| |
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 Federal Investment in Genomics
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 sequencing.
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 sequencing.
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 priorities.
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.
Appendix
The Venter Science Foundation's Affiliated Nonprofit Organizations
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 adopted.
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 innovation.
|
|
