[House Hearing, 108 Congress]
[From the U.S. Government Printing Office]

                            GENOMIC RESEARCH



                               before the

                         SUBCOMMITTEE ON HEALTH

                                 of the

                        HOUSE OF REPRESENTATIVES

                      ONE HUNDRED EIGHTH CONGRESS

                             FIRST SESSION


                              MAY 22, 2003


                           Serial No. 108-23


       Printed for the use of the Committee on Energy and Commerce

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


                            WASHINGTON : 2003
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               W.J. ``BILLY'' TAUZIN, Louisiana, Chairman

MICHAEL BILIRAKIS, Florida           JOHN D. DINGELL, Michigan
JOE BARTON, Texas                      Ranking Member
FRED UPTON, Michigan                 HENRY A. WAXMAN, California
CLIFF STEARNS, Florida               EDWARD J. MARKEY, Massachusetts
PAUL E. GILLMOR, Ohio                RALPH M. HALL, Texas
JAMES C. GREENWOOD, Pennsylvania     RICK BOUCHER, Virginia
CHRISTOPHER COX, California          EDOLPHUS TOWNS, New York
NATHAN DEAL, Georgia                 FRANK PALLONE, Jr., New Jersey
RICHARD BURR, North Carolina         SHERROD BROWN, Ohio
  Vice Chairman                      BART GORDON, Tennessee
ED WHITFIELD, Kentucky               PETER DEUTSCH, Florida
CHARLIE NORWOOD, Georgia             BOBBY L. RUSH, Illinois
BARBARA CUBIN, Wyoming               ANNA G. ESHOO, California
JOHN SHIMKUS, Illinois               BART STUPAK, Michigan
HEATHER WILSON, New Mexico           ELIOT L. ENGEL, New York
JOHN B. SHADEGG, Arizona             ALBERT R. WYNN, Maryland
Mississippi                          KAREN McCARTHY, Missouri
VITO FOSSELLA, New York              TED STRICKLAND, Ohio
ROY BLUNT, Missouri                  DIANA DeGETTE, Colorado
STEVE BUYER, Indiana                 LOIS CAPPS, California
GEORGE RADANOVICH, California        MICHAEL F. DOYLE, Pennsylvania
CHARLES F. BASS, New Hampshire       CHRISTOPHER JOHN, Louisiana
JOSEPH R. PITTS, Pennsylvania        JIM DAVIS, Florida
MARY BONO, California                THOMAS H. ALLEN, Maine
GREG WALDEN, Oregon                  JANICE D. SCHAKOWSKY, Illinois
LEE TERRY, Nebraska                  HILDA L. SOLIS, California
DARRELL E. ISSA, California
C.L. ``BUTCH'' OTTER, Idaho

                  David V. Marventano, Staff Director

                   James D. Barnette, General Counsel

      Reid P.F. Stuntz, Minority Staff Director and Chief Counsel


                         Subcommittee on Health

                  MICHAEL BILIRAKIS, Florida, Chairman

JOE BARTON, Texas                    SHERROD BROWN, Ohio
FRED UPTON, Michigan                   Ranking Member
JAMES C. GREENWOOD, Pennsylvania     HENRY A. WAXMAN, California
NATHAN DEAL, Georgia                 RALPH M. HALL, Texas
RICHARD BURR, North Carolina         EDOLPHUS TOWNS, New York
ED WHITFIELD, Kentucky               FRANK PALLONE, Jr., New Jersey
CHARLIE NORWOOD, Georgia             ANNA G. ESHOO, California
  Vice Chairman                      BART STUPAK, Michigan
BARBARA CUBIN, Wyoming               ELIOT L. ENGEL, New York
HEATHER WILSON, New Mexico           GENE GREEN, Texas
JOHN B. SHADEGG, Arizona             TED STRICKLAND, Ohio
Mississippi                          BART GORDON, Tennessee
STEVE BUYER, Indiana                 DIANA DeGETTE, Colorado
JOSEPH R. PITTS, Pennsylvania        CHRISTOPHER JOHN, Louisiana
ERNIE FLETCHER, Kentucky             JOHN D. DINGELL, Michigan,
MIKE FERGUSON, New Jersey              (Ex Officio)
W.J. ``BILLY'' TAUZIN, Louisiana
  (Ex Officio)


                            C O N T E N T S


Testimony of:
    Collins, Francis, Director, National Human Genome Research 
      Institute, National Institutes of Health, Department of 
      Health and Human Services..................................     9
    Khoury, Muin J., Director, Office of Genomics and Disease 
      Prevention, Centers for Disease Control and Prevention, 
      Department of Health and Human Services....................    29
    Patrinos, Aristides, Director, Office of Biological and 
      Environmental Research, Department of Energy...............    15
    Venter, J. Craig, President, J. Craig Venter Science 
      Foundation.................................................    22
    Waterston, Robert H., Professor, William Gates III Chair, 
      Department of Genome Science, University of Washington.....    18



                            GENOMIC RESEARCH


                         THURSDAY, MAY 22, 2003

                  House of Representatives,
                  Committee on Energy and Commerce,
                                    Subcommittee on Health,
                                                    Washington, DC.
    The subcommittee met, pursuant to notice, at 10 a.m., in 
room 2123, Rayburn House Office Building, Hon. Michael 
Bilirakis (chairman) presiding.
    Members present: Representatives Bilirakis, Brown, Eshoo, 
Green, Strickland, and Capps.
    Staff present: Steve Tilton, health policy coordinator; 
Cheryl Jaeger, majority professional staff; Eugenia Edwards, 
legislative clerk; John Ford, minority counsel; and Jessica 
McNiece, minority staff assistant.
    Mr. Bilirakis. I now call to order this hearing of the 
Health Subcommittee, and I'd like to start by welcoming our 
witnesses and thanking them for joining us today, in addition 
to thanking them for all their great work on this subject over 
the years.
    Your thoughts and recommendations should prove valuable as 
we consider Congress' role in ensuring that genomic research 
continues to advance.
    In particular, I'd like to take a moment to note that we 
have two of the brightest minds in this field, and I really 
shouldn't say this because it looks like I'm belittling the 
roles of the others, but that's the way my remarks are written. 
In any case, I'm referring to Doctors Collins and Venter, who 
are testifying this morning. Your contribution to the 
development of a comprehensive sequence of the human genome has 
been invaluable, we wouldn't be where we are today if not for 
your efforts.
    The sequencing of the human genome is one of the most 
significant scientific achievements of the 20th Century. Of 
course, the impetus for this promising research can be traced 
back to one seminal event, James Watson and Francis Crick's 
Nobel Prize winning description of the DNA double helix 50 
years ago, and I know the members of this committee are well 
aware that we recently approved a resolution recognizing both 
of these monumental events.
    As this research moves forward, I believe it's incumbent 
upon this committee and on Congress to ensure that the National 
Institutes of Health, which is truly the crown jewel of our 
biomedical research enterprise, continues to play an active 
role, and that's why it's important for us to learn more about 
how NIH's organizational structure has fostered both the 
sequencing of the human genome and the dissemination of this 
information to the research community.
    As we will no doubt discuss today, genomic research at NIH 
is spread across a number of institutes and centers, each of 
which receives its own line item congressional appropriation, 
considering that the Director of NIH is only allowed to 
transfer 1 percent of each institute and center's budget I am 
interested in learning how NIH plans to continue development 
and implementing the comprehensive genomic research plan for 
the 21st Century.
    I'm also looking forward to hearing from our panelists 
today about the challenges they see facing us in the future in 
this field. While Congress will certainly have to deal with 
some of the ethical, legal and social implications this new 
field of research is presenting, I know we all hope that we 
will be able to take this information and translate it into new 
diagnostic and therapeutic products that will greatly improve 
the health of everyone.
    I'd like to again offer a warm welcome to all of our 
panelists and thank them for their time and effort in appearing 
before the subcommittee this morning, and now I'm pleased to 
recognize the ranking member, my friend from Ohio, Mr. Brown, 
for his opening statement.
    Mr. Brown. Thank you very much, Mr. Chairman, and I welcome 
all of you all here. Doctor Collins, it's nice to have you 
again in front of our subcommittee.
    Last month, this committee reported out, as the chairman 
said, H.Con.Res 110, a resolution particularly relevant to our 
hearing today, it recognized the 50th anniversary, as the 
chairman said, of discovery of the double helix structured DNA. 
And now, with genetics and the burgeoning field of genomics we 
truly moved into a new era. The people in front of us today we 
should thank for much of that progress.
    Doctors will have tools to assess diseases in terms of 
their causes, not just their symptoms. The human genome of an 
organism can be known in a matter of weeks or months now, and 
not years or decades. CDC's efforts in sequencing the corona-
virus linked to the recent SARS outbreak provided us a glimpse 
of what this new era may, in fact, hold. Scientists will begin 
to know why some people and not others get sick from certain 
infections or environmental exposures. I can only begin to 
imagine what this means for healthcare delivery in this 
country. Clearly being asked by your doctor about your family 
history will take on a full new meaning.
    There are also critical non-medicine applications of 
genomics. Organisms will begin to play critical roles in 
solving environmental and energy challenges like cleaning up 
contaminated waste sites and generating hydrogen for clean 
energy production. The Federal Government has invested wisely 
in genomic research, their returns promise to be extraordinary, 
providing friends and loved ones benefit from what we have 
learned about genetic links to diabetes, to Parkinson's, to 
Alzheimer's, to breast and ovarian cancer, to colorectal 
cancer, to Cystic Fibrosis, to Huntington's disease, to a whole 
host of illnesses.
    I think we can all agree genomics will play a central role 
in our Nation's biodefense. Within 6 months of the anthrax 
attacks, genomic tools were used to improve our ability to 
characterize the lethal Ames strain. We should also not 
overlook the impact this investment has on the public health 
infrastructure as a whole. When we invest in research, we are 
also investing in education.
    NIH reports that Ph.D. faculty in U.S. medical schools has 
increased by double digits, as a result of the Federal 
investment in research. We talk about Federal involvement, we 
are talking about investing taxpayer money. Taxpayers pay for 
this research, the taxpayer are entitled to the fruits of his 
or her investment.
    Thomas Jefferson, a stalwart proponent of a knowledge-based 
society, recognized, ``the illimitable freedom of the human 
mind,'' in that each generation must advance the knowledge and 
well-being of humankind indefinitely. The free and unfettered 
access to discoveries, free and unfettered access to 
information, are critical, not only because it's the right 
thing to do, but because locking it uplocking up information or 
the use of that information will not only slow progress, but 
also undermine our intent to improve the lives of everyone, not 
just those who can afford it.
    Information sharing was certainly a component of making 
international efforts to the Human Genome Project a success, we 
should ask for nothing less as we move forward.
    I'm hoping our witnesses today will provide insight on what 
we need to think about as policymakers as genomic research 
translates into every-day application. One issue is 
intellectual property. Are we spending taxpayers money to 
create a drug or a therapy only to have them pay again, and 
again, and again, for access to it? Something we have done far 
too much in this Congress, in this society, with the FDA, with 
NIH, with CDC.
    Another issue is the importance of strong genetic, non-
discrimination policies. My colleague, Ms. Slaughter, from New 
York, has introduced legislation that would address the 
particular abuse of genetic information by insurers and by 
employers. I co-sponsored this legislation and hope this 
subcommittee will consider taking an active position on this 
issue, rather than waiting for press reports detailing how 
health insurance providers provide coverage or employees are 
fired because of genetic profiling. Genomics offers exciting 
opportunities to strengthen our public health system, to 
strengthen our public health infrastructure. We are entering a 
new era as a result in health and in healthcare.
    I'm glad our subcommittee is celebrating the Human Genome 
Project for the landmark achievement that it is.
    I thank the chairman.
    Mr. Bilirakis. I thank the gentleman.
    Mr. Green, for an opening statement.
    Mr. Green. Thank you, Mr. Chairman, for holding this 
hearing on what is an exciting field of genomic research. For 
more than two decades, the science community has worked 
diligently to map the human genome. This is an undertaking that 
has broad implications for how we study and treat almost every 
disease known to man, and we all thrilled to see this program 
succeed, when just last month on Doctor Collins' birthday I 
note when it was announced that the genome had essentially been 
completely sequenced. It is even more impressive that the 
mapping of the genome has been completed ahead of schedule and 
under budget, and I think that's something we don't hear in the 
halls of Congress very often.
    This project is a perfect example of how our investment in 
biomedical research can yield significant results that will 
greatly improve the health of all Americans, and while I enjoy 
hearing about NIH because they give me the opportunity to brag 
about the work being done in my own hometown, Baylor College of 
Medicine. The human genome sequencing Center at Baylor has been 
NIH's partner in the Human Genome Project since its inception, 
along with the Whitehead Institute, for biomedical research at 
MIT and Washington University in St. Louis, and the Joint 
Genome Institute at DOE, and the Sanger Institute in England. 
Baylor has recently completed its portion of the Human Genome 
Project, chromosomes 312 and a portion of X, and is nearly 
completing their rat genome project.
    As we know, the laboratory rat is widely used in disease 
models and research programs directed at understanding and 
treating and preventing many human diseases. In addition to the 
work being done on the human rat genome project, the Baylor 
Center is currently engaged in many other sequencing projects, 
including the sequencing of the honey bee, the fruit fly and 
the sea urchin. These projects will help science better 
understand evolution specification, how genes turn on and off 
during the development of the animal from the fertilized egg, 
and genome genetics influences on social behavior. In addition, 
Baylor will soon be beginning to work on the rhesus macaques, 
the widely used primate for biomedical research, and the rhesus 
monkey is particularly important because its response to the 
SIV and is widely recognized as the best animal model for the 
human immune deficiency virus, HIV infection.
    And again, Mr. Chairman, there are so many things we could 
all talk about, and I'd like to put the rest of the statement 
in the record, but I'm glad you are having this hearing today, 
and I apologize there are not other members, but I guess some 
of us who have watched this project, and supported it, and 
encouraged the funding for years, it's a great day to have a 
hearing and talk about the good things that we can do.
    Thank you.
    Mr. Bilirakis. I thank the gentleman.
    Ms. Capps, for an opening statement.
    Ms. Capps. Thank you, Mr. Chairman, and thank you for 
holding this hearing and for your commitment to the National 
Institutes of Health.
    You know, some days it doesn't look there's very much to 
find good about my job, being here in Congress, and on those 
days and on days when I see a lot of bashing of government, 
Federal Government particularly, in the media, or get a lot of 
complaints from my constituents about various of our 
enterprises here, I stop and think aboutand generally, when I'm 
looking for something positive to think about with respect to 
our Federal Government I think about that campus in Bethesda 
and the National Institutes of Health, a wonderful use, in my 
opinion, of taxpayer dollars, an international Ambassador of 
good will and scientific research around the world, and it's a 
pinnacle to me, and I'm pleased that all of you are here and 
that we cannot give recognition to what you do, particularly as 
we are doing today, to discuss and hear from you about the 
Human Genome Project, certainly one of the great scientific 
discoveries of all times.
    No measure of pride in myself, but we are alive here to see 
this, and I think about the charts on my chemistry wall when I 
was a kid in high school and how those used toit's 
revolutionary what's been discovered. The example of what can 
be accomplished in this country when our society, through the 
Federal Government, comes together behind a goal.
    And, I wanted to today at least use part of the time to 
look at that as an example, and a testament to the benefits 
that we can derive by properly funding the National Institutes 
of Health. Hopefully, the results in the Human Genome Project 
will mean a whole new era of medical advances and treatment, 
and that's where we wantI wantguidance from you and ways that 
we should support what you do so that that can be an outcome.
    This hearing and your discoveries also raise so many new 
questions about how we should proceed with research, how new 
treatments are developed, and who will benefit from them. There 
are choices to be made all along this path. It is going to 
undoubtedly lead to many fractious debates and contentious 
legislative battles for this committee on issues we have not 
even yet begun to think about, and I know that for some 
ideology often get in the way, and there, too, I hope we can 
look to you to assist us in that fine line or that delicate 
balance that we will be uncovering.
    I believe, with all my heart, that the opportunities that 
this project, the Human Genome Project, have provided us far 
outweigh any of this fractious debate that's going to ensue. I 
think it's very worthwhile to pursue along and for us to be 
partners with you and supporters of what you do. I look forward 
to seeing what you are able to develop from this project, and I 
support the resolution that we put forth.
    This hearing also is a start of a series of hearings on the 
structure and effectiveness of NIH, and that is something I 
salute our leadership, that's a project I wholeheartedly 
    I'm proud of the fact that I've been here as we have just 
completed doubling of the NIH budget, and this committee 
examined what NIH is doing with the added resources, but even 
as we examined the structure and the funding I hope that we 
will not shortchange NIH on future funding. The proposed 
budget, I believe, asks for far too little increases for the 
NIH, increases so small that many in the scientific community 
are concerned that the gains that have been won may now be 
lost, and I believe this is a poor way for us to handle the 
investments that we have made in previous funding sources to 
what you are doing.
    So, I want that to be part of our discussion. I look 
forward to ways that we can capitalize on the investments that 
have already been made, and I thank the Chair for yielding to 
    Mr. Bilirakis. The Chair recognizes the gentlelady from 
California, Ms. Eshoo, for an opening statement.
    Ms. Eshoo. Good morning, Mr. Chairman, and to my 
colleagues, and to the very, very distinguished panel that's 
here today. I thank you, Mr. Chairman, for holding this very 
important hearing.
    The Human Genome Project is, I think, the most exciting 
topic that this committee has had before it in years, and I've 
been here, this is my, I think, ninth year on the committee. 
Our witnesses, all of whom I believe took part in this 
magnificent effort, have changed the course of science and of 
medicine forever. Your work on the human genome is the key to 
unlocking many of the mysteries of how our bodies function and 
why they function the way they do.
    Genomics is the future of medicine. It will help doctors 
and scientists determine why one person gets ALS, why another 
gets Alzheimer's, and why, perhaps, another lives to the age of 
105. It will also help determine how to fix problems in the 
body that lead to these diseases. It will help biotechnology 
and pharmaceutical companies tailor medicines to combat one 
type of breast cancer over another. It will help doctors 
establish early on, when we're still babies, what we're at risk 
for and how we can prevent or minimize these diseases we are 
coded to get.
    I think that you have helped to bring us to the threshold 
where we tiptoe into the mind of the Creator, and this is, I 
think, the most exciting thing of all. I've always been a 
supporter of funding for research at NIH, which I call our 
national institutes of hope, and for basic science research at 
agencies like the Department of Agency and the National Science 
Foundation. It's efforts like the Human Genome Project that are 
crystal clear examples of why Congress has a duty and a role to 
play in funding basic research.
    And, while this Human Genome Project is a key to unlocking 
many of life's mysteries, it also opens up a whole host of 
questions, many of which it will be up to Congress to answer 
and with you as our guides. How to protect, how do we protect 
against genetic discrimination? How do we ensure that everyone, 
across all social and economic divides, have access to the 
miracles that genomics bring? How does our healthcare system 
bear the costs associated with knowing about disease years in 
advance? How will Medicare handle the costs of a potentially 
elongated life span? These are only a sample of the issues that 
will come up over the next few decades as we work to know more 
about ourselves and use that knowledge for the overall good of 
the people of our Nation.
    As a Member of Congress who represents a congressional 
district known for its advancements in science and technology, 
I look forward to hearing each one of the witnesses in their 
testimony address and, perhaps, hear their thoughts on some of 
the questions I've raised. I also look forward to working with 
each one of you over the years to help harness and guide the 
extraordinary knowledge that you have given to us. It's 
absolutely magnificent, and I want to salute you for it, and I 
look forward to the testimony that you are going to offer 
    Thank you, Mr. Chairman.
    Mr. Bilirakis. I thank the gentlelady.
    [Additional statement submitted for the record follows:]

 Prepared Statement of Hon. W.J. ``Billy'' Tauzin, Chairman, Committee 
                         on Energy and Commerce

    Thank you, Mr. Chairman, for holding this timely hearing today. 
Last month, the country and the world celebrated two of the greatest 
scientific achievements of all time: the discovery of the double helix 
structure of DNA and the completion of the sequencing of the human 
genome. Testifying before us today are five of the most renowned 
scientists in the field of genomics research. It is truly an honor to 
have all of you before our Committee at the same time.
    Both Dr. Collins and Dr. Venter should be commended for their 
leadership in mapping the human genome and providing all scientists 
will the tools and technology to really move the field of genomics 
forward. Dr. Patrinos and Dr. Waterston, I understand you both played 
pivotal roles in the Human Genome Project. Dr. Patrinos, as you are 
aware, the Energy and Commerce Committee has broad jurisdiction over 
the Department of Energy and its programs and management. Our 
jurisdiction includes national energy policy generally, the 
exploration, production, storage, supply, marketing, pricing and 
regulation of energy resources, including all fossil fuels, solar 
energy, and other unconventional or renewable energy resources. 
Therefore, we have a keen and continuing interest in the activities of 
the Office of Science. I know the Department of Energy has allocated 
funding to its own genomics program. I look forward to learning more 
about how this program will operate and its potential.
    Dr. Waterston, many people do not readily recognize that NIH 
research is primarily conducted extramurally. I know your testimony 
will help all of us better understand how NIH partners with the 
university research community. And finally, Dr. Khoury from the Centers 
for Disease Control and Prevention, thank you for being here with us 
today. Without question, whenever we discuss the importance of medical 
research, someone is always quick to point out that the true potency of 
medical research is realized when we can translate and apply it to 
patient care. I know CDC is working on this important issue. I look 
forward to learning more about your plans.
    Just as scientists have decoded the genetic map that defines us as 
human beings, here today we will try to decipher how well the federal 
bureaucracy is working to advance this promising area of genomics 
research. Congress has devoted considerable resources to medical 
research. At the National Institutes of Health alone, in fiscal year 
2003, we appropriated $27.2 billion. Genomics research transcends every 
institute and center at NIH. It has implications for how we study every 
disease. But, the current structure of NIH, and funding allocations for 
that matter, may not adequately recognize its importance.
    As the authorizing committee for the National Institutes of Health, 
it is our responsibility to review how the National Institutes of 
Health operates and try to determine what inefficiencies exist that 
slow the progress of medical research. This is a critical activity for 
our Committee. All of us have been touched by someone inflicted with a 
terrible disease. In my district, for example, a rare childhood 
neurodegenerative disorder, Friedreich's ataxia, occurs at a higher 
frequency in the south Louisiana Cajun population than in the rest of 
the nation. With the help of NIH, in 1996, scientists identified the 
genetic mutation that leads to Friedreich's ataxia. Once the gene was 
identified, scientists were able to study the mutation at the DNA level 
and identify the disease protein and its function. Just last year, NIH 
began its first phase of a clinical trial on a drug compound that has 
shown promise in addressing the most life-threatening symptom of 
Friedreich's ataxia--the heart condition. Because of the advances in 
sequencing the Human Genome, and the doubling of the NIH budget over 
the past five years, more progress has been made in understanding the 
underlying mechanisms of this disorder than in the previous 133 years. 
Research advances like this means something real to patients. It's the 
hope they are looking for when they need all the courage they can 
muster to fight a debilitating disease like Friedreich's ataxia.
    Let's bring hope to all patients suffering from disease. It is our 
responsibility to ensure that NIH is held accountable on behalf of all 
patients. It is our responsibility to remove barriers that 
unnecessarily delay the incredible progress we are making in improving 
human health. This is one of many hearings our Committee expects to 
hold to review the research and grant programs of the National 
Institutes of Health. I appreciate all of your assistance in helping us 
move forward with this project.
    I look forward to the witness testimony.

    Mr. Bilirakis. Our panel today consists of five pretty 
special people. Doctor Francis Collins is Director of the 
National Human Genomic Research Institute. Since 1993, Doctor 
Collins has served as the Director of Human Genome Research at 
the National Institutes of Health. As the Director of the 
National Human Genome Research Institute, Doctor Collins 
oversees the international Human Genome Project, and serves as 
its primary leader. He will discuss the unique role of the 
National Human Genome Research Institute at NIH, and present an 
overview of his experience managing the Human Genome Project, 
and outlining NIH's vision for the future of genomics research.
    Doctor Aristides Patrinos is Director of the Office of 
Biological and Environmental Research with the Department of 
    Mr. Brown. Mr. Chair, are you Greek, you say that so well. 
That was very impressive.
    Mr. Bilirakis. I thought I'd impress you a bit.
    Mr. Brown. You did.
    Mr. Bilirakis. The staff usually with some of these names 
will try to translate them for me, you know, they didn't even 
attempt that one. They said, oh, well, you will know how to 
handle that.
    Anyhow, Doctor Patrinos receives research activities within 
the Department of Energy Office of Science, which includes the 
DOE's Human and Microbial Genome Programs. He also represents 
DOE on the International Human Genome Project, he will discuss 
DOE's involvement in genomic research, including how DOE 
interacted with NIH, a very significant point to my way of 
thinking, during the sequencing of the human genome, as well as 
DOE's current Genomes to Life research program.
    Doctor Robert Waterston is Professor, William Gates III 
Chair, Department of Genome Science, University of Washington. 
Doctor Waterston was the principal investigator at Washington 
University in St. Louis, one of the five extramural institutes 
that worked extensively on the Human Genome Project.
    In January of this year, he moved west to the University of 
Washington. Doctor Waterston will discuss his experience in 
working with the NIH during the Human Genome Project, and in 
general how the university community interacts with the NIH.
    Doctor J. Craig Venter is President of J. Craig Venter 
Science Foundation. Doctor Venter led the competing private 
sector initiative to sequence the human genome. Doctor Venter 
will discuss broadly his involvement with both NIH and DOE, as 
a predominantly private sector-based researcher.
    And, Doctor Muin Khoury is the Director of the Office of 
Genomics and Disease Prevention, Centers for Disease Control 
and Prevention Headquarters. He is the first Director of the 
Office of Genomics and Disease Prevention at the CDC. The 
office was formed in 1997, to assess the impact of advancements 
in human genetics and the Human Genome Project, public health 
and disease prevention.
    Doctor Khoury will discuss how the CDC is translating 
research information generated by the NIH and integrating 
genomics into public health research and programs for disease 
prevention and health promotion, the bottom line of all of this 
I would suggest.
    Gentlemen, your written statements are part of the record, 
we would hope that your comments will complement and supplement 
those. I'm going to set the clock at 5 minutes for each of you, 
but if you are in the middle, if you are on a roll on something 
I certainly won't shut you off, but, hopefully, somewhere 5 and 
10 minutes you might be able to finish up.
    Doctor Collins, we will start off with you, sir, please 


    Mr. Collins. Thank you, Mr. Chairman and distinguished 
members of the Subcommittee on Health.
    We gather at a historic moment. I want to thank you up 
front for the wonderful resolution that you recently passed 
recognizing the milestones that occurred in April. In fact, 
this was a rather remarkable month, where three simultaneous 
events occurred; the 50th anniversary of the double helix, the 
completion of all of the goals of the Human Genome Project, 
ahead of schedule and under budget we are happy to say, and a 
publication of a vision for the future of genome research, a 
document which you have at your place, published in Nature, 
also just 3 weeks ago.
    You have at your place, in addition to that reprint, I just 
thought I'd bring to your attention a little square packet here 
which has two DVDs in it that I thought you'd be interested in. 
One of those is a series of interviews with some of the 
legendary figures in the scientific community who have worked 
hard over the last 50 years to get us where we are, and who 
talk about that, as well as their speculations about the 
future. And, the other DVD, simply enough, is the sequence of 
the human genome. It's rather amazing that I can hold that in 
my hand, the 3 billion letters of our own instruction book, 
packaged on to this DVD in a fashion that you can stick it into 
your computer and begin to help us figure out what it all 
means, because that's very much the phase that we now move 
into. We are at the end of the beginning, and we can now move 
into the really exciting part of genomics, which is to 
understand how it works and how to apply that beneficially to 
human health.
    In that regard, I also bring to your attention this 
publication about a vision for the future of genomics research, 
which you have at your place. If we could have the visuals up 
on the screen I want to just quickly show a couple of things 
that you will find in that document.
    The first one of these is a time line to put this all into 
perspective, taking us back to Mendel in 1865, who discovered 
the principles of genetics, working with pea plants in his 
garden in Czechoslovakia, and then carries us up through 1953, 
Watson and Crick's revelation of the double helical structure 
of DNA, followed shortly thereafter by a number of other major 
milestones, the discovery of the genetic code, recombinant DNA 
technology. If you will click the button we will go to the next 
level here, and then an accelerating pace of technological and 
biological discoveries leading to the discussion about the 
possibility of reading out the entire sequence of the human 
genome, a very controversial discussion I might say, and one 
which would not have led to an organized effort without the 
support of the U.S. Congress. The Congress got behind the 
genome project while many in the scientific community were 
still somewhat uncertain about whether this was a risk that 
they thought could be taken successfully.
    The next image will show you the first 6 years of the 
genome project and some of the milestones that were achieved. 
Again, there's a common misunderstanding that there was only 
one goal of this project, to read out those 3 billion letters, 
in fact, that was one of more than a dozen goals, all of which 
had specific milestones and deliverables, and included the 
study, not only of human DNA, but also that of several 
important model organisms, without which we would still be left 
puzzling over the letters of the code that we now see in front 
of us.
    Those first 6 years were full of challenges, of the need to 
scale up and cut costs. The next image shows you what happened 
more recently in the last 7 years, as we went from pilot 
efforts to sequence genomes to the full-scale effort, resulting 
in a publication of the draft of the human genome sequence in 
early 2001, from the International Human Genome Sequencing 
Consortium on the one hand, in Nature, and from Celera Genomics 
in Science.
    And then, just a few months ago, we witnessed publication 
of an advanced draft of the mouse genome, a very valuable 
property, indeed, in order to be able to interpret the human. 
If you will click the button the thing that we celebrated just 
a few weeks ago, and which I'm sure Doctor Waterston may say 
more about because he was a major leader in this effort, was 
going beyond the draft to the finished version of the human 
genome sequence which we will be using for all time.
    There are three little words, though, in the middle of this 
image on the right, ``to be continued,'' and that's what I now 
want to focus on. We are not done with genomics, we are really 
just getting started.
    The next image shows you our metaphor of where we think 
genomics can now go. This is a house that we want to build, not 
a real house, but a metaphorical house. It rests, as you can 
see, on a foundation, the Human Genome Project. It has three 
floors, applying genomics to biology, to health, and to 
society, and it has six vertical crosscutting elements; 
resources, technology development, computational biology, 
training, ELSI--which stands for the ethical legal and social 
issues--and education, and those touch on all three of the 
floors and hold the building together.
    This vision for the future is the output of more than 600 
scientists over about 18 months, whom we asked to participate 
in more than a dozen workshops, focused on what the major 
priorities could now be, now that we have this foundation in 
front of us. It is an ambitious, one would even say audacious, 
blueprint of where we want to go next.
    In the genomics to biology arena, we would like to get lots 
more DNA sequence on lots more organisms, and we'd like to do 
that ever more cheaply, so that, ultimately, we could sequence 
your genome or mine for $1,000 or less. That would transform 
the way we do research. We are about four orders of magnitude 
away from that right now, so that's a very bold goal, indeed.
    We need to understand how the genome works, what are the 
functions of all the elements. We need to understand the 
protein products of those genes, which actually do the work of 
the cell, and to apply the same grand scale approach to 
proteins that has worked so successfully for DNA.
    I'm a physician, the genomics to health floor is, perhaps, 
the one that I have the greatest excitement about, because 
after much hard work in building this foundation we can now 
accelerate our pace toward the applications to prevention and 
cures of disease.
    One major effort that we are in the middle of already on 
that floor is to understand that .1 percent of our DNA where we 
differ, because that holds within it the clues of why I might 
be at risk for diabetes, and you for some other disorder. We 
have the opportunity now to understand that for virtually all 
diseases in the course of the next 5 to 7 years if we apply 
ourselves appropriately with this new opportunity and 
    In the genomics to society floor, which I will argue is 
just as important as the scientific and medical applications, 
because there are many non-medical consequences of knowing our 
own instruction book. Among those issues are genetic 
discrimination, intellectual property, concepts of race and 
what that means, and how science can actually benefit that 
discussion by applying some reality to the often-confused 
discussions about what race means anyway.
    With regard to the discrimination issue, I was delighted to 
note that just yesterday the Senate Help Committee passed 
unanimously a piece of genetic discrimination legislation that 
covers both health insurance and the workplace. I gather 
Senator Frist has indicated that this will come to the Senate 
floor in June. It would be wonderful if, in fact, this 
particular legislative issue, which has been in the works now 
for some 6 years, if this were to be the year where we saw the 
American public given the kind of protections that many of them 
are asking for. The absence of which those protections is 
impeding research at the present time.
    So, we have a wonderful opportunity here, this future that 
we want to build. We need to stick to a variety of principles, 
especially collaboration particularly between institutions, and 
I want to assure you that I and my colleagues here representing 
DOE and CDC talk about those things on an extremely regular 
basis. I would think in the course of this discussion this 
morning you will get many examples of how our agencies are 
working in a very collaborative and complementary way. 
Certainly representing here the NIH, all of the institutes of 
NIH are deeply interested in the topic of genomics are 
investing in the kinds of outcomes that I've mentioned here, 
and have participated in a major way in the construction of 
this vision document that you see in front of you.
    So, I think if we, in fact, can buildupon the foundation 
that's now in front of us, you can imagine a time, perhaps, 6 
or 7 years from now, where each of us will have a chance to 
learn our individual susceptibility for illness, based upon a 
genetic analysis, and then be enabled to practice 
individualized preventive medicine based on what we are at risk 
for instead of a one-size-fits-all approach. Even more 
importantly, the understanding of the molecular underpinnings 
of diseases like diabetes, and mental illness, and heart 
disease, will enable us to develop a new generation of 
therapies that are specifically targeted to the problem, as 
opposed to treating some downstream consequence.
    We have a bright future, and I think the genomics 
revolution will catalyze much of that. I'd just like to 
conclude by reading a few sentences, from the wonderful book 
which I would recommend to those who are trying to learn more 
about the genome, and this is a book by Matt Ridley, called 
``Genome: An Autobiography of A Species in 23 Chapters,'' in 
the introduction he writes the following words: ``In just a few 
short years we will have moved from knowing almost nothing 
about our genes to knowing everything. I genuinely believe that 
we are living through the greatest intellectual moment in 
history, bar none. Some will protest that the human being is 
more than his genes, I do not deny it . . .,''--personally I 
strongly agree with that, we are much more than our genes--``. 
. . but . . .,'' he writes, ``. . . there is much, much more to 
each of us than a genetic code, but until now human genes were 
an almost complete mystery. We will be the first generation to 
penetrate that mystery. We stand on the brink of great new 
answers, but even more, of great new questions.''
     Members of the subcommittee, it's a pleasure to have a 
chance to meet with you this morning and discuss those 
questions and answers.
    Thank you very much.
    [The prepared statement of Francis S. Collins follows:]

  Prepared Statement of Francis S. Collins, Director, National Human 
Genome Research Institute, National Institutes of Health, Department of 
                       Health and Human Services

    Mr. Chairman and Members of the Committee: It is a pleasure to 
appear before you at this historic moment when we have just completed 
all of the goals of the Human Genome Project (HGP). I look forward to 
discussing with you the future of genomics at the National Institutes 
of Health (NIH), as well as the rest of the broader scientific 
community. I will start by giving a brief history of the HGP, 
highlighting our recent success. I will then discuss the National Human 
Genome Research Institute's (NHGRI) efforts to coordinate our work with 
other federal agencies, other governments, and the private sector. I 
will also describe our new vision for the future of genomics, as well 
as some new initiatives already under way. I hope to make clear that 
while we have just sequenced the 3 billion letters of the human DNA 
code, our work is really just beginning. The successful conclusion of 
the HGP heralds the true dawning of the genomic era. There is an 
ongoing vital role for the federal government in enabling the future of 
genomics, and especially in applying it to benefit human health.


U.S. National Academy of Science Study on the Human Genome Project
    The main goals of the HGP were first articulated in 1988 by a 
special committee of the U.S. National Academy of Sciences (NAS), and 
later adopted through a detailed series of five-year plans jointly 
written by the NIH and the Department of Energy (DOE). In 1988 Dr. 
James D. Watson, who won the Nobel Prize along with Francis Crick for 
discovering the structure of DNA, was appointed to head the then Office 
of Human Genome Research, which has grown into the National Human 
Genome Research Institute that I now have the privilege of directing. 
As of April 14, 2003, the principal goals laid out by the NAS have all 
been achieved more than two years ahead of schedule and $400 million 
dollars under budget, including the essential completion of a high-
quality version of the human sequence. Other goals included the 
creation of physical and genetic maps of the human genome, which 
provided a necessary lower resolution view of the genome and have major 
value to research in their own right. The HGP also accomplished the 
mapping and sequencing of a set of five model organisms, including the 
mouse. That information generally empowers the ability to interpret the 
human genome, rather like the Rosetta stone allowed the decryption of 
the ancient languages. The NAS study also recommended that, ``access to 
all sequence and materials generated by these publicly funded projects 
should and even must be made freely available [to all].'' We have 
adhered to that noble standard throughout the last 13 years.

Congressional and Administrative interest
    Neither the NAS study nor the HGP would have occurred without the 
visionary leadership and determination of the Administration and the 
Congress. At the outset, many in the scientific community did not think 
that the HGP could be completed in a timely fashion or for an 
affordable cost. But the Administration and key members of the Congress 
felt that it was essential the United State government play a leading 
role in this project, and they correctly predicted that the project 
could be completed without taking resources from other important 
science. With the support of the Administration and the Congress, the 
recent doubling of the NIH budget allowed a dramatic increase in the 
pace of the HGP.
    Last month, we were able to observe a major anniversary, the 
fiftieth anniversary of the discovery of the double helix structure of 
DNA by Drs. Watson and Crick, while simultaneously celebrating the 
completion of the DNA sequence of the human genome. In June 2000, the 
NHGRI and its partners in the International Human Genome Sequencing 
Consortium had already completed a ``working draft'' of the human 
genome sequence; at that same time, Celera Genomics, under Dr. Craig 
Venter's leadership, released its own draft version of the human genome 
and participated with us in a joint announcement at the White House. 
Since then the federally funded sequencing centers and our 
international partners have been working to correct all the remaining 
spelling errors and fill in the gaps in the draft sequence, leading to 
the public release of the essentially complete sequence on April 14, 
2003. This is the reference sequence we will be using for all time. The 
availability of the 3 billion letters of the human instruction book 
could be said to mark the starting point of the genomic era in biology 
and medicine. There is now much important work to do to deliver on the 
promise that these advances in genomics offer for human health.

Coordination with Federal Agencies, other Governments, and the private 
    The HGP would have been impossible without an outstanding 
partnership between federal agencies, international organizations, and 
the private sector. From the inception of this project, the NIH has 
worked very closely with the DOE, and especially its Office of Science. 
In particular, I have had the great privilege of working with Dr. 
Aristides Patrinos, who has skillfully managed the DOE's efforts in 
this regard. We have also worked very closely with the governments and 
genome sequencing centers of five other countries: the United Kingdom, 
France, Germany, Japan, and China. In the United States the three main 
sequencing centers funded by the NHGRI are at the Baylor College of 
Medicine, Washington University in Saint Louis, and the Whitehead 
Institute of the Massachusetts Institute of Technology. Dr. Robert 
Waterston will be describing for you in a moment his work as the former 
Director of the sequencing center at Washington University.
    The success of the HGP partnership was cited in a recent 
PricewaterhouseCoopers report, ``Managing `Big Science': A Case Study 
of the Human Genome Project,'' in which the author noted that: ``A 
major implication for the future lies with the partnership model of R&D 
that HGP's organization revealed. Partnerships across agencies, sectors 
and nations are likely to be the wave of the future for large-scale 
public efforts at the frontier of knowledge. As a result of the HGP 
partnership, the first chapter of the human genome revolution is coming 
to a successful end, and next steps are underway.''


    This April also witnessed the publication in the journal Nature of 
a bold vision for the future of genomics research, developed by the 
NHGRI. This vision, the outcome of almost two years of intense 
discussions with literally hundreds of scientists and members of the 
public, has three major areas of focus: Genomics to Biology, Genomics 
to Health, and Genomics to Society. Genomics to Biology: The human 
genome sequence provides foundational information that now will allow 
development of a comprehensive catalog of all of the genome's 
components, determination of the function of all human genes, and 
deciphering of how genes and proteins work together in pathways and 
    Genomics to Health: Completion of the human genome sequence offers 
a unique opportunity to understand the role of genetic factors in 
health and disease, and to apply that understanding rapidly to 
prevention, diagnosis, and treatment. This opportunity will be realized 
through such genomics-based approaches as identification of genes and 
pathways and determining how they interact with environmental factors 
in health and disease, more precise prediction of disease 
susceptibility and drug response, early detection of illness, and 
development of entirely new therapeutic approaches.
    Genomics to Society: Just as the HGP has spawned new areas of 
research in basic biology and in health, it has created new 
opportunities in exploring the ethical, legal, and social implications 
(ELSI) of such work. These include defining policy options regarding 
the use of genomic information in both medical and non-medical settings 
and analysis of the impact of genomics on such concepts as race, 
ethnicity, kinship, individual and group identity, health, disease, and 
``normality'' for traits and behaviors.
    This vision for the future of genomics is not just about the NHGRI. 
It encompasses the whole field of genomics, including the work of all 
the other Institutes and Centers at the NIH and of a number of other 
federal agencies. All of the NIH Institutes are already taking full 
advantage of the sequence and will apply its data to the better 
understanding of both rare and common diseases, almost all of which 
have a genetic component. A recent example of the way that the HGP and 
the knowledge and new technologies it has spawned are already 
facilitating science is the extremely rapid sequencing by groups in 
Canada and at the Centers for Disease Control and Prevention (CDC) in 
Atlanta of the genome of the virus that causes Severe Acute Respiratory 
Syndrome (SARS). The sequencing of the SARS virus genome provides 
insight into this new and deadly disease at a speed never before 
possible in science. In turn, this should lead to the rapid development 
of diagnostic tests and, in time, vaccines and effective treatments.

                         NEW NHGRI INITIATIVES

    The NHGRI has already begun several new initiatives, and is 
planning others, to meet the challenge of realizing this new vision for 
the future of genomics. Many of these initiatives will be co-funded by 
other NIH Institutes, other federal and international partners, and the 
private sector. Some examples of these cutting edge programs include:

The Creation of a Human Haplotype Map
    Multiple genetic and environmental factors influence many common 
diseases, such as diabetes, cancer, stroke, mental illness, heart 
disease, and arthritis; however, relatively little is known about the 
details of the genetic basis of such common diseases. Together with 
international partners, the NHGRI has begun to create a ``haplotype 
map'' of the human genome to enable scientists to find the genes that 
affect common diseases more quickly and efficiently. The power of this 
map stems from the fact that each DNA variation is not inherited 
independently; rather, sets of variations tend to be inherited in 
blocks. The specific pattern of particular genetic variations in a 
block is called a ``haplotype.'' This new initiative, an international 
public/private partnership led and managed by NHGRI, will develop a 
catalog of haplotype blocks, the ``HapMap.'' The HapMap will provide a 
new tool to identify genetic variations associated with disease risk or 
response to environmental factors, drugs, or vaccines. It will allow 
more efficient genomic research and clinical applications, thus making 
for more economical use of research and health care funds. Ultimately, 
this powerful tool will lead to more complete understanding of, and 
improved treatments for, many common diseases.

The ENCODE Project: the ENCyclopedia Of DNA Elements
    To utilize fully the information that the human genome sequence 
contains, a comprehensive encyclopedia of all of its functional 
elements is needed. The identity and precise location of all 
transcribed sequences, including both protein-coding and non-protein 
coding genes, must be determined. The identity of other functional 
elements encoded in the DNA sequence, including signals that determine 
whether a gene is ``on'' or ``off'', and determinants of chromosome 
structure and function, also is needed. The NHGRI has developed a 
public research consortium to carry out a pilot project, focusing on a 
carefully chosen set of regions of the human genome, to compare 
existing and new methods for identifying functional genetic elements. 
This ENCyclopedia Of DNA Elements (ENCODE) consortium, which welcomes 
all academic, government, and private sector scientists interested in 
facilitating the comprehensive interpretation of the human genome, will 
greatly enhance use of the human genome sequence to understand the 
genetic basis of human health and to stimulate the development of new 
therapies to prevent and treat disease.

Genome Technology Development
    The NHGRI continues to invest in technology development that speeds 
the applications of genomics. Technical advances have caused the cost 
of DNA sequencing to decline dramatically, from $10 in 1990 to less 
than $0.09 per base pair in 2002, but this cost must decline even 
further for all to benefit from genomic advances. The NHGRI, along with 
many partners, will actively pursue the development of new technologies 
to sequence any individual's genome for $1,000 or less. Other areas of 
technology development are also ripe for expansion, and the NHGRI plans 
to pursue them vigorously.


    While it always is somewhat risky to predict the future, I want to 
leave you with my view of where I believe genomic medicine is headed. 
In the next ten years, I expect that predictive genetic tests will 
exist for many common conditions in which interventions can alleviate 
inherited risk, so that each of us can learn of our individual risks 
for future illness and practice more effective health maintenance and 
disease prevention. By the year 2020, gene-based designer drugs are 
likely to be available for conditions like diabetes, Alzheimer's 
disease, hypertension, and many other disorders. Cancer treatment will 
precisely target the molecular fingerprints of particular tumors, 
genetic information will be used routinely to give patients more 
appropriate drug therapy, and the diagnosis and treatment of mental 
illness will be transformed.


    This year marks a very exciting transition in the field of 
genomics, with the full sequencing of the human genome marking the 
successful achievement of all of the HGP's original goals, and thus the 
advent of the genomic era. When Congress decided to fund the HGP, it 
did so with the justifiable belief that this work would lead to 
improved health for all. Those advances are already occurring all 
around us, and the ability to accelerate the realization of this vision 
now lies before us. At the same time, we must be sure that these 
technological advances can benefit all our citizens in a safe and 
appropriate manner. It is our sincere belief that the newly created 
discipline of genomics will make a profound difference to the health 
and well being of all the people of this world.
    While I am very optimistic about the future of genomic medicine, we 
clearly have a great deal more work to do to realize these lofty goals. 
The vision for the future of genomic medicine that I have described 
will require major breakthroughs in technology and scientific 
knowledge. But I am confident that by supporting our best and brightest 
scientists to work together with our partners within the government and 
around the globe, we will meet these challenges. We are profoundly 
grateful for the support the Congress has given to this endeavor. We 
would not be where we are today without your vital support. Thank you.

    Mr. Bilirakis. Thank you very much, Dr. Collins.
    Doctor Patrinos, please proceed.


    Mr. Patrinos. Thank you, Mr. Chairman. I am really honored 
to be invited to testify before you and the members of the 
subcommittee on genomics research, and I'm particularly honored 
also to be testifying in the presence and along with my 
colleagues and friends, some of the top scientists in genomic 
research, as you pointed out.
    Doctor Francis Collins likes to start his story with 
Mendel, I usually go back a couple of thousand years with 
Aristotel who wondered how an acorn turns into an oak tree. 
That's one small point where we disagree a little bit.
    Anyway, DOE has made important contributions to biological 
research since the early days of the Atomic Energy Commission, 
including the field of nuclear medicine. The Atomic Energy 
Commission, of course, is our predecessor agency.
    The NIH and the Department Of Energy joined forces in 
launching the Human Genome Project in 1990. Since then our two 
agencies have worked very closely in managing this seminal 
research endeavor. This partnership has been a model of 
interagency collaboration with each agency contributing its 
unique strengths and capabilities and creating, indeed, a whole 
that's greater than the sum of the individual parts.
    NIH and the Department of Energy, as you've heard from 
Doctor Collins, with a strong international involvement, 
completed the Human Genome Project just last month, and as has 
also been mentioned, 2 years almost ahead of schedule, 2\1/2\ 
years ahead of schedule, and under budget.
    Secretary Abraham has, in fact, said that with all the 
contributions that DOE has made in the field of science none 
compares with what the Department of Energy has done in the 
Human Genome Project, echoing many of the things that I heard 
this morning from you and the members of the subcommittee.
    Indeed, it is true that the Human Genome Project inspired 
what can be a called a paradigm shift in biological research 
from a pure hypothesis-driven ``small science'' approach to 
more of a resource-driven approach. The Human Genome Project 
also highlighted the importance of interdisciplinary research, 
including the physical sciences, automation engineering, and 
computational science.
    Modern biological research, including genomics and the 
study of proteins, like Doctor Collins has already mentioned, 
rely on many research tools that are developed, in fact, by the 
physical sciences, such as the synchrotron radiation sources 
and nuclear magnetic resonance systems for protein 
crystallography, determining the structure of the individual 
proteins as a way to understand their function.
    The Department of Energy's Office of Science builds and 
operates many of the scientific user facilities [such as the X-
ray sources] for the benefit of the entire scientific 
community, and those scientific user facilities are 
increasingly being used by life scientists in their research, 
maybe a few percentage points about a decade ago, up to almost 
40 percent today. This symbiotic NIH and Department of Energy 
relationship is expected to continue and even grow.
    For us in the Department Of Energy, our follow up to the 
Human Genome Project is, in fact, described in a copy of 
Science that you have before you, and the chairman has already 
mentioned it, the Genomes to Life program or GTL. GTL was 
developed over the last 3 years by our advisory committee, the 
Biological and Environmental Research Advisory Committee, with 
broad input from many folks in the wide scientific community 
from many disciplines. This program adopts a ``systems 
biology'' approach to the study of microbes and microbial 
communities. GTL does not include any research on human 
    Genomes to Life is a basic research approach that is aimed 
at the long-term solution of many of the Department's problems 
that Mr. Brown has already mentioned. They include the 
bioremediation of mixed waste at many of the contaminated DOE 
sites, the witch's brew that we have left from the legacy of 
cold war; also, the enhanced sequestration of carbon by the 
terrestrial and marine biosphere in order to reduce the 
atmospheric concentrations of greenhouse gases in the 
atmosphere; and also, as has already been mentioned, the 
production of clean fuels such as hydrogen, through the 
miracles of biotechnology.
    We expect that the Genomes to Life program will marry the 
tools of modern molecular biology with advanced scientific 
computing. Advanced scientific computing is an integral partner 
with us in this effort, and we expect highly accurate 
simulations of microbial systems and their interactions with 
the environment.
    We also are proposing to build four scientific user 
facilities to enable, for example, the high-throughput research 
activities, including the production of proteins and protein 
tags as well as advanced systems that would allow us to view 
intra cellularly the microbes and their functions.
    Looking to the future, we expect continuing close 
collaborations with our partners in the NIH on the Genomes to 
Life program and other programs as well. Our programs will 
involve scientists from the academic community, from our 
national laboratories and private institutions such as Craig 
Venter's Institute for Biological Energy Alternatives. Craig 
Venter is a major principal investigator with us in the Genomes 
to Life program.
    Thank you for the opportunity you gave me and I'm, of 
course, ready to answer any of your questions.
    [The prepared statement of Aristides Patrinos follows:]

     Prepared Statement of Aristides Patrinos, Director, Office of 
      Biological and Environmental Research, Department of Energy

    Mr. Chairman and Members of the Subcommittee: I am pleased to 
testify before the Subcommittee about the future of genomic research at 
DOE. I am also prepared to discuss the Genomes to Life program and our 
interactions with the National Institutes of Health (NIH).
    DOE is proud of the contributions we have made to biological 
research since the early days of the Atomic Energy Commission and of 
the role we have played in the Human Genome Project (HGP). The NIH and 
DOE joined forces in 1990 to launch the HGP and we have worked closely 
over the years to reach the successful completion of the project last 
month almost two years ahead of schedule and several hundred million 
dollars under the original estimate of $3 billion. The partnership with 
the NIH in the HGP has been a model of interagency cooperation with 
each agency contributing its unique culture and strengths to create a 
whole that was truly greater than the sum of the parts. The DOE brought 
to the HGP its strengths in the managerial arena: an impressive network 
of national laboratories, each with its own area of scientific 
expertise. DOE leaders' experience in managing large-scale projects 
(mostly in the physical sciences) provided critical input to the HGP, 
starting during the formative years and continuing through today.
    With the successful completion of the HGP we are entering an 
exciting new era of biological research greatly enhanced by the modern 
tools of molecular biology that have been enabled by genomics. This new 
era of biological research offers the promise of revolutionary 
solutions to challenges we face across a remarkable spectrum--from 
agriculture to carbon sequestration to clean affordable energy to the 
environment to industrial processes to medicine to national security to 
name but a few. While technologies and research tools will be developed 
and shared across disciplines, Federal agencies, academia, industry, 
and international borders, as they were in the Human Genome Project, 
the specific research challenges and needs will not be shared.
    Strategies that NIH will use for understanding disease processes 
and for developing improved diagnostics and cures will differ greatly 
from those needed to develop new ways to sequester excess carbon 
dioxide from the atmosphere, produce abundant and affordable supplies 
of clean energy, and clean up contaminated waste sites. Although 
completion of the HGP will thus lead to somewhat divergent research 
paths, NIH and DOE will continue to coordinate research efforts and 
explore opportunities for collaboration and cooperation. Such 
opportunities will emerge from both the many NIH-DOE ties as well as 
through the interagency forums led by the Office of Science and 
Technology Policy in the Executive Office of the President.
    DOE's entry into this new era is the Genomes to Life (GTL) program 
that has been developed with broad scientific community input and led 
by the Biological and Environmental Research Advisory Committee 
(BERAC). The focus of the GTL program is on microbes and microbial 
communities and seeks to harness their properties and capabilities to 
address DOE needs in environmental bioremediation, carbon 
sequestration, and clean energy production such as generating hydrogen.
    The research approaches and tools that DOE needs to understand 
microbes so well that we can use them to help solve DOE challenges 
will, in many cases, be very different than those used by NIH to study 
disease-causing microbes. DOE needs to understand the nature and 
biochemical capabilities of microbes in the oceans and in subsurface 
environments--sites and microbes not likely to be of significant 
interest to NIH--since the microbes in those environments are the ones 
that we need to put to work to help us solve energy and environmental 
challenges. In addition, most of the microbes that DOE needs to 
understand, live and ``work'' as parts of complex communities made up 
of hundreds or thousands of different microbes--a scientific challenge 
very different from the challenges faced by NIH's need to understand 
disease-causing microbes.
    We believe that many of the scientific discoveries in this new 
century will happen at the interfaces of scientific disciplines, 
including the interfaces between biology and the physical and 
computational sciences. Modern biological research will increasingly 
rely on the scientific tools that are developed by the physical 
sciences. One example is the determination of the structure of 
biological molecules using the synchrotron radiation sources, neutron 
sources and nuclear magnetic resonance facilities. Most of these 
facilities are built and operated by DOE and the number of their users 
from the life sciences has grown from a few percentage points to 
approximately forty percent in just the last ten years. Another example 
is advanced simulation of cellular processes using high performance 
supercomputers. The new generation of medical imagers will also require 
significant computational resources for the processing of vast amounts 
of data.
    We envision many significant opportunities for future 
collaborations between NIH and DOE as scientific research becomes more 
interdisciplinary and more reliant on cutting-edge scientific tools. 
Many of these tools will be developed by the DOE research programs for 
DOE applications and some of these tools will be considered by NIH for 
applications to human biological research and for medical applications. 
We expect to continue our regular and productive dialog with our NIH 
colleagues to identify such opportunities for collaboration and to help 
make them happen.
    Despite its microbial focus the GTL program will enable many 
collaborations with our NIH colleagues, including those from the 
National Human Genome Research Institute, the National Institute for 
General Medical Sciences, and the National Institute for Allergy and 
Infectious Diseases. Discoveries that may serve the DOE missions in 
bioremediation, carbon sequestration, and clean energy production may 
prove relevant to applications in human health and medicine. Similarly, 
insights derived form the study of human biology may help us properly 
tweak microbial systems to serve DOE needs.
    Many have called this new century the ``century of biology'' 
because of its promise in providing new solutions to many of humanity's 
problems. At DOE we plan to exploit these new biological advances for 
the benefit of the Nation and we expect that our productive research 
partnership with the NIH will continue and even expand.
    I would be pleased to answer your questions.

    Mr. Bilirakis. Thank you very much, sir.
    Doctor Waterston.


    Mr. Waterston. Well, thank you for the opportunity to 
testify about the many opportunities that lie before us for 
U.S. biomedical research, but I'd also like to take the 
opportunity to thank Congress for its continuing and unstinting 
support of the Human Genome Project throughout the years. It's 
been critical.
    I'd love to talk about all the opportunities in more 
detail, but I'm going to, in fact, direct my remarks to the 
role of the NIH and, particularly, the NHGRI in bringing genome 
to fruition. In my role as Director of the Center at Washington 
University, I've been able to witness first hand all of this 
    Initially, the project demanded just a definition of what 
the goals were, and Jim Watson, in particular, was highly 
successful at drawing people into the project, but the 
traditional, very successful system of investigator-initiated 
peer review grants operated to draw the many ideas from the 
community and to sift through them. Successful program were 
renewed and expanded.
    As the project moved into it's production phase, the 
proposals from individual centers were still subjected to 
rigorous peer review, but the projects required much more 
oversight to coordinate the efforts from the various centers. 
And, NHGRI took on this much less traditional role of 
organizing the groups. Doctor Collins and his staff kept us 
focused on the task at hand, while never losing sight of the 
overall goal of a complete finished human sequence.
    One key early decision was that of the group to release 
immediately all the data generated. No patents were filed, and 
the rapid unfettered access to this data has worked, speeding 
discovery of the genes behind many genetic diseases already. 
More will follow.
    With the success of the project, we are now in the position 
of deciding how best to utilize this information to improve 
human health and well-being. We know that the genome contains 
all the genetic information passed on from generation to 
generation, but we understand that information only dimly. 
Using that information to move from knowing the genetic basis 
for a disease to an effective therapy is an even greater 
    Doctor Collins and Doctor Patrinos have already mentioned 
the plans of their institutions for the future, and they 
developed these after extensive consultation with the 
community. Centers for Excellence in Genomics and the HapMap 
project are just two of the already initiated programs.
    One activity that I'm particularly interested in is the 
sequencing additional animal genomes. We learned a tremendous 
amount by comparing the sequence of the human with the sequence 
of the mouse. We were, basically, peering into evolution's 
notebook and looking at the results of 75 million years of 
tinkering. Additional sequences from other animals such as the 
cow, dog, chicken and chimpanzee will be invaluable as we try 
to understand the contents of the human genome.
    But, as others have mentioned, the genome is fundamental to 
all kinds of biomedical research and it impacts research both 
public and private. The doubling of the NIH budget has come at 
a most appropriate time, and as the Congresswoman already 
mentioned, it's important that this support be continued, 
because the task ahead of us is truly enormous, but the results 
will be worth it.
    And, I believe that for both the NHGRI plan and the NIH as 
a whole this traditional system of investigator-initiated peer 
review research should continue to serve us well, as we explore 
the best ways to go forward. And, at this point I think it's 
really unclear what the best way to go forward is.
    But in addition to these initiatives, the NIH and the NHGRI 
in particular should continue to seek out big, novel goals that 
will capture the imagination, and are of obvious medical 
relevance, and will spur the best science.
    One example of such a goal might be the sequencing of a 
very large cohort of well-characterized individual. We would 
uncover our evolutionary roots and begin to understand how 
sequence variation contributes to variability in disease 
susceptibility and to many other traits.
    A project like this would push science and society closer 
to the goal of using the genome for the benefit of all.
    I thank you for the opportunity to appear, and I look 
forward to your questions.
    [The prepared statement of Robert H. Waterston follows:]

  Prepared Statement of Robert H. Waterston, Professor, University of 

    Mr. Chairman and Members of the Committee: Thank you for the 
opportunity to appear before you. I welcome the chance to share with 
you my thoughts about the opportunities in biomedical research made 
possible by the success of the human genome project, and the role that 
NIH might play in bringing these opportunities to fruition. Congress 
led in the initiation of the project at a time when many scientists 
were skeptical, and generous support by Congress throughout the project 
was essential. Congress will continue to play a major role in 
determining the next steps.
    I will begin by providing you with some brief background about 
myself and my role in the Human Genome Project. I'll then describe how 
the genome project worked from a grantee's perspective. Finally I'll 
describe where we are today and some of the opportunities that lie 
ahead for NIH and biomedical research.


    I am currently Professor and William Gates III Chair of the 
Department of Genome Sciences at the University of Washington. But 
until December of last year I was the director of the Genome Sequencing 
Center at Washington University in St. Louis, where I experienced first 
hand the emergence of this project. I saw it grow from the ideas of a 
few visionary scientists to the recent completion of the human sequence 
under the skillful leadership of Dr. Collins, Dr. Patrinos and others. 
Over a dozen years, the St. Louis Center grew from a team of just half 
a dozen staff producing about 10,000 bases of DNA sequence a day to a 
staff of over 150 producing more than 50 million bases of DNA sequence 
daily. The St. Louis Center was one of the three large NIH-sponsored 
centers in the human genome project and produced more than 20% of both 
the draft and finished human sequence. It also played leadership roles 
in the completion of the genomes from the baker's yeast, Saccharomyces 
cerevisiae, the round worm, Caenorhabditis elegans, and the mustard 
weed Arabidopsis thaliana. Today its efforts are directed at completing 
the mouse genome sequence, as well as producing draft sequences of both 
the chimpanzee and chicken genomes.

                           SEQUENCING CENTER

    The Genome Sequencing Center received most of its funding from the 
NIH through what is now the NHGRI. But at critical junctures it has 
also received funding from Merck and two different consortia of 
pharmaceutical companies, as well as NSF. In 1990 we were one of 
several laboratories funded to begin the effort of adapting and 
improving sequencing methods to the task of sequencing whole genomes. 
This was an exploratory period, in which the NHGRI set clearly defined 
overall goals and invited proposals from scientists with their many 
different ideas about how to realize these goals. James Watson, the 
first head of the NHGRI, played a critical role in fashioning this as 
an exciting project that would draw in the top scientists of the day. 
Many groups responded, and the proposals were rigorously evaluated, 
following the tradition of investigator-initiated, peer-reviewed 
research that has made US NIH-sponsored biomedical research the envy of 
the world.
    Out of that process came several pilot projects exploring a variety 
of ways to sequence DNA at an ever-increasing scale. Some worked while 
others didn't, and as these grants came up for renewal, winnowing 
occurred, through rigorous evaluation of results--and costs--by panels 
of peers. By 1997, the community coalesced around the most effective 
DNA sequencing technology and reached a broad consensus that the 
technology was now up to the task of sequencing the human genome. While 
peer review of proposals continued to be the means of evaluating 
applications, collaborative discussions among all players--both NIH 
staff and scientists in the labs--became the instrument for 
establishing direction and policy in the project as a whole.
    As the major partner in the international public project, which 
included some 20 laboratories from 6 countries, the NHGRI and Dr. 
Collins in particular played a central role in coordinating the effort. 
Through weekly conference calls, quarterly meetings and many emails, 
Dr. Collins and his staff kept the group focused on the task at hand 
and at the same time never lost sight of the long term goal of 
complete, highly accurate human sequence.
    Of the various decisions made by the group, perhaps none was more 
important than the decision at one of the first gatherings of the 
international human sequencing community to release all the sequence 
data immediately upon generation for all the world to use without 
constraint. No patents would be filed. The sequence was held to be of 
fundamental importance, like the atoms of the periodic table, and all 
recognized the many steps between discovery of a sequence and its 
application to improving human health. This decision gained the 
confidence of the wider scientific community, but more importantly it 
meant that the sequence stimulated research in labs both public and 
private throughout the world from the day the project was begun.


    The patience and persistence of Dr. Collins and his staff have paid 
off. After the joint announcement with our colleagues from Celera 
Genomics of the draft sequence in June 2000, the public scientists 
continued to refine the sequence. As a result, we have before us today 
the effectively complete sequence of a reference human genome. About 
99% of the sequence is represented. We have closed more than 99.5% of 
the gaps that existed in the draft sequence. The error rate has been 
pushed to below 1 per 100,000 bases. This highly accurate, complete 
sequence speeds the work of researchers trying to find the genes behind 
genetic diseases. It enhances the ability of computational biologists 
to interpret the sequence. And most importantly it provides a solid 
foundation for scientists to build upon.
    But of course the sequence is a beginning, not an end in itself. 
While we know that the genome contains all the genetic instructions 
handed down in the form of DNA from one generation to the next, we can 
only read those instructions poorly. It is likely to take decades to 
understand this instruction set thoroughly, but the effort will be 
worth it. As we unravel the complexity and as we learn what happens 
when some part of the code is disrupted by mutation, we will uncover 
opportunities for improving human health and well-being.
    The plans for the future developed over the past year by the NHGRI 
and DOE and described by my colleagues Dr. Collins and Dr. Patrinos in 
their testimony outline some of the important next steps. The HapMap 
that Dr. Collins described begins to explore human diversity. And the 
Centers of Excellence in Genome Science program that NHGRI began in 
2001 seeks to foster innovative approaches toward understanding and 
integrating genomic information. The University of Washington was the 
recipient of two of the first three awards.
    One important ongoing activity I'd like to highlight is the 
sequencing of additional genomes. We have learned an enormous amount by 
comparing the sequences of the mouse and human. We are reading 
evolution's notebook, the results of 75 million years of mutation and 
selection. The functional parts of the genome begin to stand out in 
these comparisons and to tell us important things about how the human 
genome came to be and how it works. Additional sequences from animals 
like the cow, dog, pig and chimpanzee will yield still more insights 
into our genome, while at the same time bringing the power of genomic 
approaches to the study of these important animals.
    But the impact of the genome sequence extends beyond the purview of 
the NHGRI and even that of the whole NIH. Virtually all areas of 
biomedical research, in both the public and private sectors, are deeply 
affected by its availability. Opportunities abound. The doubling of the 
NIH budget came at an essential time, as researchers scramble to 
exploit this new knowledge. The broad approach advocated in the NHGRI 
plan and likely to be reflected in any road map for the NIH will ensure 
steady progress in our understanding of disease and in developing novel 
    But in addition to these initiatives, the NIH should continue to 
search for new goals analogous to the Human Genome Project of 15 years 
ago, goals that catch the imagination, that are of obvious relevance to 
medicine and that focus research for years to come. One example would 
be the sequencing of a large cohort of carefully characterized 
individual humans. We would uncover our evolutionary roots and begin to 
understand at a profound level how sequence variation leads to 
variation in the population, variation in susceptibility to disease and 
variation in many different traits. A project such as this would push 
science and society closer to the goal of using the genome for the 
benefit of all.
    The Human Genome Project required significant adaptations in the 
time-tested procedures of the NIH. But the NIH responded by taking on 
this big, novel effort, initially defining the goals and later assuming 
the oversight role needed to bring the project to fruition. The peer-
review system served us well throughout, allowing many avenues to be 
explored and providing time for the successful technologies to mature. 
Building on its success the NIH is well positioned to take on this next 
complex stage of translating this knowledge for practical benefit.

    Mr. Bilirakis. Thank you so much, sir.
    Doctor Venter, you are on.

                  STATEMENT OF J. CRAIG VENTER

    Mr. Venter. Thank you, Mr. Chairman, it's, indeed, a 
pleasure to be here with my distinguished colleagues that have 
covered so much of the genome field over the last few decades.
    I think of this group I have sort of a unique vantage 
point, in terms of I've been extremely privileged to have close 
to 30 years of federally supported research in a variety of 
capacities, first for 10 years as a university researcher, then 
close to 10 years as an intermural NIH researcher, where the 
unique type of funding in an intermural NIH program is often 
misunderstood, but is probably the best type of funding we have 
in this country. It allows scientists like myself to make 
breakthroughs without having to go through year-long reviews of 
ideas that are more than often turned down in the extramural 
    I left NIH in 1992 to form a new not-for-profit basic 
research institute that has had just the most enviable Federal 
funding over the past 11 years. That's expanded now to a group 
of five 501(c)(3) organizations that I'm representing here 
    That funding has come from almost every part of the U.S. 
Government, much of which is represented here. The very first 
funding we got was from the Department of Energy, and many 
people have not understood the DOE's role in genomics and 
biology, but I think it's becoming clearer as we move into the 
energy field of applying what we are learning in microbial 
genomics to maybe create a new hydrogen economy.
    We've also had wonderful funding from the NIH from the 
Department of Allergy and Infectious Disease, starting back 
with early collaborations with the CDC in the early `90's we 
sequenced the smallpox genome in collaboration with the CDC, 
with Allergy and Infectious Disease funding. That went on 
recently in collaborations with NIH and the FBI, where Claire 
Fraser led a team at TIGR Sequencing as Mr. Brown commented on, 
the anthrax genome, sorting out the difference between the Ames 
strain and the strains that infected people with the anthrax 
    In addition, we've used this funding to sequence almost 
every key human pathogen, including the malaria genome and most 
recently in a wonderful collaboration that initiated at Celera, 
included TIGR and included the public funded labs, the mosquito 
    So, we are at a point where we have the human genome 
sequence, the malaria pathogen, and the Anopheles mosquito 
vector that carries it. We have the ability to look at 
variations in the genetic code of the pathogen of the vector 
and our own genetic code to find new ways to come up with what 
is the No. 1 infectious disease killer of children in the 
world, over 5 million a year from malaria alone, that genomics 
is providing wonderful new tools, and there's already new 
vaccines in development based on this recently published 
    The DOE itself is responsible for funding approximately one 
third of the genomes that have been completed and published to 
date, but we also have funding from USDA and NSF that have been 
the key funders of plant genomics work, and we've also been 
privileged to be recipients of funding from Doctor Collins' 
institute, and we currently have pending a very large grant 
with his institute to help with the goals that, in fact, I 
think Doctor Waterston laid out very nicely. The key to 
understanding the genetic code at this point probably lies in 
comparative genomics.
    We can't read our genetic code. We know what a fraction of 
our genes do, and we have very little understanding of what the 
other 99 percent of the genetic code does. As Doctor Waterston 
said, by looking at comparative genomics, and we have to have a 
very large number of species, mouse was wonderful, but we 
probably need 100 or more different Mamayan and closely related 
and distantly related genomes, using the history of evolution 
to tell us what's important and what's not.
    I think one of the biggest challenges of this next century 
will be the interpretation of the genetic code, so I disagree 
somewhat with Matt Ridley's quote that within a few years we 
will understand the function of all our genes, I wish that were 
so. I don't think there's enough funding in the Federal 
Government or enough scientists to make that happen in the next 
few years, but we should definitely be working in that 
    I think the most important issue is what this committee is 
asking, Mr. Chairman, what are the public health aspects and 
what do we do next. I agree with Doctor Waterston's suggestion 
that we don't let the first two human genomes that have been 
sequenced by the last two human genomes that have been 
sequenced. In my view, the only way that these wonderful 
discoveries will benefit the American public is if we get it so 
each of us can have our genetic code determined and understand 
the differences in our genetic code and how those will lead to 
the prevention of disease.
    We have a chance to transform medicine from reactionary 
medicine to preventative, and the economic benefits of that are 
the only hope we have to dramatically change healthcare costs 
in this country. So, I think in addition to this wonderful 
comparative genomics work that's being funded, we would like to 
see the challenge, and I'm delighted to see it in Mr. Collins' 
testimony, this goal that we jointly have to get to a $1,000 
genome. That's going to take dramatic new technological 
breakthroughs, but if you look at the pace that things have 
changed over the last few years it's very likely within a 
decade, before a baby leaves the hospital they will have the 
opportunity to have their genetic code on a DVD that will be 
used to help decide which diseases they might have prevalence 
toward, and to be able to do something about them in advance.
    Doctor Collins and I have been two of the biggest 
supporters of getting the non-discrimination bill passed, and 
I'm delighted also to see the progress that took place in the 
Senate. It's had, I think, what, over 200 to 300 co-sponsors in 
the House for the last 6 years, I'm delighted to see Mr. Brown 
is one of the co-sponsors of the House bill. I think this is 
the single-most important legislation for affecting the future 
health benefits from the genomic discoveries that have taken 
place and will take place. And, I think this panel and this 
committee could go an awful long way to helping get that passed 
this year.
    I think personalized medicine, not in the way most people 
have thought about it, one drug for each individual, but 
understanding the statistics associated with disease will give 
power to individuals over their health outcomes for the first 
time in human history.
    I look forward to this new era in science. I look forward 
to a positive collaboration with my colleagues in the Federal 
Government, Doctor Collins, Doctor Patrinos and Doctor Fauci 
and others. I think this is the most exciting era in the 
history of science, and I'm, indeed, privileged to be part of 
    Thank you very much.
    [The prepared statement of J. Craig Venter follows:]

   Prepared Statement of J. Craig Venter, President, J. Craig Venter 
                           Science Foundation

    Mr. Chairman and Subcommittee members, I welcome the opportunity to 
testify today before your Subcommittee to present my observations and 
recommendations regarding the continuing Federal investment in genomic 
research. My name is J. Craig Venter, and I am the President of the 
Venter Science Foundation and Chairman of five affiliated nonprofit 
organizations in Rockville Maryland, that are devoted to pursuing and 
supporting genomic research and its impact on the public. They are 
described in the Appendix to my testimony.
    I have been honored to participate in federally-funded research 
from several distinct vantage points: From more than 10 years as an NIH 
grant recipient at universities; nine years as an NIH intramural 
researcher and Laboratory Chief at the National Institute of 
Neurological Diseases and Stroke; and 11 years as the founder and 
president or Chairman of The Institute for Genomic Research (TIGR), a 
nonprofit, 501(c)(3) institution. In addition, for three years out of 
more than a 30-year career in science, I was the President and Chief 
Scientific Officer of Celera Genomics, a private sector company. As 
indicated, I now head a new group of affiliated nonprofit basic 
research institutions devoted to genomic research and public policy. 
Each experience has shaped my current views on the role of the 
Government in supporting the many-faceted science of genomics.
    The science and technology of genomics have become the foundation 
of research in biology in the 21st century. Genomics will play a 
central role in advances in medicine and public health, as well as 
agriculture, the environment, energy and the economy. During the past 
decade, we have made unprecedented strides in genome sequencing--the 
entryway into the genomic era. From the historic decoding of the first 
genome of a living species by my team at TIGR only 8 years ago, we now 
know the genome sequence of more than 100 species, including medically 
important microbes that cause diseases such as anthrax and 
tuberculosis, the parasite that causes malaria, and the mosquito that 
carries it. In 2001, to wide acclaim, two independent teams of 
researchers, both represented here, announced that each had sequenced 
the human genetic code.
    These are profound accomplishments reflecting the cumulative 
efforts of numerous scientists around the world working in diverse 
areas of science, technology and basic and applied research. These 
advances would not have been possible without funding support from a 
wide range of public, private and federal institutions that sponsored 
this revolution in science. Prominent among them the National 
Institutes of Health, the Department of Energy, the National Science 
Foundation, the U.S Department of Agriculture, private not-for-profit 
foundations including The J. Craig Venter Science Foundation and the 
Wellcome Trust in England; and public and private for-profit commercial 
organizations including large pharmaceutical companies, Celera 
Genomics, and technology companies including Applied Biosystems, 
Beckman and Amersham. It is clear to most that we would not have a 
sequenced human genome without substantial private sector involvement.
    We have learned important lessons from genomic research that has 
been undertaken to date, and anticipate even greater advances having 
applications to everything from medicine to energy to Homeland defense.
    But we have even more to learn. I have estimated that 99% of the 
discoveries that will ever take place in biology remain to be made. We 
are at the earliest stages of beginning to be able to interpret the 
genetic code. With very few exceptions, we do not yet have enough 
information to understand which genes in a genome are biologically 
significant and why. We lack sufficient information to understand how 
groups of genes function as an ``operating system'' whose programming 
sometimes promotes health or longevity and sometimes leads to disease. 
As we go forward, however, we can draw some lessons from the past about 
how best to fund genomics in the future, in order to serve the public 
good as efficiently, imaginatively, and inclusively as possible.


    The investment by Federal agencies in genomics research is the 
focus of the hearing today, and I am privileged to be invited to give 
my views about how we should proceed.
    I think that it would be useful to describe the broad support of 
the federal government in funding basic genomic research from my 
vantage point. The not-for-profit basic research institutes that I am 
representing today have had a broad array of federal funding in the 
field of genomics for more than a decade now, and this has included 
funding from the major funding agencies within the United States 
including DOE, NIH, NSF, and USDA. The DOE was the first to fund basic 
research at TIGR dating back to its formation in 1992 and this funding 
included support for the development of the whole genome shot-gun 
sequencing strategy, particularly as it was applied to the study of 
microorganisms relevant to bioremediation and the environment. DOE has 
funded approximately one third of the microbial genomes sequenced and 
published to date. Most recently, the DOE through its Genomes-to-Life 
program is funding our research that will apply shotgun sequencing to 
the study of large, complex environments starting with the Sargasso 
Sea. The DOE is also funding our energy institute, IBEA, to use 
genomics in attempt to sequester carbon dioxide and produce hydrogen.
    The Institute of Allergy and Infectious Disease (NIAID) within NIH, 
has also been a key supporter of genomics research at TIGR for more 
than a decade. Starting with a project at TIGR in 1992 to sequence the 
genome of the smallpox virus, work that was done as part of an 
international treaty, NIAID has been a world's leader in the use of 
genomics approaches to understand and treat infectious disease. As a 
direct result of NIAID funding to my teams, we have the sequenced of 
the genomes of most major human pathogens including those that cause 
tuberculosis, cholera, syphilis, various respiratory infections, 
malaria, and the Anopheles mosquito vector that carries the malaria 
parasite, the fourth largest genome sequenced to date. NIAID, working 
with the FBI and other agencies, has funded TIGR to sequence multiple 
strains of the anthrax bacterium, with the goal being the development 
of a microbial forensics database that will hopefully provide new 
insights into the source of the anthrax attacks that occurred in the 
fall 2001. NIAID has also funded a multi-million dollar Pathogen 
Functional Genomics Resource Center at TIGR that is providing genomic 
reagents, laboratory services, and training to the nation's infectious 
disease researchers.
    NSF has been a major funder of basic research at TIGR in both plant 
and microbial genomics. Beginning in 1996, TIGR was the recipient of a 
multi-year award from the NSF to participate in an international 
consortium to sequence the first plant genome, Arabidopsis thaliana, 
which serves as a model for 250,000 other plant species. This work was 
completed in 2000, four years ahead of schedule. Because of the 
continued strong federal investment in plant genome research, TIGR has 
initiated a number of other NSF-funded, genomics-based research 
programs on important crop species including rice, potato, tomato, and 
soybean. In parallel with these studies are related efforts on some of 
the most important bacterial and fungal plant pathogens that are 
responsible for millions of dollars in losses each year.
    TIGR was one of six centers initially funded by the NHGRI in 1995 
to begin work on the sequencing of the human genome. Recently, TIGR and 
our new state of the art DNA sequencing facility have submitted a $156 
million grant to the NHGRI that is pending review to apply our 
expertise in genomics and our interest in developing novel, more cost-
effective technologies to the sequencing of large, complex genomes.
    Because genomics is the underpinning of virtually all areas of 
biological and biomedical research in the 21st century, it is important 
to every institute within the NIH family as well as to every academic 
and private institution in the world. And, because genomics is a 
uniquely interdisciplinary area of science, its success will require 
imaginative approaches to funding innovative experiments in which 
genomics specialists, biologists, physician-scientists, computer 
scientists, software engineers, and others can work together. Genomics 
will flourish only if we as a nation develop ways to simultaneously 
support large-scale science, as well as studies by small groups of 
innovative researchers working in the more traditional mode.
    If the promise of genomics is to be fulfilled, we need to adapt 
current approaches for peer-review and funding decisions for a new era. 
We'll have to think boldly, increase the community of scientists who 
are part of the decision-making process, pay attention to ideas for new 
technology as well as basic research, and, most important, be willing 
to take a chance on original ideas that could be wildly successful but 
that could also fail. We have to take chances.
    In this regard I want to say how pleased I am to serve on a new NIH 
committee, established with foresight by Director Elias Zerhouni, to 
offer guidance about funding highly innovative, ``out-of-the-box'' 
research proposals throughout the institutes. I applaud Dr. Zerhouni's 
judgment in creating this group and look forward to its success. It is 
a good start to thinking about innovation across the board at NIH, in 
its support of intramural science as well as at academic and nonprofit 
research institutions.
    Now I'd like to suggest six objectives that the Government should 
consider as you contemplate the opportunities and challenges for 
genomic research today.

1. Large-scale genome sequencing should be funded and managed to 
        extract the best value for the American public, in terms of 
        output, innovation and cost.
    This objective is based on the reality that, at the present time, 
genome sequencing is very expensive and requires special expertise. For 
example, at present, it still costs tens of millions of dollars to 
sequence a complete human genome, and hundreds of thousands of dollars 
to sequence all the human genes from one person. We need genome 
sequencers that are the equivalent of personal computers, but we are 
not there yet.
    While the actual sequencing of human and other genomes is the 
backbone of genomic research, the promise of genomics to improve the 
health of individuals will not be achieved until DNA sequencing becomes 
much faster and much less expensive. Going forward, it is critical that 
both the NIH and DOE continue to support innovative projects that 
constantly encourage technological innovation and drive down the costs 
of sequencing. This is a complicated proposition, as many of the 
advances are likely to come from the commercial sector, but the 
government will help create the market that drives the necessary 
innovation, as it has in the past, by supporting large scale human 
    In the medical arena, to enjoy the promise of personalized and 
preventative ``genomic'' medicine, we must compare the genomes of tens 
of thousands of people to better understand the genetic causes of 
complex diseases. And with that understanding, we then might develop 
strategies to prevent or better treat disease.
    My own Foundation has set an ambitious goal: to work toward 
reducing the cost of human genome sequencing to $1,000 per person. The 
Federal government should have a similar goal. This is a massive 
challenge for all of us in technology and bioinformatics, as well in 
genome analysis--one that I think of as ``big science''--science that 
costs a lot to develop, must be highly accurate to be useful, and must 
be scaleable in order to serve the public good. It requires a network 
of centers capable of rapid, mass sequencing, a national resource that 
can be tapped, but does not need to be replicated at every university. 
Indeed, this is an area that might benefit from the DOE model of the 
National Laboratories, modified to the needs of this new science. And 
achieving this price point may well require as broad and diverse a 
collaboration as did the sequencing of the human genome itself.

2. Special attention should be given to the needs of individual 
        investigators who do not have easy access to large-scale genome 
    This objective derives from the recognition that ``genome 
sequencing'' is a basic tool for research critical to the work of every 
NIH institute. We must find better ways to expand the science of 
sequencing to apply genomics across scientific disciplines and 
throughout the NIH. And to encourage innovation for public benefit as 
well as to put pressure on costs, we must allow researchers the freedom 
to use these tools in new and expanded capacities.
    This objective is also based on the importance of giving all of the 
NIH (and Public Health Service) institutes access to major sequencing 
centers. It is becoming clear that we need new strategies to apply 
genomics to ``systems biology,'' and high-risk studies to understand 
the associations between genotype and phenotype. Precious Federal 
resources like the NIH and DOE genomic sequencing programs must be 
aware of, and responsive to, the needs and priorities of a very diverse 
federally funded research community.

3. Rapid, open access to all federally funded genome data so that it 
        can be used freely by scientists throughout the world.
    Access to data funded by hundreds of millions of dollars of Federal 
investment must be available rapidly and openly to the research 
community. It must be made clear that this research is not being done 
for the benefit of the heads of the few centers that receive massive 
federal funding. And, another less obvious, but equally important, 
benefit of this approach is that the availability of these data will 
stimulate advances in associated computing and informatics 
technologies. Users will demand much faster and more stable distributed 
grid systems. This will move us much faster down the pathway of 
integration of multiple research centers and private physicians, and 
ultimately improve the health of the American public.

4. NIH-wide genomics advisory board
    As a significant driver of success, we must decentralize decision 
making about genomic sequencing priorities as much as possible, 
allowing researchers across disciplines to determine what genomic 
sequencing support they need rather than be confined to a current model 
in which a single Institute both develops the relevant tools and 
determines how they should be used and applied. The various institutes 
at NIH that support genomic sequencing and ``applied'' genomic research 
must jointly address priorities and policies that provide the highest 
value. In my own view, genomic sequencing has become a commodity item 
for which the contract mechanism is preferable. I make this observation 
even though my institutions receive federal grants as well as 
contracts, and we have recently applied to NHGRI to for a cooperative 
agreement to become one of a few major sequencing centers. At the 
least, an NIH-wide genomics advisory committee could usefully discuss 
which support mechanisms are preferable for various kinds of programs 
and consider why, for example, NIAID and NHGRI use different funding 
mechanisms for similar genomic sequencing awards. This advisory 
committee, taking advantage of NIH's broad and diverse expertise, might 
take as an initial goal the determination of how best to stimulate 
competition, innovation and cost reduction. Perhaps shorter term 
contracts, regional technology development centers, and other models in 
NIH's funding repertoire should be included in the strategy for funding 
genomics research going forward.

5. Inter-agency genomics advisory board (NIH-CDC-DOE-NSF-USDA-DHS)
    Similar to the foregoing recommendation, a broader inter-agency 
genomics committee, could apply a more diverse experience base and a 
higher level perspective to cost-containment, innovation and research 

6. Appropriate and clear position on patents which remain the basis of 
        the free enterprise system and the avenue through which most 
        basic research reaches application.
    We learned a number of important lessons during the past several 
years during the so-called ``race'' to sequence the human genome. No 
one can seriously disagree about the important role of competition in 
developing and utilizing technologies and sequencing techniques in 
genomics as well as in any other area of biomedical research. It is a 
plain fact that innovation and investment by both the public and 
private sector will be necessary in genomics for the public good that 
we all strive to achieve. Thus, the norm for genomic research going 
forward must be an open and accepting partnership between the private 
sector and public sector.
    We also learned, however, that competition has its negative side, 
as was evident from the ill-will that occasionally developed between 
HGP scientists and their counterparts in the private sector. I, for 
one, regret that. Competition is a useful thing, particularly when it 
is marked by good sportsmanship, and that will be essential to the 
public welfare as we move forward. As one component of that public-
private partnership, each sector must understand their respective 
cultures, funding opportunities and limits, research and product-
development time-horizons and other business realities, like return on 
investment and intellectual property. Patents, for example, do raise 
issues, including one that the Supreme Court has been asked to review, 
as to whether the experimental use exemption applies to nonprofits. But 
the private sector cannot be excluded or disparaged because of its own 
business norms. Genomic research is simply too expensive and ambitious 
an undertaking for our nation not to rely on every worthy contributor 
and potentially useful technique.
Concluding remarks
    We are now at a crossroads in genomic research and must think 
strategically if we are to fulfill the promise of this science. In many 
ways, sequencing has arrived at the point where it's a commodity--a 
tool for which all the applications are yet to be discovered. So our 
challenge, both for government agencies like NIH and DOE and those of 
us in the private sector--whether nonprofit or for-profit, is to 
determine how to use scarce research dollars most effectively to fund 
this technology so that it reaches its ultimate potential.
    To rise to this challenge we must acknowledge and accept that while 
the cultures of industry and academia differ--there is still much to 
gain from collaboration. We must combine the resources of the federal 
government with the innovation and technology development of the 
private sector to advance this science and discover practical 
applications critical to its success.
    We must create an open marketplace for genomics research and its 
applications, encouraging competition and collaboration to reduce 
costs, encourage private sector investment and bring new technologies 
to market.
    I look forward to working closely with this Subcommittee and the 
many teams of accomplished scientists you support. I hope to contribute 
energetically to this cause and lend my support to a new culture of 
collaboration in this crucial field.
    By working together, we will succeed. And society, as a whole, will 
reap the benefits. The approaches I've described above need to be 
integrated across all of NIH and all of biological science, and if it 
doesn't happen the public will be the loser. But if it does happen, we 
will truly embark on the golden age of genomics.


    The Venter Foundation includes five affiliated nonprofit entities, 
three of which conduct basic, scientific research: The Institute for 
Genomic Research (TIGR), The Center for the Advancement of Genomics 
(TCAG), and the Institute for Biological Energy Alternatives (IBEA).
    The Institute for Genomic Research was founded in 1992 with venture 
capital funding and an initial goal to identify as many human genes as 
possible using Expressed Sequence Tags (ESTs)--a controversial, but 
rapid, cost-effective method that I developed while doing research in 
the intramural program at NIH. I left NIH to create TIGR in part 
because, at the time, NIH was not in a position to conduct a large-
scale human gene discovery study within the intramural program. In our 
first two years, we at TIGR used the EST strategy to identify more than 
half of the genes in the human genome. Then, using many of the 
laboratory and computational methods that we developed for the human 
gene discovery program, we pioneered the whole-genome shotgun 
sequencing of the first complete genome of a free-living organisms, 
Haemophilus influenzae, a bacterium that causes ear infections in 
children. Interestingly, an NIH study section said this couldn't be 
done with available technology. Ultimately, this approach became widely 
    In its first decade, TIGR has become one of the leading genomics 
institutions in the world, developing research critical to the fields 
of medicine, energy and environmental science.
    With financial support from the National Institute of Allergy and 
Infectious Diseases (NIAID), the Institute has determined the complete 
genome sequence for forty microbial species, including important human 
pathogens that cause tuberculosis, cholera, syphilis, stomach ulcers, 
anthrax, and malaria.
    In addition, TIGR has also sequenced a wide range of important 
environmental microbes--some of which live in extreme environments but 
may be critically important to the health of the planet--and that carry 
out a variety of interesting metabolic reactions, including degradation 
of cellulose and other organic matter, precipitation of heavy metals 
such as uranium from solution, and production of methane and hydrogen 
as potential new sources of fuel. These are areas relevant to the field 
of bioremediation and are of great interest to DOE.
    TIGR has also played a leading role in the sequencing and analysis 
of many important plant species, including Arabidopsis thaliana, a 
small weed that serves as a model for understanding approximately 
250,000 other more complex plants--rice, soybean, potato, and tomato 
among them. Together, these efforts are helping in the search for genes 
that control the rate of plant growth, yield, and resistance to 
diseases and drought.
    The Institute for Biological Energy Alternatives will use microbes, 
microbial genomics, microbial pathways, and plants as potential 
solutions to carbon sequestration and clean energy production. IBEA 
will work to produce new fuels with higher energy output in an 
environmentally sound manner, thereby reducing the production of carbon 
dioxide. In addition, IBEA will examine removing carbon dioxide from 
the atmosphere by using genomics to enhance the ability of terrestrial 
and oceanic microbial communities to remove carbon from the atmosphere. 
This work also could have a profound impact on the understanding of 
microbial biology and life definitions, as well as a better 
understanding of evolutionary biology.
    The Center for the Advancement of Genomics is dedicated to 
incorporating the results of genomic studies into practical use and 
government policy through scientific and policy-oriented research, 
education, and enlightenment of the general public, elected officials 
and students. A particular focus will be to accelerate the pace with 
which genomics is incorporated into the practice of medicine. To this 
end, TCAG is building formal collaborations with academic medical 
centers to conduct the large-scale research that is the necessary 
foundation of the first fully-integrated genomic medicine practice. 
TCAG will also seek to better understand evolutionary issues, as well 
as broad social, public policy and ethical issues, such as genetic 
discrimination and the role of biology/genomics in mitigating 
greenhouse gas concentrations and biological energy production.
    Indeed, it is because of the vast scope of genomics that TIGR, 
TCAG, and IBEA were created as nonprofit institutions that complement 
one another in their research efforts.
    Each of these entities shares a common need for rapid, accurate, 
and low-cost DNA sequencing. Thus, we established a fourth nonprofit, 
the J. Craig Venter Science Foundation Joint Technology Center, which 
will provide sequencing and informatics support to the research 
institutions. The JTC, which functions as both a resource and 
technology development center, will work collaboratively with a wide 
variety of technology leaders in the private sector, as well as with 
academic and federal scientists, in our work to advance the efficiency 
and lower the cost of genomic sequencing.
    The JTC will utilize the latest in automated DNA sequencing, 
supercomputing, networking, and high performance storage technologies 
to rapidly and accurately sequence and analyze genomes in a more cost-
effective manner. The JTC will have a sequencing capacity of 45 million 
``reads'' per year by late 2003 and an ultimate capacity in excess of 
100 million ``reads'' per year. The JTC will support the DNA sequencing 
needs of TIGR, TCAG and IBEA. A goal of the JTC is to substantially 
reduce the cost of genomic sequencing so that everyone can benefit from 
the great promise that genomics holds.
    The fifth organization, the J. Craig Venter Science Foundation 
provides administrative and legal support for, and coordinates policy 
and research activities between, these organizations. In addition, the 
Foundation explores new ways to foster science education and scientific 

    Mr. Bilirakis. Thank you very much, Doctor Venter.
    Doctor Khoury, you are on, sir.

                   STATEMENT OF MUIN J. KHOURY

    Mr. Khoury. Good morning. I am, indeed, honored and 
privileged to be here with you today, especially with these 
gentlemen on my right-hand side. I must admit I personally or 
CDC had nothing to do with the sequencing of the human genome, 
but I suppose we are here to describe what happens next and how 
we can begin to integrate advances in genomics into disease 
prevention and public health.
    I'd like to describe to you a little bit of CDC's 
priorities in genomics that, essentially, complement and try to 
achieve NIH's vision and put it into reality for the next few 
years. CDC, as the Nation's prevention agency, is working with 
NIH very closely and with many partners, including our State 
and local health, to begin to close this widening gap between 
gene discovery and our ability to use genetic information to 
improve the Nation's health and prevent disease.
    I think we have a long way to go to help translate gene 
discoveries and to figuring out what genes mean for health and 
disease in real communities and real time and, perhaps, more 
importantly, how we can use that information and what its 
value-added is going to be for the factors of disease 
prevention and to improve the health of our citizens.
    CDC has developed three priorities for applied genomics 
research that I'd like to tell you about briefly, and they 
directly tie with prevention programs that already exist at the 
State and local levels.
    First, is assessing how genomic factors influence 
population health. CDC uses epidemiologic studies to examine 
the impact of genetic variation on health and disease in real 
communities, and how such variation interacts with 
environmental causes of disease, such as infectious agents and 
environmental factors, which are the usual target of public 
health interventions. Integrating genomics, for example, into 
the acute public health response, (for example investigation of 
infectious disease outbreaks, will be a critical challenge. 
Genomics, undoubtedly, will provide new incites into why some 
people will get sick, but not others given the same exposures. 
And, this information will be more and more essential to target 
interventions to reduce the burden of disease in the 
    The second priority will be in assessing the public health 
impact of genetic tests for screening and prevention. CDC is 
providing a public health assessment of genetic tests with a 
special focus on screening. The recent direct-to-consumer 
marketing of genetic tests for breast and ovarian cancer is the 
first such effort to increase awareness of genetic testing in 
an entire community. CDC is assessing changes in women and 
health professionals' knowledge, attitudes and behaviors toward 
genetic testing. This kind of public health assessment will 
give timely information on genetic tests that will help guide 
policy and practice. It will show what information is working 
and what is not working, as we all try to examine the 
transition of genomics from research to practice.
    The third area of priority is assessing family history as a 
tool for prevention and public health. Advances in genomics 
have highlighted family history as one of the most exciting, 
but under-utilized, areas in public health. All of us have the 
family history of one or more diseases in our relatives. This 
family history, for the most part, reflects combined effects of 
numerous genes, along with many shared environmental factors, 
such as diets and behaviors. And, the bottom line is, for most 
diseases we are at increased risk of what runs in our families. 
Family history then may be useful for stratifying risks and 
developing early disease prevention messages.
    In 2002, CDC, along with NIH and others, initiated a public 
health effort to develop and evaluate in the community family 
history tools starting with four common chronic diseases, heart 
disease and stroke, diabetes and colorectal cancer.
    We expect that a fully developed and implemented applied 
genomics research agenda with these three priority areas will 
begin to produce practical information that would lead to the 
integration of genomics into community prevention programs that 
actually work.
    In addition, to develop public health workforce competency, 
CDC keeps responding to State and local requests for training 
and technical assistance. For example, we've established three 
centers for genomics and public health at three schools of 
public health, to prepare professionals for genomics in the 
21st Century.
    In closing, public health assessment and research will 
assess the ability and impact of genetic information in 
practice in the real world. It will ensure that all segments of 
the population will benefit from new genetic knowledge.
    If I may elaborate a little bit on the wonderful image of 
the genomics building that Doctor Collins showed us earlier, 
truly the success and functionality of this building will 
depend on the foundational infrastructure of what's already 
happening in health care and public health systems, including 
the flow of essential utility like gas, power and electricity. 
With that we can make this building work in real life.
    And, it's part of the crucial work that CDC and many 
partners, including State and local public health, must do in 
order to get this building up and running on a daily basis. 
This work is essential to close the widening gap between gene 
discovery and the ability of genetic information to improve the 
Nation's health and prevent disease.
    Thank you for your attention.
    [The prepared statement of Muin J. Khoury follows:]

  Prepared Statement of Muin Khoury, Director, Office of Genomics and 
    Disease Prevention, Centers for Disease Control and Prevention, 
                Department of Health and Human Services

    Good morning. I am Muin Khoury, Director of CDC's Office of 
Genomics and Disease Prevention. I want to thank you for the 
opportunity to discuss CDC's role in integrating advances in genomics 
into disease prevention and public health. I will describe CDC's work 
in translating discoveries in genomics into improvements in public 
health that complement NIH's genomics research agenda. In this genomics 
era, we need the entire research continuum, from gene discovery to 
development of practical tools, for integrating genomics into 
population-based disease prevention programs. In this context, the 
applied public health research at CDC will evaluate what genes mean for 
health and disease in real communities in real time and, as 
importantly, how genomic information can be used to improve the 
public's health. (1)
    CDC, the nation's prevention agency, is keen on integrating new 
genomic knowledge into public health strategies through training of 
public health professionals, education, and information dissemination 
to the public. CDC activities encompass a large array of topics such as 
acute communicable diseases investigations and developing prevention 
programs for common diseases like diabetes and asthma. In anticipation 
of the impact of genomics on all aspects of health, in 1997, CDC 
developed a strategic plan and formed the Office of Genomics and 
Disease Prevention (OGDP) to help integrate genomics into public health 
research, policy, and practice at the national, state, and local 
levels. (2) Over the past 6 years, the Office has provided national 
planning and assistance and has developed partnerships with other 
federal agencies including NIH, public health organizations, 
professional groups, and the private sector. CDC has initiated a number 
of public health research projects to assess the impact of genes on the 
risks of chronic diseases, birth defects, and infectious, 
environmental, and occupational diseases to specific populations. On 
May 5, 2003, CDC held a symposium on Genomics and the Future of Public 
Health to take stock of the great accomplishments in genomics, and to 
look at how we can best use these accomplishments to maximize their 
public health benefit. (3)
    Applied public health research in genomics is critical to building 
disease prevention capacity and programs at the state and local levels. 
In consultation with our partners, CDC has developed 3 priority areas 
for applied public health research in genomics that will be essential 
in the next 3-5 years. (1) As I tell you about each of these 
priorities, I will also highlight some of the ongoing collaborations 
with the NIH in these areas.

1. Assessing how genomic factors influence population health
    CDC uses epidemiologic studies to examine the impact of genetic, 
environmental, and behavioral interactions on population health. 
Integrating genomics into the acute public health response, (for 
example investigation of infectious disease outbreaks, toxic exposures, 
or adverse events following vaccination) is a critical challenge for 
public health. Genomics can provide new insights into why some people 
but not others get sick from certain infections, environmental 
exposures, and behaviors. Knowing who will or how many are more likely 
than most to get sick is useful to targeting behavioral or 
pharmaceutical interventions and reducing the population burden of 
various diseases. Understanding the population prevalence of the 
thousands of genetic variants in different population groups and 
geographic locations and their associations with health and disease is 
crucial for planning screening programs and guiding future research. A 
CDC-wide team recently identified more than 50 genes of public health 
importance (e.g. genes involved in metabolism of cancer-causing 
chemicals, and those involved in nutritional factors like folic acid) 
and has proposed measuring population variation of these genes from 
stored DNA samples collected during the third National Health and 
Nutrition Examination Survey (1988-1994), a national representative 
sample of the US population. (4) This work is planned in collaboration 
with NIH. Understanding the prevalence of genetic variability in the 
population for these genes is crucial for public health program 
planning and future research.

2. Assessing the public health impact of genetic tests for screening 
        and prevention
    CDC is evaluating the use of genetic tests as tools for disease 
prevention. Population screening, a traditional public health interest, 
requires special attention in this rapidly evolving scientific, social, 
and legal context. The recent direct-to-consumer marketing of genetic 
tests for breast/ovarian cancer is the first of many commercial efforts 
to increase consumer awareness about the potential value of genetic 
tests in health care or disease prevention. CDC is exploring 
collaboration with the industry developing these tests to determine the 
current level of utilization as well as knowledge, attitudes, and 
behaviors of consumers and health care providers. A population-based 
approach in collecting valid clinical and laboratory data will ensure 
that consumers, practitioners, and policy makers have access to timely 
and current information on genetic tests in the real world and their 
impact on the public's health. These efforts will also allow a smoother 
integration of validated genetic tests into practice. One example of 
these efforts is a 1997 expert panel workshop jointly held by NIH and 
CDC to explore issues around population screening for iron overload due 
to hereditary hemochromatosis, including the cost effectiveness of 
screening for this condition. (5) This collaboration led to the 
identification of important gaps in research about this condition, some 
of which are currently being addressed by NIH-funded research. As new 
research findings emerge, CDC will continue to translate scientific 
knowledge into useful and effective public health strategies, such as 
its physician training program that promotes family-based detection of 

3. Assessing family history as a tool for disease prevention and public 
    Family history of disease can reflect the interactions of multiple 
genes with many risk factors such as diet and behaviors. Although 
family history is routinely collected in health care encounters, it is 
inconsistently used to guide individual health care and disease 
prevention. In 2002, CDC initiated an interdisciplinary public health 
research effort to develop and evaluate family history as a public 
health tool for identifying families at increased risk of common 
chronic diseases and intervening to prevent disease by effecting 
positive changes in health behaviors. (6) A large proportion of the 
population has family histories for one or more of the common chronic 
diseases where people are at increased risk for these conditions as a 
result of shared genetic, environmental, and behavioral factors. A 
multidisciplinary working group from CDC, NIH, academia and 
professional organizations is developing a prototype family history 
tool for use in assessing adult risk of several common chronic diseases 
(including heart disease, diabetes and colorectal cancer). This tool 
will be tested and refined through a series of pilot studies in a 
variety of community settings. Ideally, it will be used to reduce the 
burden of chronic diseases by providing personalized risk reduction 

Concluding Remarks
    A recent report by the Institute of Medicine identified genomics as 
one of the eight cross-cutting priorities for the education of all 
public health professionals in the 21st century.(7) In addition to 
public health research on genomics, since 1997 CDC has been promoting 
the integration of genomics across all public health functions 
including training and workforce development. In collaboration with 
many partners, CDC developed public health workforce competencies in 
genomics (8), established 3 Centers for Genomics and Public Health at 
schools of public health to develop training and provide technical 
assistance to state and local health departments (9), and is actively 
engaged in offering training and career development opportunities in 
genomics and public health (10). As public health programs become 
increasingly capable of using genomic information in preventing common 
diseases, CDC is committed to sustaining research that ensures the 
integration of genomics and family history into prevention efforts at 
the state and community levels.
    In closing, as we enter the genomics era, CDC realizes the 
importance of research that answers practical questions about the 
utility of new science for the public's health. A balanced research 
portfolio in genomics, from the test tube to public health research in 
the ``real'' world, is essential. Public health research allows the 
nation to have a ``reality check'' on how genetic information is being 
used in practice and ensures that all segments of the population will 
benefit from new genetic knowledge. The translation from basic research 
to the more directly applied research by CDC allows us all to 
capitalize on the phenomenal achievements of the Human Genome Project 
to improve health and prevent disease for citizens of the 21st century.
    Thank you for your attention. I will be happy to answer any 
questions you may have.

    Mr. Bilirakis. Thank you very much, Doctor Khoury.
    Well, I will start the questioning. I can't tell you how 
pleased I am to at least hear you talk, hopefully, of what 
reflects the real world and what's happening out there, of the 
cooperation, the collaboration, to use some of your words, the 
interaction and what not, that takes place among all of you 
and, hopefully, that reflects what truly takes place, not only 
at your level, but at every level of the research community.
    Let me ask first that question. Is that true, is that a 
true assessment on my part? Are there any problems? I mean, 
isn't there--politics exists everywhere, I always say that 
probably the least bit of politics is in Washington, DC, 
because we all kind of know each other, we all have labels and 
things of that nature, which the politics that takes place in 
our real world, such as in our churches, in our clubs, in our 
families and what not is amazing, and sometimes I think it's 
much, much worse than what takes place up here. We usually get 
along pretty well.
    But, so from a politics standpoint, from a competitive 
standpoint, are there problems out there, and if there are, is 
there anything that we can do to help out in that regard? Or, 
is everything honky dory, as you seem to make it?
    Mr. Collins. Let me start. I think that in general things 
are in very good shape, Mr. Chairman, and I think one of the 
main reasons for that is that the interactions between our 
respective agencies occur at all levels, and they are primarily 
based upon scientific opportunity.
    In my experience over 10 years, having this incredible 
privilege of overseeing this international project, to sequence 
the human genome, the reason it worked is because the 
scientists at every level, from the principal investigators, to 
the technicians working at the bench, to the funding agency 
heads, all believed in this as a goal that was extremely 
compelling from a scientific perspective and a public health 
perspective. And, I've often reflected what might have 
happened, for instance, on the international scene, if the 
effort to sequence the human genome project had been imposed 
upon the scientific community by, say, their ministers of 
health and ministers of science. I'm not sure it would have 
worked out so well, because it really was a bottom-up, 
grassroots enterprise, and it was based upon science and a 
shared sense of the vision. It worked remarkably well.
    Now, I won't tell you that there was always pure harmony in 
our weekly conference calls 11 on Friday mornings, there were 
often some jitters and bruised feelings about this or that, but 
there was never any wavering from the sense that we were in 
this together, the stakes were very high here, we had to 
succeed. Failure was not an option, and that came up out of the 
scientific vision and passion that everybody felt. I think that 
has characterized the way in which we've interacted with the 
Department of Energy, my friend Ari Patrinos and I live very 
close to each other in the same group of townhouses. We have 
breakfast at the Silver Diner on a regular basis that nobody 
else gets to go to.
    Mr. Bilirakis. Owned by a Greek probably.
    Mr. Collins. But, we do, in fact, I think on a regular 
personal individual level, make sure that things are on track.
    I was just at the CDC a few weeks ago for a wonderful 
symposium they had on genomics, spoke with Doctor Gerberding 
about our shared vision of this future for genomics in public 
health, again, person to person, talking about the science, 
that works really well.
    Mr. Bilirakis. Did Doctor Collins reflect, basically, the 
viewpoint of the rest of you? This is your opportunity to, 
basically, you know, tell us and tell the world if you've got 
any problems there or whatever.
    Mr. Venter. I think we'd be remiss not to point out that 
competition plays a very healthy role in almost every aspect of 
our society, and the scientific community is certainly not 
immune in any way from that.
    And, I think competition in genomics has probably resulted 
in us having the genome sequence today instead of at the end of 
this decade, and so it certainly benefits the public at large. 
I think a lot has been made in the press about the so-called 
competition between Doctor Collins and myself, but I certainly 
applaud Doctor Collins, and particularly our referee, Doctor 
Patrinos, who with pizza and beer diplomacy led to wonderful 
cooperation and timed simultaneous publications in this field.
    I think competition needs to be encouraged to move things 
faster, to lower cost, to make sure that Federal programs don't 
get stagnated, and I think all that needs to happen is to make 
sure that that competition is truly open and productive. And 
again, I applaud Doctor Collins for recently opening up the 
competition on the Federal grant cycle for new genome centers.
    So, I think we are very much moving in the right direction. 
Nothing is ever rosy in any group, but I think competition is 
probably the most healthy thing we have in this country.
    Mr. Bilirakis. Yes, Doctor Khoury.
    Mr. Khoury. I'd like to echo what Doctor Collins said 
earlier. I mentioned earlier that CDC had, essentially, no role 
in the human genome project thus far.
    Mr. Bilirakis. Yes.
    Mr. Khoury. But, we alwaysI mean, since the formation of 
our office in 1997 we've maintained and continued an active 
dialog with NIH and several other agencies. We held to gather 
national conferences on genomics and public health, actually, 
we had three of them so far, and as we embark on the next phase 
I see that there will be increased cooperation and 
collaboration and more synergy after the completion of I guess 
the end of the beginning, or the beginning of the end, whatever 
you said, Doctor Collins, from here thereon we are going to 
translate together what it means for real people and real time, 
and that I expect will occur.
    And, as Doctor Collins mentioned, he's had active 
discussions with our boss recently, and will continue to have 
    Mr. Bilirakis. Because all of the great work that they do, 
and their people do and others like them do, if it isn't used, 
if it isn't put to real use to help people, you know, what good 
is it, I suppose is one way of looking at it. Isn't that right, 
Doctor Khoury?
    Mr. Khoury. Right.
    Mr. Bilirakis. And so, you feel that you see CDC and other 
departments, and agencies, and offices and what not, which 
directly deal with, you know, our people, are able to put these 
into use. You have great cooperation in that regard.
    Mr. Khoury. Yes, I hope so, I mean that's, to me, the 
ultimate goal of what we are doing here, is to put into action 
all that great science, and it really has to be built in on a 
platform of already existing prevention services and public 
health approaches in what we do. And, we have to together 
evaluate the value-added of what it means, and how and when 
it's going to change the way we do business and the way we 
promote chronic disease prevention, for example, or investigate 
infectious disease outbreaks, to name a few.
    Mr. Bilirakis. I have a couple more things, and I'm just 
going to defer at this point in time and announce, for those 
who have been here, Ms. Capps, Mr. Green, Ms. Eshoo, if she 
returns, we will have a second round if anybody is interested 
in doing so. But, I would now yield to Mr. Brown.
    Mr. Brown. Thank you, Mr. Chairman.
    I want to thank both Doctor Collins and Doctor Venter, 
without the intervention of referee Patrinos, for your comments 
on the non-discrimination, the genomic non-discrimination 
issue. Thank you for your support on that, and I hope the three 
of us, and many beyond, can work on that together. Thank you 
for that.
    I wanted to talk about something that hasn't been brought 
up, that I would expect especially Doctor Collins and Doctor 
Khoury might have thoughts about, with their involvement with 
NIH and CDC, the issue of antibiotic resistance, the whole 
antimicrobial resistance, antiparasitic resistance, 
antiretroviral resistance. There are, obviously, it's a growing 
problem, obviously, in this country, and domestic health and 
international health, domestic health especially with staph 
infections, strep, other diseases that can, ultimately, be life 
threatening certainly international, probably the biggest 
problem is what's happened with tuberculosis, as you know, 
where in the Russian prison system where I visited 10 percent 
of Russian prisoners have tuberculosis, 25 percent of those 
have multi-drug resistance tuberculosis. Would the two of you 
especially, because we have charged CDC and NIH to participate 
in an interagency task force on antimicrobial resistance, and 
we have come forward with more ideas about how to deal with 
this issue, we clearly don't have enough new antibiotics, new 
powerful antibiotics in the pipeline, where does your work come 
together? Is there some synergy with those agencies, coupled 
with what's happening with the Human Genome Project, and can we 
see, can we expect to see some synergy there that could help us 
deal with this more quickly and more optimistically, perhaps, 
than we are today?
    Mr. Collins. So, I will start, and, yes, I think that's a 
very important subject, and one where genomics does have a lot 
to contribute. I will say at NIH my colleague, Tony Fauci, is 
the lead in this particular arena, as he directs the National 
Institute of Allergy and Infectious Disease, and is the major 
source of funding for sequencing of microbial genomes and the 
application of that information to try to understand resistance 
and to develop new antibiotics.
    But, I think that, this topic in fact, is a major reason 
for excitement about the field of genomics as applied to 
pathogens. Doctor Venter already mentioned the example of 
malaria, where here we finally have the genomes for the 
culprits, and we can, therefore, begin to design, in a very 
intentional molecular way, the strategies for the future.
    We have the genome of mycobacterium tuberculosis, the agent 
of TB. I've worked in Africa as a volunteer physician, and the 
ravages of that disease in parts of West Africa are truly, 
truly distressing, and we don't have good drugs in that 
circumstance that take care of the disease quickly enough, and 
there's a lot of resistance, as you well know, in that 
circumstance as well, because of inadequate treatments leading 
then to the spread of partially resistant strains.
    So, I believe between NAIAD and CDC there is a very strong 
recognition and a determination to do something about it, of 
this problem. The information provided by understanding the 
full instruction book of pathogens, from staphylococcus on down 
the line, provides us with new insights into ways to interfere 
with their growth and, therefore, design new antibiotics that 
are totally different than the ones we currently have, many of 
which, as you point out, are not as useful as they used to be 
because of the resistance problem, but we have to continue to 
work very hard to stay ahead of the curve in this rapidly 
developing, worldwide problem of antibiotic resistance.
    I think we have a good set of tools and a good strategy, 
but it's going to take a lot of work, a lot of hard research, a 
lot of funding.
    Mr. Khoury. Thank you for the question.
    To echo Francis' remarks, the CDC has taken the issue of 
antibiotic resistance very seriously, and there is the 
counterpart to the NIAID. We have at least two centers that 
deal with infectious disease issues.
    And so, I think from the perspective of the discussion 
today and our involvement in developing general tools that 
could be used for genomics in public health, we have, for the 
most part, at least the discussion that I mentioned earlier, 
focused on the human genome and the genetic variation in 
people, but it's, basically, the bug genomes that have to be 
dealt with as well.
    I mean, you mentioned earlier, Francis, the 
characterization of the SARS virus very quickly, and those 
things have to be taken into account together, because 
eventually it's genome versus genome, and antibiotic resistance 
may be one of those mechanisms that the genomes are adapting to 
our genome.
    And so anyway, to get to the specifics of what CDC is doing 
in antibiotic resistance I will have to confer with the leaders 
of that effort at CDC and get back with you on that.
    Mr. Venter. I think the issue you raised is one of the most 
important healthcare crises we are facing right now, not only 
in this country but worldwide.
    Our team has decoded most of these pathogen genomes, and in 
every single one we found a novel mechanism of how they 
constantly evolve in real time to avoid our immune system and 
to develop resistance against our antibiotics. So, we have to 
have a continuing warfare against them.
    We made the mistake in this country at the end of the `60's 
of saying we've won the war against antibiotics, and microbial 
departments shut down around the country, as did funding. We 
are now spending more, actually billions of dollars, just for 
drug resistance staph aureus, that's almost as bad as the pre-
antibiotic era. And, in the midst of this crisis we have our 
major pharmaceutical companies shutting down their 
antimicrobial groups, laying off their entire teams, because 
these are short-term, acute products, not the long-term chronic 
ones they need.
    I absolutely applaud what the President is doing with the 
initiative, with the bioshield initiative, because that's 
providing at least a unique type of incentive for biotech and 
pharmaceutical companies to try to develop new vaccines, new 
antibiotics, new antivirals.
    While I'm very discouraged and pessimistic of what I see on 
that side, the genomic side of what we do see also gives us 
hope. I think the best example of this is the collaboration 
that TIGR had with Kyron Corporation to develop a new vaccine 
against meningitis, within the same time period of less than a 
year that it took to sequence that genome we, with the Kyron 
team, found several new self-surface antigens that turned out 
to be very susceptible for antibody development, and there's 
now two new vaccines in clinical trials. It's the fastest, from 
start to clinical trial, vaccine development to date.
    And so, genomics can that us in that direction, but somehow 
our major healthcare companies are abandoning it, in part 
because of liability issues, in part because they don't see the 
right profits there, so nobody has incentive to do something 
about tuberculosis. We have very little incentive in this 
country to do something against malaria, those are 
thetuberculosis is the biggest infectious disease killer of 
adults in the world.
    So, genomics can help with the answer, but only if there's 
the infrastructure to deal with it, and we are losing it very 
    Mr. Waterston. Yes, I think of it in this larger context of 
the long-term struggle that we are in with the microbial world. 
This is an arms race between us and microbes, and genomics, not 
only gives us the hope that we can understand the particular 
susceptibilities of pathogens, but we can also understand our 
own defense mechanisms against those.
    And, by this integrated approach to understanding how we 
can fight these pathogens, we should be able to come up with 
much more effective strategies. But, it is a long-term 
approach, and it's not going to be something that is going to 
turn around things immediately.
    Mr. Bilirakis. Mr. Green.
    Mr. Green. Thank you, Mr. Chairman.
    Doctor Khoury, in your testimony many of the illnesses you 
talked about, for example, that you work on at CDC, are either 
caused or exacerbated by behavioral factors. For example, we 
know that tobacco use causes a host of health problems, 
including cardiovascular, lung and certain cancers, and 
elevated blood pressure and others. Additionally, we were 
troubled by the recent article in Health Affairs indicating the 
cost to treat obesity related to illness now was equal to that 
of tobacco-related illnesses. All this occurs despite the fact 
that as Americans we've known for decades that smoking and 
sedentary lifestyle and poor diets are unhealthy.
    I appreciate the knowledge that risk factors may encourage 
individuals to change their behavior, but certainly with the 
obesity and overweight problem in our country that doesn't seem 
to be the case. Certainly, there are genetic influences in 
these cases, and I know certain individuals are predisposed to 
certain conditions, but behavior does play a part in these 
    How can genomics research affect human behavior, and aren't 
lifestyle factors always going to be a problem, even if we do 
inherit our genes?
    Mr. Khoury. Thank you for this question.
    Actually, this is a very pertinent question, because as I 
mentioned earlier the traditional public health routes of 
intervention have been not on the genomic side, except for the 
bugs, but on the environment side, which means behavioral 
change, diet, exercise, putting fluoride in the water, et 
cetera, et cetera. And, I think the genomics era is opening up 
the possibility to understand the whole domain of gene 
environment interaction, or gene behavior interaction, or gene 
infectious disease interactions, in order for us to do better 
on the environmental side. Let me be a bit more specific.
    Our family history initiative, for example, one of the 
three areas I talked about, essentially, builds on what the 
existing messages are for disease prevention, physical 
activity, diet, seek, you know, preventive testing for 
colorectal cancer early on, and we know as society we have our 
traditional one-size-fits-all public health messages has only 
given us partial success so far. Two thirds of the population 
are still overweight or obese, only 20 percent of people 
exercise daily, and the statistics are really not in our favor.
    So, family history, the way we conceived it, was an 
additional tool to target and personalize the prevention 
messages to people who need them. That doesn't mean our 
traditional public health messages should stop, on the 
contrary, but for a substantial fraction of the population that 
is at high risk because of the genes that they have inherited, 
although we don't know what they are yet, and we probably can't 
measure them for at least a few years, part of the public 
health approach we are developing is developing those tools 
that would be used in community settings to change behaviors 
and personalize the messages on seeking appropriate early 
interventions and physical therapy, and it's not going to be 
easy because behavior modification is very hard to do, and no 
amount of genomics is going to cure that in a hurry. So, there 
is a long way ahead of us.
    Mr. Green. When scientists talk about populations when 
discussing genetic distinctions within various diseases, what 
should we be looking for as paradigms we should have in mind in 
assessing genomic and prototomic advances so that we know 
whether appropriate distinctions are made, again, dealing with 
these special populations?
    Mr. Khoury. I'm not sure I understand the question, what do 
you mean by that?
    Mr. Green. Is there an effort that's being done with--well, 
for example, racial or ethnic differences in these special 
    Mr. Khoury. Our population approach at the CDC, to 
understand the distributional genes in the whole population and 
the various groups, essentially, focuses and treats all the 
populations in a way that will give us enough statistics and 
information to generalize the intervention messages to 
appropriate groups. For example, the M. Haines Project that is 
in my written testimony, which is a national representative 
sample of the U.S. population and all the ethnic groups in it, 
essentially, will lead to information that's generalizeable on 
the prevalence of important genes that may be relevant to a 
wide variety of diseases.
    So, our approach is, essentially, to understand what's 
going on in the whole population and then try to deliver the 
interventions that work for everybody.
    Mr. Green. Thank you, Mr. Chairman. I know I have brief 
time left, and I'd like Doctor Venter or Doctor Collins to 
respond if possible.
    Mr. Bilirakis. Oh, by all means. I know Doctor Venter has 
been trying to get your attention, too, so you have the time.
    Mr. Green. I'd like to have a response from him.
    Mr. Venter. Well, I'd just like to add a little bit to the 
comments that were made. I think the partial answer to both 
your questions get down to what we define as personalized 
medicine. I can give you a case history of one, and I think 
when we give people sort of very generalized information that 
you should lose weight, or you should exercise more, we all 
know that, but people who smoke, for example, look for the 
exception of the 100-year old three-pack-a-day smoker and say, 
see, there's really no correlation.
    I think understanding our own direct genetic predisposition 
for some diseases takes it from the general to the specific. In 
my own case, I knew I had a very strong family history of heart 
disease, but until I learned from looking at some aspects of my 
own genetic code that I had genetic changes where I could see a 
very specific risk factor, did I start to take it much more 
    So, I think going from general information that we have 
down to the specific individuals, it may not be a panacea for 
everybody, but quite often after somebody has a heart attack 
they have much more incentive for exercising and eating right, 
maybe we can move that forward a few steps and get it from 
looking at the genetic code.
    On the race issues, I think this committee, this panel, 
would certainly probably agree that, both Doctor Collins and I 
have commented on it extensively, we don't think race is a 
scientific concept, it's a social concept, and so this attempt 
with categorization based on census categories to applying that 
to drug responses we think is a very dangerous trend. And 
again, as you get down to individual medicine, what we want to 
know are the group categories that would indicate a response to 
a drug or a treatment, not somebody's skin color where we doubt 
that there will be any correlation whatsoever.
    Mr. Collins. If I could just expand briefly on that. I 
agree that we need to be very careful in using racial 
designations as if they had strong biological context and 
significance. At the same time I think we are all deeply 
disturbed about health disparities, for instance why is it that 
prostate cancer occurs at a higher frequency and with greater 
lethality in African American males than it does in Japanese 
males? Why is it that diabetes is so common in the Pima 
    One should not assume by that observation that that means 
it is somehow hard wired into DNA. It could well be that a lot 
of the health disparities that we observe are related to other 
things that are in the environment, among which are, of course, 
diet, cultural practices, socioeconomic status and access to 
healthcare. They are all in there.
    So to point the finger at DNA is probably a mistake at the 
onset. At the same time, we do know that there are some 
variations in DNA that tend to occur at a different frequency 
depending on where your ancestral geographic origins happen to 
be. And, it may be that some of those variants will account for 
some part of those health disparities and we need to learn that 
as soon as possible if we are going to apply this sort of 
personalized and benevolent medical care to everyone.
    But, I think of race as a surrogate, for a surrogate, for a 
surrogate, in terms of what we really want to know. What we 
really want to know is what are those individual variants in 
your genome or mine that place us at risk for illness and that 
might have an effect on whether we respond well or badly to a 
drug intervention. That is very poorly reflected by the Census 
designations of race, very poorly, but it's not a complete 
disconnect, there may be a weak correlation there which may be 
why people are making claims of this sort.
    We need to, as quickly as possible, move beyond this blurry 
and potentially stigmatizing and misleading information based 
upon race to the precise genetic information which is going to 
be medically more valuable and also much less likely to add to 
the prejudicial aspects that all too often color the 
conversations about race and health, or race and anything else.
    Mr. Green. Thank you, Mr. Chairman. I appreciate, again, 
representing a district that's predominantly Hispanic and the 
concern about diabetes and a host of other things in a Hispanic 
community, it's good to know it may not be genetic based, but, 
obviously, cultural, environmental, and that's something we can 
deal with.
    Mr. Collins. We need to figure that out.
    Mr. Green. Mr. Chairman, thank you again. I'd also like to 
join my colleague in thanking Doctor Venter about the most 
important legislation is the deal with the genetic 
discrimination issue that's out there, and, hopefully, we'll be 
able to deal with that this session.
    Thank you.
    Mr. Bilirakis. Ms. Capps.
    Ms. Capps. Ditto on the genetic discrimination. I'm on the 
bill as well.
    I'm sitting here looking, Doctor Collins, at your 
structure, and the Human Genome Project at the foundation to me 
feels, in this discussion, as like the floodgates, and that it 
kind of is, what's now, and I know it's already, what's next is 
already happening, and has been happening for a long time.
    Maybe I'm going to betray my vitae, but I would like to 
hear from you, Doctor Collins, well from anyone actually, and 
maybe all of you, on how the decisionmaking process, in terms 
of choosing or going the next step after the gate, after coming 
out of the starting gate, research as kind of ethical 
decisionmaking, we can't do everything, at least not all at 
once, and what guides you, both in NIH and then from the 
public/private sector as well, and from the teaching 
facilities, perhaps, as well.
    I'll give you one example of where I was participating in 
this body that I work in, in terms of some decisionmaking 
regarding stem cell research and therapeutic cloning, where I 
think we just totally went ideological without understanding. 
And, I guess I bring that example up because I think we need, 
in this body, a lot of guidance because we are going to be 
related to your decisionmaking process in terms of how we 
allocate funding, and I take that really seriously.
    With Parkinson's, I hear Shared talked about drug 
resistance, and, you know, there are ethical decisions that are 
at the basis of this, and I guess I'd really be interested in 
how you do and how we should make some decisions in that arena.
    Mr. Collins. Thanks for the question, Congresswoman Capps. 
I think you are absolutely on target, that we have to be very 
explicit and careful about how we set the priorities for the 
next phase, because saying that now the floodgates have opened 
up and we have all sorts of opportunities is both an incredible 
blessing and a historic moment, but it's also a great 
    We knew many months, many years ago, that we would, if all 
went well, finish the goals of the Human Genome Project, which 
have directed our efforts since 1990. Not wanting to get to 
that finish line and sort of look around and say, ``oh, gosh, 
what are we going to do next,'' we, in fact, have been planning 
for that for several years in a very formal planning process to 
lead up to this vision for the future, which is a science-
based, priority-setting exercise. It began just about 2 years 
ago in the summer of 2001.
    We convened, over the course of those 2 years, a series of 
about 14 separate workshops, some of them on specific topics, 
like what can we do now to understand the variation in the 
human genome that influences disease risk, that was one of them 
that was particularly interesting. What could we do now about 
proteomics? What could we do now to expand and accelerate the 
rate by which we go from gene discovery to drug treatment 
development? How can the academic sector participate in that in 
a more vigorous way?
    In the midst of all those specific topic discussions, we 
also had a large meeting, about a couple hundred people, at the 
beginning of the process and another near the end, to take the 
temperature about whether we were getting it right from all of 
these inputs. All told, some 600 or more scientists, both from 
the public and the private sector, and both from the U.S. and 
abroad, dropped everything to come to these meetings, and we 
rarely got turned down by anybody who was invited to come and 
be part of this process, because they were all excited about it 
and appreciated its importance.
    Out of that process we originally prepared a draft of this 
document. It was presented in a public meeting to a couple 
hundred scientists back in November. They liked a lot of it, 
they hated some parts of it, so we tore those parts up and 
rewrote them. We depended upon our own advisory council, a 
distinguished group of senior scientists, for input in this, 
and, ultimately, the final draft then got recirculated to all 
of the major leadership of the last two or three major 
gatherings, until they were happy with it, and then it was 
published in a very visible journal for all the world to see 
this past month.
    So, I think as planning processes go, this one was pretty 
thorough. It also involved every single one of the other NIH 
institutes, they all had major participating roles in the 
definition of what the priorities should be, because we wanted 
them not to look at this as our document from the Genome 
Institute, but their document that would guide their priority 
setting as well, and we had multiple involvement from other 
agencies as well, from the Department of Energy, from the CDC, 
from NSF, from USDA, all of whom had a chance to put in their 
dibs in terms of what they thought the priorities ought to be.
    Now, this is not going to be a document that just sits 
there to guide us for the next 10 years. We will have to 
revisit this on a very regular basis, because things change so 
quickly. But I do think from a scientific perspective, a 
medical perspective, and, yes, even an ethical, legal, social 
and policy perspective, this document aims to accomplish what 
we are asking for, and I'm pretty confident that we have 
captured in that process for human health the areas that we 
ought to pay the most attention to.
    Now, some of our colleagues have their own planning 
process. Doctor Patrinos has already described to you the 
Genomes To Life process that they followed with the DOE's 
enterprise, which is nicely complementary to what NIH is doing. 
The CDC has had their planning process, which we've been 
fortunate to be part of, all of us talking, I think rather 
closely, with each other.
    So, I think we could, basically, put this forward as a 
pretty good model of how to arrive at priorities, recognizing 
that those priorities will have to be revisited very regularly.
    Ms. Capps. Mr. Chairman, I would hope that at least I could 
get a copy, if you think it's appropriate, for our discernment, 
because I think it would be useful for us to have that 
information as we make some decisions that affect at least the 
dollars that you work with.
    Mr. Collins. A copy of the process that we followed?
    Ms. Capps. And where you are now.
    Mr. Collins. Yes, this document is, this captures, 
basically, in the series of 15 grand challenges----
    Ms. Capps. Okay.
    Mr. Collins. [continuing] that you see outlined here, what 
those 600 people said ought to be our highest priorities.
    Mr. Bilirakis. Without objection, we'll make that part of 
the record.
    Mr. Collins. That would be wonderful.
    Ms. Capps. So that this could be then our working document 
as well.
    Mr. Collins. That would be fabulous.
    Ms. Capps. Thank you, surely.
    Mr. Patrinos. I'm very pleased to say that we followed, as 
Doctor Collins said, a very similar process with our Genomes To 
Life program over the last 2, 2\1/2\ years, primarily led by 
our Biological and Environmental Research Advisory Committee, 
again, a committee of distinguished scientists from the 
academic community, from industry, and from our national 
laboratories, but extending also much beyond to the broader 
scientific community that participated in similar workshops.
    There was an additional dimension for us, because we knew 
as the end of the Human Genome Project was coming up we would 
be shifting more and more toward the microbial genomics, which 
is also an effort that we had started in the early 1990's and, 
therefore, we saw a significant shift in what we were doing on 
human genomics to microbial genomics.
    And, I'd like to use this opportunity to take issue a bit 
with my colleague, Bob Waterston, when he declared war against 
the microbes, and to tell you that only a very, very small 
percentage of that microbial world is pathogenic.
    Ms. Capps. Yes.
    Mr. Patrinos. The rest of it is, in fact, the actors that 
are enabling the whole process of life to happen. So, I rise in 
their defense.
    Thank you.
    Mr. Waterston. I stand corrected.
    Ms. Capps. Are there other comments? Go ahead, until I get 
banged down.
    Mr. Venter. I just wanted to pick up very quickly on your 
stem cell comment, because I think that's one of the most 
important issues facing a combination of what Congress does and 
what the scientists do. The best laid plans can go awry when 
one of the most important areas in modern biology, probably one 
of the few means that we have of understanding how we go from 1 
cell to 100 trillion cells if we can't undertake adequate 
research in that field. And so, we go from what appears to be a 
complex field of science to public slogans that has basically 
derailed and is taking a very big risk of putting the U.S. much 
behind the rest of the modern research world in this field.
    And so, I would turn the question back to you, how do we 
get it so we can educate Congress appropriately on these 
issues, so we don't have this type of disaster again?
    Ms. Capps. I take that challenge, I think it's one that we 
really need to be very, very thoughtful and as deliberative as 
we can, and I would suggest to my colleagues that the process 
that Doctor Collins described, and I'm sure there was not 
unanimity all along the way, is one that you were willing to 
set aside that much time to do. And, I would agree that it's 
that important that we all also in this body ought to be 
willing to set aside some differences and really use your 
process as a way to focus on how we can be supportive and not 
impede that, and also mindful of ethical roles that we need to 
play as well.
    Mr. Khoury. In addition to the processes that you just 
heard, I mean CDC has gone----
    Mr. Bilirakis. Where are we here?
    Ms. Capps. I was hoping you would keep talking, Mr. 
    Mr. Bilirakis. Well, all right, just go ahead and respond. 
She takes advantage of me every chance she gets.
    Mr. Khoury. In addition to the scientific process for 
choosing priority, the CDC is primarily driven by the need to 
develop practical tools that work in real life. And so, we tend 
to listen a lot to our primary constituents and State health 
departments and local health departments, and we have been 
regularly convening and talking with these people from the 
health officers, the State epidemiologists, each State has 
chronic disease directors, maternal child health directors, and 
as a matter of fact last year the chronic disease directors got 
together and developed their own plan of action, which focuses 
on 4 or 5 priority diseases, including cancer, heart disease 
and obesity, and asking CDC to developtake the knowledge from 
the lab and translate it into meaning that affects their 
practice and what it means to deliver prevention programs at 
the State and local level. So, this is another set of 
constituents that we relate to, and, obviously, it has to be 
driven by the best science that's available, and that's why the 
collaboration and dialog across agencies occurs.
    Ms. Capps. Excuse me, if I could just comment, Mr. 
    Doctor Khoury, in some ways you are like us at CDC, I see, 
because we have constituents, they are the same ones.
    Mr. Khoury. Right.
    Ms. Capps. The county doctors and medical personnel in our 
communities. And, we go home also and get that read from our 
constituents in that same way.
    And so, you are balanced within this panel, I appreciate 
very much your being here today.
    Thank you.
    Mr. Bilirakis. And, I'm going to probably hitch hike on 
that in a moment.
    Mr. Strickland, to inquire.
    Mr. Strickland. Thank you, Mr. Chairman, and I want to 
thank the witnesses. I think you represent the heroes of our 
time, and you may not feel that way about yourselves, but my 
colleague, Ms. Eshoo, and I were sitting here earlier and as 
you were testifying she was saying, ``This is the kind of thing 
that our government, as representatives of the people, should 
be supporting and encouraging.'' And, one of you, I don't know 
which one, made a comment about a very practical matter, and 
that was probably the only way we're ever going to effectively 
lower the cost of health care, is to focus on preventive care, 
rather than reactive medicine, and I think that's absolutely 
true, and that's one of the reasons why this research is so, I 
think, exciting to all of us.
    I would just like to return to the matter of the possible 
interface or the intersection of the work that you are doing 
with the work that is going on in terms of stem cell Research 
or therapeutic cloning, because I do think that's something 
that we can't ignore. And, the threat to progress that some of 
the actions that we've taken pose, you know, it just seems 
incredibly unreasonable that some of us who have almost, you 
know, the most superficial understanding of what you know would 
impose restrictions on the potential that this research offers 
to the American people and to the world.
    And so, I'm just wondering if you could say a little more 
about the ways that these research efforts could or do 
intersect, and why it's so important to have the ability to 
pursue this kind of research without artificial restrictions 
being placed on it.
    Mr. Collins. So, they do intersect in the sense that the 
genome is the instruction book that directs human biology, 
directs the biology of all living organisms. One of the major 
questions that we now have the opportunity to begin to unravel 
is how genes turning on or off result in a cell going down a 
pathway to be a neuron, or a liver cell, or a bone marrow cell, 
they all have the same instruction book, they all started with 
the same instruction book, they still have it, but they 
developed along the way a wonderful cascade of genes turning on 
or off to allow that cell to take on a variety of a remarkable 
diversity of phenotypes, of ways in which that cell can behave.
    Obviously, the stem cell, as sort of the granddaddy of all 
of those, is one of great interest. As you know, there are 
federally approved human stem cell lines that investigators may 
work with under current guidelines, and we are engaged right 
now in a very aggressive way in trying to determine what genes 
are already on in those cells that seem to have the greatest 
potential to go down all of these different pathways, 
basically, by looking very explicitly at which genes are making 
RNA, which is an indication that the gene is on. So, that's a 
direct example of an intersection.
    But, I think from my perspective, as one who oversees the 
genomics arena, the study of stem cells, in fact, crosses all 
the institute lines, and NIH is perhaps particularly relevant 
in some of the institutes that are looking at diabetes, or 
Parkinson's disease, or at Alzheimer's disease, and as you know 
those discussions have been complicated because of the 
intersection, in that case not of genomics and stem cell 
biology, but of stem cell biology and concepts of when human 
life begins.
    In my current position, I do not want to weigh in 
particularly on that debate. Perhaps some of my other 
colleagues would feel inclined to do so, but I do think you are 
correct, there is an intersection here, but it's one that we 
need to understand a little more carefully, it's not a direct 
    Mr. Strickland. Thank you.
    Can I just, I understand your position, I would just like 
to know from your personal opinions, are you personally 
concerned that our government may be engaging in actions that 
could have a detrimental impact upon your research? Just your 
personal opinions as we go down the line, and then, Doctor 
Venter, you can speak.
    Mr. Venter. Well, let me start, I think we are crossing 
potentially dangerous boundaries in terms of, I think what's 
going on in the government is a reflection of the concern in 
society of not understanding these complex issues.
    We learn from every newspaper headline and Super Bowl ads 
that there's a direct link between genes and behavior, even 
though I doubt anybody on this panel would support that view. 
So, I'd argue, we think very much in a deterministic way in our 
    So, I think people fear cloning as an issue for much the 
wrong reasons. I am absolutely against reproductive cloning, 
it's human experimentation, there's no justification on the 
planet for doing it, but I think most people are against it for 
confused and wrong reasons.
    When we are dealing with the stem cell activities, the 
scientific community has to learn to police itself or learn 
that it will get policed by others.
    I don't know of any reputable scientist that wants to push 
the boundaries, but the headlines are full of headline seekers 
that are clearly not even doing science, let alone reputable 
science, that confuse the issues profoundly.
    So, it's a philosophical discussion, it's an emotional 
discussion, but I think it's very dangerous when we start to 
interfere with basic science.
    Mr. Bilirakis. The gentleman's time has expired.
    Mr. Brown?
    Mr. Brown. I should have asked earlier a procedural 
question, I'd ask unanimous consent to enter into the record 
Mr. Dingell's statement and statements of any other members who 
have submitted them.
    Mr. Bilirakis. Without objection, that will be the case.
    I wanted to, Doctor Venter, is it realistic, getting into 
the preventative, is it realistic that a newly born, that a 
road mapto kind of use your term there, a road map will be 
taken of that child some day and that information, the genomic 
information, will be made available to the family?
    When you talk preventative, you know, preventative care and 
what not, is that one of the ways, or is that essentially the 
way that you were thinking?
    Mr. Venter. I think it would be the most important outcome 
of the technology side, the challenge would be in interpreting 
that information.
    We all like yes/no answers, but our genetic code will very, 
very rarely give us a yes/no answer, we are going to have to 
deal with probabilities, what does it mean to have a 30 percent 
increased risk of colon cancer? People think in absolute 
determinations you should have this drug and not that drug, 
it's not going to work, but if you know you have a 30 percent 
chance of having severe side effects or dying from a certain 
class of drugs there's no justification for having you take 
them. That's the type of information we will get from our 
genetic code.
    But, the colon cancer example, I think, is a wonderful one. 
The statistics are pretty overwhelming that when colon cancer 
is detected early there's over a 90 percent chance of a 10-year 
survival, and fairly low cost associated with treatment. If 
it's detected after symptoms appear, that drops well below 65 
percent, in fact, the numbers are pretty staggeringly bad, at a 
tremendous increased dollar cost.
    So, if you know that you have an increased risk of getting 
colon cancer from the genetic changes in DNA paraenzymes, for 
example, discovered by us in collaboration with Bert 
Fogelstein, you can have more frequent early checkups, and as 
new advances getso we have a simple blood test for it, it 
becomes a very cost-effective way, it can be detected early, it 
can be treated early, we have very effective treatments for 
colon cancer, it's called surgery. It's wonderfully effective 
if it's detected before there's any metastasis.
    The challenge is, we are at such an early stage in our 
understanding of our genetic code we don't know most of the 
implications of how to interpret that data right now.
    Mr. Bilirakis. So, when we--I'm sorry, go ahead, Doctor 
    Mr. Collins. Could I just add one small caveat to this 
notion of giving the genome sequence to the parents when the 
child is born, I believe technologically we ought to be able to 
do that. I believe that based upon the momentum that's 
currently occurring in the Congress we'll be able to do that in 
a fashion that people won't be afraid of the information, 
because they will have protections against misuse.
    But, there will still be, I think, some who don't wish to 
know about aspects of their genome that places them at risk for 
things that we currently can't do anything about. Colon cancer 
is a great example of where we can, I think most people would 
want to know that one, but if there's information in there that 
says you are at risk for Alzheimer's disease, and at the moment 
there is nothing we can do about that, some will want to know 
that, some will not.
    And, arguments have been made, and I think they are fairly 
compelling, that that is a decision which the individual ought 
to make for themselves, and, obviously, a newborn doesn't have 
the opportunity to do that. So, a slight modification of this 
future view is that you would reveal the part of the genome 
that's relevant for childhood health, but you might save the 
parts that are only relevant to adulthood until that person 
gets to be 18 and then they can decide whether they want the 
information or not. That's my one modification.
    Mr. Bilirakis. Well, but that all falls in the category of 
the question that I think practically every one of you raised, 
what do we do next? That's certainly part of all that, isn't 
it? Fascinating.
    Doctor Patrinos, as you know it's been discussed already so 
much, this committee has substantial interest, of course, in 
your Genomes To Life program, and as I understand it there's a 
roadmap for the Genomes To Life program which was published in 
April 2001.
    This roadmap indicated that DOE would use DNA sequences 
from high organisms, including humans, as starting points for 
analyzing critical life processes. Isn't that correct?
    Mr. Patrinos. You may be referring, Mr. Chairman, to an 
earlier draft of the document that underwent subsequently many 
    Mr. Bilirakis. But, not the April 2001 document?
    Mr. Patrinos. It may be, I don't recall the April 2001 
specifically, but the real roadmap or an article describing our 
project is really in the April 2003 issue, that speaks to the 
use of only microbes and microbial communities.
    Mr. Bilirakis. But, not humans?
    Mr. Patrinos. But, not humans.
    Mr. Bilirakis. All right.
    So, was----
    Mr. Patrinos. This document that the counsel just raised is 
a much earlier version that is now null and void.
    Mr. Bilirakis. [continuing] should we say then that this 
determination whether humans should be used was sort of a work 
in progress, and that, in other words, was there a change in 
mind and a change in determination, or was it sort of just a 
part of an overall work in progress?
    Mr. Patrinos. It was very much an early part of the work in 
progress, one that was excised very, very quickly. But, like 
Doctor Collins described, our process also took a very long 
time and input from many members of the scientific community. 
So, we went through several drafts, I would say a lot of 
    Mr. Bilirakis. I'm told, and I don't know this, but I'm 
told that it's on your web sites, so you may want to check that 
    Mr. Patrinos. It may be the web site that describes some of 
the earlier documents.
    Mr. Bilirakis. Yes.
    Mr. Patrinos. We keep a lot of the earlier documents, but 
if it is in there we probably should remove it, and we will do 
    Mr. Bilirakis. All right.
    All right, I have, you know, I have really nothing further 
other than, well, first of all, there will be, as per usual, a 
number of questions that the committee will be sending to you 
in writing, and we would appreciate a response back, and 
additionally, gentlemen, you know, what you do is very 
fascinating, it's got to be pretty darn self-rewarding, too, we 
are Congress here, somebody mentioned that we did double NIH 
funding. That's one of the promises that Congress made quite a 
while ago and we kept. I realize that we don't always have the 
best image in that regard, but we kept that one, and we're very 
proud of it, and it was a bipartisan thing, we all worked 
together toward that end.
    But, are there any other ways that we can at least consider 
to help your efforts to alleviate your efforts, I mean, other 
than money obviously, money is always there, please let us 
know. And, hopefully, I speak for Mr. Brown, too, when I say 
that, but let us know how we can help in terms of any 
legislation or anything of that nature.
    I've always been concerned about duplication of effort. 
I've always been a bit concerned when it comes to research in 
general, and I've been kind of convinced by researchers that 
there's going to have to be some overlap, some duplication of 
effort, and a lot of good things come from that. Hopefully, 
it's, you know, not sort of a wasted duplication of effort, and 
I get the feeling that it isn't in this particular case.
    Yes, sir, Doctor Collins.
    Mr. Collins. Yeah, with your permission, Mr. Chairman, I 
certainly would like to take this opportunity to thank the U.S. 
Congress for the way in which you have supported the work that 
brings us here this morning. We would not be here without that 
strong support, tracking back to the late 1980's when the 
Genome Project was only a glimmer in certain scientists' eyes, 
and a lot of the scientific community was unconvinced of its 
possible success. Despite that, the Congress took that risk. 
Throughout the course of the 1990's and right up to today you 
have stood behind that and encouraged us at times when things 
were not necessarily easy to see through the lens that we were 
trying to examine the future.
    And, I want to thank you also for the way in which 
Congress, has achieved this doubling of the NIH, that has made 
it possible to expand the opportunities into a host of areas 
that would otherwise still be waiting for attention.
    We are all very excited, as you can tell, about what we can 
now do, and I promise you we will be back telling you about all 
of the excitement that we can accomplish and, again, 
appreciating your strong support, both financially and in terms 
of legislative initiatives to make that happen.
    We are very much in your debt, in terms of a specific thing 
which this Congress could now do, I guess you've heard from 
several others this morning that if we could in this year of 
2003, the year of the completion of the genome, the 50th 
anniversary year of the double helix, also give the American 
public a present, a freedom from fear about knowing your own 
genome, by this effective piece of Federal legislation, by the 
House taking up what the Senate has already now brought through 
its committee, that would be a wonderful accomplishment, a 
bipartisan accomplishment, one which the administration 
strongly supports, and that would certainly be first on my wish 
    Mr. Bilirakis. Sir, that's pretty fundamental, isn't it, to 
your continued work?
    Mr. Collins. Absolutely.
    Mr. Bilirakis. There's no question about it.
    Doctor Patrinos?
    Mr. Patrinos. How can I not use this opportunity to also 
urge you, Mr. Chairman and members of the subcommittee, to also 
support the science budgets of other agencies, like the Office 
of Science in the Department of Energy. I think the strength of 
the American scientific establishment, just like the strength 
of America, is really the diversity of its people, and the 
strength of the scientific establishment also depends very much 
on the diversity of funding sources.
    We are unique in the world in that respect, and we need to 
nurture and enable that diversity of the funding sources. There 
should not be a one-stop shopping when it comes to scientific 
    Thank you.
    Mr. Bilirakis. Thank you so much, gentlemen, we appreciate 
you very much, and we are indebted to you.
    [Whereupon, at 12:02 p.m., the subcommittee was adjourned.]