, gene expression, apoptosis (programmed cell death), and 
other cell functions, currently undergoing or awaiting investigation in 
clinical trials.
    A striking example of the benefit of this kind of molecularly 
targeted therapy is all-trans retinoic acid (ATRA) for the treatment of 
acute promyelocytic leukemia (APL). ATRA works essentially by reversing 
the effects of a specific chromosomal translocation that disables both 
differentiation and apoptotic processes in affected cells. The 
introduction of this agent has increased the cure rate for APL from 40 
percent to over 70 percent in just 10 years. Some patients who have 
been treated successfully with ATRA experience relapse, and recently, 
arsenicals, a group of rediscovered compounds that induce apoptosis via 
a different, more broadly applicable mechanism, have shown great 
utility as a second line of defense against APL. Arsenic trioxide is 
now being evaluated for use in a variety of lymphoid malignancies, as 
well as other cancers, and for use in childhood APL, and also for use 
as a first line treatment.
    Finding effective treatments for multiple myeloma has proven 
extremely challenging for cancer researchers. Recently, the success of 
thalidomide in treating MM patients has been very encouraging. 
Thalidomide effectively arrests tumor growth by stimulating anti-tumor 
immune response, interfering with communication between tumor cells and 
the surrounding tissue, and inhibiting the growth of new blood vessels 
(angiogenesis) near the tumor. Thalidomide's anti-angiogenic activity, 
was first recognized as the feature that caused birth defects in the 
children of women who took thalidomide in the 1950's and 1960's. Astute 
researchers theorized that the same feature could prove useful in 
restricting the blood supply to tumors. NCI-sponsored investigators 
recently report a 30 percent response rate for MM patients receiving 
thalidomide on a clinical trial. New trials are seeking to optimize the 
role of this agent, and some other antiangiogenic agents are being 
evaluated, as well. Because anti-angiogenic drugs have the potential to 
cause defects in a developing fetus, pregnant woman are excluded from 
participating in clinical research on these drugs.
    Bone marrow transplantation and peripheral blood stem cell 
transplantation techniques continue to be tested in clinical trials for 
certain LLM patients. Sometimes cancers become resistant to treatment 
with radiation therapy or chemotherapy. Very high doses of chemotherapy 
may then be used to treat the cancer. Because the high doses of 
chemotherapy can destroy the bone marrow, marrow is taken from the 
bones before treatment. The marrow is then frozen, and the patient is 
given high-dose chemotherapy with or without radiation therapy to treat 
the cancer. The marrow is then thawed and given back to the patient to 
replace the marrow that was destroyed. This type of transplant is 
called an autologous transplant. If the marrow is taken from another 
person, the transplant is called an allogeneic transplant. Another type 
of autologous transplant is called a peripheral blood stem cell 
transplant. The patient's circulating stem cells are collected, treated 
with drugs to kill any cancer cells, then frozen until they are 
returned to the patient. This procedure may be done alone or with an 
autologous bone marrow transplant.
    The role of stem cell transplantation in caring for patients with 
LLM varies with tumor type. Autologous stem cell transplantation 
clearly benefits patients in a chemotherapy-sensitive relapse of their 
disease, but its role as initial treatment is undefined. A national 
trial is comparing the efficacy of initial transplantation with 
transplantation at the time of first relapse. Other studies are 
evaluating the role of biological therapies such as interleukin-2, and 
immune response stimulator, and rituximab for their effectiveness in 
enhancing the benefit of transplantation.
    Many patients do not benefit from stem cell transplantation, and 
major efforts are directed at identifying the reasons and to develop 
methods to improve on these results. Some investigators are developing 
methods to harness patients' own immune responses. Alternatively, other 
researchers are using a technique called donor leukocyte infusion (DLI) 
that introduces T cells capable of generating a graft-versus-tumor 
effect (in which the donor cells attack the patient's cancerous cells). 
However, they are also capable of generating a potent graft-versus-host 
disease (GVHD, in which the donor cells attack the healthy tissues of 
the patient) that could be fatal to the patient. Studies of the array 
of T cells that are present post DLI are being conducted to better 
understand which T cell populations are necessary to achieve the 
desired result while minimizing GVHD.
    Allogeneic bone marrow transplant may cure patients who do not 
respond to standard chemotherapy, but the mortality of this procedure 
in patients with LLM has been very high. Moreover, age restrictions 
limit the number of patients who might be eligible for this procedure. 
There has now been an expanded information base on the use, for non-
Hodgkin's lymphoma, of non-myeloablative transplants (in which the bone 
marrow is not completely destroyed) with DLI. Recently, investigators 
have described their experience with patients over the age of 55 years. 
GVHD occurred less frequently than expected and many patients were able 
to go through the procedure without requiring hospitalization. As a 
consequence, the notion that more intensive treatment is better is 
being challenged, and the role of the immune system in cancer 
progression is being better delineated.
    The NCI sponsors the International Bone Marrow Transplant Registry, 
which is the world's largest body of data on outcomes following 
transplantation for LLM and other cancers. Data are provided from more 
than 400 centers and there are now data for more than 65,000 
transplants worldwide. The information collected is used for 
determining transplant regimens for specific clinical situations, 
identifying prognostic factors, comparing transplant regimens, 
comparing transplant with non-transplant approaches, evaluating cost 
and cost-effectiveness, planning clinical trials, and developing 
approaches to evaluate outcomes.
    Clinical trials for LLM treatment have demonstrated remarkable 
success and are a vital component of the NCI's research program. 
Currently, our clinical trials database contains descriptions of 177 
NCI-sponsored leukemia treatment trials, 170 for lymphoma, and 67 for 
multiple myeloma. Our clinical trials program is the place where 
promising new strategies discovered at the laboratory bench are applied 
to real human problems at the bedside. Clinical trials offer cancer 
patients access to state-of-the-art care, and provide us the 
opportunity to learn something from every patient that may help someone 
else. Our rapid pace of discovery in the basic biology of cancer is 
refining our knowledge of how to intervene in cancer development, and 
clinical trials are the crucial final step in bringing these 
discoveries to people who are battling cancer.

                               CONCLUSION

    Progress in our understanding of cancer and our ability to detect 
and treat it have led to a real and continuing decline in the cancer 
incidence and death rates. However, our excitement over important 
scientific progress and the very real human gains that result is 
tempered by the knowledge that far too many Americans continue to 
suffer and die from cancer each day. Moreover, all groups of people are 
not benefiting equally from our advances against cancer. NCI is 
embracing the challenge of understanding the causes of health 
disparities in cancer and developing effective interventions to reduce 
them. Plans call for increasing fundamental research into the social 
causes of health disparities, the psychosocial factors that mediate 
them, and the biologic pathways that can explain their impact. In 
addition, we will expand our cancer control intervention and population 
research on disparities, better define and monitor cancer-related 
health disparities, and strengthen training and education in this 
research area. Effective communication empowers people to make informed 
cancer-related decisions and to engage in behaviors that will improve 
their health. Few other initiatives have the potential to 
simultaneously improve health outcomes, decrease health care costs, and 
enhance community satisfaction. Our intent is to learn how to help 
people distinguish important from insignificant health risks and deal 
with contradictory or inaccurate health messages so they can make 
informed choices.
    Too many Americans, for a host of reasons, lack access to high 
quality, cutting-edge cancer treatment and care. NCI is launching 
research to improve the quality of cancer care by strengthening the 
information base for cancer care decision making. Researchers seek to 
better understand what constitutes quality cancer care, with an 
emphasis on the patient's perspective; identify geographic, racial/
ethnic, and other disparities in who receives quality care; and 
strengthen the scientific basis for selecting appropriate 
interventions. Our goal is to enhance the state of the science for 
defining, monitoring, and improving the quality of cancer care and 
inform Federal decision making on cancer care delivery, coverage, and 
regulation.
    We have learned the value of including as broad a constituency as 
possible in our review, advisory, and planning activities, and we have 
forged new relationships with patients, practitioners, scientists in 
different fields of research and medicine, other government agencies, 
private sector companies, innovators in technology, and many other 
partners where such alliances were rare or non-existent only a few 
years ago. Illustrating our commitment to this philosophy as we seek to 
accelerate progress against LLM, the NCI convened a Progress Review 
Group (PRG) last year to conduct an intensive review of our research 
portfolio in LLM. This initiative, one of a highly beneficial series of 
PRG's fitting within NCI's new disease-specific planning framework, 
featured expert panels who provided a comprehensive view of the state 
of our current knowledge, and you will see that many of our research 
priorities will reflect the recommendations the PRG described in their 
report, issued last month, and available on our website at: http://
osp.nci.nih.gov/prg__assess/prg/llmprg/llm__rpt.htm.
    We have a special interest in enlisting the help of cancer 
survivors. The NCI created the Consumer Advocates in Research and 
Related Activities (CARRA) program to encourage people affected by 
cancer to provide their viewpoint and ideas directly to NCI staff so 
that the NCI can incorporate this perspective into our programs and 
activities. Our goal is to recruit 150 consumer advocates (cancer 
survivors, family members, or those who are involved in cancer-related 
activities like support groups, cancer hot lines, or advocacy groups) 
to become members of CARRA and represent many different cancer types, 
age groups, and ethnic groups from across the Nation. In addition to 
participating in NCI activities, CARRA members will represent the 
opinions of their groups and play critical roles as two-way information 
links between their own communities and constituencies and the NCI.
    NCI has been entrusted with guiding our Nation's commitment to a 
complete understanding of cancer: from understanding how a normal cell 
becomes cancerous to understanding why some people get cancer and 
others do not; and across the continuum through detection, diagnosis, 
treatment, survivorship, and ultimately prevention. NCI's mission is 
broad and our approach is necessarily ambitious, because, while our 
primary role and our expertise is research, our interest is people: our 
families, friends, neighbors, and colleagues--and yours. Our goal is to 
eradicate cancer and save the lives of those who would otherwise be 
lost to us.
    Thank you, Mr. Chairman, for giving me this opportunity to share 
with you our progress against hematologic cancers. I will be pleased to 
answer any questions you may have.

                   STATEMENT OF SENATOR ARLEN SPECTER

    Senator Specter [presiding]. Well, thank you very much, Dr. 
Klausner for your lucid testimony, as usual.
    First, I want to acknowledge the generous comments made by 
Senator Harkin who noted his chairmanship of this subcommittee 
from 1989 through 1994, and mine from 1995 through a few days 
ago. We have worked really for a common purpose. I learned a 
long time ago if you want to get something done in Washington, 
you have to cross party lines, and so far as this 
subcommittee's activities, I think it makes little, if any, 
difference as to who has the gavel.
    We have pursued funding for NIH in a very vigorous way, as 
everyone knows. We have added more than $8 billion in increases 
for the NIH and we are on a path to double funding over 5 
years. This year we have targeted and increase of $3.4 billion. 
Each time we have gone to the Budget Committee for more money, 
we have gotten congratulations but no additional cash. We have 
had to establish priorities within the subcommittee.
    We have had a whole series of hearings on a variety of 
special ailments, muscular dystrophy, amyotrophic lateral 
sclerosis, Parkinson's, Alzheimer's, so many, many ailments. We 
responded to a special request by our colleague, Senator Kay 
Bailey Hutchison, whose brother suffers from myeloma, and also 
made the subcommittee aware former Congresswoman, Vice 
Presidential candidate Geraldine Ferraro has this ailment.
    We have held these hearings because of an effort to create 
public awareness as to the fact that some serious malady can 
affect anyone of you or your family. We try to get public 
support for research for NIH and, beyond that, research for 
implementing the NIH funds. For example, on stem cell research, 
you testified in this room just a few weeks ago, Dr. Klausner, 
as to the impact stem cells could have on cancer. We had a 
private follow-up conversation.
    I regret that we do not have a bigger room. We have a line 
which goes for several blocks outside, which signifies how much 
public interest there is in this subject and all taxpayers 
should have the opportunity to hear the testimony.
    Senator Hutchison. Mr. Chairman, could I just make a 
suggestion on that point? There are so many people outside, 
that I wondered if after about 30 minutes, some of you might 
rotate out and let them come in, just on a voluntary basis so 
that everyone has a chance to see some part of the hearing.
    Senator Specter. I think that is a good idea, Senator 
Hutchison.
    You folks in the rear can move up to the sides, and anybody 
who would like to be a Senator for a hearing can take some of 
these seats. You may have to leave if some more of our 
colleagues come. But come on up. Come on up to the side so that 
we can have the maximum number of people come in at the present 
time.
    I want to make one additional comment this morning that I 
had not intended to make, but there is a front-page story in 
the Washington Post today which I find very disquieting, and 
that is about administration testimony given yesterday to a 
subcommittee of the House of Representatives on the issue of 
stem cells.
    This is generally known. These stem cells are extracted 
from embryos which are going to be thrown away. At the present 
time, there is a ban on any Federal funding being used to 
extract stem cells from embryos. But there is currently a 
ruling by the general counsel for the Department of Health and 
Human Services that once the embryos are removed, that Federal 
funds can be used for stem cell research.
    The administration, according to this morning's press--and 
I am going to have to read the transcript and get the 
statements--is making the suggestion that that is subject to 
change by the President. I do not know about that. If you have 
a lawyer's opinion given by the general counsel for the 
Department of Health and Human Services that it is appropriate 
to fund research on stem cells, once extracted, it seems to me 
that is that, especially in the context where that ruling was 
made some time ago, and the Congress has not changed it. There 
is a presumption which attaches to a ruling of that sort where 
Congress has not made a change. If Congress disagrees with 
that, Congress can make a change in it.
    Senator Harkin and I and others have been working very hard 
on the issue to get support, even to rescind the ban on use of 
Federal funds for extracting stem cells from embryos. One of 
our colleagues, Senator Gordon Smith, a very strong pro-life 
Republican--and many who favor use of Federal funds to extract 
stem cells on the research are pro-life Republicans. But 
Senator Gordon made a very valid point, that it is different if 
you have an embryo in a dish as opposed to having an embryo in 
a womb. If you have an embryo in a woman's womb, there is 
movement toward life. If you have an embryo in a dish and so 
many of them are destroyed, there is just no real reason not to 
use those embryos to save lives since they are going to be 
discarded.
    Now, it may well be that the scope of the administration's 
position is narrow enough so that it will not impact on either 
of the two questions: one, use of Federal funds on the stem 
cells once taken from the embryos; or on the second question, 
use of Federal funds to remove stem cells from embryos.
    We have been talking among Senators and it may well be that 
we have more than 70 votes in the U.S. Senate to remove the ban 
on using Federal funds for extracting stem cells from embryos. 
Senator Lott had agreed to bring the bill up which Senator 
Harkin and I and many others have introduced as a freestanding 
bill, and I have talked with the new Democratic leadership and 
bringing the bill up may be right around the corner. In the 
meantime, we are trying to deal with the administration to see 
to it they will make the ruling to allow Federal researches to 
extract their own stem cells.
    After I yield to Senator Hutchison, Dr. Klausner, I am 
going to come back to you on the issue of stem cells as an 
assist on the kinds of research and treatment you are 
describing here today.
    Senator Hutchison, we thank you for suggesting this hearing 
and give you the floor.

               STATEMENT OF SENATOR KAY BAILEY HUTCHISON

    Senator Hutchison. Thank you, Mr. Chairman and ranking 
member. When Senator Specter was the chairman of this 
subcommittee, I did talk to him about having this hearing. When 
Senator Harkin then became chairman, he agreed to continue. I 
want to thank you so much for leading the way and thank Senator 
Harkin for continuing his interest because this is such an 
important issue, one which I think has not gotten as much of 
the research and the focus as perhaps now we will be able to 
do.
    When I first started looking into the Federal commitment to 
the deadly blood cancers, leukemia, lymphoma, and multiple 
myeloma, I was really amazed to know that 11 percent of all 
cancer deaths come from these blood diseases, but only 5 
percent of the research funding from the National Cancer 
Institute is going to find the cure to these cancers.
    I talked to Dr. Klausner about that personally 2 years ago, 
and he could not have been more responsive. I appreciate so 
much your willingness to listen and to act on the concerns that 
we had. You set up the Progress Review Group, which now is able 
to review and advise the National Cancer Institute, and I 
really appreciate that. I think that is a major step forward.
    Nevertheless, this is now, I think, an area where we are 
seeing new innovations, and, because of my personal interest in 
it, I know that some of the innovations, such as thalidomide, 
are coming forward. There are others. So, now I think there is 
something to really invest in.
    Because of that, I want to say that I am introducing a bill 
today with my colleague, Senator Barbara Mikulski, that will 
direct the National Cancer Institute to establish a program for 
research of lymphoma, multiple myeloma, and leukemia. It will 
authorize $250 million for that purpose and it will also add 
$25 million for education efforts because, as you know, early 
detection can save lives in any kind of cancer. We have seen 
the incredible results in breast cancer of early detection 
through education and awareness. I want to do that for the 
blood cancers as well.
    Along that line, more than anything that I could ever have 
done, there are people who have been willing to step up to the 
plate and say, wait a minute. I have now come in contact with 
this disease. I now see how neglected it has been in the area 
of research. I think what Geraldine Ferraro is doing for the 
future of the research capabilities is beyond any of our 
expectations, and I want to thank her for coming forward and 
saying let us do something about this.
    It was Geraldine Ferraro who called me several months ago 
and said she wanted to make sure that we do something that will 
push this issue to the forefront, which resulted in this 
hearing. I went to Senator Specter and I told him of her 
willingness to come forward and be helpful in the education and 
awareness efforts. Thank you. What you are doing is going to 
have huge benefits.
    I want to also just thank one other person, Kathy Giusti, 
because it was Kathy who never gave up. She is the head of the 
Multiple Myeloma Research Foundation. I call her a human 
hurricane. It is true. She has done so much to make this 
happen. She came forward. It takes time to get these things 
done, but I think the culmination of your efforts is happening 
this week. I thank you for that bravery.
    Dr. Ken Anderson, Geraldine Ferraro's physician, is doing 
so much and is so committed from his heart to the research.
    I also want to thank Dr. Kantarjian, who is a renowned 
physician and researcher in the area of leukemia at the 
Nation's number one cancer center, M.D. Anderson. Dr. 
Kantarjian actually cut short his much deserved vacation to 
testify today, and I thank him for his efforts.
    Last but not least, I want to say that I would not have 
really been aware of this had my brother not been willing to 
step forward. I went through a bone marrow transplant. We will 
be there for you. Thank you.
    Senator Specter. Thank you very much.
    Senator Murray, would you care to make an opening 
statement?

                   STATEMENT OF SENATOR PATTY MURRAY

    Senator Murray. Mr. Chairman, let me thank you and Senator 
Harkin and Senator Hutchison for your tremendous passion on 
this. I think it is shared by clearly all the people in this 
room. This is really an impressive hearing to have so many 
people here today. I know how difficult it has been to schedule 
this hearing with all that is going on on the floor in the 
Patients' Bill of Rights and all of the changes in the Senate, 
but clearly this is important.
    I have a number of constituents who have come here from 
Washington State. I had to spend a few minutes in the hall with 
them because they cannot get in the room. They have traveled 
3,000 miles to be here. So, I hope at some point they do get to 
get in the room and hear part of this hearing.
    But I just want to thank everybody who has come because I 
think your presence alone shows the impact on this country.
    I too want to thank Geraldine Ferraro for her courage. I 
think in the last few days the awareness of the American public 
of this impact on people and their lives and the awareness that 
they have of the importance of research has just grown 
unbelievably large, and that is because of your courage. I just 
want to tell you how much I appreciate your doing this. We are 
in this fight with you, and thank you for being here today.
    Mr. Chairman, I know we have a number of panels who are 
coming before us. I look forward to offering our questions as 
they come through. Thank you very much.
    Senator Specter. Thank you very much, Senator Murray.
    We still do have some more room here. We have some more 
chairs. If anybody in the hall wants to come up and sit on the 
floor, it is not the most gentile, but you would be a part of 
the hearing. Let us make that offer to those who are outside. 
We have a very large group of people outside who we regret are 
not accommodated here.
    Dr. Klausner, Senator Harkin, the chairman, has yielded to 
me for the first round of questions. We will have 5-minute 
rounds. Let me say we are going to have to move right along. We 
have a lot of witnesses, and we have a markup on the 
supplemental appropriation bill at 11:30 this morning. So, 
everybody on this panel will be involved in that.
    Dr. Klausner, I want to start with a statement which you 
made which summarizes the issue of stem cells on this 
particular ailment. The subcommittee had asked you for your 
views on stem cells, and you wrote the following. ``Probably 
the most dramatic recent advancement which arose from stem cell 
research is the development of the drug Gleevec for the 
treatment of chronic myelogenous leukemia, CML. The development 
of this drug came as a result of the careful step-wise studies 
of CML cells compared to normal cells. This drug is unique in 
that it results in remissions in nearly 100 percent of patients 
who take it as initial therapy, has minimal side effects, and 
is a pill. Furthermore, there are data that this drug may have 
even broader application.''
    I want to move to an issue raised in yesterday's House 
hearing which talks about cloning of embryos. Certainly we can 
use existing embryos that are going to be discarded without 
having the cloning of embryos. To the extent that there is a 
consensus against cloning, we do not have to use that as a 
reason for not using stem cell research.
    The question I have for you is that apparently there was 
some testimony from biomedical researchers, as the news report 
says, who believe that studies on stem cells from 5-day-old 
cloned human embryos offers the best chance of developing 
promising new therapies for a variety of debilitating diseases. 
My question to you, is there anything to that? Are the cloned 
embryos which produce stem cells superior to the discarded 
embryos?
    Dr. Klausner. There is no scientific data that I am aware 
of that compares cloned human embryos to the embryonic stem 
cells that can be removed from and then grown as permanent 
lines from early embryos.
    Senator Specter. Among the varieties of stem cells which 
are possible, adult stem cells, fetal tissue, the whole range, 
I think it would be good for you to put on the record the 
superiority of embryonic stem cells in scientific research such 
as you have been referring to.
    Dr. Klausner. Yes. We have that information from the mouse 
where we have been able to compare adult stem cells to 
embryonic stem cells. In the mouse it is very clear that in 
embryonic stem cells, the capacity to grow, the persistence, 
the reliability, the lack of genetic problems, the question of 
genetic mistakes or genetic damage in cells, and the true 
pluripotentiality, the ability of those cells to give rise to 
many, many different types of cell specificities or lineages 
are superior characteristics to adult stem cells.
    Senator Specter. I would like to have your verification and 
comment on other statements made by you that in cancer 
treatment you destroy cells. It is a destructive process to try 
to eliminate cancer, and then the stem cells are critically 
important as they come into the human body to replace the cells 
which have been destroyed. Would you amplify on that please?
    Dr. Klausner. Yes. We have talked a lot about the promises 
of stem cells for a variety of different diseases. Most of 
these diseases are degenerative diseases where you need to 
replace cells, and so it is regenerative medicine, this hoped-
for field, that people put most of their hopes on for direct 
impact of stem cells.
    And as I have said to you, cancer is sort of the opposite. 
It is not a degenerative disease; it is the opposite, a disease 
where cells proliferate. But in that process normal tissues are 
damaged, injured, or even killed both from the disease and from 
the current therapy. So, the indirect place where stem cell and 
regenerative medicine is hoped for to be helpful, or useful, in 
cancer would be to replace damaged tissue.
    Senator Specter. One final question. The yellow light just 
turned to red, but let me ask just one final question. And that 
is, from your letter, you make the comment, probably the most 
dramatic advancement is the drug Gleevec in the treatment of 
CML. A two-part question. Absent the stem cells, could you have 
had this dramatic advance and what are the prospects for stem 
cells to be equally as effective on other forms of cancer?
    Dr. Klausner. In the letter, I actually was referring to 
hematopoietic stem cells, which can be adult stem cells. 
Studying the derivation of the specialization of blood cells 
from blood forming stem cells, which are adult stem cells and 
not embryonic stem cells, allowed the research to go on to 
understand the molecular changes that happen in CML, chronic 
myelogenous leukemia. So, this was a general discussion of stem 
cells. In that particular case, it was not embryonic stem cell 
research, but rather adult stem cell research.
    Senator Specter. Well, answer the second part. How badly 
would you be disadvantaged if you could not use embryonic stem 
cells in the work which you are pursuing with these very large 
grants we have gotten for you?
    Dr. Klausner. I think the reality is as a scientist, if we 
cannot do experiments to compare embryonic stem cells to non-
embryonic or adult stem cells, we cannot answer the question 
about what advantages they might have and what we may be 
missing. As I said, our best experience is from the mouse where 
the differences are quite clear and the advantages of embryonic 
stem cells for scientific research are clear.
    Senator Specter. Thank you very much.
    Senator Harkin.
    Senator Harkin [presiding]. Thank you very much, Senator.
    Dr. Klausner, I just have one question. I wanted to get 
into just one small area of this, but it is a very important 
area, again a report that came out in the Washington Post 
yesterday. It was the National Cancer Policy Board had a report 
that said that we are focused so much on finding a cure that we 
are neglecting research in how to care for people who are 
dying. The report noted that NCI spent less than 1 percent of 
its 1999 budget on research and training related to palliative 
care.
    This is an important topic for this hearing because so many 
people are living with incurable blood cancers. Of course, we 
do not want to cut down the research on finding the cure, but 
what can we do to help the people who today are living it deal 
with the pain and the depression and other symptoms?
    I noted that in the press report yesterday, it quoted you 
as saying that you were very enthusiastic about the report and 
that you are planning to convene a group to determine how to 
implement its recommendations. I just wonder if you have 
anything else that you could tell us about how you plan to 
proceed on this.
    Dr. Klausner. This is a very important report, and it does 
suggest that all of us need to pay more attention to this. The 
National Cancer Policy Board, which raised this issue, was 
actually an idea of mine and I went to the academy to have this 
set up to provide to the Nation advice about policy issues 
relevant to cancer that not only affect NCI but actually affect 
all aspects of decision making in the Federal Government and 
outside the Federal Government.
    This issue of end of life and palliative care is a critical 
one. We do need to do more research. I am really pleased with 
the recommendations that the Policy Board has made. Many 
members of the Policy Board are on our advisory committees. We 
met last week and we will be looking at ways that we can act on 
their recommendations to increase research in this area.
    Senator Harkin. I appreciate it. If there is anything this 
subcommittee can do to be helpful, please let us know.
    Dr. Klausner. Thank you.
    Senator Harkin. I would now recognize Senator Hutchison.
    Senator Hutchison. Thank you, Mr. Chairman, and thank you 
for holding this hearing, along with Senator Specter. It was a 
great team effort.
    Dr. Klausner, I wanted to ask you specifically what you see 
going forward with the recommendations of the Progress Review 
Group and if you foresee the NCI going in a certain direction 
in advancing research on the blood cancers now and in the near- 
to mid-term.
    Dr. Klausner. One of the things that I felt about the PRG 
group, which was a terrific group, and was very satisfying, 
although you may want to hear from them, was the very nice 
alignment between their recommendations of where we need to go 
and the dozens of new programs that we have put in place at NCI 
to capture the possibilities of new science, new ways of asking 
questions, to direct them specifically to blood malignancies. I 
think the PRG recognized that we had set up these structures 
and we were really set to go, and with these explicit 
recommendations, we already are working with the members of the 
PRG within the NCI to figure out what needs to be initiated, 
what needs to be expanded, and what we will be able to afford 
to do.
    What I really like about the PRG report is the clarity with 
which it describes how we are going to capture the types of 
scientific possibilities that I just briefly touched on at the 
beginning of the hearing in order to make progress. So, we have 
been mapping all of their recommendations, every single one, 
against our initiatives, our mechanisms of funding, our funding 
areas, and then we will be meeting with the PRG group again 
soon, when we will agree on the mapping and the prioritization 
of how to go forward.
    Senator Hutchison. In the last 3 years, it seems that there 
has been more success at stemming the fatalities, the mortality 
of the blood cancers. I just wondered if that means that you 
can do more in research because you have started to build a 
solid base of research? And where do you think the most 
promising avenues of research are in the near-term future?
    Dr. Klausner. Well, I think there are two issues. One, I 
think we finally have the tools to correctly classify and 
diagnose these diseases. I know that sounds very abstract, but 
if we do not have the right diagnosis for a disease, you cannot 
actually figure out the right treatment. This is the 
characteristic of modern medicine. For the first time we 
believe we have definitive, new tools to correctly classify all 
these different diseases. Is myeloma one disease? Is it two 
diseases? Is it five diseases? And it is very hard to find a 
single treatment for many different diseases.
    So, that is the first thing that we have now available to 
us and if we had enough time, which we do not, we could talk 
about exactly what we have put in place to challenge the 
community. In fact, it is a large program around the country 
called the Director's Challenge where we put out money to 
definitively molecularly classify all of these diseases for the 
first time in history.
    Then the second part is to finally make use of knowing the 
difference between each disease. What precisely is wrong in 
each disease? We need to know the molecular machinery, just 
like we need to know the machinery that is wrong in a car if we 
are going to fix it. And finally we need a set of drugs or the 
immune system to not non-specifically try to kill the cancer, 
which often does not work, but to very specifically go after 
what is different between the cancer and the non-cancer, the 
way antibiotics go after the difference between bacteria and 
human cells. It is in that arena that we really expect to move 
forward.
    Senator Hutchison. Let me just end, because my time is just 
about up, by asking you a simple question. Are you willing to 
say that you will be able to put more focus on these blood 
cancers now that you do have a little more to go on?
    Dr. Klausner. Oh, absolutely.
    Senator Hutchison. Thank you very much.
    Senator Harkin. Thank you, Senator Hutchison.
    Senator Murray.
    Senator Murray. Thank you very much, Mr. Chairman, and 
thank you for accommodating all the people now. I can see that 
my constituents have made it into the back of the room and I am 
delighted.
    Senator Specter. Senator Murray, there is no one in the 
hall. We have a lot of people sitting. We brought the last 
group in to sit on the floor up front.
    Senator Murray. I appreciate it. As some of you know, 
traveling 3,000 miles to get to a hearing is a large 
undertaking. These people have made a tremendous effort. So, I 
appreciate your allowing them in.
    I just have one question for Dr. Klausner. I know we have a 
number of other panels.
    I am delighted we have been joined by Senator Mikulski who 
has been such a great, great advocate for these issues for a 
long time. I will just ask one so she can get to hers.
    I just wanted to ask about one of the contentious issues 
that is contained in the McCain-Edwards-Kennedy Patients' Bill 
of Rights that we have been discussing on the floor of the 
Senate, and that is access to clinical trials and innovative 
new treatments. Some of the opponents of the legislation have 
been arguing that access to clinical trials is too costly. It 
seems to me that if we save lives and move forward, that those 
costs are offset.
    But could you just talk for a minute about how important 
clinical trials are in treating blood-related cancers?
    Dr. Klausner. Yes, I feel very passionate about this. All 
of the progress we have made, when we have made progress, is 
the result of clinical trials. We will not make progress 
without clinical trials. I think it is wrong and unfair to deny 
patients access to clinical trials.
    But we have also studied this issue whether care in the 
context of a cancer clinical trial is more expensive than care 
outside the clinical trial. We have done at least four studies. 
We are waiting for a much larger study we have done with the 
RAND Corporation, and every study shows that there are no 
significant added clinical costs. So, I think the cost argument 
is unacceptable, and I think we need to move to make sure that 
patients are not denied that opportunity for themselves as well 
as to contribute to society at large.
    Senator Murray. Thank you very much. I appreciate that 
response.
    Thank you, Mr. Chairman.
    Senator Harkin. Thank you very much, Senator Murray.
    Senator Mikulski.

                STATEMENT OF SENATOR BARBARA A. MIKULSKI

    Senator Mikulski. Thank you very much, Mr. Chairman. First 
of all, let me thank you for affording me the courtesy of 
participating with this subcommittee. Though I am an 
appropriator, I am not a member of this subcommittee.
    I hope though, as the chair of the VA/HUD appropriations 
subcommittee, that we could have lessons learned from this 
hearing on how there could be applicability for the information 
in veterans' health care, in terms of detection, treatment, and 
certainly on VA clinical research.
    I am here because I want to learn. I am a very proud 
cosponsor of the Hutchison bill. I want to learn because, like 
all of us, we come because it affects people in our family. A 
very close member of my family is Geraldine Ferraro. I regard 
her like a sister, and when I heard of this information and her 
situation, I was determined to work on a bipartisan basis on 
this.
    I know that we are going to hear testimony from Mr. Larry 
Lucchino, who used to be in Baltimore with the Orioles and now 
is CEO with the Padres. We went out in Little Italy together. 
We drank wine.
    I even took him to an inaugural dance, and here we are. But 
he has gone on to another life and love. And, well, I am an 
appropriator.
    So, I am just happy to be here. I am going to waive my 
questions to Dr. Klausner. We meet often and talk, and I know 
the subcommittee is running late.
    But, again, thank you so much and I will have other 
questions.
    Senator Harkin. Thank you very much, Dr. Klausner, for 
everything. We will dismiss you and we will bring up the next 
panel: Dr. Sandra Horning, Mr. Larry Lucchino, Dr. Hagop 
Kantarjian, Mr. Miles Pendleton, Jr.
    Because of the tightness of time--11:30 we have a full 
committee hearing that we must tend to--I am going to ask if 
each person can just try to limit it to 4 minutes. I am going 
to try to get this timer light, if I could. I hate to do that, 
but it is just simply a time problem. We will move ahead as 
aggressively as possible.
    When you finish, if you could come up here and sit 
someplace. Those of you in back, we have some empty seats up in 
front. So, those who may really need to sit down, please come 
up here and take some of the seats.
    So, we will start with Dr. Sandra Horning, Professor of 
Medicine, Stanford University, a member of the Board of 
Directors of the American Society of Clinical Oncology, and as 
I said, from my back yard of Creston, Iowa. Dr. Horning.
STATEMENT OF SANDRA J. HORNING, M.D., STANFORD 
            UNIVERSITY SCHOOL OF MEDICINE
    Dr. Horning. Thank you. As stated, I am a professor of 
medicine at Stanford University where I do clinical research in 
Hodgkin's disease and non-Hodgkin's lymphoma. I am also pleased 
to serve on the Scientific Advisory Board of the Cure for 
Lymphoma Foundation and also as a member of the Board of 
Directors of the American Society of Clinical Oncology.
    Mr. Chairman, I would like to thank you and your 
colleagues, Senator Specter and Senator Hutchison, for your 
leadership in scheduling this timely hearing upon the release 
of the Leukemia-Lymphoma-Myeloma Progress Review Group report. 
As you have heard we are currently poised to make significant 
advances in the treatment of blood-related cancers. I am 
especially honored to appear before a fellow Iowan with a 
strong commitment to biomedical research, and as this 
represents my own 5-year survivorship of malignancy, I also 
identify strongly with the large number of advocates present 
here today.
    Lymphoma, as you heard, with some introduction from Dr. 
Klausner, is a general term for cancer of the lymphatic system, 
which is part of the immune system. There are two-broad based 
categories of lymphoma, the relatively common non-Hodgkin's 
lymphoma, which I will refer to as lymphoma and the more rare 
Hodgkin's disease.
    From 1973 to 1998, the incidence rate for lymphoma 
increased by 83 percent with the current estimate of more than 
56,000 cases annually. This is actually the highest rate of 
increase for any cancer, an increase that is unexplained. 
Further, lymphoma represented the second greatest increase in 
mortality among all cancers over the same period. The success 
of treatment varies with an overall 5-year survival rate of 54 
percent.
    The lymphomas are complex disorders with more than 30 
unique subtypes. As you have heard, molecular profiling of the 
lymphomas is now underway on a large scale. This work promises 
great benefits for diagnosis and new targets for therapy, but 
it also poses a significant challenge, the challenge inherent 
in conducting clinical research for rare diseases.
    There is great enthusiasm for the new immunotherapies 
modeled after the body's own immune system that are 
revolutionizing the treatment of lymphoma. The monoclonal 
antibody Rituxan targets the marker on the surface of 80 
percent or more of the lymphomas. Because antibodies like 
Rituxan have few side effects, they are favored by patients and 
they can be combined with chemotherapy or radiation therapy.
    Several new antibodies that target different markers 
expressed on lymphoma cells are being tested currently in 
clinical trials. Antibodies can also be used as a targeted 
delivery system for toxins or radiation. Two new products, 
Bexxar and Zevalin, combine a radioisotope with an antibody 
targeted to B-cell lymphoma. Promising data from clinical 
trials has been reported with both.
    Recent technological advances have made it possible to 
custom-make vaccines for B-cell lymphoma on a scale sufficient 
for testing in large clinical trials. These vaccines are 
designed to stimulate an anti-lymphoma effect among patients in 
remission after chemotherapy, but destined to relapse after 
conventional treatment.
    Discoveries in lymphoma and other hematologic cancers have 
often blazed the trail for the common solid tumors, and it is 
our belief that the pioneering development of immunotherapy for 
lymphoma will also lead to improved treatments in other 
cancers.
    I see my light is turning red.
    I want to put a plug in for the integral role of clinical 
research that has been mentioned. It represents a major success 
of the federally supported cancer program. However, clinical 
research in rare diseases can be a daunting task due to the 
time and costs involved. The participation of community 
oncologists is absolutely critical to timely and full accrual 
to clinical studies in lymphoma and Hodgkin's disease. Thus, 
appropriate allocation of resources to the design, 
organization, and execution of clinical research in the 
community is needed.
    The NIH and the pharmaceutical industry are important 
partners in drug development and clinical research. We believe 
for that reason that the Patients' Bill of Rights must include 
comprehensive coverage of cancer clinical trials, coverage that 
would ensure access to both FDA-sponsored and Government-funded 
trials.
    On behalf of all of us who are passionate about 
understanding and effectively treating the hematologic cancers, 
researchers, the 700,000 patients who currently have these 
diseases, and their practitioners, I would like to thank you 
for holding this hearing. The hematologic cancers pose serious 
challenges and offer unprecedented opportunities.
    May I just have 30 more seconds?
    Senator Harkin. Yes.
    Dr. Horning. Thank you.

                           PREPARED STATEMENT

    So, our recommendations are to implement the 
recommendations of the Progress Review Group, to heighten 
efforts to identify the reasons for the increased incidence of 
lymphoma, to improve coordination among the NCI, FDA, and the 
pharmaceutical industry, and enactment of the Patients' Bill of 
Rights with comprehensive clinical trials coverage.
    Thank you.
    [The statement follows:]

                PREPARED STATEMENT OF SANDRA J. HORNING

    Good morning, I am Dr. Sandra J. Horning, Professor of Medicine at 
Stanford University School of Medicine. My clinical research in 
Hodgkin's disease and non-Hodgkin's lymphoma (NHL) focuses on improving 
therapeutic outcomes, reducing treatment complications, and elucidating 
the biology of the diseases. I am also pleased to be here today in my 
capacity as member of the Scientific Advisory Board of the Cure For 
Lymphoma Foundation, an organization that supports lymphoma research 
and education, and as a member of the Board of Directors of the 
American Society of Clinical Oncology (ASCO), the world's leading 
medical specialty society for cancer researchers.
    Mr. Chairman, I would like to thank you and your colleagues, 
Senator Specter and Senator Hutchison, for your leadership in 
scheduling this hearing on hematological cancer research. This hearing 
is timely because the report of the Leukemia-Lymphoma-Myeloma Progress 
Review Group (LLM-PRG) has just been published and because we are 
poised to make significant advances in the treatment of blood-related 
cancers. We welcome the opportunity to review recent research progress 
and consider policy changes that might accelerate the development of 
new treatments for these cancers.
    As a native of Creston, Iowa and graduate of the University of Iowa 
School of Medicine, I am especially honored to appear before a fellow 
Iowan. Your strong commitment to biomedical research has ensured that 
we have the financial resources to support basic biomedical research 
and to expand the clinical trials network of the National Cancer 
Institute (NCI) across the nation. A balanced approach of support for 
basic and clinical research is essential to achieving improvements in 
the treatment of all cancers.

                           A LYMPHOMA PRIMER

    Lymphoma is a general term for cancer of the lymphatic system, 
which is part of the immune system. There are two broad categories of 
lymphoma, one relatively common--non-Hodgkin's lymphoma, or NHL, and 
one relatively rare--Hodgkin's disease. There are approximately 64,000 
cases of NHL and 7,400 cases of Hodgkin's disease diagnosed annually in 
the United States. Taken together, lymphomas rank as the fifth most 
common cancer behind prostate, breast, lung, and colorectal cancer.
    The non-Hodgkin's lymphomas (NHL) are categorized based on their 
appearance under the microscope and their expression of immune system 
markers, which allows them to be classified as originating from B- or 
T-cells. These are complex disorders, with more than 30 unique 
subtypes. Some NHL grow and spread quickly, whereas others develop more 
slowly. Thus, the NHL have been broadly characterized as aggressive or 
indolent. Utilizing current technology to assess the expression of many 
genes, potential new subtypes of NHL have been identified based on 
molecular ``profiles.''
    Between 1973 and 1998, the incidence rate for NHL increased by 83 
percent, the highest rate of increase for any cancer. Although 
occupational exposure to chemicals has been implicated, the increased 
incidence of NHL is unexplained. The importance of NHL is highlighted 
by the fact that this disease also represented the second greatest 
increase in cancer mortality over the same period. The treatments for 
NHL include radiation, chemotherapy; stem cell transplantation; and 
immunotherapy. The success of treatment varies according to NHL subtype 
and clinical features, resulting in a collective five-year survival 
rate of only 53 percent.
    In contrast, the incidence of Hodgkin's disease has been stable and 
the five-year survival rate has improved steadily to the current figure 
of 85 percent. However, Hodgkin's disease remains a very important 
disorder because the young patients with this disease, median age less 
than 30 years, may have serious long-term adverse effects, such as 
second cancers, as a result of chemotherapy and radiation treatments. 
Studies of risk assessment, risk reduction and prevention are critical 
not only to the long-term survivors of Hodgkin's disease but for all 
cancer patients treated with chemotherapy and radiation therapy.

                           LYMPHOMA SUBTYPES

    Significant insights into the underlying biology of the NHL have 
resulted from recent research efforts. In work that Dr. Richard 
Klausner has already described, researchers at the NCI, Stanford, and 
the University of Nebraska and other institutions utilized microarray 
technology to assess gene expression in the most common NHL subtype, 
diffuse large B-cell lymphoma.
    This research suggested that the clinical behavior of diffuse large 
B-cell lymphoma corresponds to the expression of genes in the immune 
cell of origin, such that two distinct diseases were identified. For 
patients with one subtype, roughly three-quarters were alive five years 
after chemotherapy, whereas less than one-quarter of those with the 
other subtype were alive five years after treatment.
    Currently, molecular profiling of lymphomas and leukemias is 
underway on a much larger scale. This work promises not only to help 
determine prognosis for individual patients but to provide new 
therapeutics targeted to the underlying biology. Ultimately, research 
initiatives will be more focused, physicians will assist patients in 
making more informed decisions, and the survival of NHL patients will 
improve.
    Although molecular sub-typing of NHL will surely yield important 
benefits, it also poses significant research challenges. The further 
sub-classification of NHL changes a collectively common cancer into 
many orphan diseases, with all the challenges inherent in conducting 
clinical research for rare disorders. The same circumstance will 
ultimately be true of the most common cancers as their biology is 
further understood. Thus, it is important to address this challenge 
with the NHL here and now.

            CURRENT TREATMENT OPTIONS AND TREATMENT ADVANCES

    Treatments for NHL have traditionally included chemotherapy and 
radiation therapy. For those with recurrent lymphoma, high dose 
chemotherapy or radiation with stem cell transplantation may be a 
treatment option.
    New immunotherapies, modeled after the body's own immune system, 
are revolutionizing the treatment of NHL. A monoclonal antibody called 
Rituxan is approved for the treatment of recurrent, indolent B-cell 
non-Hodgkin's lymphoma. Rituxan targets a B-cell antigen, CD20, found 
on normal and malignant B-cells. (Because the youngest B cells do not 
express the CD20 antigen, normal B-cells regenerate after treatment). 
In addition to killing lymphoma cells by traditional immune mechanisms, 
Rituxan may send a direct death signal. Most exciting, antibodies like 
Rituxan have few side effects, allowing their combination with 
chemotherapy or radiation therapy. Some studies already demonstrate a 
benefit for such combinations compared with conventional therapies.
    Several new monoclonal antibodies that target different antigens 
expressed on B- and T-cells are being tested in clinical trials. These 
new therapeutics create the possibility of ``combination 
immunotherapy.'' Antibodies can also be used as a targeted delivery 
system for cell toxins or radiation. Bexxar and Zevalin are two 
products in advanced stage of development that combine a radioisotope 
with a monoclonal antibody targeted to the CD20 antigen of B-cells. 
Promising data from clinical trials has been reported with both of 
these new agents.
    Vaccines derived from the B-cell antigen that is unique to an 
individual's NHL have been applied after conventional chemotherapy for 
indolent lymphoma. Recent technological advances have made it possible 
to ``custom make'' these vaccines on a scale sufficient for testing in 
large clinical trials. Based on preliminary studies, researchers hope 
these vaccines will have an anti-lymphoma effect for patients with 
minimal disease or in remission but destined to relapse after 
conventional treatment.
    It is our hope that these immunotherapies, used as a complement to 
other therapies or in combination with other therapies, will 
significantly and favorably impact the survival rates for NHL. In 
addition to their therapeutic promise, immunotherapies have fewer and 
less severe side effects than those of chemotherapy and radiation.
    The moderation or elimination of the serious side effects of 
treatment is of great concern to patients. As mentioned, success in 
treating Hodgkin's disease has been accompanied by serious adverse 
effects, including second cancers, sterility, organ dysfunction, and 
psychosocial effects, all of which impact quality of life. It is 
imperative that we strive not only for cures, but also for the least 
complicated cures, in our research efforts.
    Discoveries in lymphoma and other hematological cancers have often 
blazed the trial for the common solid tumors, and it is our belief that 
the pioneering development of immunotherapy for lymphoma will also lead 
to improved treatments in other cancers.

              CHALLENGES FOR CLINICAL RESEARCH IN LYMPHOMA

    The integral role of clinical research in patient care represents a 
major success of the federally supported cancer program. In a 1998 ASCO 
(American Society of Clinical Oncology) survey, more than 80 percent of 
physicians indicated that they enroll patients in clinical trials. The 
active participation of the academic and community oncologist in 
clinical research is essential for the rapid clinical testing of 
promising new therapies. Patients often make decisions about enrollment 
in clinical trials, which may represent the best treatment option, in 
consultation with a community oncologist.
    Despite the enthusiasm among oncologists regarding clinical 
research, there are obstacles to participation that result in a small 
percentage of eligible patients who actually enroll in clinical trials. 
The ASCO study of clinical trials uncovered serious strains in this 
system, including the fact that oncologists often receive inadequate 
reimbursement for the costs of enrolling patients in clinical trials. 
In addition to the added time to inform and consent patients, fixed 
costs associated with enrolling patients in trials include the approval 
of trials by an institutional review board (IRB), data management 
requirements during and after treatment, and the reporting of adverse 
events.
    These obstacles become more daunting in rare disorders, where the 
time and costs may prove overwhelming for busy practitioners. As we 
move toward the subclassification and further sub-classification of 
cancer, first with the NHL and later with other cancers, these issues 
must be addressed in order to promote clinical trials of new therapies. 
The participation of community oncologists is absolutely critical to 
timely and full accrual to clinical studies in NHL and Hodgkin's 
disease. Thus, appropriate allocation of resources to the design, 
organization and execution of clinical research in the community is 
needed.

                 ROLE OF INDUSTRY IN CLINICAL RESEARCH

    Support of basic biomedical research and a nationwide clinical 
trials network by the National Institutes of Health (NIH) and support 
of clinical research by the pharmaceutical industry represents an 
important partnership. The pivotal trials of new agents are often 
conducted exclusively by industry, with Rituxan and Gleevec as recent 
examples. Subsequently, important trials for new indications of 
approved drugs frequently emanate from the cooperative groups, as 
evidenced by multiple ongoing trials incorporating Rituxan in NHL.
    The translation of basic research into new NHL treatments occurs in 
academic research centers like Stanford (usually the result of NIH 
funding), small biotechnology companies, and large pharmaceutical 
companies. The new immunotherapies--Rituxan, Bexxar, Zevalin, as well 
as new lymphoma vaccines--represent the results of this partnership.
    Both patients and physicians prize access to industry-sponsored 
trials. For patients, they often represent the only avenue to 
potentially life-extending new agents. Physicians wish to offer their 
patients novel therapies at the earliest possible time. Industry trials 
are attractive because they are designed and conducted with a sense of 
urgency, leading to timely results. Significantly, industry trials pay 
for enrollment of patients at a rate that approximates the actual cost 
of necessary clinical trial activities. In contrast, the ASCO study 
found that reimbursement rates for these activities in NCI-sponsored 
trials were well below the actual costs incurred by physicians.
    Thus, industry-sponsored trials play an essential part in the 
overall clinical research enterprise and should not be considered of 
lesser significance than trials sponsored by NIH. It is for this reason 
that the cancer community has advocated a clinical trials coverage 
provision in the various Patients' Bills of Rights that would ensure 
access to industry-sponsored as well as government-funded trials. When 
Congress eventually passes a Patients' Bill of Rights, it must include 
comprehensive coverage of cancer clinical trials.

                RESEARCH RECOMMENDATIONS OF THE LLM-PRG

    Researchers and advocates commend the NCI for convening the 
Leukemia, Lymphoma, and Myeloma Progress Review Group (LLM-PRG), 
comprising more than 180 researchers, clinicians, patient advocates, 
industry representatives, and government officials. In May 2001, this 
group released its evaluation of research on hematologic malignancies.
    One of the most important benefits of the PRG process is its 
inclusion of advocates in the deliberations. Advocates brought to the 
PRG deliberations a sense of urgency and an insistence on removal of 
bureaucratic barriers to the development of new therapies.
    The core recommendations of the PRG relate to methods for 
shortening the time for translating basic research findings into new 
treatments. Among the research and development strategies identified in 
the PRG report are:
  --Fostering partnerships among NCI, academics, advocates, cooperative 
        groups, the Food and Drug Administration (FDA) and industry;
  --Developing education and training programs for certification of 
        physicians and centers for diagnosis, treatment, and clinical 
        trials in hematological malignancies
  --Establishing innovative new research mechanisms to foster 
        collaboration among experts from multiple disciplines and 
        institutions.
    New treatments, in many cases, may be integrated with established 
treatments. Appropriate allocation of resources to the design, 
organization and execution of clinical research in the community is 
needed to study the resultant, multiple combinations and permutations. 
The advocates emphatically endorse improved communication between 
physician and patient regarding increasingly complex treatment 
decisions. Further, the advocates strongly support research efforts 
directed toward the late effects of treatment.

                RECOMMENDATIONS FOR CONGRESSIONAL ACTION

    On behalf of all of us who are passionate about understanding and 
effectively treating the hematologic cancers--patients, researchers, 
and practitioners--I would like to thank you for holding this special 
hearing to consider the state of their research.
    The hematological cancers pose serious challenges and offer 
unprecedented opportunities. The incidence of NHL is increasing for 
reasons that we do not understand and the five-year survival rates for 
NHL, myeloma, and leukemias remain unacceptably low. Breakthroughs in 
molecular diagnostics promise new, targeted treatments based on 
increased understanding of the biology of these diseases. Meanwhile the 
era of specific immunotherapy has begun with resounding success and we 
see much more on the horizon. In order to accelerate the realization of 
these unparalleled opportunities, we recommend several actions by 
Congress to improve the environment for research on lymphoma and the 
other blood-related cancers:
  --Implementation, facilitated by the NCI, of the collaborative 
        strategies for research and development of hematological cancer 
        therapies recommended by the LLM-PRG;
  --Heightened efforts to identify the reasons for the increased 
        incidence of lymphoma; Improved coordination among NCI, FDA, 
        and industry to bring new drugs to market sooner;
  --A system of payment for enrolling patients in lymphoma clinical 
        trials commensurate with their complexity and costs; and
  --Enactment of a patients' bill of rights with comprehensive clinical 
        trials coverage, including industry-sponsored trials under 
        regulatory authority.
    This is an exciting time to be involved in research on 
hematological cancers. I would again like to express the deep 
appreciation of the research community for the strong Congressional 
support for biomedical research. We look forward to a continued strong 
partnership, advancing our understanding of cancer, developing new 
therapies, and rapidly testing these new treatments in patients, 
continually striving for cures with the best quality of life.

    Senator Harkin. Thank you very much, Dr. Horning. I had to 
cut you off. They would think I was playing favorites if I let 
you go on.
    Mr. Lucchino.

STATEMENT OF LARRY LUCCHINO, PRESIDENT AND CEO, SAN 
            DIEGO PADRES
    Mr. Lucchino. Yes, good morning. I am Larry Lucchino. I am 
the president and CEO of the San Diego Padres. I speak to you 
today as a survivor of non-Hodgkin's lymphoma in the 1980's and 
prostate cancer in the 1990's. I would like to thank you as 
well for the opportunity to discuss my experiences and to 
highlight the need for strong Federal support for biomedical 
research.
    Senator Harkin, I would like first to thank you and to 
thank Senator Specter, Senator Hutchison, Senator Murray, and 
my old, dear friend, Senator Mikulski, for your strong interest 
in leukemia, lymphoma, and myeloma. These diseases have been 
too long off the radar screen. As a Pittsburgh native, I would 
especially like to salute Senator Specter from my home State 
for his leadership in the fight for biomedical research.
    In the fall of 1985, I was diagnosed with non-Hodgkin's 
lymphoma. I was told the odds were very much against me. I went 
to a physician to determine the source of a persistent cough 
and was given a life-altering diagnosis. I was told only one-
third of us would survive. Fortunately, I was referred to the 
great Tom Fry and the Dana-Farber Cancer Institute in Boston 
where I underwent aggressive chemotherapy and an autologous 
bone marrow transplant. As I recall, I was only the 33rd 
patient to receive this treatment at Dana-Farber. Bone marrow 
transplantation, an experimental for lymphoma 15 years ago, is 
now considered standard treatment around the country for 
thousands of lymphoma patients.
    Almost a decade and a half after that experience, the 
numbers on non-Hodgkin's lymphoma do not tell a promising 
story. As Dr. Horning referred to, between 1973 and 1998, the 
incidence rate for non-Hodgkin's lymphoma increased almost 83 
percent. The 5-year survival rate for non-Hodgkin's lymphoma 
still hovers at about 54 percent. For those who are treated 
successfully, the long-term side effects can be devastating.
    I applaud the NCI for convening its blue ribbon panel to 
review the current program on lymphoma, leukemia, and myeloma 
and proposing new strategies for accelerating the translation 
of basic research findings into new treatments. My own 
physician, the inestimable Dr. Lee Nadler of Dana-Farber, was a 
member of that group, so I know it took an aggressive approach.
    My message today is simple. We must accelerate the research 
and development process, and we need to do it now. For those of 
us who have been diagnosed with cancer, time is a precious 
commodity. We believe that old structures must be reformed and 
new systems created to bring treatments to patients at a faster 
pace. The time and distance from a scientist's laboratory bench 
to the patient's bedside must be shortened.
    The NCI's blue ribbon panel specifically emphasized 
collaboration and cooperation among researchers, industry, 
Government, and advocates. I would like to specifically 
acknowledge the contribution of the Cure for Lymphoma 
Foundation, a private organization that funds research, as an 
example of the partnership that will be critical to moving the 
research agenda forward.
    More specifically I would like to recommend some concrete 
action steps.
    Please maintain a strong Federal role in the funding of 
biomedical research.
    Please implement a balanced approach of support for basic 
and clinical research so that laboratory discoveries can be 
translated quickly.
    Please develop a budget for the recommendations included in 
the PRG panel and hold the NCI accountable for implementing 
that research plan.
    Please encourage additional collaboration between the 
private and the public sectors, between industry, academia, and 
the Government. We need a new alliance.
    Please implement on a pilot basis new methods for 
evaluating and collaborating in research.
    Senator Specter [presiding]. Mr. Lucchino, I am very 
reluctant to interrupt anyone, especially an ex-Pennsylvanian.
    But we are on a very tight time table and have to be at a 
markup on the supplemental. So, we are going to have to ask you 
to take 30 more seconds.
    Mr. Lucchino. I will do so. Thank you.
    Senator Specter. We are going to have to ask everybody else 
to observe the red light meticulously. Thank you.

                           PREPARED STATEMENT

    Mr. Lucchino. I would like to make perhaps a reference to 
the sports world in which I operate these days. It is a real 
privilege and I think a duty for someone in the toy department 
of life, the world of baseball, to come and have a chance to 
contribute to issues as important to all of this. Perhaps I can 
take from the sports world an expression, if Nike will excuse 
the borrowing. Life is short; research hard.
    Thank you very much for this opportunity.
    [The statement follows:]

                  Prepared Statement of Larry Lucchino

    Good morning, I am Larry Lucchino, President and CEO of the San 
Diego Padres. I speak to you today as a survivor of non-Hodgkin's 
lymphoma in the 80's and prostate cancer in the 90's. I would like to 
thank you for this opportunity to discuss my experiences and to 
highlight the need for strong federal support for biomedical research 
and innovative strategies for public and private research partnerships.
    Senator Harkin, I would like to express my appreciation to you, 
Senator Specter, and Senator Hutchison for your strong interest in 
cancer research and your willingness to hold this special hearing 
focusing on leukemia, lymphoma, and myeloma. As a Pittsburgh native, I 
would especially like to salute the senior Senator from my home state 
of Pennsylvania, Senator Specter, for his leadership in the fight for 
federal funding for biomedical research.

                  TREATMENT FOR NON-HODGKIN'S LYMPHOMA

    When I was diagnosed with non-Hodgkin's lymphoma in the fall of 
1985, I was told that the odds were very much against me. I went to a 
physician to determine the source of a persistent cough and was given a 
life-altering diagnosis. Fortunately, I was referred to the great Dana-
Farber Cancer Institute in Boston, where I underwent aggressive 
chemotherapy and an autologous bone marrow transplant. As I recall, I 
was only the 33 patient to receive this treatment at Dana-Farber. Bone 
marrow transplantation, an experimental treatment for lymphoma 15 years 
ago, is now considered standard treatment for certain lymphoma 
patients.
    Just two years ago, I was diagnosed with prostate cancer and 
underwent treatment at Johns Hopkins. I will focus my remarks today on 
lymphoma and the other blood-related cancers, but the research 
strategies and public policies that will make a difference for lymphoma 
patients will also make a difference for prostate cancer patients and 
all other cancer patients, as I understand that discoveries in lymphoma 
have frequently pioneered advances in other cancers.
    The numbers on NHL do not tell a promising story. Between 1973 and 
1998, the incidence rate for non-Hodgkin's lymphoma increased almost 83 
percent, among the highest rate of increase for any cancer. For that 
same time period, the death rate for NHL increased by 45 percent. 
Although significant progress has been made in treatments for some 
cancer, including Hodgkin's disease and certain childhood leukemias, 
the five-year survival rate for non-Hodgkin's lymphoma still hovers at 
about 54 percent. Even for those who are treated successfully, the 
long-term side-effects can be devastating.
    The challenges are obvious. We must still answer fundamental 
questions about the causes of NHL and at the same time accelerate the 
pace of development for new treatments.

                     ADVANCES IN LYMPHOMA RESEARCH

    In the last several years, there have been some important 
developments in the treatment of NHL. The most promising broad category 
of treatments are those that are referred to as immunotherapies, or 
therapies that utilize the body's own immune system to fight cancer. A 
monoclonal antibody has been approved for the treatment of a form of B-
cell lymphoma, and radioimmunotherapies, which combine monoclonal 
antibodies with radiation, are in development for the same type of 
lymphoma. Monoclonal antibodies for additional forms of lymphoma are 
being investigated, and researchers are designing and testing vaccines, 
which are created for each individual from the tissue from his or her 
tumor.
    There is great hope that these treatments will improve the outlook 
for lymphoma patients, but it is still too soon to know if they will 
have a significant impact on the lymphoma survival rate.

                    CONVENING OF A BLUE RIBBON PANEL

    The National Cancer Institute (NCI) deserves commendation for 
convening a blue ribbon panel to review its current program of research 
on lymphoma, leukemia, and myeloma and to propose new strategies for 
accelerating the translation of basic research findings into new 
treatments. I was not a participant in this group, but I was pleased to 
learn that cancer survivors like myself were an integral part of the 
deliberations and that my own physician, the inestimable Dr. Lee Nadler 
of Dana-Farber Cancer Institute, was a member of the group.
    I have read the recommendations of the blue ribbon panel, and I 
believe they point us in an important direction for hematological 
cancer research. However, I would like to echo a theme that was central 
to the report, a theme that I imagine was pressed by the cancer 
survivors and other advocates: accelerate the research and development 
process. And please do it now!
    For those of us who have been diagnosed with cancer, time is a 
precious commodity. We believe old structures must be reformed and new 
systems created to bring treatments to patients at a faster pace. The 
report emphasizes collaboration and cooperation among researchers, 
industry, government, and advocates to achieve this goal.
    I would like to acknowledge the contribution of the Cure For 
Lymphoma Foundation (CFL), a private organization that funds research 
and supports educational and informational programs for physicians, 
researchers, patients, and their families. CFL and other private 
organizations like it make a valuable contribution to the field, and 
their financial resources are an important complement to federal 
research funding. This is but one example of the partnership that will 
be critical to moving the research agenda forward.

                     ACTION ON THE RECOMMENDATIONS

    I would like recommend some concrete action steps if I may:
    1. Maintain a strong federal role in the funding of biomedical 
research. The Congress and Bush Administration have committed to 
doubling the budget between 1999 and 2003, but there appears to be no 
plan beyond that time. To prevent disruption in research and sustain 
the progress we are making, Congress and the Administration must 
develop and endorse a funding strategy beyond 2003.
    2. Implement a balanced approach of support for basic and clinical 
research so that laboratory discoveries can be translated into improved 
patient outcomes.
    3. Develop a budget for the recommendations included in the Blue 
Ribbon Panel, and hold the NCI accountable for implementing the 
research plan offered by the leaders in lymphoma, leukemia, and myeloma 
research.
    4. Encourage additional collaboration between the private and 
public sectors. At present, new drug development is, at least 
initially, almost exclusively the domain of pharmaceutical and 
biotechnology companies. Basic science discoveries made in publicly 
funded laboratories in academia and the National Institutes of Health 
(NIH) could be translated by industry into clinical applications more 
quickly if the flow of information were more efficient. This should be 
a priority of NIH in order to ensure that the public benefits from the 
nation's research investment at the earliest possible juncture.
    5. Implement on a pilot basis, with rigorous methods for 
evaluation, new structures for collaborative research. The patient 
advocates in the PRG were captivated by the concept of a multi-
institutional and multi-disciplinary consortium that would accelerate 
the drug development process. The Chronic Lymphocytic Leukemia Research 
Consortium, centered at one of my favorite institutions, the University 
of California at San Diego, may serve as a model for the kind of 
collaboration involving researchers from different fields and different 
institutions.
    I was a healthy young man when I was diagnosed with non-Hodgkin's 
lymphoma. Since my initial diagnosis, many more in the world of sports 
have been diagnosed and treated for cancer, hockey players Mario 
Lemieux and John Cullen, golfer Arnold Palmer and cyclist Lance 
Armstrong. The first reaction for many of us was a desire to understand 
why we had cancer, but for some of us that initial instinct has 
developed into activism aimed not only at answering why we were 
diagnosed with cancer but also aimed at educating the public about 
cancer, solidifying support for federal funding of biomedical research, 
and improving the environment for private sector research efforts. It 
is my honor to be here with you today and to join with other advocates 
in support of bold and creative approaches to cancer research. To 
paraphrase an expression from the world of sports advertising, `` Life 
is short; research hard (and fast).'' Thank you.

    Senator Specter. Thank you very much, Mr. Lucchino.
    Senator Harkin has had to leave us for other commitments, 
and he has left the gavel in my hands.
STATEMENT OF MILES S. PENDLETON, JR.
    Senator Specter. We turn now to Mr. Miles Pendleton, a 
retired Foreign Service Officer, diagnosed with CLL leukemia in 
1989 while serving in London. Mr. Pendleton is a graduate of 
Yale, Harvard, and the National War College. Thank you for 
joining us, Mr. Pendleton, and we look forward to your 
testimony.
    Mr. Pendleton. Thank you very much, Senator Specter. I 
appreciate it.
    I will not describe the disease. Think of CML without a 
cure. Think of lots of us having pretty ugly chemo and 
experiences that you can all imagine that go with it. From 
looking at me, you can tell that I am perhaps a lucky person. 
This room is full of courageous blood disorder patients who are 
worse off than I am. Despite being heavily treated over the 
years, I am determined to beat back this dragon with the help 
of all of those who are doing CLL research. In the process, no 
institution is more central than NCI and no army in the field 
is more important than the recently established CLL Research 
Consortium, which needs a higher level of funding now.
    When I was first told that I had leukemia, I was running 
the political section in London and I was called out of a 
meeting, and a doctor told me on the phone, Mr. Pendleton, you 
have leukemia, but it is chronic. It is the good kind.
    Members of the committee, I can assure you there is no good 
leukemia. I can also assure you that having leukemia is not 
career-enhancing.
    We are all encouraged to take a tape recorder to the first 
meeting with the doctor who diagnoses us and invites us to come 
in for a little chat about our blood tests. That is because 
after we hear the word ``leukemia,'' we are not going to 
remember a thing. I can guarantee you. Try it sometime.
    A few words about CLL and the effort to cure it, 
particularly through the Research Consortium funded by NCI. CLL 
is the most common form of adult leukemia. More voters in your 
States have it than any other form of leukemia. There are about 
100,000 of us alive today. Nobody knows what triggers it, and 
so there is not yet a Gleevec, but we are on the march. Nobody 
knows what to target. Unfortunately, because of the toxins, we 
are not living any longer than when I graduated from college 10 
years ago--40 years ago.
    I was just back at my reunion and it seems like 10.
    It really destroys your life in many ways, a lot like AIDS.
    But there is an accelerated measure of hope on the research 
front through the consortium which brings together in an 
unprecedented way institutions from Boston to La Jolla. It is 
funded with a $16.5 million grant which sounds like a lot, but 
it is split amongst nine institutions and to be spent over 4 
years. Basically that ain't much. It is about what was spent by 
Mrs. Casey to buy the site for the new mayor's residence here 
in Washington.
    To my astonishment, the consortium is unique in that for 
the first time in NCI history it brings together the top 
researchers from places like the Dana, from places like M.D. 
Anderson. They are really making headway.
    Senator Specter. Mr. Pendleton, the red light has been on. 
Would you summarize please?
    Mr. Pendleton. Yes. I will quote you.
    Senator Specter. Take all the time you need.
    Mr. Pendleton. You once said that druthers do not dollars 
make. The consortium needs more dollars. It needs about $20 
million now.
    Thank you, Senator.
    Senator Specter. Thank you, Mr. Pendleton.
    We had a sense of a Senate resolution which expressed 
druthers, but they do not translate to dollars. So, I think 
that is where it ought to be identified.

                           PREPARED STATEMENT

    Mr. Pendleton. Well, there is some report language out 
there too which are druthers.
    [The statement follows:]

             Prepared Statement of Miles S. Pendleton, Jr.

    Thank you Senator Harkin, Senator Specter, and members of this 
Committee for inviting me to appear today. Right at the outset, I want 
to say how much millions of patients and our families appreciate what 
this Committee has done over the years for patients, medicine and 
medical research.
    My name is Miles Pendleton. For three decades I was a U.S. Foreign 
Service Officer serving in the Department of State and in embassies 
abroad. I visited with members of the Senate and House on many 
occasions, both formal and informal. But, frankly, I am not entirely 
happy to be appearing before you today because I do so as a leukemia 
patient--no matter how robust I may appear at the moment.
    I have long had and been treated for Chronic Lymphocytic Leukemia, 
known as CLL. This is not CML, the chronic leukemia that may be cured 
by the recently approved and much heralded pill called Gleevec. In CML 
the target is known. In CLL it is not. I will focus on CLL.
    In CLL patients, our bodies produce abnormal lymphocytes, a subtype 
of white blood cells that migrate to the lymph nodes or other lymphoid 
organs. They clog the body, crowding out the good cells in the blood 
and marrow. They are relentless and refuse to die.
    This is happening to my body, which is also residually impregnated 
with a decade of toxins from oral chemo and infusions through the arm 
that kill good and bad cells alike. As we say in the Foreign Service, 
this is not ``career enhancing''.
    Mr. Chairman, as you know, this room is full of blood disorder 
patients, many who have come to Washington under the new umbrella of 
Leukemia, Lymphoma, Myeloma-ACT to lobby for more research funding for 
blood disorders. Many in this room are worse off than I am. I was 
diagnosed years ago, in 1989, and despite many ups and downs, am still 
kicking with a measure of ferocity. I can commiserate totally with 
fellow patients who have engaged in bigger, more immediate, and more 
desperate battles. In particular, I am in pain to find that that 
distinguished American, Geraldine Ferraro, has reason to testify as a 
patient today. She is an inspiration.
    To many with CLL and other blood disorders, a twelve-year survival 
must seem like a dream come true. It is. But I have had my turn at 
harsh treatments with the resulting nausea, fatigue and mental 
disorientation. Last time, it got bad enough that I could not ride on 
the Washington Metro because the smell of the seats reminded me 
powerfully of the chemo infusion chair. I will have my turn at heavy 
treatment soon again--my turn to fight directly with what that 
remarkable patient and CLL activist Barbara Lackritz calls ``our 
dragon''.
    I am determined to beat it back over and over again with the help 
of all those who are doing CLL research, not only in the United States 
but in the world. In that process, no institution is more central than 
the National Cancer Institute, and no army in the field is more 
important that the groundbreaking CLL Research Consortium, which needs 
a higher level of funding now.
    Let me tell you how I was told I have leukemia. At that time, I was 
running the Political Section at the U.S. Embassy in London and 
complaining of fatigue that led to a blood test. I was called out of a 
meeting on the Human Rights Report to take a call from a doctor who 
said--on the phone and all too briefly--that I had leukemia. But the 
``good'' chronic kind. I should see a specialist. Soon I was told I 
could expect to live five years or more. I heard five years. One of my 
colleagues later told me that I seemed a bit disoriented when I 
returned to the meeting. I did not tell him or anyone else but my wife 
about the diagnosis.
    I was 48. My wife and I suddenly had to ponder all those questions 
about the future of our family and careers as we faced my mortality. 
You can imagine what issues arise. If you can't, ask any one of many 
patients in this room. We are all encouraged to take a tape recorder to 
the first meeting with the doctor who diagnoses us and invites us to 
come in for a little chat about out blood test--if we are not told on 
the phone. That is because after we hear the word ``leukemia,'' we 
generally will not remember a thing.
    Mr. Chairman, you will recall that I was told I have a good 
leukemia. There is no good leukemia or any other blood disorder. There 
is no good cancer. As a doctor said at a conference at the National 
Cancer Institute last week, the only good cancer cell is a dead cancer 
cell. Another doctor told me that I am a lucky patient. And of course I 
am. The fact that I am very much alive and generally thriving at age 62 
means that I have not faced the ultimate immediacy of death that 
Representative Joe Moakley bore with such grace and dignity.
    Allow me to say a few more words about CLL and the effort to cure 
it, particularly through the CLL Research Consortium funded by NCI--and 
all the intramural and extramural research and researchers who are 
working throughout the country and around the globe. As you listen to 
these words about one subset of leukemia, CLL, please multiply by many 
fold the impact on patients, families and the economy of blood 
disorders and other forms of cancer.
    CLL is the most common form of adult leukemia in the United States 
and in the western world. More voters in each of your states have this 
form of leukemia than any other. In the United States somewhat under 
10,000 people are diagnosed with CLL each year, and 5,000 die. There 
are about 100,000 of us alive at any given time. More men than women, 
but women are hardly excluded. Unlike CML, nobody knows what triggers 
CLL. Nobody really knows what to target, but CLL researchers are 
getting closer every day. There are increasing indications that 
environmental factors play a role in the process, causing abnormalities 
in genes.
    To date, CLL can not be cured. Indeed, those of us with CLL are not 
living any longer in the aggregate than when I graduated from college 
40 years ago. And this is despite intensifying and gratifying research 
efforts and new but risky ways of managing the disease. For instance, 
we have all heard about bone marrow transplants, but unfortunately 
almost one quarter of those going the transplant route using marrow 
from matching siblings are dying, usually from graft-versus-host 
disease following the procedure.
    Clearly CLL needs a Gleevec. We need a Gleevec in less than the 40 
years it took to develop that drug. Breakthroughs may be near. We need 
to know first what to target. And fortunately some extraordinary 
genetic work is being done under the leadership of NCI and the CLL 
Research Consortium in an effort to identify subgroups, targets and 
cures like Gleevec. (Incidentally, Medicare will not cover Gleevec as a 
pill. Only as an infusion via a vein. Legislation is needed to change 
that, and it is needed now.)
    CLL is not unlike AIDS in the way it destroys patients' health and 
lives. It is quite parallel to the notion of starting with HIV and then 
becoming full blown. The median age of diagnosis is 64. This may help 
to account for the relative historic lack of public health concern 
about the disease. However, a growing number of patients are being 
diagnosed in their 30's and 40's. You will recall that I was diagnosed 
at age 48.
    CLL patients eventually have come to learn that while many of us 
live only three to five years, many others survive for ten years--or 
measurably longer. It depends on your subset and whether your CLL 
mutates or not, markers that are only now becoming apparent.
    And over time we come to cope with complications such as a 
suppressed immune system, swollen lymph nodes, weakness, weight loss 
(myself excluded so far). The most frequent immediate causes of death 
are bleeding and systemic infections like pneumonia. CLL is truly a 
devastating disease. Former Secretary of State Larry Eagleburger once 
said to me ``You like wars'' as he moved me at the State Department 
from the Falklands Island War Task Force to run the Office of Israel 
and Arab-Israel Affairs when Israel was in Lebanon. However, this 
cancer is a war that I would not have wished on anyone.
    Mr. Chairman, I am glad to say that there is now a measure of hope 
on the research front for CLL patients and their families. The 
Committee's dedication to funding at adequate levels both NIH and NCI 
has played a central role in this renewed hope. Everything you do to 
increase funding for medical research translates directly or indirectly 
into giving hope to patients in every state and around the world. I say 
this as someone treated in Europe as well as the U.S.
    There is report language going ahead in both the Senate and House 
strongly encouraging NCI to give full and fair consideration to 
expanding the scope of research activities through the CLL Research 
Consortium that I have previously mentioned. But as Senator Specter has 
said over the years about report language and sense of the Senate 
resolutions, ``druthers do not make dollars''. If I had my druthers, I 
would have Congress earmark $20 million more for the CLL Research 
Consortium now, but I more or less understand the process. In this case 
both Congress and NCI with its bypass budget and ability to make 
decisions internally have to play a role.
    This Consortium is a remarkable and long-overdue initiative. It is 
worthy of more support now, and with the help of doctors, I calculate 
that it could very usefully expend the $20 million I mentioned 
previously And use it fruitfully now. NIH and NCI have, of course, long 
sponsored really productive intramural and extramural research on CLL. 
But now thanks to NCI a small cadre of researchers in centers ranging 
from Boston to La Jolla is attempting to discover not only better 
treatment options but the holy grail of a cure for CLL. I say a small 
cadre because last week I was privileged to attend a CLL State of the 
Science meeting at NCI, and a high proportion of the great CLL bench 
researcher and clinician from the United States and Europe were there. 
They could all fit in one not-too-large room.
    Many of these researchers are going forward under the umbrella of 
the Consortium itself. It was started last year with an NCI program 
project grant of $16.5 million to be shared among nine institutions 
over four years. For that we are grateful, but we can all do the math. 
That is a humble sum on an annual and institutional basis with which to 
do lifesaving work. The program project grant is exactly the same 
amount Mrs. Casey spent to buy the site on Foxhall Road here in 
Washington for a new residence for our mayors.
    To my astonishment, the Consortium is unique. It is a model. It 
must succeed and is succeeding. Why is it unique? Because for the first 
time in NCI history it brings together that nation's top researchers on 
a given type of cancer from different disciplines--genetics, cell 
biology, immunology and pharmacology, to conduct an integrated program 
of basic and clinical research. It is also unique in that it brings 
together many of the great battleships of the cancer wars, ranging from 
Dana Farber to Johns Hopkins, to M.D. Anderson to Walter Reed. And they 
are all under the leadership of Dr. Thomas Kipps at the University of 
California at San Diego. It is not only unique. It is a model in terms 
of how we might combat other cancers.
    The hope is that cross fertilization among leading research 
institutions which might not otherwise work together will generate 
life-saving insights, not only about CLL--and this is important--but 
about many other types of cancers as well. The interaction is already 
generating new opportunities, opportunities that can not be pursued 
vigorously at present funding levels. A remarkable CLL Consortium 
specialist seated near me at last weeks NCI meeting forgot to bring his 
pen. He told me later that he initially thought he would not need it 
because he was up on all the latest development. But within the first 
few minutes of cutting-edge presentations, he had borrowed a pen and 
went on to scribble all morning. There is much that is new and 
exciting.
    More specifically, more funding is now needed by the Consortium for 
a stronger research infrastructure, to support further clinical trials 
on at least six new agents, to fund additional institutional 
participation, attract additional researchers--particularly in gene 
therapy, to support expensive data and tissue flow and to encourage the 
kind of breakthroughs that would attract even more support. The 
recently developed (and often quite harsh) treatments like Rituxan and 
Campath are not enough, although desperate patients welcome them. They 
are not a cure, far from it. They have their costs as well as their 
benefits. Nevertheless, they show what can be done by NIH, NCI, the CLL 
Research Consortium and other academic researchers and the 
pharmaceutical companies.
    Simply take as an example the tissue sharing done by the 
Consortium. Researchers around the country can now secure blood and 
tissue samples for CLL research purposes. But the process involved in 
freezing fbrzshipment and-assuring tissue quality at the other end is 
highly sophisticated and extremely expensive. So is the exchange of 
data developed by the Consortium. But it is an absolutely vital 
process.
    A measure of success in the model Consortium program is leading the 
way for other potential collaborative efforts to fight an array of 
cancers and other diseases that affect the lives of so many of us in 
this room and millions of other Americans every day. But all this will 
cost even more money. I believe it is money the American people are 
willing to spend.
    In conclusion, permit me to quote from Dr. Brian Druker, the 
principal investigator on Gleevec when he was asked how it feels to 
have made the breakthrough towards a cure for CML. He recently said:

    ``It's something that is very hard to put into words, and I will 
share with you what a senior clinical researcher shared with me the 
other day, and he really put it succinctly. And that was, right now its 
enjoyable to go to clinic to see our patients being treated with 
(Gleevec) in a way he never thought imaginable. Patients are grateful 
in a way we never thought imaginable because of the way they feel and 
because of the hope that we have restored for the future for them. For 
me to hear those sorts of words and to know that this is something I 
have dreamed about for my entire career, this is something I have 
worked toward, and to actually see it come true is something that I 
really just can't put into words, but I can tell you, it just feels 
incredibly good.''

    Mr. Chairman, if it feels so good to a compassionate doctor like 
Brian Druker, who once treated me when I fell ill in Portland, Oregon, 
you can imagine how it must feel to patients and their families--to 
know that a cure may be in sight and that for now their lives are being 
restored to them. Let's make it possible to do the same for CLL and all 
other blood disorders.
    Thank you very much.

STATEMENT OF HAGOP M. KANTARJIAN, M.D., CHAIRMAN, 
            LEUKEMIA DEPARTMENT, M.D. ANDERSON CANCER 
            CENTER

    Senator Specter. We turn now our final witness on this 
panel, Dr. Hagop Kantarjian, chairman of the Leukemia 
Department at M.D. Anderson Cancer Center. He received his B.S. 
and M.D. from American University of Beirut in Lebanon. Thank 
you for joining us and we look forward to your testimony.
    Dr. Kantarjian. Thank you, Senator Specter and Senator 
Hutchison, for the opportunity to talk about leukemias. I am 
going to be brief, but I would like to include by written 
document in the permanent records, if you wish.
    Senator Specter. The full statement will be made a part of 
the record, without objection.
    Dr. Kantarjian. Thank you.
    For children and adults, leukemia still presents a major 
health problem and it affects about 50,000 individuals in the 
United States every year. Thirty years ago, a diagnosis of 
leukemia was a death sentence. But today, with the discoveries 
and the research, we can offer the hope that we will help most 
of these patients and that we can probably cure over half of 
these patients.
    Aside from the need to cure, treat, and prevent leukemias 
ultimately, leukemias are an excellent model to study because 
of the accessibility of the leukemic cells so that a lot of the 
lessons that we learn from leukemia help other cancers.
    How did we improve the cure in leukemia? This was the 
result of multiple approaches, including chemotherapy, biologic 
modalities, bone marrow transplantation, and most importantly, 
the targeted therapies which I will discuss briefly.
    But it is important to note that chemotherapy today cures 
about 80 percent of children with acute lymphocytic leukemia 
and about 40 to 50 percent of adults with acute leukemia. There 
are certain acute leukemias which can be treated with only 1 
week of chemotherapy, like hairy cell leukemia, or even without 
chemotherapy but only using vitamin A analogs or arsenic 
trioxide. Of course, transplant, when it is available, cures 
about 50 percent of the patients with leukemias and other 
hematologic cancers.
    But as I mentioned, the greatest progress has happened over 
the past 5 years with the targeted therapies, and in simple 
terms, leukemias send messages to the outside that identify 
them as very specific. So, with developed drugs, which are 
called targeted therapies that look for those signals and there 
are two kinds which have been very successful: the monoclonal 
antibodies, which many of them have been approved by the FDA, 
and then the Gleevec, which is really a magic pill which has no 
side effects, and based on the research, we think will cure 
about half of the patients with chronic myeloid leukemia.
    M.D. Anderson from the great State of Texas and many other 
institutions have been involved in this research, and this is 
made possible only through the granting mechanisms of the NCI 
and the NIH. The reason is leukemia is a small market for drug 
companies, so they do not usually do the research. We have to 
do it, and when there is a lead, they go for that.
    But another important point is we have to have a balanced 
funding of that research. I personally believe that clinical 
research has been neglected, and acceleration of the success 
will come through a balanced funding of both the laboratory and 
clinical research.

                           PREPARED STATEMENT

    The final question, which I am sure Senator Specter will 
ask me, so I will ask it to myself, is when will we cure all 
these leukemias. I truly believe from my heart and also from my 
mind that based on the base of the discoveries, that we will be 
able to cure most, if not all, of the leukemias in next 10 
years. Thank you.
    [The statement follows:]

               Prepared Statement of Hagop M. Kantarjian

                               BACKGROUND

    Leukemias are categorized by the aggressiveness of their course 
when untreated (acute versus chronic), and the cell involved (myeloid 
versus lymphoid). Thus, we often refer to four major types.

----------------------------------------------------------------------------------------------------------------
                             Acute                                                   Chronic
----------------------------------------------------------------------------------------------------------------
               Myeloid                         Lymphoid                 Myeloid                  Lymphoid
----------------------------------------------------------------------------------------------------------------
acute myeloid leukemia or AML........  acute lymphoid leukemia  chronic myeloid          chronic lymphoid
                                        or ALL.                  leukemia or CML.         leukemia or CLL
----------------------------------------------------------------------------------------------------------------

    The overall yearly incidences of leukemias in the USA are:

                                                             Approximate
        Leukemia                                        yearly incidence

AML............................................................... 8,000
ALL............................................................... 5,000
CML............................................................... 7,000
CLL...............................................................10,000

    Another group related to AML myelodysplastic syndrome (MDS) affects 
12,000 to 20,000 individuals/year. Thus leukemias affect overall 
40,000-50,000 people in the USA.
                current status and progress in leukemias
    Over the past 20 years, we have made major progress in the 
treatment of each of the leukemias. The cure rates in year 2000 for 
each leukemia and reasons for progress are shown below.

----------------------------------------------------------------------------------------------------------------
                                            Potential cure
               Leukemia                       (percent)             Average survival            Treatment
----------------------------------------------------------------------------------------------------------------
Childhood ALL........................  80.....................  NA.....................  Combination
                                                                                          chemotherapy.
Adult ALL............................  40-50..................  NA.....................  Same.
Adult AML............................  20-60..................  NA.....................  Same.
    acute promyelocytic leukemia.....  70.....................  .......................  All trans retinoic acid
                                                                                          arsenic trioxide.
CML..................................  50 with transplant.....  > 7 years..............  Transplantation
                                                                                          Interferon alpha,
                                                                                          Gleevec.
CLL..................................  .......................  6-8 years..............  Fludarabine, Rituxan.
    -hairy cell leukemia.............  80.....................  NA.....................  chlorodeoxyadenosine.
----------------------------------------------------------------------------------------------------------------
NA = Not applicable.

    Major areas of treatment discoveries have included:
    (1) new chemotherapy drugs
    (2) transplant modifications
    (3) agents that differentiate leukemias to normal cells such as 
all-transretinoic acid (vitamin A-like drug) and arsenic trioxide
    (4) targeted therapies in the form of:
      --monoclonal antibodies: Rituxan, campath 1H, Zevalin, Mylotarg, 
            Bexxar
      --small molecules that block signals that stimulate/cause cancer 
            cells: the best example is Gleevec; others include 
            angiogenesis inhibitors, (i.e. agents that block vessels 
            that feed cancers), and others.

                      WHAT ARE TARGETED THERAPIES

    Cancer cells in general, and leukemic cells in particular produce 
signals or messages which (1) can cause the cancer/leukemia, or (2) 
identify them selectively (e.g. surface proteins). The past five years 
have been very exciting in leukemia research because we successfully 
developed many monoclonal antibodies that target the surface proteins 
on leukemic cells, and also several ``small molecules'' that block the 
signals that may cause leukemias.
    Several monoclonal antibodies have now been approved by the FDA for 
leukemias and are already improving patient prognosis: Rituxan, Campath 
1H, Mylotarg. The best example of a ``signal inhibitor'' is STI571 or 
Gleevec which blocks the function of protein that causes CML. We 
believe this very simple small molecule (Gleevec) which is given by 
mouth, and has almost no side effects (unlike chemotherapy) may lead to 
the cure of half of all CML patients without requiring transplant. We 
would like to develop similar selective targeted therapies for most 
leukemias. Research in these areas is progressing very rapidly. 
Research in leukemia often cross fertilizes other areas of research in 
cancer and serves as a useful model to identify new treatments that 
also help other cancers. Thus funding research in leukemia helps 
research in other cancer.

                  FUTURE HOPES, EXPECTATIONS AND NEEDS

    Based on the current pace of discoveries, I predict we will be able 
to cure most leukemias with treatments that have good tolerance in the 
next 10 years.
    To accomplish this, funding by the NIH/NCI is crucial to support:
    (1) research projects that investigate new chemotherapy agents, 
immunologic strategies (e.g. vaccines), targeted therapies, and others.
    (2) translational research that translates the laboratory 
discoveries into clinical research realities.
    (3) clinical research, an often neglected area of grant support, 
without which progress will be inhibited. We need to support clinician-
scientists who conduct superior clinical research and make discoveries 
in human trials that improve the outcome of leukemias.
 a brief glimpse at the leukemia program at m.d. anderson cancer center
    Our group at M.D. Anderson includes 15 leukemia specialists who are 
probably the best in the world. Our leukemia service treats about 2,000 
new leukemia cases per year. This is by far the largest program in the 
world with total dedication to curing one disease--leukemia.
    Our cumulative expertise is by far superior to any other program in 
the world, and we have been responsible for, or associated with most of 
the discoveries in leukemia therapies. Our program has been funded to a 
significant extent by the NIH and NCI grant support. Such continued 
funding mechanisms are vital to the continued success in leukemia 
research.

    Senator Specter. That is very encouraging. You are right. I 
always do ask that question because if you can put something 
tangible on the line, it impresses Members of the Senate and 
House.
    We have been joined by the senior Republican on the full 
committee and former chairman. Senator Stevens, would you care 
to make a statement or question?

                    STATEMENT OF SENATOR TED STEVENS

    Senator Stevens. I regret I was not here to hear Dr. 
Klausner. I had fully intended to be here, Doctor, but we are 
working on the supplemental right now, and I have just dropped 
by as a fellow cancer survivor, prostate cancer, Mr. Lucchino, 
to welcome you all and to tell you of our continued support for 
your endeavors. We hope we can get as much money as possible to 
meet this medical research schedule. I am not sure how much 
money yet there is available, but we will get all there is. Let 
us put it that way.
    Thank you.
    Senator Specter. I might add that Senator Stevens has been 
enormously supportive of what this subcommittee has recommended 
and has vigorously supported the doubling of funding within 5 
years for the NIH. So, we thank you.
    We are going to have 4-minute rounds by the members.
    Let me address the first question to Mr. Pendleton. You 
comment that you are a sufferer of leukemia without any 
discernable cure in the offing. How do you feel about a 
situation where embryos are available which are going to be 
discarded and these embryos can produce stem cells which have 
enormous promise for answering and providing a cure for 
precisely the kind of ailment which you have? How do you feel 
about that?
    Mr. Pendleton. Senator, you can imagine that I and many and 
I think perhaps most other patients feel extremely strongly 
that research must go forward on every front. It is necessary 
to save the lives of Americans and to make the lives of 
millions of Americans more bearable.
    Senator Specter. Mr. Lucchino, the same question. Senator 
Gordon Smith of Oregon, a very strong pro-life Senator, has 
made the point that it is very different if you have an embryo 
in the womb of a woman where there is progress toward the 
creation of life, contrasted with a discarded embryo in a dish. 
As someone who has suffered from a variety of forms of cancer, 
how do you feel about legislation which is now on the books 
which prevents the National Institutes of Health from using 
Federal funding to extract stem cells from embryos which might 
provide a broader range of cures for cancer and other ailments?
    Mr. Lucchino. Senator, I echo Mr. Pendleton's observations. 
I readily admit that I am deeply biased on this. I hate these 
blood diseases so severely that I think that not to avail 
ourselves of every opportunity is a terrible tragedy.
    Senator Specter. One of the really critical factors about 
these hearings is to mobilize public opinion, and if these 
embryos were to produce life, I would never propose using the 
stem cells for research. But where they are going to be 
discarded and you have the positive testimony by the 
scientists, it seems to me that the point has to be made again 
and again until it resonates through America.
    To Drs. Kantarjian and Horning, brief answers. How 
important do you think the potential for stem cells are in 
curing cancer? Ladies first.
    Dr. Horning. Well, as my focus is clinical research, I will 
speak from that vantage. I would echo what my co-panelists have 
to say from the patients' perspective and from the physician or 
clinical researcher perspective. I feel that all leads must be 
followed. That is going to take many minds and many methods to 
achieve the cure. As we have heard from Dr. Klausner, there are 
certain diseases in which the use of embryonic stem cells will 
be more needed.
    Senator Specter. With all these embryos available, Dr. 
Kantarjian, despite that 10-year estimate?
    Dr. Kantarjian. Right. I think you have put it very 
clearly. I do not think that stem cell research is debated in 
the scientific issue. I think it is a political issue because 
of its potential association to abortions. But from the 
scientific point of view, stem cell research is very important 
and discarded embryonic tissue is important for this kind of 
research.
    Senator Specter. Thank you very much.
    Senator Murray.
    Senator Murray. Well, thank you very much, Mr. Chairman, 
and thank you to all of our panelists for excellent testimony. 
I think it was very clear the bottom line is research, 
education, and funding, funding, funding. So, I appreciate your 
message.
    I just have one question. I know we have other panelists, 
so we need to move along. That is the same question I asked to 
Dr. Klausner earlier. We are debating the Patients' Bill of 
Rights and one of the contentious issues is whether or not 
patients should have access to clinical trials. Could either 
Dr. Kantarjian or Dr. Horning comment on that?
    Dr. Kantarjian. I think the only way you can make progress 
is through the clinical trials, and it is a false notion that 
clinical trials increase the cost. I think clinical trials 
reduce the cost because they allow accessibility to high 
quality research that will benefit everybody.
    Dr. Horning. I agree there are data that indicate that the 
cost of care is not increased by clinical trials and studies 
show that the quality of care is improved for participants in 
clinical trials.
    Importantly, clinical trials help us to determine the leads 
that are promising, and when we find the ones that are, we move 
ahead, and if they are dead ends, then we turn to a different 
direction. I think the experience of bone marrow 
transplantation in breast cancer is an excellent example of 
that.
    Senator Murray. Thank you very much. Thank you, Mr. 
Chairman.
    Senator Specter. Thank you very much, Senator Murray.
    Senator Hutchison.
    Senator Hutchison. Thank you, Mr. Chairman.
    Sometimes I think we need a little definition of terms 
here. For you, we have been throwing around markup of a 
supplemental, and I wanted to explain to you that the 
supplemental is the emergency appropriations bill for the needs 
that we do not have available funds for in the rest of this 
year for our budget. The markup means we are trying to get the 
bill out of committee.
    Now I want to ask you a question on definition of terms and 
make sure that we are clear on clinical trials. I want you to 
define the difference between clinical trials and pure lab 
research.
    Dr. Kantarjian, I want to thank you for being here from 
M.D. Anderson, which is doing such a wonderful job in cancer 
research and treatment. I want to ask you to also expand on 
your point that much of this research needs to be done through 
NCI and NIH because the pharmaceutical companies cannot focus 
as much when it is a small number of patients who would use it 
in the end. I want you to go forward and tell us in the 
clinical trials, if the NCI and NIH funding is helpful in the 
clinical trials as much as it could be.
    Dr. Kantarjian. Let me define a clinical trial. A clinical 
trial is a controlled investigation where we put forward our 
best knowledge and we offer it to the patients. So, it is 
really not what people refer to as experimentation or a guinea 
pig process. There are no guinea pigs. A clinical trial, or an 
investigation, offers our best knowledge to the patients. So, 
it is a two-way benefit where the patients benefit from the 
most advanced knowledge and we benefit from gathering the data 
and publishing it. So, clinical trials are very important as 
opposed to clinical practice, and they are different from 
laboratory research where you are just looking at the basis 
mechanisms. You have to translate that knowledge into the 
clinic. Remember that if you put all your money in the 
laboratory research, you are not going to cure a single patient 
and oftentimes the first experience in the first individual 
will give us a lot of information.
    Senator Hutchison. Do NCI and NIH do enough to help in the 
clinical trials? We have been talking about whether insurance 
should cover it, but are we doing enough in the research area 
in Government or do we need to make changes there?
    Dr. Kantarjian. I think we are in the right direction, but 
there are two areas which need to be improved. One is the 
process where the insurance companies would pay for the 
clinical trials, and the second is enough and continuous 
funding because, as I mentioned, drug companies look for block 
buster drugs, a billion dollar drug. This does not exist in the 
leukemias, and this is why the leukemias have been a neglected 
entity. In fact, most of the discoveries has been made through 
the funding by the NCI and the FDA and academic institutions 
and then were taken by the drug companies. So, it is very 
important to continue that Federal and State funding to the 
leukemia and hematologic cancer research.
    Senator Hutchison. Thank you for being here.
    Dr. Kantarjian. Thank you.
    Senator Specter. Thank you very much, Senator Hutchison.
    Senator Mikulski.
    Senator Mikulski. Thank you, Mr. Chairman. To all of the 
witnesses, thank you for your most poignant and instructive 
testimony.
    In the interest of time, I am only going to address one 
question to Mr. Lucchino. It goes to public education in early 
detection. In the bill Senator Hutchison and I are working on--
and she has been the lead architect--we establish a program at 
the Centers for Disease Control and Prevention (CDC) and 
instruct them to create a public awareness program. Also, I 
think everyone testifying will talk about the need for early 
detection and screening.
    So, let me then get to my question. While we have been 
strong fighters for women's health, we are often worried that 
men do not go see doctors. They do not get the early detection 
and this cuts across all social class lines. My question to 
you, because you are really, as the Padre guy and the former 
Orioles guy and Edward Bennett Williams law firm, you have 
really been with the male culture.
    Mr. Lucchino. Is that in the nature of a criticism?
    Senator Mikulski. No. An observation.
    My question to you is what advice or insights would you 
give to really encourage men to go to the doctor and also what 
could we have the CDC focus on in terms of the kinds of 
examinations needed or getting men to go in for the early 
detection? Yours was detected through an annual health exam. 
Quite frankly, most guys do not go for it.
    Mr. Lucchino. Right. Well, I consider myself reasonably 
well informed and well educated, but when I was diagnosed with 
lymphoma, I had no idea what lymphoma was. At that time, I had 
no idea what a prostate was. I think there is a crying need for 
the kind of public awareness that you are talking about.
    How to go about it is a multi-faceted question. Certainly 
events like this hearing today go a long way. I have read more 
about blood cancers in the last 3 days than I have read in my 
lifetime. I think that that has a lot to do with Geraldine 
Ferraro and it has a lot to do with the focus of this committee 
today. I think that what the baseball world is doing with 
prostate cancer is an example of what the private sector can 
and must do. What the Cure for Lymphoma Foundation does is 
another example of what the private foundation can do. We must 
talk about it a lot. We must talk about it publicly, privately 
and certainly with the media. And men need to talk about it as 
much as possible.
    Senator Mikulski. Do you think men would be influenced by 
sports figures and through public service announcements?
    Mr. Lucchino. I do. I think there is no doubt about that. 
The cyclist, Lance Armstrong; golfer, Arnold Palmer; hockey 
player, Mario Lemieux; former Oriole, Eric Davis. I think the 
experience of these people and the public nature of their 
experience, talking about it, coming forward, and making the 
world aware that there is life after a cancer diagnosis is 
enormously important to the public awareness you are talking 
about.
    Senator Mikulski. Well, thank you. Thank you, Mr. Chairman, 
and to all the panel and to those who, if we had time, ought to 
be on the panel, the other survivors, thank you.
    Senator Specter. Thank you very much, Senator Mikulski, and 
thank you very much.
    We will now turn to the next panel. Geraldine Ferraro, Dr. 
Kenneth Anderson, Dr. John Holaday, and Ms. Kathy Giusti.
    We will begin with the Honorable Geraldine Ferraro, who has 
had an extraordinary career. A lawyer by profession, elected to 
the House of Representatives in 1978, and then an historical 
candidacy for the Vice Presidency of the United States with 
Vice President Mondale in 1984. I join Senator Kay Bailey 
Hutchison, Congresswoman Ferraro, in praising you for your 
courage in coming forward.
    Ms. Ferraro. Thank you.
    Senator Specter. It carries a lot of weight when people see 
someone of your stature who is willing to come forward, and 
also if it can happen to Geraldine Ferraro, it can happen to 
anybody. We need all of the public support we can get to push 
forward the funding and the stem cell research, et cetera. So, 
thank you for joining us and the floor is yours.

STATEMENT OF GERALDINE FERRARO, FORMER MEMBER OF 
            CONGRESS FROM NEW YORK

    Ms. Ferraro. Thank you, Senator, and thank you for having 
this hearing. I want to thank Senator Harkin and thank you, 
Senator Hutchison, for helping make it happen, and my two 
buddies, Senator Mikulski and Senator Murray, for being here. I 
appreciate it.
    I am all too aware of how many things there are to do when 
you are in session and how little time there is to do them all. 
So, I am particularly grateful for your allowing us to appear 
before you to discuss and issue which is, to some of us here, a 
matter of life and death.
    Several months ago I was at home watching the news and saw 
our former colleague, Joe Moakley, at his press conference 
disclosing that he had been diagnosed with a blood cancer, 
leukemia, which is neither curable nor treatable and announcing 
that he would not seek reelection. My heart went out to him in 
part because he was such a terrific person who really loved the 
Congress, and his announcement was so terribly final. But also 
because I knew what he was going through emotionally dealing 
with this disease. In December of 1998, I too was diagnosed 
with a blood cancer, multiple myeloma, which is also not 
curable. Let me hasten to add, however, that unlike Joe's 
situation, at least for the present, my cancer is treatable.
    I have chosen not to be public about my health until now. 
That is one of the benefits of losing an election.
    You can keep your private life private. But I am here 
because I want to make sure that the public got to know about 
multiple myeloma and I wanted to point out to you just how 
important research dollars are to dealing with this disease.
    Let me start by saying I am a very lucky woman. First of 
all, I have the best doctors caring for me. It is because of 
one of those doctors, Ronald MacKenzie, my internist, that I 
was diagnosed very early. I had gone for my annual checkup and 
he noticed in looking over my blood test results that my white 
blood count was slightly elevated. He went back and checked my 
previous years' records and saw that there was a steady but 
slow progression upward of the white cell count over the years. 
He called me and said he wanted to see me and that he was 
sending my blood out for additional tests because it seemed 
that I had either leukemia, lymphoma, or multiple myeloma.
    I must say I was a bit taken aback. I did not even know 
what multiple myeloma was. I had never heard of it. Dr. 
MacKenzie explained that it was a blood cancer that attacks the 
bones. Most people do not find out that they have it until a 
symptom appears that needs explanation, like aching or broken 
bones. And I had no symptoms.
    My initial reaction was thank God it is me and not one of 
my children. As much as we want to believe that we are 
indispensable to our families, my children are all grown and 
quite independent. But they are also married and they have 
little children of their own who most definitely do need them.
    My second reaction was: Why cancer? That is not a disease 
that is in my family. We are big on strokes and heart attacks.
    Even my mother who smoked died of emphysema, not lung 
cancer. So, how did I get multiple myeloma? Was it the 
environment? Was it stress? And we all know I have had a little 
of that over the years. Was there some hidden genetic 
disposition to the disease, and if so, can we check my children 
and grandchildren to be sure I have not passed that cancer gene 
on to them? And going beyond me, what is it that make African 
Americans almost two and a half times more likely than 
Caucasians to come down with this disease? Why is it that 
multiple myeloma historically manifests itself in people who 
are older? Hopefully, future research will be able to answer 
all of those questions.
    When we left Dr. MacKenzie that day, we were feeling pretty 
down. But the holidays were fast approaching, and after seeing 
John's devastation on hearing the news, I just did not have the 
heart to tell my kids until after Christmas. But once the 
holidays were behind us, we told them, and then we went to see 
my second wonderful doctor, Jeffrey Teppler, who is an 
oncologist.
    Before I go on, I want to point out that I keep using the 
term ``we.'' That is not the royal ``we.'' That is my husband 
John Zaccaro and me. We have been best friends since college. 
Next month we will be married for 41 years. We totally enjoy 
each other's company but professionally we have led rather 
independent lives. Since my diagnosis, however, John drops 
everything at the office to drive me to the doctor, to sit with 
me for 2 hours at the hospital when I am getting an infusion, 
to fly to Boston to meet with my third wonderful doctor, Ken 
Anderson, from whom you will hear shortly. And as a matter of 
fact, my husband is here today with my eldest daughter Donna.
    But back to Dr. Teppler. When I was first diagnosed, my 
cancer was inactive. No protein showed in my blood, none in my 
urine. So, Dr. Teppler took rather frequent bone marrow samples 
and did blood and urine tests on a monthly basis. And I started 
monthly infusions of a bone-strengthening drug called 
pamidronate.
    In June of last year, he called me and told me that the 
cancer had become active and that he had spoken with Dr. 
Anderson, whom I had met shortly after diagnosis, and they 
agreed that I should start taking steroids.
    Now, I thought I was going to be able to hit the golf ball 
further, swim faster, run like the wind once I got on steroids.
    Unfortunately, this type of steroid has none of the 
beneficial effects that the steroids that athletes take. It did 
deal with the cancer, though it was mood altering and made me 
terribly irritable. It also made me slightly puffy which was 
not all that bad since all of my wrinkles temporarily 
disappeared without the cost or inconvenience of a face lift.
    I continued taking the steroids through the summer and 
early fall and they worked beautifully, reducing the cancer 
protein, until November. And then I plateaued. It was time to 
go to Dr. Anderson to discuss stem cell transplants.
    Though I was not happy about it, I was resigned to the fact 
that I would need the procedure since I had been told it was my 
next step in treating the disease. And without treatment, quite 
simply I will die. I was told the stem cell transplant would 
involve 3 weeks in the hospital, that I would be getting 
massive doses of chemotherapy, followed by radiation, that my 
immune system would be totally destroyed and that I would need 
approximately 3 months at home to recuperate.
    I was worried about how I would deal with that amount of 
time out of circulation. I worried about my business, my 
family, and to be quite frank, I worried about myself.
    The one thing I was not worried about was the cost. I am 
told the price tag for the procedure is $50,000 to $100,000. I 
am now eligible for Medicare and Medicare covers the procedure. 
But even if it did not, my insurance does, and if my insurance 
did not cover it, I could still afford to pay for the procedure 
myself if I need it. But what about those who cannot? What 
about those who do not have health care coverage? I guess those 
are two questions that will properly be answered at a future 
hearing on health care legislation instead of here today.
    Dr. Anderson went through the whole process with John, my 
youngest daughter Laura, and me. And then he said that several 
of his patients had opted to take thalidomide as an alternative 
to having the stem cell procedure done. I was intrigued. I was 
having babies in the 1960's when thalidomide was making 
headlines as a dreaded pill that, when taken by pregnant women, 
caused severe damage to fetuses. Children were being born with 
all kinds of deformities. But what destroyed healthy growth 
then was now being used to prevent cancer growth. Dr. Anderson 
described for us just how thalidomide works, which I am sure he 
will do for you, and when we heard that it had the potential 
for treating the disease with minimal side effects, that if it 
did not work, we were not precluded from doing the stem cell 
transplant in the future, we opted to try thalidomide.
    I have been taking thalidomide since November. It is 
working. Once a month, I still go for an infusion, and once a 
month I get blood and urine tests. Then I wait for three very 
long days until my test comes back to hear from Dr. Teppler. Am 
I still doing well? Have the cancer cells figured out a way to 
fight the thalidomide? And if they have, what if any option do 
I have before I deal with a stem cell transplant?
    I do not expect you to answer those questions, Senators. 
Those I reserve for Dr. Anderson. And I have such confidence in 
him and the other researchers who are dealing with multiple 
myeloma that I know they will have the next step ready for me 
when I need to take it.
    But they need you and your colleagues in the Congress to 
help. They need more awareness and attention being paid to 
blood cancers so that people will test early and be diagnosed 
earlier. They need research dollars to continue to search for 
new treatments and a cure, and they need faster approval by the 
FDA of new drugs.
    Pharmaceutical companies have been slow to underwrite 
research for multiple myeloma because each different blood 
cancer requires different treatment. What is good for leukemia 
or lymphoma will not help me. So, if you take each of the blood 
cancers separately, we are talking about orphan drugs since 
there just are not enough potential users of each to make it 
financially worthwhile for the pharmaceutical companies.
    On the other hand, this is still a huge problem for this 
country, for if we lump together leukemia, lymphoma, and 
multiple myeloma, last year's figures show that the mortality 
rate for blood cancers is second only to lung cancer, 20 
percent higher than colon blood, one-third higher than breast 
cancer, and almost twice as high as prostate cancer. Those 
diseases receive far more attention and far more funding.
    Now I am not suggesting for 1 minute that attention or 
funding to the other diseases be reduced. My husband is a 
survivor of colon cancer because of early detection. I nagged 
my two older children until they got a colonoscopy, and I will 
get up on a soapbox and tell the world how important it is to 
be tested to detect that disease because it is curable. I also 
served when I was in the House and even after on a breast 
cancer task force, and I have spoken out and walked more than 
once to raise money for that cause which I will continue to do. 
But what I am suggesting is that blood cancers are a serious 
and costly health concern and they too need our attention and 
funding.
    Multiple myeloma is hitting a lot of elderly, and though I 
wince when I refer to myself that way, I am not an unusual 
candidate for this disease. But just think about the 
consequence of that demographic. I mentioned before that if I 
need a stem cell transplant, it will cost between $50,000 and 
$100,000 and that Medicare will pay for it. Instead, my 
insurance company is paying $264 a month for a prescription of 
thalidomide. A year ago, that cheaper option of thalidomide was 
not available. Research made the difference. Now, what happens 
when thalidomide stops working, and I go month to month not 
knowing when Dr. Teppler will call and tell me that? Will Dr. 
Anderson be able to give me some new drug, or will he have to 
tell me that it is in clinicals and he is not quite sure when 
it will be approved, so it is time for a transplant? It almost 
goes without saying that combining investment and research with 
faster Government approval of drugs is a cost effective way of 
dealing with the expense of this disease to our health care 
system.
    I told you when I started that I am a lucky woman. I have 
great doctors, an early diagnosis, and up-to-the-minute 
treatment that works. But cancer does not only eat at your 
body. It is a disease that can destroy you both emotionally and 
psychologically. I am blessed with a family that is always 
there to boost me up. In addition to their constant concern for 
me, my daughter Donna has taken her business and media 
experience and put it to work to help the Multiple Myeloma 
Research Foundation raise awareness and money. My son John, who 
is a lawyer, has filled in and taken over the headaches of 
John's business so his dad can be with me. Laura is the doctor 
who keeps an eye on my test results and asks the questions I 
forget to ask and answers the ones that I am too embarrassed to 
ask. My four grandbabies give me hugs and kisses and a 
thousands reasons a day I want to fight this thing. They and 
John, of course, and a few close friends--and Barbara Mikulski 
was one of the people I confided in almost immediately after I 
found out that I had this--have given me the emotional support 
that all of us need when we are slapped in the face with our 
mortality. Living in New York City, I am never quite sure when 
I run into a street to hail a cab that I am going to live long 
enough to ride in it.
    But hearing that you have a disease that is incurable with 
an average life span of just 3 years does make one stop and 
notice.
    I expect that with my trio of medical miracle workers, with 
the love of my family and friends, with my mother and all the 
nuns who took care of me a as little girl praying for me, that 
I will be around at least until 2010 so that I can take 
advantage of President Bush's elimination of the inheritance 
tax--hopefully even after that so that I can be invited to the 
inauguration of the first female President of the United 
States, Senators.

                           PREPARED STATEMENT

    In the meantime, however, I, as well as every other 
multiple myeloma patient, am hoping that you, Senators, will 
provide help to these doctors so they can continue their 
research and eventually find a cure to this disease.
    Again, thank you, Mr. Chairman, Senator Specter, Senator 
Hutchison, Senator Murray, Senator Mikulski.
    [The statement follows:]

               Prepared Statement of Geraldine A. Ferraro

    I want to begin by thanking you, Mr. Chairman, and Senator Spector 
for holding this hearing and Senator Hutchinson for helping to make it 
happen. As a former member, I am all too aware of how many things there 
are to do when you are in session and how little time there is to do 
them all, so I am particularly grateful for your allowing us to appear 
before you to discuss an issue which is, to some of us here, a matter 
of life and death.
    Several months ago I was at home watching the news and saw our 
former colleague, Joe Moakley at his press conference disclosing that 
he had been diagnosed with a blood cancer, leukemia, which was neither 
curable nor treatable and announcing that he would not seek reelection. 
My heart went out to him in part because he was such a terrific person 
who really loved the Congress and his announcement was so terribly 
final. But also because I knew what he was going through emotionally 
dealing with his illness. In December of 1998, I too was diagnosed with 
a blood cancer, multiple myeloma, which is also not curable. Let me 
hasten to add, however, that unlike Joe's situation at least for the 
present, my cancer is treatable.
    I have chosen not to be public about my health until now. That's 
one of the benefits of losing an election, you can keep your private 
life private. But I am here because I wanted to make sure that the 
public got to know about multiple myeloma and I wanted to point out to 
you just how important research dollars are to dealing with this 
disease.
    Let me start by saying I am a very lucky woman.
    First of all, I have the best doctors caring for me.
    It is because of one of those doctors, Ronald MacKenzie, my 
internist, that I was diagnosed very early. I had gone for my annual 
checkup and he noticed in looking over my blood test results, that my 
white blood count was slightly elevated. He went back and checked my 
previous years records and saw that there was a steady but slow 
progression upward of the white cell count over the years. He called me 
and said he wanted to see me and that he was sending my blood out for 
additional tests because it seemed that I had either leukemia, lymphoma 
or multiple myeloma.
    I must say I was a bit taken aback. I didn't even know what 
multiple myeloma was, I had never heard of it. Dr. MacKenzie explained 
that it was a blood cancer that attacks the bones. Most people don't 
find out that they have it until a symptom appears that needs 
explanation--like aching or broken bones. I had no symptoms.
    My initial reaction was: Thank God it's me and not one of my 
children. As much as we want to believe that we are indispensable to 
our families, my children are all grown and quite independent. But they 
are also married and they have little children of their own who most 
definitely do need them.
    My second reaction was: Why cancer? That's not a disease that's in 
my family. We're big on strokes and heart attacks. Even my mother who 
smoked, died of emphysema, not lung cancer. So how did I get multiple 
myeloma? Was it the environment? Was it stress? (And we all know I've 
had a little of that over the years.) Was there some hidden genetic 
disposition to the disease? And if so, can we check my children and 
grandchildren to be sure I haven't passed that cancer gene on to them? 
And going ``beyond me--What is it that makes African Americans almost 
two and a half times more likely than Caucasians to come down with this 
disease? Why is it that multiple myeloma historically manifests itself 
in people who are older? Hopefully, future research will be able to 
answer all of those questions.
    When we left Dr. MacKenzie that day, we were feeling pretty down. 
But the holidays were fast approaching and after seeing John's 
devastation on hearing the news, I just didn't have the heart to tell 
my kids until after Christmas. But once the holidays were behind us, we 
told them and then we went to see my second wonderful doctor, Jeffrey 
Teppler who is an oncologist.
    Before I go on, I want to point out that I keep using the term 
``we''. That is not the royal we. The ``we'' is my husband John and me. 
We have been best friends since college and we've been married for 41 
years. We totally enjoy each other's company but professionally we've 
led rather independent lives. Since my diagnosis, however, John drops 
everything at the office to drive me to the doctor, to sit with me for 
two hours at the hospital when I'm getting an infusion, to fly to 
Boston to meet with our third wonderful doctor, Ken Anderson whom you 
will hear from shortly and as a matter of fact, my husband is here 
today with my eldest daughter, Donna.
    But back to Dr. Teppler. When I was first diagnosed, my cancer was 
inactive. No protein showed in my blood, none in my urine. So Dr. 
Teppler took rather frequent bone marrow samples and did blood and 
urine tests on a monthly basis and I started monthly infusions of a 
bone-strengthening drug called pamidronate. In June of last year, he 
called me and told me that the cancer had become active and that he had 
spoken with Dr. Anderson, whom I had met shortly after diagnosis, and 
they agreed that I should start using steroids.
    Now I thought I was going to be able to hit the golf ball farther, 
swim faster, and run like the wind once I got on steroids. 
Unfortunately, this type of steroid has none of the beneficial effects 
of the steroids that athletes take. It did deal with the cancer though 
it was mood altering and made me terribly irritable. It also made me 
slightly puffy which wasn't all that bad since all of my wrinkles 
temporarily disappeared without the cost or inconvenience of a 
facelift!
    I continued taking the steroids through the summer and early fall 
and they worked beautifully, reducing the cancer protein. Until 
November. Then I plateaued. It was time to go back to Dr. Anderson to 
discuss stem cell transplants.
    Though I wasn't happy about it, I was resigned to the fact that I 
would need the procedure since I had been told it was my next step in 
treating the disease. And without treatment, quite simply, I will die. 
I was told a stem cell transplant would involve three weeks in the 
hospital, that I would be getting massive doses of chemotherapy 
followed by radiation, that my immune system would be totally destroyed 
and that I would need approximately three months at home to recuperate. 
I was worried about how I would deal with that amount of time out of 
circulation. I worried about my business, my family and to be quite 
frank, myself. The one thing I wasn't worried about was the cost. I am 
told the price tag for the procedure is $50,000 to $100,000. I am now 
eligible for Medicare and Medicare covers the procedure. But even if it 
didn't, my insurance does. And if my insurance didn't cover it, I could 
still afford to pay for the procedure myself if I need it. But what 
about those who can't? What about those you don't have health care 
coverage? I guess those are two questions that will properly be 
answered at a future hearing on health care legislation instead of here 
today.
    Dr. Anderson went through the whole process with John, my youngest 
daughter Laura and me. And then he said that several of his patients 
had opted to take thalidomide as an alternative to having the stem cell 
procedure done. I was intrigued. I was having babies in the 60's when 
thalidomide was making headlines as a dreaded pill that when taken by 
pregnant women caused severe damage to fetuses. Children were being 
born with all kinds of deformities. But what destroyed healthy growth 
then was now being used to prevent cancer growth. Dr. Anderson 
described for us just how thalidomide works, which I'm sure he will 
also do for you, and when we heard that it had the potential for 
treating the disease with minimal side effects, that if it didn't work 
we were not precluded from doing the stem cell transplant in the 
future, we opted to try thalidomide.
    I have been taking thalidomide since November. It's working. Once a 
month I still go for my infusion and once a month I get blood and urine 
tests. Then I wait the long three days until my test comes back to hear 
from Dr. Teppler. Am I still doing well? Have the cancer cells figured 
out a way to fight the thalidomide? And if they have, what if any 
option do I have before I deal with a stem cell transplant?
    I don't expect you to answer those questions, Senators, those I 
reserve for Dr. Anderson. And I have such confidence in him and the 
other researchers who are dealing with multiple myeloma that I know 
they will have a next step ready for me when I need to take it. But 
they need you and your colleagues in the Congress to help. They need 
more awareness and attention being paid to blood cancers so that people 
will test early and be diagnosed earlier; they need research dollars to 
continue to search for new treatments and a cure; and they need faster 
approval by the FDA of new drugs.
    Pharmaceutical companies have been slow to underwrite research for 
multiple myeloma because each different blood cancer requires different 
treatment. What's good for leukemia or lymphoma will not help me. So if 
you take each of the blood cancers separately, we're talking about 
orphan drugs since there aren't enough potential users of each to make 
it financially worthwhile for the pharmaceutical companies.
    On the other hand, this is still a huge problem for this country 
for if we lump leukemia, lymphoma and multiple myeloma together, last 
year's figures show that the mortality rate for blood cancers is second 
only to lung cancer, 20 percent higher than colon cancer, one third 
higher than breast cancer and almost twice as high as prostate cancer. 
Those diseases receive far more attention and far more funding. Now I'm 
not suggesting for one minute that attention or funding to the other 
diseases be reduced. My husband is a survivor of colon cancer because 
of early detection, I nagged my two older children until they got a 
colonoscopy and I will get up on a soap box and tell the world how 
important it is to be tested to detect that disease because it is 
curable. I also served when I was in the House and even after on a 
Breast Cancer Task Force and I have spoken out and walked more than 
once to raise money for that cause which I will continue to do. But 
what I am suggesting is that blood cancers are a serious and costly 
health concern and they too need our attention and funding.
    Multiple Myeloma is hitting a lot of elderly and though I wince 
when I refer to myself that way, I'm not an unusual candidate for this 
disease. But just think about the consequence of that demographic. I 
mentioned before that if I need a stem cell transplant it will cost 
between 50 and 100 thousand dollars and that Medicare will pay for it. 
Instead, my insurance company is paying $264.00 a month for a 
prescription for thalidomide. A year ago that cheaper option of 
thalidomide was not available. Research made the difference. Now what 
happens when thalidomide stops working, and I go month to month not 
knowing when Dr. Teppler will call and tell me that. Will Dr. Anderson 
be able to give me some new drug? Or will he have to tell me that it's 
in clinical trials and he's not quite sure when it will be approved so 
it's time for a transplant. It almost goes without saying that 
combining investment in research with faster government approval of 
drugs is obviously a cost effective way of dealing with the expense of 
this disease to our health care system.
    I told you when I started that I am a lucky woman. I have great 
doctors, an early diagnosis and up to the minute treatment that works. 
But cancer doesn't only eat at your body; it is a disease that can 
destroy you both emotionally and psychologically. I am blessed with a 
family that is always there to boost me up. In addition to their 
constant concern for me, my daughter Donna has taken her business and 
media experience and put it to work to help the Multiple Myeloma 
Research Foundation raise awareness and money. My son John who is a 
lawyer has filled in and taken over the headaches of John's business so 
that his dad can be with me. Laura is the doctor who keeps an eye on my 
test results and asks the questions I forget to ask and answers the 
ones that I'm too embarrassed to ask. My four grandbabies give me hugs 
and kisses and a thousand reasons a day to want to fight this thing. 
They, and John of course, and a few close friends in whom I confided 
have given me the emotional support that all of us need when we're 
slapped in the face with our mortality. Living in New York City, I'm 
never quite sure when I run into a street to hail a cab that I'm going 
to live long enough to ride in it, but hearing that you have a disease 
that is incurable with an average lifespan of just three years, does 
make one stop and notice.
    I expect that with my trio of medical miracle workers, with the 
love of my family and friends, and with my mother and all of the nuns 
who took care of me as a little girl praying for me, that I will be 
around at least until 2010 so that I can take advantage of President 
Bush's elimination of the inheritance tax and hopefully even after, so 
that I can be invited to the inauguration of the first female President 
of the United States. In the meantime, however, I, as well as every 
other multiple myeloma patient, am hoping that you, Senators, will 
provide help to these doctors so they can continue their research and 
eventually find a cure to this disease.
    Again, thank you, Mr. Chairman and Senator Spector for holding this 
hearing.

    Senator Specter. Thank you very much. We very much 
appreciate your coming forward and the quality of your 
testimony. We are pleased that you used this occasion to 
announce your candidacy for the presidency.
    Some may have noticed that the red light was on a little 
longer than usual. The prerogative of the chair is to allow 
that when you have ex-vice presidential candidates who are 
women.
    Ms. Ferraro. I appreciate that, Senator. Thank you.
    Senator Specter. I am going to waive my 4 minutes to make 
up for most of the extra time.
    Senator Murray has a commitment and wanted to make just one 
brief comment before excusing herself. Senator Murray.
    Senator Murray. Thank you, Mr. Chairman, for accommodating 
me.
    Ms. Ferraro, I just want to thank you. You have been a role 
model for so many women who are in politics, I being one of 
them. Watching you run for Vice President was an inspiration to 
many of us, and I know to many, many young women in this 
country still today who now see politics as something they can 
do. I would not be sitting on this committee in this place 
without people like you who paved the way.
    You are doing it again with your courage and your humor, 
enlightening all of us about how we need to take on another 
little issue, blood cancers. And I just want to thank you so 
much for all you have done for so many of us. Thank you very 
much.
    Senator Specter. Thank you, Senator Murray.

STATEMENT OF KATHRYN E. GIUSTI, PRESIDENT, MULTIPLE 
            MYELOMA RESEARCH FOUNDATION

    Senator Specter. We now turn to Ms. Kathy Giusti, who 
founded the Multiple Myeloma Research Foundation in 1996 after 
being diagnosed with the ailment. She brings 16 years of 
experience as a pharmaceutical executive to her role as 
President of the foundation. Thank you for joining us, and we 
look forward to your testimony.
    Ms. Giusti. Thank you so much, Mr. Chairman and Senator 
Hutchison.
    My name is Kathy Giusti. I am a multiple myeloma patient, 
and I am also president of the Multiple Myeloma Research 
Foundation. I just want to thank you for your support of blood 
cancers.
    I was, indeed, diagnosed with myeloma in 1996 at the time I 
was 37, a wife, the mother of a 1-year-old little girl named 
Nicole, and I was also in the height of my career as the 
highest ranked woman executive at G.D. Searle Pharmaceuticals 
in Chicago.
    When I was diagnosed, I heard the same statistics that 
Geraldine did. I heard that multiple myeloma has no cure, and I 
heard on average multiple myeloma patients live about 3 years. 
So, of course, I transferred that into my own life, and what I 
realized was I would die before my 40th birthday and I would 
die before I ever saw my little girl go to kindergarten.
    I really could not believe then that a cancer existed that 
had absolutely no cure, but I can tell you that my experience 
in the pharmaceutical industry helped me to understand why. 
With 14,000 patients diagnosed with myeloma each year, it is 
really hard to make myeloma a top priority by pharmaceutical 
companies. When you compare the return on investment for 
myeloma with other cancers such as breast cancer or prostate 
cancer, it does not compare. So, when I kept searching every 
annual report looking for a new drug in the pipeline in 1996, I 
was pretty devastated.
    I think for me one statistic said it all. Basically it was 
the fact that 28 percent of myeloma patients will be alive 5 
years after they are diagnosed, and I compared that to the 90 
percent survival that we now see with breast cancer and 
prostate cancer. So, it was obvious. Multiple myeloma has been 
neglected for decades.
    So, I resigned from my career in the pharmaceutical 
industry and dedicated my time to trying to raise money for 
multiple myeloma research. I founded the foundation with my 
twin sister, Karen Andrews, who is an attorney, and basically 
what our foundation does is we serve as a venture capital 
company raising money for early myeloma research, making sure 
we validate the best ideas and then we turn them over to the 
pharmaceutical companies and the NCI to move them forward.
    In 3 short years, we have raised over $10 million. We have 
funded over $8 million in myeloma research grants. Over 75 
percent of the grants we fund have been published or presented. 
I think the true results of what we have done, stem cell 
transplants are now safer, patients are enrolling in new 
vaccine trials, and we are helping to pay to understand why 
thalidomide is working for patients like Geraldine Ferraro.
    The MMRF is just one of several private foundations funding 
myeloma research. I am joined here today by the International 
Myeloma Foundation, by the Leukemia Society, the McCarty 
Foundation, and together we will fund between $10 million and 
$15 million in myeloma research. The NCI will fund about $18 
million. So, you are seeing one of the highest ratios of 
private to public sector funding in oncology.
    Now I can tell you that Geraldine Ferraro and I are not 
your typical multiple myeloma patients. We both sit here before 
you looking perfectly healthy and living as active lives as we 
can. But running the foundation, my job is to talk to hundreds 
of patients every month who are dying, who are facing 
excruciating pain, severe anemia, and who are living very 
difficult lives.

                           PREPARED STATEMENT

    So, I urge you to work with us to make sure that the PRG 
priorities are implemented. I know that I will dedicate 
whatever time Dr. Klausner needs me to to turn those PRG 
priorities into a good business plan, and I know Geraldine and 
her daughter Donna will help me as well. So, I ask you to be 
part of our team and help move the progress forward.
    Thank you.
    [The statement follows:]

                Prepared Statement of Kathryn E. Giusti

    Mr. Chairman, my name is Kathy Giusti. I am a multiple myeloma 
patient and President of the Multiple Myeloma Research Foundation 
(MMRF). I am pleased to appear here today and thank you and the 
Committee for your commitment to the issues that surround blood 
cancers.
    I was diagnosed with multiple myeloma in 1996. I was 37, a wife, 
the mother of a one year old little girl. I was also at the height of 
my career in the pharmaceutical industry-the most senior female 
executive at G.D. Searle in Chicago.
    I heard the same statistics that Congresswoman Ferraro did. 
Multiple myeloma has no cure. Multiple myeloma patients live on 
average, three years. I quickly put the doctor's words in real terms. I 
would die before my 40th birthday. I would die before seeing my little 
girl go to kindergarten.
    I could not believe a cancer existed that had absolutely no cure, 
but my experience in industry helped me understand why. With 14,000 
Americans diagnosed with multiple myeloma each year, multiple myeloma 
could not be a priority for the pharmaceutical industry. The return on 
investment for myeloma could never compare with the return on more 
prevalent forms of cancer such as breast and prostate cancer. I read 
every pharmaceutical journal searching for new compounds in the 
pipeline for myeloma. I found none. I contacted the National Cancer 
Institute (NCI). But with so little awareness, the NCI was investing 
just 12 million dollars in myeloma that year.
    One statistic said it all . . . only 28 percent of myeloma patients 
would be alive five years after diagnosis compared with the 90 percent 
five-year survival seen in breast and prostate cancer and the 62 
percent survival for all cancers combined.
    It seemed clear to me that myeloma had been neglected for decades. 
In 1997, I resigned from my career in the pharmaceutical industry and 
with my twin sister Karen Andrews, an attorney, founded the MMRF with 
one goal in mind-to fund research. We knew the MMRF could act as a 
venture capital firm by funding early myeloma research and validating 
new ideas. The pharmaceutical industry and NCI could then take the most 
promising ideas and move them forward. In three short years, we've made 
tremendous progress. The MMRF has raised over ten million dollars. We 
have committed eight million dollars to research grants and research 
grants with the remaining funds supporting education. Over 75 percent 
of the grants we have funded have been published or presented at major 
medical meetings.
    The result of our efforts? Stem cell transplants are safer and more 
effective than ever before. New vaccine trials are enrolling patients. 
We are learning why thalidomide and proteasome inhibitors are working. 
Our patient and physician outreach is expediting clinical trials.
    The MMRF is one of several groups in the private sector raising 
funds for myeloma research. Together with the Leukemia and Lymphoma 
Society, the McCarty Foundation, and the International Myeloma 
Foundation, we will fund ten million dollars in myeloma research this 
year alone. The NCI will distribute approximately $18 million in funds. 
This is one of the highest ratios of private to public support seen in 
the cancer field.
    How can you help us keep this momentum going? How can you help the 
700,000 patients suffering with blood cancers today? You can make the 
Progress Review Group priorities a reality. Right now, we have a list 
of priorities that will reduce the time it takes to bring new compounds 
to market from the current 7.2 years to the 2 years we saw with 
Gleevec. That list must now be developed and quantified in terms of 
manpower, time and funding. We need a clear action plan by year-end.
    Why do we have this sense of urgency? Because this year alone, 
60,000 Americans will die from blood cancers, second only to lung 
cancer. We have promising compounds in the clinic. We need to get them 
to the bedside . . . quickly.
    I am one of the lucky ones. I have lived five years with myeloma. 
In those years, I have celebrated my 40th birthday, watched my daughter 
Nicole start kindergarten and first grade and was blessed with a son 
named David. But I am not a typical myeloma patient. The many friends I 
have met through this illness I have also lost. The many funerals I 
attend are a constant reminder that while we have come so far . . . we 
are not yet there. I urge you to help us implement the PRG priorities 
quickly. Your efforts will bring new treatments to Congresswoman 
Ferraro and the hundreds of patients you see here today. And when the 
inevitable day comes for my husband and me to tell our young children 
mommy has cancer, we can also tell them it's ok, mom has a fighting 
chance. Thank you.

    Senator Specter. Thank you very much for your testimony, 
Ms. Giusti.

STATEMENT OF KENNETH C. ANDERSON, M.D., PROFESSOR OF 
            MEDICINE, HARVARD MEDICAL SCHOOL

    Senator Specter. We turn now to Dr. Kenneth Anderson, 
Professor of Medicine at Harvard Medical School and Medical 
Director of the Kraft Family Donor Center. He is a member of 
the Department of Adult Oncology at Dana-Farber Cancer 
Institute. Thank you for joining us, Dr. Anderson, and we look 
forward to your testimony.
    Dr. Anderson. Thank you very much. It is a pleasure to be 
here and I thank you all for your consideration and support of 
the blood cancers, illustrated here for us today.
    As was said, I am a professor of medicine at Dana-Farber 
Cancer Institute and also a Doris Duke Distinguished Clinical 
Research Scientist, which means plainly I am committed to 
developing new treatments in the laboratory to get to the 
bedside for blood cancers.
    I focus in particular on multiple myeloma. It is 1 percent 
of all cancers. It accounts for 2 percent of all cancer deaths. 
Some 14,000 new Americans get it every year, 50,000 total are 
affected, and 11,200 individuals died last year of myeloma.
    What does it do? Myeloma is the accumulation of these 
abnormal tumor plasma cells in the bone marrow. Patients get 
infections, bleeding, and they get fractures of their bones 
because of thinning of the bone, which precludes just simple 
activities of daily life. They also get high blood calciums, 
renal failure, and devastating nerve damage.
    What can we do about it? We can treat it with conventional 
therapy to extend the average survival to 3 to 4 years. High 
dose therapy and stem cell transplant can modestly improve 
that, perhaps to 4 to 5 years. Unfortunately and tragically, we 
cannot cure it.
    There is very great reason for promise and optimism. You 
have already heard of the novel use of thalidomide to treat 
myeloma. The novel concept is it not only kills the tumor cell 
directly, but it acts in the bone marrow neighborhood in a way 
to make it impossible for the myeloma cell to grow and live 
there. You have heard beautiful testimony earlier this morning 
about Gleevec, which specifically is a targeted drug to inhibit 
the protein that causes chronic myelocytic leukemia. I call 
these designer drugs, and in myeloma we have such drugs coming 
that will either blow the fuse on the growth circuit or turn on 
the death circuit in myeloma cells.
    Finally, there is that strategy based on vaccines which 
will stimulate the patient's own immune system to reject 
myeloma, just like the natural immunity clears an infection.
    You heard nicely from Dr. Klausner earlier about the 
Progress Review Group process in blood cancers that has 
recently concluded. One important priority that was identified 
was, in fact, an initiative, a collaboration between academia, 
Government, industry, and patients, to shorten the time, which 
is now 5 to 10 years, down to 2 years that it takes to get a 
novel compound into general clinical practice.

                           PREPARED STATEMENT

    I know that you have all been inspired, as have I, this 
morning by the courage that has been demonstrated in the face 
of incredible adversity by Geraldine Ferraro, by Kathy Giusti, 
by Alan Bailey, and by so many other patients who are in this 
room who have currently incurable diseases. The Progress Review 
Group process has laid out a road map for us to make a 
difference in the next 5 years. If we fail to do that, we will 
be condemning patients with blood cancers to needless pain, 
suffering, and premature death. In contrast, if you partner 
with us, we are now poised to make a huge difference in 
prolonging the overall survival and quality of life for 
patients with blood cancers worldwide.
    [The statement follows:]

               Prepared Statement of Kenneth C. Anderson

    Good morning. I am Ken Anderson, M.D., a Professor of Medicine at 
Harvard Medical School and Dana-Farber Cancer Institute in Boston, and 
I thank you most sincerely for the chance to speak here today. I am 
also pleased to be here as a Doris Duke Distinguished Clinical Research 
Scientist; a member of the Boards of Directors and Scientific Advisors 
of the Multiple Myeloma Research Foundation and the International 
Myeloma Foundation; as chairman of the National Comprehensive Cancer 
Center Network Myeloma Guidelines Panel; as a member of the Medical and 
Scientific Committee of the Leukemia & Lymphoma Society of America, and 
as a member of National Cancer Institute Scientific Review Group D, 
Subcommittee D, for Clinical Research Studies. I was also honored and 
privileged to serve as a Co Chairperson of the recent Lymphoma, 
Leukemia, and Myeloma Progress Review Group (LLMPRG), which was a 
multidisciplinary panel of prominent scientists, clinicians, advocates, 
and industry representatives convened by the National Cancer Institute 
to prioritize the national research agenda for blood cancers. In the 
past the blood cancers have represented a model for the treatment of 
cancer with chemotherapy. Specifically, chemotherapy was pioneered 50 
years ago in childhood acute lymphoblastic leukemia, and increasing the 
dose and combining drugs has led to cure in the majority of cases. Use 
of high doses of chemotherapy followed by bone marrow or blood stem 
cell transplantation was also pioneered in blood cancers, and is 
curative in some patients with leukemia. Most excitingly, the recently 
approval of Glivec represents the first example of a designer drug 
which specifically targets the abnormal protein that causes chronic 
myelocytic leukemia. Such specifically targeted drugs represent a new 
treatment paradigm with great promise for improving the outcome of 
patients with cancer generally, as well as those with other illnesses 
such as HIV infection. Therefore implementation of the initiatives 
proposed by the recent LLMPRG will have broad and important 
implications for improved medical practice.
    My specific basic science and clinical interests focus on multiple 
myeloma. Multiple myeloma is the second most common blood cancer, 
representing 1 percent of all cancers and accounting for 2 percent of 
cancer deaths. There were 14,400 new cases, 50,000 total patients 
affected, and 11,200 deaths from myeloma in the United States in 2000. 
Myeloma is the fourth fastest growing cancer in terms of mortality, and 
importantly, is in the top 10 causes of death among African Americans. 
Although traditionally considered as a disease of the elderly, the 
average age of affected individuals is approximately 60 years. With the 
aging of the U.S. population, its incidence is expected to further 
increase. Myeloma, a bone marrow cancer like leukemia, is characterized 
by the excess accumulation of antibody forming (plasma) cells in the 
bone marrow, in association with the abnormal antibody (monoclonal 
protein) made by these plasma cells accumulating in patients' blood 
and/or urine. Affected patients develop anemia or low red blood cells 
with fatigue, low white blood cells with related increased risk of 
infection, and low platelet count with related risk of bleeding. The 
most debilitating feature of myeloma is thinning of bone (osteoporosis) 
or holes in bone (lytic lesions), with related fractures, pain, and 
major limitations in quality of life and activities of normal daily 
living. Other less frequent complications include kidney failure, high 
blood calcium, and nerve damage. Conventional chemotherapy prolongs 
survival to a median of 3 to 4 years, and high dose therapy followed by 
a blood stem cell transplant can modestly extend median survival to 4 
to 5 years. Tragically, few, if any, patients are cured. Treatment of 
myeloma-related complications can improve quality of life for patients 
and includes transfusions or growth factors to treat patients with low 
red blood cell, white blood cell, or platelet counts. Importantly, the 
use of bisphosphonates can slow the development of bone-related 
complications, decrease related pain, and thereby improve the quality 
of life of patients with myeloma.
    Although conventional and high dose therapy extends survival, 
disease almost always recurs and becomes resistant to all known 
treatments. As a result few, if any, patients have been cured to date. 
Importantly, however, major progress in our understanding of the 
biology of myeloma has occurred in the past two years, providing the 
framework for novel very promising therapies. The first major novel 
concept is the use of drugs which not only target and kill the myeloma 
cells directly, but also target their bone marrow environment to 
inhibit the localization of myeloma cells in marrow, to abrogate the 
production of factors in marrow which promote the growth and survival 
of myeloma cells, and to block new blood vessel formation or 
``angiogenesis''. Excitingly some of these new drugs also augment a 
patient's own immune system to recognize and kill his own myeloma 
cells, much as an infection can be cleared by our natural immune 
response. Examples of these drugs include thalidomide and its 
potentimmunomodulatory (IMiD) analogs, as well as proteasome 
inhibitors. Even in patients whose myeloma has recurred despite all 
conventional and high dose therapies, thalidomide achieves significant 
responses and prolongs survival of 30 percent patients, demonstrating 
that these new drugs can overcome resistance that myeloma cells have 
developed to conventional therapies. Once these drugs are tested and 
found to be safe and effective in patients with advanced disease, they 
are rapidly evaluated as treatment for newly diagnosed patients. 
Excitingly, early clinical trials suggest that treatment with these new 
biologically based therapies can have an even greater impact (80 
percent responses) when used as the initial therapy for myeloma. Major 
laboratory research is currently ongoing to specifically identify the 
targets of these new drugs in both myeioma cells and the bone marrow in 
order to develop even better drugs, more selective against tumor cells, 
which are both more efficacious and have fewer side effects. For 
example, the revolution in our understanding of the human genome allows 
for characterization of the temporal sequence of changes in expression 
of up to 20,000 genes which are either upregulated or decreased in 
response to drug treatment, markedly enhancing our ability to define 
mechansims of drug anti-myeloma activity on the one hand, versus 
mechanisms whereby tumor cells escape or resist therapy on the other.
    In addition to these novel drugs targeting not only the tumor 
cells, but also its interaction with the bone marrow neighborhood, two 
other novel treatment approaches offer great promise. The first is 
based upon basic scientific studies which can delineate those circuits 
inside myeloma cells which mediate their unregulated growth, as well as 
those molecular circuits which allow them to resist normal death 
processes. Definition of these pathways has allowed for the development 
of ``circuit breakers'', novel drugs which specifically interrupt tumor 
cell growth; or ``circuit makers'', which specifically turn on death 
signals inside myeloma cells. The promise of this approach is best 
illustrated by Glivec, the novel drug which specifically inhibits the 
abnormal protein which causes chronic myelocytic leukemia. It has 
already markedly improved outcome for patients with this illness, and 
has recently received FDA approval.
    A third major area of promise for the treatment of blood cancers, 
in particular multiple myeloma, are the immune-based therapies. These 
can consist of specialized transfusions of the patient's own or a 
sibling's cells which are programmed to recognize and kill patient 
myeloma cells. Immune therapies also include vaccines against the 
patient's tumor cell or fingerprint proteins on the tumor cell surface. 
The goal here is to stimulate the patient's immune system to recognize 
and reject their own tumor cells, just as natural immunity readily 
clears an infection. An important advantage of these approaches is 
their high selectivity and efficiency in targeting and killing tumor 
cells, thereby avoiding the side effects attendant to current 
conventional therapies which are non-selective and kill normal, as well 
as tumor, cells.
    Once novel therapies such as these are identified to be of 
potential benefit to patients in laboratory preclinical studies, there 
is an urgent need for rapidly moving these agents from the bench 
(laboratory) to the bedside (clinic), where their clinical utility can 
be assessed in treatment protocols. The need is particularly immediate 
for patients with myeloma, for whom no curative therapy currently 
exists. As I mentioned at the outset, a panel of prominent scientists, 
clinicians, advocates, and industry representatives was convened by the 
National Cancer Institute and identified research priorities in blood 
cancers. Most importantly, the LLMPRG has proposed a new initiative--
The Cancer Translational Research Allied Consortium (C-TRAC). C-TRAC 
represents a unique opportunity to shorten drug development time in the 
United States from the current 5-10 years to 2 years through a novel 
alliance among academia, industry, government, and patients, and holds 
great promise to get novel targeted therapies to our patients with 
blood cancers who so desperately need them.
    In summary, basic science advances now offer an unprecendented 
opportunity to solve the mysteries of the past and specifically and 
effectively treat blood cancers. The roadmap to achieve this goal has 
been laid out by the LLMPRG process of the National Cancer Institute. I 
am sure that you are both personally moved and inspired by the 
extraordinary courage in the face of personal adversity exemplified 
here today by Geraldine Ferraro, Kathy Giusti, and the numerous other 
patients here today. As a basic science and clinical researcher and 
caregiver, I extend my heartfelt and genuine admiration and thanks for 
your consideration and support for these research initiatives which 
will markedly enhance the survival and quality of life of affected 
patients worldwide.

    Senator Specter. What do you think you can do within 5 
years, Dr. Anderson?
    Dr. Anderson. I think that within 5 years there will be 
many more of the leukemias which are cured. I think that if 
myeloma may not be cured, certainly it will be turned into a 
chronic illness not unlike hypertension or other illnesses with 
which patients can grow old gracefully, as I like to say.
    Senator Specter. Thank you very much, Dr. Anderson.
    I have presided at a lot of hearings. I have never heard so 
much applause.

STATEMENT OF JOHN W. HOLADAY, Ph.D., CHAIRMAN AND CEO, 
            ENTREMED, INC.

    Senator Specter. Dr. John Holaday, Chairman and CEO and Co-
founder of EntreMed, Inc., a biotech company in Rockville, MD. 
He served as Chief Biochemist at the Division of 
Neuropsychiatry at Walter Reed Hospital. We very much 
appreciate your being here, Dr. Holaday, and look forward to 
your testimony.
    Dr. Holaday. It is my pleasure. I thank you, Senator 
Specter, also Senator Hutchison, and my favorite Senator, 
Senator Mikulski, who represents the great State of Maryland 
where Rockville and certainly EntreMed are located.
    It is my pleasure to tell you today that there is some good 
news on the horizon. I want to share with you a story that is 
part of our common passion at EntreMed and shared by many 
researchers throughout the world that a new field of medicine 
that has evolved around understanding the growth of new blood 
vessels in various diseases like cancer might have great 
promise in the treatment of multiple myeloma and various other 
forms of blood cancers.
    Specifically over 30 years ago, Dr. Judah Folkman, when 
working at the Navy, realized that it is impossible for tumors 
to grow, whether they are solid tumors or blood tumors, without 
the proliferation of new blood vessels to feed that growth. 
Now, in retrospect, that seems to be a rather intuitive 
thought, but it has taken quite some time for that to be 
recognized as a potential forefront in the field of medicine.
    Subsequent to his years of effort, a young man by the name 
of Dr. Robert D'Amato realized that the drug thalidomide, which 
was known to cause the birth defects in the early 1960's, very 
likely caused these defects by blocking the growth of blood 
vessels, and thus the normal limb formation could not occur. 
So, with this great step of realization, Dr. D'Amato said maybe 
thalidomide is an anti-angiogenic drug that could inhibit the 
growth of blood vessels and thus have efficacy in the treatment 
of a variety of forms of cancer. Indeed, teaming up with Dr. 
D'Amato, who first published this with Dr. Folkman in the 
proceedings of the National Academy of Sciences in 1994, we at 
EntreMed, along with the National Cancer Institute and Dr. 
Klausner's team, proceeded rapidly toward phase II studies to 
demonstrate that thalidomide has effects on a number of 
different forms of cancer.
    It was Dr. Folkman who actually recognized the potential of 
its use in multiple myeloma who recommended to another pioneer 
in this field, Dr. Barlogi, that he try thalidomide for the 
treatment of that particular cancer patient. And subsequently 
other leaders, such as Dr. Anderson, are continuing in this 
quest to find new ways of using this old drug for a good and a 
new purpose.
    When we were developing this molecule, we found it was 
tough to get big pharmaceutical companies, unlike us small 
ones, to buy into the concept that you could resurrect a drug 
with this terrible heritage. We succeeded in finding a 
relationship with Celgene which was a small company like us, 
but they had the opportunity to distribute thalidomide, and 
through that relationship, we have been at EntreMed able to 
have this drug on the market for the last 3 years, or at least 
available to patients, with the leadership of such people as 
Dr. Anderson and with the great hope that is provided to people 
like Geraldine Ferraro. We are pleased to have had this 
opportunity.
    I want to also say that we are on the cusp of many new 
developments in this field. It is not true that all of the 
research comes from Government laboratories. We in the biotech 
industry represent a very committed and dedicated group of 
people whose passion it is to make a difference in the lives of 
patients. In that context, we have a new series of molecules 
that will come along as next generation relatives of 
thalidomide, and another drug called Panzem, or 2-
methoxyestradiol, a natural substance where we have phase II 
studies presently underway at the Mayo Clinic in patients with 
multiple myeloma and shortly to begin with Dr. Anderson at the 
Dana-Farber.

                           PREPARED STATEMENT

    So, again, there is reason for hope. We encourage patients 
as always to be very proactive in the management of their 
disease and to consider, as they look forward, the 
opportunities that this new field of medicine, inhibition of 
angiogenesis, pioneered by Dr. Folkman so many years ago, might 
have as a new way of looking at diseases and particularly 
diseases of the blood.
    I thank you.
    [The statement follows:]

                 Prepared Statement of John W. Holaday

    Chairman Harkin, members of the Committee, I wish to thank you for 
your kindness in allowing me the opportunity to testify before the 
Committee today.
    My name is Dr. John Holaday. I am the founder, Chairman and CEO of 
EntreMed, Inc. a biotechnology company located in Rockville, Maryland, 
just outside the Beltway. I formed EntreMed in 1991 to bring 
entrepreneurship to medicine. In doing so, EntreMed has assumed the 
risk of revolutionizing drug discovery and development for the benefit 
of patients. We now employ 120. exceptional scientists and staff, all 
sharing a common passion to bring new drugs to cancer patients--
including those with solid tumors and blood cancers--in the hope of 
providing them with a more livable life, and allowing them to live with 
their disease, not die from it.
    I would like to inform the Committee of one cancer breakthrough 
that has dramatically changed thinking about how to conquer this 
horrible disease and the role EntreMed plays in bringing these new 
weapons to the fight against cancer. Over thirty years ago, Dr. Judah 
Folkman, while working as a Naval Officer at Naval Medical Research 
Institute in Bethesda, Maryland, discovered an ingenious method to 
stopping tumor growth. He demonstrated that cancerous tumors require 
the simultaneous growth of blood vessels to feed their malignant cells. 
In doing so, he pioneered the field of medicine called 
``angiogenesis.''
    His quest to challenge conventional thinking in the entrenched 
practice of oncology has been long and arduous, but fortunately it is 
now beginning to pay off for cancer patients. Dr. Folkman's research at 
Children's Hospital, an affiliate of Harvard Medical School in Boston, 
has produced revolutionary molecules, such as Thalidomide, Endostatin, 
Angiostatin and Panzem, that are shown to arrest cancer growth in mice 
by starving tumors of their blood supply. EntreMed took these promising 
molecules from the laboratory to the cancer clinic in record time, in 
collaboration with Dr. Folkman, Children's Hospital and the National 
Cancer Institute.
    But this story goes back even further, and with the Committee's 
indulgence, I will take a moment to explain it. Over twenty years ago, 
Robert D'Amato was finishing high school when he won the International 
Science Fair for his discovery of a new way to detect multiple 
sclerosis by measuring changes in vision. His prize provided him with 
the opportunity to work in my laboratories at the Walter Reed Army 
Institute of Research for a summer. While there, he learned the basics 
of academic medical research and went on to become one of my best 
students, co-authoring twelve scientific publications with me over the 
next four summers. Robert went on to earn his MD and Ph.D. degrees at 
the Johns Hopkins University School of Medicine in Baltimore.
    In 1992, Dr. D'Amato, now an ophthalmologist finishing his training 
at the Massachusetts Eye and Ear Hospital discovered that blindness, 
like cancer, depended on the growth of new blood vessels. In blindness 
arising out of diabetes or age-related macular degeneration, new blood 
vessels grow in the retina of the eye and block vision. In cancer, new 
blood vessels sprout to feed the growth of tumors. Dr. D'Amato wondered 
if there were existing drugs that could stop the growth of new blood 
vessels without affecting existing ones. In this vein, he explored 
whether drugs causing birth defects or changes in reproductive cycles 
in women did so by blocking the growth of new blood vessels. His search 
suggested the possibility that the drug thalidomide, a drug scorned for 
its effects in causing deformed children in the early 1960s, might 
provide the answer.
    Teaming up with Dr. Folkman, the father of angiogenesis, the two 
explored the idea. Soon Dr. D'Amato succeeded in convincing Dr. Folkman 
that thalidomide may be an antiangiogenic drug worth further 
investigation. Dr. D'Amato demonstrated thalidomide's effects in 
blocking new blood vessel growth and the findings were published in the 
Proceedings of the National Academy of Sciences in April 1994. Within 
less than four years, our team at EntreMed, in concert with the 
National Cancer Institute, took this early concept through Phase II 
studies in cancer patients and obtained clinical data to authorize 
orphan drug designation from the Food and Drug Administration for the 
use of thalidomide in the treatment of certain forms of cancer.
    We knew that it would take years for us to bring thalidomide into 
routine patient use due to the notorious history of the drug and the 
requirements for arduous clinical testing by the Food and Drug 
Administration. As such, we sought a large pharmaceutical partnership 
to help speed the process. We licensed thalidomide to Bristol Myers 
Squibb, the world's largest cancer company, while continuing our 
clinical trials. They decided that the challenge was too daunting, and 
returned thalidomide to us after a year of study. Fortunately, we 
learned that another small biotechnology company, Celgene, in Warren, 
New Jersey, recently obtained orphan drug designation from the FDA for 
the use of thalidomide in treating leprosy and felt they might be right 
for this use as well. In December 1998, we reached an agreement between 
EntreMed and Celgene that allowed thalidomide to be prescribed by 
physicians on an ``off label'' use for cancer, accelerating its 
availability to patients by at least three years.
    After promising laboratory results at Children's Hospital and 
EntreMed, pioneering clinical studies by Dr. Bart Barlogi in Arkansas 
and Dr. Ken Anderson in Massachusetts, who is here today, thalidomide 
has shown its benefit in treating patients with multiple myeloma.
    Mr. Chairman, as the ``Angiogenesis Company,'' EntreMed is 
dedicated to uncovering new treatments for cancer, including cancers of 
the blood. We have shown that angiogenesis in the bone marrow plays a 
major role in the progression of these ``liquid tumors,'' causing bone 
erosion and progressing the disease, and antiangiogenic drugs such as 
thalidomide have been shown in preclinical studies to block the 
progression of myelomas and leukemias.
    Today, Geraldine Ferraro is doing well as a consequence of our 
collective efforts. We are proud of the role that EntreMed and our 
collaborators at Children's Hospital have played in making thalidomide 
available to patients with this form of blood cancer. But thalidomide 
is not yet approved for use in cancer, and it has limiting side 
effects. Right now in our laboratories and with collaborators at 
Children's Hospital and elsewhere, we have found new and more powerful 
chemical cousins of thalidomide that have fewer side effects. These 
promising drug candidates are moving rapidly towards clinical trials.
    Dr. D'Amato also has discovered another drug, Panzem (2-
methoxyestradiol); that in preclinical studies shows great promise in 
treating multiple myeloma. It is orally available, and was shown by 
EntreMed's Phase I studies in breast cancer to be without dose-limiting 
toxicities. Because of EntreMed's successful efforts in demonstrating 
the safety of this drug, Panzem is now in Phase II clinical trials in 
multiple myeloma patients at the Mayo Clinic in Rochester, Minnesota 
and further studies are to begin shortly with Dr. Anderson at the Dana 
Farber Cancer Institute, in Boston.
    But our passion to accelerate drug discovery and approval is not an 
easy one. Industry statistics for drug development reveal a daunting 
challenge. According to the Pharmaceutical Research and Manufacturer's 
Association, on average only one in 5,000 potential drug discoveries 
results in an approved drug twelve years later, at a cost in excess of 
$400 million. Biotechnology companies are trying to discover and 
develop drugs better, faster, and cheaper, and we are highly creative 
in addressing unmet medical needs. Unlike big pharmaceutical companies, 
however, we have limited resources.
    Despite their potential to revolutionize medicine, from the 
financial perspective, drug discovery and development efforts in 
biotechnology are by their very nature risky, capital intensive and 
protracted. The search for new drugs by biotechnology companies is like 
drilling for oil or prospecting for gold. There are no guarantees, and 
they are not always successful in developing products and rewarding 
their shareholders that took the financial risk. We seek your 
assistance in this effort. We are succeeding at providing exciting new 
solutions to deadly diseases that have gone unsolved for far too long. 
We need Congress' help in continuing.
    Failure to nurture these new revolutionary new discoveries is like 
leaving ripe apples in the orchard. Dr. Alexander Fleming is said to 
have sadly lamented: ``Penicillin sat on my shelf for 12 years while I 
was called a quack. I can only think of the thousands who died 
needlessly because my peers would not use my discovery.'' We need to 
open minds to invent new ways of attacking cancer, such as 
angiogenesis. In the war on cancer, the battlefield tactic of blocking 
blood vessel growth is like attacking the enemy's supply lines.
    Mr. Chairman, in record time EntreMed has taken antiangiogenic 
drugs like thalidomide into the clinic. Now, cancer patients receiving 
EndostatinTM infusions in our Phase I human trials in the 
United States and Europe are showing no adverse events while some 
patients have achieved disease stabilization and tumor responses in 
studies designed only to assess the safety of our drugs. 
Panzem is now in Phase II studies in patients with multiple 
myeloma and prostate cancer. We are making great progress in realizing 
our goal of ``cancer without disease,'' where cancer patients may be 
able to live full lives like diabetics, but instead of receiving 
insulin, they will get antiangiogenic drugs.
    Those of you with cancer or with family or friends who suffer from 
the scourge of this disease know all too well the frustration and 
helplessness of waiting for breakthroughs to become a reality. We hear 
the cry of the dying mother, father, sister, brother, and friend. Now 
we must commit the resources to win the war on cancer, and to reaffirm 
our country's prominence as the world's leader in technology and 
science. We can no longer afford to be patient. We must apply the 
strategies and tactics of the battlefield to scientific discovery and 
development in order to win this war on cancer. It is absolutely 
essential that we have your help in this great battle.
    With your help, Chairman Harkin and all the members of this 
Committee, we cart carry on the fight with promising new cancer 
strategies through the provision of greater resources to researchers 
and biotechnology companies. Now is the time to invest in research that 
will save the lives of our loved ones. This is a war that must be won 
now!
    Thank you Mr. Chairman.

    Senator Specter. Thank you very much, Dr. Holaday.
    We have 8 minutes remaining until blackout time at 11:30 
and two Senators with rounds of 4 minutes each. Senator 
Hutchison.
    Senator Hutchison. Well, thank you. I will be just very 
brief.
    I would just like to use my time to ask you, Dr. Holaday, 
to expand on the trial or study that is going on at Mayo and 
what you hope to gain from that that you do not have with 
thalidomide today.
    Dr. Holaday. We think that the approach towards any drug 
discovery process has to be multifaceted, and this particular 
molecule, Panzem, also known as 2-methoxyestradiol, is a 
natural substance that has shown great promise in preclinical 
studies in treating various forms of multiple myeloma at the 
experimental level. Based upon that promise and the fact that 
it showed no dose-limiting toxicities in phase I studies in 
breast cancer at Indiana University, we were encouraged to 
proceed rapidly and move that into phase II studies at the Mayo 
Clinic to see if what we see in the animal models is also true 
in people. And we are very encouraged by what we are seeing to 
date.
    Senator Hutchison. Would it be more of a cure or a 
treatment?
    Dr. Holaday. We would like to encourage the consideration 
of these new treatments as allowing people to have cancer 
without disease, much as Dr. Anderson said, maybe diseases like 
diabetes where you live with your insulin and you do not die 
from the disease. I think that as we look modestly at our 
future, we should consider that these molecules like 
thalidomide, analogs of thalidomide, and Panzem are going to 
offer us that opportunity.
    Senator Hutchison. Well, thank you. I just once again want 
to thank all of you. Every one of you on the panel has offered 
something wonderful: Geraldine Ferraro for helping us start 
this awareness which Senator Mikulski and I and Senator Specter 
are going to try to continue; and Kathy Giusti, for your early 
pioneering efforts when you did not have a whole lot of 
support, but now I think you do; and Dr. Holaday and Dr. 
Anderson for your commitment. We certainly look forward to 
working with each of you to find a cure for each of these 
diseases. Thank you.
    Senator Specter. Thank you, Senator Hutchison.
    Senator Mikulski.
    Senator Mikulski. Thank you very much, Mr. Chairman.
    Just very briefly. First of all, I am so proud of my 
friend, Geraldine Ferraro, who has taken a very private matter 
and taken this as usual with her wit to come forward and turn 
this into a matter of public advocacy, both for research, as 
well as encouraging people to be bold and courageous enough to 
do the early detection. Of course, Dr. Holaday is the CEO of 
one of our biotech firms in Maryland, and we had an excellent 
conversation the other night.
    Mr. Chairman, I am going to have maybe one question for Dr. 
Holaday.
    But this is a very emotional hearing for me and I think for 
everybody because many of the people in this room we know 
personally. I can tell you exactly where I was on a Sunday 
morning when Geraldine Ferraro called me to tell me about this 
disease. I literally could not believe it. I am home Sunday 
morning drinking coffee. Gerry and I periodically talk on 
Sundays. And she said, Barbara, I have blood cancer. It took my 
breath away. So, we immediately talked about how to be 
supportive.
    Second, later on when she told me she was on thalidomide, I 
said, Gerry, this is about birth defects. Again, I was shocked.
    The reason I say all of this is that when cancer affects 
someone, it affects family and it affects friends. Part of the 
cure I believe is in family and friends. So, we are all in this 
together. Gerry, we want you to know I think all of America, 
Larry, and Ms. Giusti and all who testified, that you are part 
of an American family, and we are just going to pull for you. 
This is not about being a Democrat. This is not about being a 
Republican. This is about being part of an American family and 
really seeing what we can do to help you. So, we thank you.
    And Dr. Holaday, we want to have other conversations with 
you on how we can encourage biotech. Not all research is going 
on at NIH. We need to have a continuum of research. We need to 
have policies and tax breaks for research and development to 
really have these breakthroughs.
    My only concluding remark is to the doctors, to the 
scientists, to the patients, may the force be with you and may 
God be with the United States Senate to help you. Thank you.
    Senator Specter. I thank you very much, Senator Mikulski, 
and thank you all, all the witnesses, for a very extraordinary 
hearing. I thank you, ladies and gentlemen, for being here and 
for your enthusiasm. Now our work is cut out for us to get 
increases in funding for the National Institutes of Health and 
to get Federal support for stem cell research so that we can 
move ahead to solve these tremendous problems.
    We have received written statements that we will include in 
the record.
    [The statements follows:]

 Prepared Statement of Beverly S. Mitchell, M.D., President, American 
                         Society of Hematology

    Senator Harkin and members of the Subcommittee, thank you for 
holding this very important hearing today on the hematologic 
malignancies. My name is Beverly Mitchell and I'm Chief of the Division 
of Hematology and Oncology and Associate Director of the Lineberger 
Comprehensive Cancer Center at the University of North Carolina at 
Chapel Hill. I am President of the American Society of Hematology 
(ASH), which has over 10,000 scientists and clinicians united by their 
common interest and commitment to understanding and curing blood 
disorders. The Society thanks the Subcommittee for their unwavering 
support of biomedical research and fully supports the Ad Hoc Group for 
Medical Research Funding recommendation of an appropriation of $23.7 
billion for the National Institutes of Health in fiscal year 2002.
    ASH is proud that NIH-sponsored research in hematology has led to 
important discoveries with broad applicability to treating heart 
disease, strokes, end-stage renal disease, cancer and AIDS, among other 
human diseases. For this reason, the Society is firmly committed to 
broad-based support for biomedical research and to the existing peer-
review process as the best way to identify and prioritize scientific 
grants. Since the study of blood and its disorders involves a number of 
areas, hematologists receive funding from multiple NIH Institutes. The 
Society would like to particularly commend the leadership of the NHLBI, 
NIDDK, and NCI for their vision and superb stewardship.
    I would specifically like to congratulate Dr. Richard Klausner and 
his colleagues at the NCI as well as the many scientists, clinicians, 
and advocates that worked on the Leukemia, Lymphoma, and Myeloma 
Progress Review Group, also known as the blood cancers PRG. 
Historically, research in the blood cancers supported by NCI has 
provided the biological framework for new directions and progress in 
the research and treatment of all cancers. Now, the convergence of new 
tools and technologies presents us with the opportunity to place 
discovery and development of cancer prevention and treatment 
interventions on a firm scientific footing. There is a sense of 
excitement in the hematology community particularly with the rapid 
evolution of molecular biology that has already led to a number of 
major discoveries. The Lymphochip, for instance, is a DNA microarray 
that gives us an unprecedented view of the molecular machinery of blood 
cancer and will be used to study samples of thousands of patients with 
all varieties of lymphoma and leukemia. You have also heard of Gleevec, 
or the leukemia pill, which offers effective new treatment for chronic 
myelogenous leukemia or CML.
    It is on the heels of these and of other important discoveries that 
the NCI's blood cancers PRG completed its excellent review of the basic 
science and clinical challenges to advancing our understanding of the 
blood cancers. The report is incredibly comprehensive, covering not 
only issues in basic biology and clinical trials methodology, but also 
epidemiology, collaboration, education, communication, and behavioral 
and outcomes research. Immediate priorities identified in the report 
include increased understanding of the basic biology and the key 
environmental factors that lead to blood cancer, increased 
translational research resources, identifying populations at high risk, 
and improving access to quality care through accurate and timely 
distribution of information and increased training of physicians. The 
centerpiece of the report is the development of a Cancer Translational 
Research Allied Consortium to bring together academia, industry, 
government, and patients to shorten drug development time for the 
hematologic cancers from between 5 and 10 years to 2 years.
    The American Society of Hematology strongly urges that a budget and 
business plan be developed to guide implementation of the blood cancers 
PRG report recommendations. ASH is concerned that without such a plan, 
specific steps for collaborative action to accelerate the development 
of new therapies for blood-related cancers will go unidentified.
    A budget and business plan would help us increase our understanding 
of myelodysplasia, for example. Myelodysplasia is a serious disorder 
that occurs in older patients and in individuals who have undergone 
previous radiation or chemotherapy treatment for cancer and/or blood 
diseases such as aplastic anemia. Standard treatment is currently 
limited to blood product transfusions, and, in some cases, chemotherapy 
treatments if the disease develops into acute leukemia. There is no 
curative treatment other than bone marrow transplantation, which is 
effective in only a small percentage of patients. Among the victims of 
myelodysplasia are the astronomer and great promoter of science, Carl 
Sagan. Also, at the end of his life, your former colleague, the 
honorable Senator Paul Tsongas, battled myelodysplasia that developed 
as a result of the treatment that he received for his lymphoma. As the 
lifespan of the average American increases, myelodysplasia, a formerly 
rare disorder, is becoming more common. A budget and a blueprint for 
the PRG will lead to recognition and support for research that will 
help us find ways to further unravel the mystery of myelodysplasia so 
that we are able in turn to extend the lives of patients, many of them 
already survivors of cancer and other devastating diseases.
    In addition to urging you to support these important follow-up 
activities to the tremendous PRG effort, I would also like to take this 
opportunity to highlight an important legislative effort in the 
reimbursement arena that complements the scientific progress in 
treating blood cancer. I would like to bring to your attention the 
Access to Cancer Therapies Act of 2001, introduced by Senator Olympia 
Snowe and Representative Deborah Pryce. If enacted, the legislation 
would update Medicare's reimbursement policy to cover all oral anti-
cancer drugs since Medicare currently only pays for an oral cancer drug 
if it has an equivalent that can be administered intravenously, 
incident to a physician's service in a doctor's office or in a hospital 
outpatient department.
    The American Society of Hematology strongly urges you and your 
colleagues to sign-on as a co-sponsor of the Access to Cancer Therapies 
Act to help ensure its passage in this session of Congress.
    The Access to Cancer Therapies Act is critical in particular 
because new oral anti-cancer drugs are emerging as an indispensable 
feature of quality cancer care and will replace or make more effective 
current therapies largely based on intravenous administration. Today, 
these and other oral cancer treatments are only 5 percent of the 
market, but are expected to increase to 25 percent or more by the end 
of this decade. Furthermore, without Medicare coverage, most of these 
oral drugs will require out-of-pocket payment and access for cancer 
patients will be unfairly influenced by the patient's ability to afford 
these new approaches to treatment. For many cancer patients, especially 
those in rural areas, oral drugs are not only preferred, but are 
absolutely necessary as life-extending treatment.
    In conclusion, this is an exciting time to be engaged in biomedical 
research and we are proud that ASH members are participating in so many 
innovative studies. ASH applauds the excellent stewardship of the 
hematology research portfolio, particularly at the NCI. The 
opportunities in hematologic malignancy research are immense. I believe 
that with a budget and a blueprint for implementing the recommendations 
of the PRG, the effort will stimulate the necessary partnerships and 
cooperative ventures involving multiple academic centers for clinical 
research projects to succeed in bringing improved therapies for 
patients. At the same time, we must make sure that mechanisms for 
reimbursement, such as that provided by the Access to Cancer Therapies 
Act, are in place so that patients can receive the very best in cancer 
treatment.
    ASH sincerely hopes that you will be able to continue your 
longstanding policy of support for cancer research and access to 
quality cancer care.
                                 ______
                                 
 Prepared Statement of Howard B. Urnovitz, Ph.D., Scientific Director, 
Chronic Illness Research Foundation and Chief Science Officer, Chronix 
                               Biomedical

    Mr. Chairman, I am grateful to the Committee for allowing me the 
opportunity to submit written testimony in support of this hearing 
being held to examine issues regarding blood cancers such as leukemia, 
lymphoma, and myeloma. After receiving my doctorate degree in 
Microbiology and Immunology from the University of Michigan in 1979, I 
did a postdoctoral fellowship at Washington University School of 
Medicine, St. Louis, studying research models for multiple myeloma. 
Currently, I am Scientific Director of the Chronic Illness Research 
Foundation and Chief Science Officer of Chronix Biomedical, a privately 
owned company conducting research focused on identifying predictive, 
diagnostic and therapeutic genomic markers and targets in chronic 
diseases.
    I am providing this testimony to emphasize the importance of 
providing effective laboratory markers in clinical trials of new 
multiple myeloma therapeutic management strategies. The correct 
selection of laboratory markers can ensure the most effective 
treatment, thereby maximizing drug efficacy and minimizing adverse 
effects.
    Multiple myeloma is like most chronic illnesses with respect to its 
unknown origins and progressive mechanisms. This disease can remain 
asymptomatic or smoldering for many years. In the symptomatic phase the 
most common complaints are bone pain and fatigue. Treatment improves 
the clinical situation in only about 60 percent of the patients. 
Multiple periods of remission and relapse can occur. Currently the 
disease is incurable.
    In December 2000, Dr. Brian G. M. Durie and I reported on the 
discovery of a new surrogate marker for Multiple Myeloma (``RT-PCR 
Amplicons in the Plasma of Multiple Myeloma Patients Clinical Relevance 
and Molecular Pathology,'' Acta Oncologica Vol. 39, No. 7, pp. 789-
796). Dr. Durie has written over 250 myeloma research papers, as well 
as numerous book chapters. He is Chairman of the Board and Scientific 
Advisor to the International Myeloma Foundation (www.myeloma.org), 
which he co-founded with Brian and Susie Novis. Dr. Durie is a 
Professor of Medicine and on staff at Cedars Sinai Comprehensive Cancer 
Center, Division of Hematology--Oncology, Cedars Sinai Medical Center, 
Los Angeles, CA.
    Our publication, which is submitted along with this testimony, 
describes the surprising discovery of genetic material, RNA, in the 
plasma (i.e., the cell-free portion of the blood) of multiple myeloma 
patients. RNA is part of the genetic machinery of our bodies and is 
rarely detected outside of cells. We identified the RNA as being part 
of the recently mapped human genome. The most important observation of 
this study was that the detection of a specific RNA marker seemed to 
correlate with the clinical status of the patient, that is, to relapse 
or remission. In patients who were in remission in response to 
successful treatment, the RNA marker became undetectable; in those 
patients in whom treatment was unsuccessful, the RNA marker continued 
to be detected in their plasma.
    Since the publication of this study, we have applied these new 
methods derived from the information catalogued by the Human Genome 
Project to identify many more RNA markers in other chronic diseases. 
With support from Dr. Durie and the International Myeloma Foundation, 
our preliminary data suggest that plasma RNA expression profiles will 
be strong candidates for monitoring the success or failure of drug 
therapies. My colleagues and I feel that the introduction of new 
concepts in identifying surrogate markers will have a strong impact on 
our fight against cancer.
    I want to thank the Committee for its attention in addressing the 
need to provide early detection and more effective treatments in the 
battle being waged against debilitating chronic diseases, particularly 
multiple myeloma.
                                 ______
                                 
                 Prepared Statement of Mrs. Rafael Mora

    I am submitting testimony on behalf of my spouse who went home to 
the Lord on April 26, 2001 who had multiple myeloma cancer. My spouse 
began to have back pain in the beginning of the year 2000, and we 
sought medical attention immediately through our HMO. Numerous delayed 
appointments took place, followed by mis-diagnosis such as back injury, 
muscle spasm, skeletal, disc, hernia, sciatic nerve, etc. Finally some 
tests, and labs were done and not until June 2000 was the cancer 
diagnosed at the Washington Cancer Institute, where our HMO had finally 
referred us to after wasting so much precious time.
    We began radiation immediately followed by chemotherapy. The goal 
was for my spouse to receive a bone marrow transplant which would take 
place at John Hopkins Hospital in November 2000. My spouses care was 
coordinated through our HMO and Johns Hopkins Hospital. Just before the 
transplant was to take place we were informed by John Hopkins that lab 
results done 3 weeks earlier by our HMO--had only now been received 
from our HMO--and it showed ``enzymes'' rising in my spouses liver and 
we would need to postpone the bone marrow transplant and begin 
chemotherapy immediately. John Hopkins said that we needed to monitor 
my spouses liver, because if his liver was not ``normal'' it would be 
fatal to move forward with the bone marrow transplant. On January 7--
the 4th cycle of chemotherapy ended and my spouse was scheduled for a 
liver biopsy which did not take place till January 18 because he became 
ill with a bad cold. On Feb. 8 we received via e-mail from John 
Hopkins--a message that it would be fatal to move forward with the bone 
marrow transplant because his liver was not normal for a transplant 
after reviewing tests and conferring with other liver/pathologist 
specialist. I and my spouse believed the chemotherapy caused the damage 
to liver.
    By this time we were unable to participate in any clinical studies 
due to my spouses stage of disease and John Hopkins recommended 
thalidomide treatment as the next course in treatment and our HMO 
agreed. However, the thalidomide treatment did not begin till 2 months 
after the chemotherapy had ended because the HMO doctor was out of town 
and no one else could write the prescription for thalidomide, although 
now--they say otherwise.
    Amazingly with all the cruel delays, the treatment of thalidomide 
showed very hopeful results. However, my spouse began taking new pain 
medicines on April 10 and became violently ill on April 19. We sought 
medical attention with our HMO and was told ``it was the myeloma and 
that we needed to manage the pain''. We did not agree and we did not 
take anymore of the pain medicines. My spouse continued to eat and 
drink fluids and have bowel movement but one day later he awoke 
disoriented and we went to the hospital emergency. The 3 doctors on 
duty informed us that his kidneys had shut down and they were trying to 
save him. Those physicians at the hospital felt that most likely the 
pain medicines my spouse received, had caused his kidneys to shut 
down--we would not know for certain till a biopsy of the kidneys were 
done. For the first 3 days in the hospital my spouse continued to eat 
and have bowel movement and although it looked like his kidneys were 
recovering, dialysis was ordered by the two attending physicians. One 
physician stated ``you will die without dialysis''. On April 25 a port 
was placed on the right side of my spouses upper chest in the vein that 
runs from the neck area. It was not properly placed and my husband 
hemorrhaged for 12 hours. We were also told that the injection of 
heparin he received during his dialysis caused the bleeding which they 
continued to refer to as ``an ooze''. My husband went into shock at 
1:30 a.m. and held on till 8:15 p.m. the next evening when he went home 
to the Lord on April 26, 2001.
    Our son never had the opportunity to have that crucial important 
time with his father before he went home to the Lord. My spouse 
suffered in the hospital due to the severe inadequate care. His 
diagnosis was well late into the disease because of the seriously 
inadequate health plan services we received from our HMO--constant 
delays of appointments, testing and lab services.
    All of this should not have happened. It has been a terrible, 
terrible, painful and hurtful experience. My spouse was 60 years old, 
he was a very active and fit person all his life and even after the 
disease struck him he continued to do all that he could to help beat 
this cancer. Our 13 year old son is still in trauma and when he grieves 
for his father he gets a nose bleed. He is afraid to cry because of the 
nose bleed. Our family has been devastated.
    The HMO health service and the Hospital health service received is 
shameful and will never be forgotten. This has been a nightmare. I hope 
this hearing will bring to light how many people have suffered, and 
their families because of health insurance providers, doctors and staff 
that are not specialized to handle cancer cases, who however, continue 
to treat patients and write prescriptions as if every person were just 
a number.
    So what do I hope this testimony will accomplish? I hope and pray 
that no more people will have to suffer due to wasted precious time by 
going to their physician, HMO or health insurance provider. I urge 
everyone to get into a cancer center immediately if there is any hint 
that you may have something cancerous or unexplainable. These cancer 
centers specialize and have the great experience needed in the battle 
against cancer, and yes it is a battle. These cancer centers will do 
all that they can for you. They will not let you suffer and lie to you. 
They will not give you pain medicines without warning you that your 
kidneys could give out--they know exactly what you should receive and 
what you should not. And if any problems arise they will have exact 
history and be able to treat you immediately without guessing or 
suggesting it is your disease. These cancer centers have very serious, 
well educated doctors, researchers and staff who desperately are trying 
to find cures to help people. They have controlled environments and 
understand and know what patients need and they are comforting. I 
firmly believe that what my spouse and many, many others have to go 
through would not happen at these cancer centers. You may ask how do I 
know these things. Well, althrough my spouses battle we continued to 
educate ourselves and looked into any study we could find and read up 
on numerous cancer centers in this country from the west to the east 
coast, and other countries as well and what they are doing. Our desk at 
home is a huge pile of cancer studies, research and information.
    I must mention that by having my spouse go through all those 
meaningless appointments in the beginning with the HMO and holding out 
to refer him to a cancer center just to save a few pennies was the 
worse situation ever encountered. That is why our health care system is 
so burdened because instead of getting to the root of problems, 
precious time is being wasted and money, by making clients go through a 
song and dance with their very own lives.
    My spouse, our sons father--can never be replaced. It is a sorrow 
that will live with us. More funding is crucial for cancer centers 
around the nation and world providing specialized treatment in cancer. 
In closing, according to NBC news release on May 11, 2001, over 98,000 
deaths occur each year due to prescription medicines (the pain medicine 
oxycotin was the feature story). We are still waiting for the full 
autopsy report from the hospital.
    Let us not waste precious time--IT IS A RACE FOR THE CURE.

                         CONCLUSION OF HEARING

    Senator Specter. Thank you all very much for being here, 
that concludes our hearing. The subcommittee will stand in 
recess subject to the call of the Chair.
    [Whereupon, at 11:28 a.m., Thursday, June 21, the hearing 
was concluded, and the subcommittee was recessed, to reconvene 
subject to the call of the Chair.]

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