[House Hearing, 113 Congress]
[From the U.S. Government Publishing Office]
POLICIES TO SPUR INNOVATIVE MEDICAL
BREAKTHROUGHS FROM LABORATORIES
TO PATIENTS
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON RESEARCH AND TECHNOLOGY
COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY
HOUSE OF REPRESENTATIVES
ONE HUNDRED THIRTEENTH CONGRESS
SECOND SESSION
__________
JULY 17, 2014
__________
Serial No. 113-87
__________
Printed for the use of the Committee on Science, Space, and Technology
______
U.S. GOVERNMENT PUBLISHING OFFICE
89-416 PDF WASHINGTON : 2015
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COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY
HON. LAMAR S. SMITH, Texas, Chair
DANA ROHRABACHER, California EDDIE BERNICE JOHNSON, Texas
RALPH M. HALL, Texas ZOE LOFGREN, California
F. JAMES SENSENBRENNER, JR., DANIEL LIPINSKI, Illinois
Wisconsin DONNA F. EDWARDS, Maryland
FRANK D. LUCAS, Oklahoma FREDERICA S. WILSON, Florida
RANDY NEUGEBAUER, Texas SUZANNE BONAMICI, Oregon
MICHAEL T. McCAUL, Texas ERIC SWALWELL, California
PAUL C. BROUN, Georgia DAN MAFFEI, New York
STEVEN M. PALAZZO, Mississippi ALAN GRAYSON, Florida
MO BROOKS, Alabama JOSEPH KENNEDY III, Massachusetts
RANDY HULTGREN, Illinois SCOTT PETERS, California
LARRY BUCSHON, Indiana DEREK KILMER, Washington
STEVE STOCKMAN, Texas AMI BERA, California
BILL POSEY, Florida ELIZABETH ESTY, Connecticut
CYNTHIA LUMMIS, Wyoming MARC VEASEY, Texas
DAVID SCHWEIKERT, Arizona JULIA BROWNLEY, California
THOMAS MASSIE, Kentucky ROBIN KELLY, Illinois
KEVIN CRAMER, North Dakota KATHERINE CLARK, Massachusetts
JIM BRIDENSTINE, Oklahoma
RANDY WEBER, Texas
CHRIS COLLINS, New York
BILL JOHNSON, Ohio
------
Subcommittee on Research and Technology
HON. LARRY BUCSHON, Indiana, Chair
STEVEN M. PALAZZO, Mississippi DANIEL LIPINSKI, Illinois
MO BROOKS, Alabama FEDERICA WILSON, Florida
RANDY HULTGREN, Illinois ZOE LOFGREN, California
STEVE STOCKMAN, Texas SCOTT PETERS, California
CYNTHIA LUMMIS, Wyoming AMI BERA, California
DAVID SCHWEIKERT, Arizona DEREK KILMER, Washington
THOMAS MASSIE, Kentucky ELIZABETH ESTY, Connecticut
JIM BRIDENSTINE, Oklahoma ROBIN KELLY, Illinois
CHRIS COLLINS, New York EDDIE BERNICE JOHNSON, Texas
BILL JOHNSON, Ohio
LAMAR S. SMITH, Texas
C O N T E N T S
July 17, 2014
Page
Witness List..................................................... 2
Hearing Charter.................................................. 3
Opening Statements
Statement by Representative Larry Bucshon, Chairman, Subcommittee
on Research and Technology, Committee on Science, Space, and
Technology, U.S. House of Representatives...................... 7
Written Statement............................................ 9
Statement by Representative Daniel Lipinski, Ranking Minority
Member, Subcommittee on Research and Technology, Committee on
Science, Space, and Technology, U.S. House of Representatives.. 11
Written Statement............................................ 13
Statement by Representative Lamar S. Smith, Chairman, Committee
on Science, Space, and Technology, U.S. House of
Representatives................................................ 15
Written Statement............................................ 16
Witnesses:
Dr. Harold Varmus, Director, National Cancer Institute (NCI) at
the National Institutes of Health (NIH)
Oral Statement............................................... 18
Submitted Biography.......................................... 21
Dr. Marc Tessier-Lavigne, President and Carson Family Professor,
Laboratory of Brain Development and Repair, The Rockefeller
University
Oral Statement............................................... 30
Written Statement............................................ 32
Dr. Jay Keasling, Hubbard Howe Jr. Distinguished Professor of
Biochemical Engineering, University of California, Berkeley;
Professor, Department of Chemical & Biomolecular Engineering,
University of California, Berkeley; Professor Department of
Bioengineering, University of California, Berkeley; Director,
Synthetic Biology Engineering Research Center
Oral Statement............................................... 39
Written Statement............................................ 41
Dr. Craig Venter, Founder, Chairman, and Chief Executive Officer,
J. Craig Venter Institute, Synthetic Genomics, Inc., and Human
Longevity, Inc.
Oral Statement............................................... 46
Written Statement............................................ 48
Discussion....................................................... 57
Appendix I: Answers to Post-Hearing Questions
Dr. Harold Varmus, Director, National Cancer Institute (NCI) at
the National Institutes of Health (NIH)........................ 70
Dr. Marc Tessier-Lavigne, President and Carson Family Professor,
Laboratory of Brain Development and Repair, The Rockefeller
University..................................................... 78
Dr. Jay Keasling, Hubbard Howe Jr. Distinguished Professor of
Biochemical Engineering, University of California, Berkeley;
Professor, Department of Chemical & Biomolecular Engineering,
University of California, Berkeley; Professor Department of
Bioengineering, University of California, Berkeley; Director,
Synthetic Biology Engineering Research Center.................. 81
Dr. Craig Venter, Founder, Chairman, and Chief Executive Officer,
J. Craig Venter Institute, Synthetic Genomics, Inc., and Human
Longevity, Inc................................................. 83
Appendix II: Additional Material for the Record
Statement submitted by Representative Eddie Bernice Johnson,
Ranking Member, Committee on Science, Space, and Technology,
U.S. House of Representatives.................................. 88
Letter submitted by Representative Larry Bucshon, Chairman,
Subcommittee on Research and Technology, Committee on Science,
Space, and Technology, U.S. House of Representatives........... 90
Article submitted by Representative Dana Rohrabacher, Committee
on Science, Space, and Technology, U.S. House of
Representatives................................................ 91
POLICIES TO SPUR INNOVATIVE MEDICAL
BREAKTHROUGHS FROM LABORATORIES
TO PATIENTS
----------
THURSDAY, JULY 17, 2014
House of Representatives,
Subcommittee on Research and Technology,
Committee on Science, Space, and Technology,
Washington, D.C.
The Subcommittee met, pursuant to call, at 9:05 a.m., in
Room 2318 of the Rayburn House Office Building, Hon. Larry
Bucshon [Chairman of the Subcommittee] presiding.
[GRAPHIC] [TIFF OMITTED]
Chairman Bucshon. Subcommittee on Research and Technology
will come to order. Good morning. Welcome to today's hearing,
entitled ``Policies to Spur Innovative Medical Breakthroughs
from Laboratories to Patients.'' I recognize myself for five
minutes for an opening statement.
As a cardiothoracic surgeon and medical professional, I
know firsthand there are many complexities surrounding the
human body, and understanding human disease is one of the most
challenging problems facing the scientific and medical
communities. Complex human diseases will likely require an
interdisciplinary and multifaceted approach, with the right
scientific questions being asked and debated, with clear goals
and endpoints being articulated.
The creative drive of American science is the individual
investigator, and I have faith they will continue to tackle,
understand, and contribute original approaches to these
problems. Medical diseases such as cancer, Alzheimer's,
Parkinson's, autism, epilepsy, dementia, stroke, and traumatic
brain injury have an enormous impact, and enormous economic
impact, and personal impact for affected Americans. For
example, Alzheimer's disease is a severe form of dementia, and
the sixth leading cause of death in the U.S. It affects both
the 5.1 million Americans that have the disease and their
friends and family, who must watch their loved ones suffer from
its symptoms. The average annual cost of care for people with
dementia over 70 in the U.S. is roughly between 157 and $210
billion in 2010.
I want to stress my support for medical science research,
in particular understanding diseases from an interdisciplinary
perspective. As our witnesses will testify today, medical
science has benefitted enormously from fields as diverse as
applied mathematics, computer science, physics, engineering,
molecular biology, and chemistry.
More important basic science research results from NSF
funded research will be the future experimental tools for a
hypothesis-based, data-driven research for brain science
researchers. I also see this as an important opportunity for
continuing interdisciplinary work between the various federal
science agencies, including NSF, NIST, and NIH, and I hope to
see more collaboration and productive research opportunities.
At the same time, I am interested in how private sector
research can complement ongoing federal R&D investment, and
what public policies may spur more innovation and investment
from medical breakthroughs. Companies must carefully balance
short term and long term interests of the company and their
shareholders. Private sector research efforts use the results
of basic science research in the physical, mathematical, and
engineering sciences. For example, advances in computing have
led to the development of software, with the goal of helping
medical sciences make sense of cancer genomes.
Watson, an advanced computer that was developed by IBM is
being enlisted not only to identify mutations from a patient's
tumor biopsy in order to help understand how these mutations
cause cancer, but also to produce a list of drugs that could
potentially treat the cancer. All of this can potentially be
done in minutes, and I had a demonstration of Watson in my
office. It was fascinating.
Our witnesses today reflect the wide spectrum of research
in the biomedical sciences, and each have been recognized in
their respective fields. I would like to thank the witnesses
for their being here today, and taking time to offer their
perspectives on this important topic. I hope you will continue
to work with us to maximize federal funding of biomedical
research. I would also like to thank the Ranking Member, Mr.
Lipinski, and everyone else participating in today's hearing.
[The prepared statement of Mr. Bucshon follows:]
[GRAPHIC] [TIFF OMITTED]
Chairman Bucshon. At this point now I recognize the Ranking
Member, the gentleman from Illinois, Mr. Lipinski, for his
opening statement.
Mr. Lipinski. Thank you, Chairman Bucshon, for holding this
hearing on policies to spur medical breakthroughs, something we
all certainly want to do what we can here to make it as likely
as possible to get those medical breakthroughs, and get them
out to market and helping people. And I want to thank all of
our witnesses for being here today. I look forward to your
testimony.
Innovation, whether in biomedical research or elsewhere, is
an ecosystem that is more than the sum of its parts. Federal
agencies, universities, and research institutions,
entrepreneurs, and the private sector all have important roles
to play. That is why I am glad we have witnesses from across
these sectors here to testify today.
In April we held a hearing in this committee on innovation
prize competitions. We heard testimony about the need for a
kidney prize to facilitate the development of more effective
treatments for kidney disease and end stage renal disease.
Innovation prizes, as well as other forms of pre-commercial
support, such as proof of concept funding, and programs like
NSF's Innovation Corps, which recently announced a
collaboration with NIH, could hold great promise for future
biomedical breakthroughs.
I hope that our panel could comment on these and other
potential mechanisms for supporting technology transfer from
the lab to the marketplace. And, of course, it bears repeating
that our ability to innovate will be greatly limited without
growing investments in the basic research that generates these
technologies.
The emerging field of engineering biology has grown out of
the decades old field of genetic engineering. In the 1800s,
Gregor Mendel established many of the rules of heredity that
became the foundation of modern genetics by studying pea
plants. But even before Mendel, farmers knew that by cross-
breeding animals and plants you could favor certain traits.
Since the 1970s, scientists have been using more advanced
tools to directly insert new genes or delete genes from plant
and microbio genomes. Engineering biology is the next step in
this field, and is being accelerated by the development of
technologies such as DNA sequencing, which has gone from taking
years, and costing billions of dollars, to taking just days,
and costing a few thousand dollars, which is truly amazing.
We have already started seeing commercial applications from
engineering biology. I look forward to hearing more about how
Dr. Keasling and his research group were able to engineer a
microorganism to produce a life-saving anti-malarial drug that
is now being produced on a large scale by a pharmaceutical
company. I also look forward to learning about other potential
applications from engineering biology research, including
energy, agriculture, chemicals, and manufacturing.
Since this is an emerging field, and it could have
significant economic benefit for the United States, it is
important that we make the necessary federal investments in
both the foundational research, and across the potential
application areas. Several of the agencies under the
Committee's jurisdiction have significant programs in
engineering biology. The Department of Energy has one of the
largest programs focused on bioenergy. The National Science
Foundation is investing more in this area, both through
individual research awards, and through their support of an
engineering research center at Berkeley. NASA and NIST also
have programs in this area. And, of course, NIH and the
Department of Agriculture are significant players this
research.
The nation would benefit not just from increased investment
at individual agencies, but also from coordination of federal
efforts under some kind of plan or strategy. Other countries
have identified this area specifically as an important area to
make investments in. The European Union's Europe 2020 strategy
calls out this field as a key element as it develops a strategy
and an action plan for investment.
I have never seen that one happen before. I didn't even run
over time yet.
Chairman Bucshon. That was your warning.
Mr. Lipinski. Don't worry, I am almost done. I am concerned
if the United States does not take the necessary steps, we will
lose our leadership position in this field. That was symbolic
of losing our leadership position, the lights going out. We
should also ensure that we are facilitating public/private
partnerships. Given the potential of commercial applications
across nearly all sectors of our economy, there is a need to
engage and encourage private sector collaboration at a pre-
competitive level. And, finally, we must pay careful attention
to issues of human environmental safety and ethics when it
comes to engineering biology research, including by supporting
research on those topics.
I look forward to all witnesses' testimony, and the Q&A.
Thank you all for being here, and I yield back the balance of
my time.
[The prepared statement of Mr. Lipinski follows:]
[GRAPHIC] [TIFF OMITTED]
Chairman Bucshon. Thank you, Mr. Lipinski. I now recognize
the Chairman of the full Committee, the gentleman from Texas,
Mr. Smith, for his opening statement.
Chairman Smith. Thank you, Mr. Chairman.
Basic biomedical research is increasingly interdisciplinary
in nature. Advances in applied mathematics, physics chemistry,
computer science, and engineering provide a better
understanding of medical conditions, and the tools to help find
cures. The National Science Foundation can play an important
and vital role in understanding the basic science behind many
debilitating conditions.
For example, developments in basic scientific research have
provided deep insight into how the brain and other neurological
structures are organized. NSF research could help us better
understand conditions such as cancer, Alzheimer's, Parkinson's,
autism, stroke, dementia, traumatic brain injury, epilepsy, and
many other disorders. Countless lives have unfortunately been
lost to these diseases, and the economic impact, physical and
emotional toll they can put on families can make them even more
devastating.
The National Science Foundation should support
interdisciplinary research in conjunction with the National
Institutes of Health to help us better understand medical
illnesses. The Frontiers in Innovation, Research, Science and
Technology Act, or FIRST Act, supports basic research that has
the potential to improve the daily lives of millions of
Americans. The FIRST Act increases funding for subjects such as
math, physical sciences, biological sciences, computer
sciences, and engineering for Fiscal Year 2015.
The FIRST Act, which was successfully reported out of
Committee this past May, includes a $270 million increase for
Fiscal Year 2015 over current NSF spending for these important
subject areas. Federally funded basic research has supported
the creation of technologies that have changed and improved our
daily lives, including the MRI and laser technology. Efficient
and effective use of NSF funding geared toward basic research
will help us better understand medical conditions, and lead to
medical breakthroughs that benefit both doctors and patients
alike.
Thank you, Mr. Chairman, for holding this hearing. And I
want to say, at the risk of offending any other panel, we have
an unusually distinguished panel of witnesses today, and we
look forward to hearing from their testimony.
[The prepared statement of Mr. Smith follows:]
[GRAPHIC] [TIFF OMITTED] T9416.010
Chairman Bucshon. Thank you, Chairman. At this point, if
there are other Members who wish to submit additional opening
statements, your statements will be added to the record.
[The prepared statement of Ms. Johnson appears in Appendix
II]
Chairman Bucshon. At this time I would like to introduce
our witnesses, and it is a distinguished panel. Thanks for
being here.
Our first witness is Dr. Harold Varmus, Director of the
National Cancer Institute. He previously served for ten years
as President of Memorial Sloan Kettering Cancer Center, and six
years as Director of the National Institutes of Health. Dr.
Varmus is a co-recipient of the Nobel Prize for studies on the
genetic basis of cancer. Dr. Varmus was a co-chair of President
Obama's Council of Advisors on Science and Technology. And Dr.
Varmus majored in English, which I found interesting,
Literature at Amherst, and earned a Master's Degree in English
at Harvard, and is a graduate of Columbia University's College
of Physicians and Surgeons. Welcome.
Our second witness is Dr. Marc Tessier-Lavigne. Did I say
that right? President of the Rockefeller University, where he
is also Carson Family Professor, and head of the laboratory of
brain development and repair. Previously he served as Chief
Scientific Officer of Genentech, a leading biotechnology
company. He obtained undergraduate degrees from McGill and
Oxford Universities, and a Ph.D. from the University College
London, and was a post-doctoral fellow over there also, and at
Columbia University. Prior to joining Genentech, he held
faculty positions at the University of California San Francisco
and at Stanford, where he was the Susan B. Ford Professor and
Investigator with the Howard Hughes Medical Institute. Welcome.
Our third witness is Dr. Jay Keasling, the Hubbard Howe Jr.
Distinguished Professor of Chemical and Biomolecular
engineering, and Professor of Bioengineering at the University
of California at Berkeley. He is the Director of the Synthetic
Biology Engineering Research Center, Associate Laboratory
Director for Biosciences at the Lawrence Berkeley National
Laboratory, and Chief Executive Officer of the Joint Bioenergy
Institute.
Dr. Keasling earned his Bachelor's Degree from the
University of Nebraska, and his graduate degrees in Chemical
Engineering from the University of Michigan. In 2006 he was
cited by Newsweek as one of the country's 10 most esteemed
biologists. Welcome.
And our fourth witness is Dr. Craig Venter, Founder,
Chairman, and Chief Executive of the J. Craig Venter Institute,
Synthetic Genomics, Incorporated, and Human Longevity,
Incorporated. Dr. Venter contributed to sequencing the first
draft human genome in 2001, the first complete diploid human
genome in 2007, and the construction of the first synthetic
bacterial cell in 2010. Dr. Venter is the recipient of the 2008
National Medal of Science.
Dr. Venter earned both a Bachelor's Degree in Biochemistry,
and a Ph.D. in Physiology and Pharmacology from the University
of California at San Diego. Thank you for being here.
And, again, thanks to all our witnesses. It is a very
impressive panel, and I think this is going to be a great
hearing. As our witnesses should know, spoken testimony is
limited to five minutes, after which the Members of the
Committee will have five minutes each to ask questions. I now
recognize Dr. Varmus for five minutes to present his oral
testimony.
TESTIMONY OF DR. HAROLD VARMUS, DIRECTOR,
NATIONAL CANCER INSTITUTE (NCI)
AT THE NATIONAL INSTITUTES OF HEALTH (NIH)
Dr. Varmus. Chairman Bucshon, Chairman Smith, Mr. Lipinski,
and other Committee Members, I thank you for your strong,
supportive opening statements, and for holding this important
hearing about the state of the American scientific enterprise.
This is a pivotal moment. On the one hand, our investments in
science and technology continue to lead the world. Our
discoveries and applications of knowledge have enriched the
country, improved the world, and expanded opportunities for yet
further discover and application.
But in recent years, we have been fiscally constrained. The
place I work, the NIH, has lost 25 percent of its buying power
over the last decade. We are able to support fewer than one in
seven of our grant applications. In the meantime, other
countries have quickened their pace of investment. Under these
circumstances, the nation needs to determine how the parts of
the enterprise can most effectively work together, and I take
that to be the ultimate goal of this hearing.
But that isn't easy. The scientific landscape is complex,
with at least four dimensions. First, many defined disciplines,
which often intersect. Second, a spectrum of activities, from
free ranging fundamental research, to more programmatic--or
pragmatic efforts to use basic knowledge. Third, a variety of
funding sources, including many government agencies, small and
large companies, academic institutions, and private
philanthropies. And fourth, several kinds of mechanisms to
support research from each of our sources. Balancing these
elements is of obvious interest to the Subommittee and to your
witnesses.
I would like to make four points about the landscape to
help guide our discussion today. The first three are operating
principles. The fourth illustrates some novel ways in which my
agency, the NCI, has tried to increase our effectiveness.
First, the importance of interdisciplinary work, which has
already been alluded to. Historically, major advances in
medicine have been especially dependent on physical sciences--
on physics and chemistry. The body is an object that can be
studied with those tools. Just consider microscopes, X-ray
machines, radio isotopes, pharmacology, electrocardiograms, Mr.
Bucshon, and the electroencephalogram.
More recently, the studies of genomes that have been
alluded to, proteins and cells, have revolutionized our
understanding of normal and diseased human beings, thanks to
inventions that required, again, physical, mathematics,
engineering, and chemistry, as well as, importantly,
computational science to handle the massive sets of data that
we have accrued. Now newly launched initiatives, such as the
President's BRAIN project, or the NCI's therapeutics efforts
that are based on genetic signatures, so-called precision
medicine, are going to require these in still other fields. In
short, the future of medicine will depend on maintaining the
vibrancy and the interaction of allied fields of science and
technology.
Second point, sustained fundamental research is essential
for further developments in medicine. Yet, when financial
support is highly competitive, as is the case now, the choice
of research projects veers toward applications of existing
knowledge, and away from basic science, posing a serious risk
to future productivity.
I have mentioned that medicine is being transformed today
by the unveiling of genetic blueprints, and by the
identification of the specific damage that occurs in most human
diseases, specifically like cancers. But discovery is not
finished. Despite these enormous increases in knowledge,
fundamental features of biological systems have yet to be
discovered. We know this from some very recent examples, the
discovery of unanticipated forms of RNA that perform functions
other than its well-known roles in the synthesis of proteins,
or the discoveries of enzymes from strange organisms that allow
rapid and efficient re-engineering of genomes of many kinds of
cells. Such unanticipated results and methods, and their
subsequent applications, can come only from unfettered basic
research.
The third point is that funders of research had aimed for a
balanced and synergistic portfolio. Each component of the
scientific landscape has a limited range of action, and
government science agencies, academic institutions, and some
charities have a strong mandate to invest in fundamental
science.
Commercial entities are constrained from a deep commitment
to unfettered basic research, but invest heavily in applied
research, and these observations articulated over 70 years ago
by Vannevar Bush have been the basis for the success of
American science. But still, all these elements need to
interact, and to learn where and how scarce resources are being
committed, to engage in collaborative work, and to accelerate
progress across the full spectrum of research and development.
Finally, the fourth point, which I will ask for some
indulgence just to describe briefly, leaders of funding
agencies, especially in government, can help in the situation
by using their various mechanisms to encourage
interdisciplinary team science to protect investigators working
in--on fundamental studies, and to work with our funding
partners, especially in these fiscally challenging times. The
NCI has exploited the flexibility of our funding mechanisms in
a variety of ways that are listed in my written testimony, just
to mention a few extremely briefly.
The Cancer Genome Atlas Project has supported many hundreds
of DNA sequences, geneticists, bioinformaticians, oncologists,
and others to compile an extensive set of characteristics about
over 20 different time--kinds of human cancer in a way that is
now transforming the way we approach cancer patients through
precision medicine.
Our Frederick National Laboratory for Cancer Research in
Frederick, Maryland, a contract program modeled on--in part on
the Department of Energy's national programs, carries out both
general service functions through nanotechnology, and clinical
collaboration with 19 other agencies, and specific projects,
like a project that addresses a collection of genes known as
rash genes that drive about a third of human tumors.
And, finally, our provocative questions exercise is
intended to bring scientists of many disciplines together to
identify the great unsolved, and sometimes not closely attended
to, problems in a way that now allows us to fund proposals to
answer those questions.
I will be pleased to answer any questions you might have.
Thank you, Mr. Chairman.
[The prepared statement of Dr. Varmus follows:]
[GRAPHIC] [TIFF OMITTED]
Chairman Bucshon. Thank you very much.
Now I recognize Dr. Tessier-Lavigne for five minutes.
TESTIMONY OF DR. MARC TESSIER-LAVIGNE,
PRESIDENT AND CARSON FAMILY PROFESSOR,
LABORATORY OF BRAIN DEVELOPMENT AND REPAIR,
THE ROCKEFELLER UNIVERSITY
Dr. Tessier-Lavigne. Thank you, Chairman Bucshon, Chairman
Smith, Mr. Lipinski, and other Members of the Subommittee for
the invitation to speak today about how best to harness public
and private sector activities to drive critical breakthroughs
for poorly treated diseases. As president of the Rockefeller
University, I bring the perspective of the academic sector.
Rockefeller is a graduate biomedical research university with a
distinguished record. Over our 113-year history, our faculty
has been honored with 24 Nobel Prizes in medicine and
chemistry, more than any other institution in the world. As
former Chief Scientific Officer at Genentech, a leading
biotechnology company, I also bring a perspective from industry
on how best to enable tomorrow's scientific and medical
innovation.
I will start by noting that, despite great advances in
health and life expectancy in past decades, as Chairman Bucshon
noted, there is an urgent need for new therapies. Death rates
from cancer remain stubbornly high, and chronic diseases, like
Alzheimer's and diabetes, are on the rise. The suffering is
immense, and the costs of care could bankrupt us.
The good news is that we are in a golden age of disease
research, thanks to technological advances like genome
sequencing. If we make the necessary investments, we can
understand why tumors spread, why nerve cells die in
Alzheimer's disease, and the secrets of our immune system. But
gaining this knowledge is only half the battle. Translating
discoveries into new therapies is a complex process with
substantial attrition.
For every 24 drug discovery projects initiated based on
basic science discoveries, only nine candidate drugs eventually
enter human clinical trials, only one of which will make it all
the way to approval to help patients in the marketplace.
Twenty-four down to one. This process takes, on average, 10 to
15 years, and more than a billion dollars for every approved
drug, a huge and lengthy investment.
Complex as it is, this process is remarkably successful
thanks to four major groups of stakeholders working closely
together. The first are biomedical scientists in academia and
government, who create new knowledge with federal support. They
explore the inner workings of cells and organs in health and in
disease, relying in important ways on instruments, tools, and
methodologies provided by the harder sciences, physics,
chemistry, math, and computer science, as has already been
noted.
Second are the large biopharmaceutical companies who lead
the complex drug development process based on that knowledge.
Two additional stakeholders, disease foundations and small
biotechnology companies, facilitate progression at the
interface of the first two. This ecosystem plays to the
strength of each participant. Academia provides an unfettered
environment where researchers can best explore scientific leads
to break open new fields, whereas companies, with their tightly
defined structure, are better suited to mounting the directed
studies needed for drug discovery and development. And only the
federal government has the resources and time horizon to invest
in basic research that may not see a return for many decades.
Companies already stretched thin by the duration and expense of
drug development do not.
Historically, this ecosystem has worked successfully, so
much so that approximately half of all new drugs today are
discovered in the United States. This investment has benefitted
patients, saved trillions in overall healthcare costs, and
boosted the economy enormously, generating high paying jobs and
increased economic activity, and it has stimulated massive
biotech and pharmaceutical investments in the U.S.
How, then, should we maximize this vital drug discovery and
development ecosystem, and what risks do we face? The logic of
the biopharmaceutical sector is simple. Companies locate their
R&D operations near the sites of scientific innovation in
academia to tap into the best scientists and a highly skilled
work force. And companies will make significant, even
multibillion dollar, investments in breakthrough therapies on
two conditions: if basic scientists provide sufficient
understanding of disease processes to justify the bets, and if
they see a path to getting an adequate return on their
investment.
The government's role in supporting a vibrant basic
research sector is, therefore, essential to understanding
poorly treated diseases. If the academic sector generates the
knowledge, the private sector will then rush in to apply it.
Programs like the NIH sponsored BRAIN initiative, and its
accelerating medicines partnership with industry can help focus
on areas of high unmet medical need, like psychiatric disease,
and facilitate translation of discoveries into drugs.
Conversely, reductions in federal support for science over
the past decade have weakened our ecosystem, with promising
young investigators turning away from the field to pursue more
stable careers, and scientists relocating to countries where
research funding is less challenging. If this trend continues,
we will see industry relocate to emerging sites of innovation
abroad. Countries in Asia, like China and South Korea, as well
as in Europe, are investing to become new epicenters of
biomedicine, and they are succeeding.
Beyond supporting the research sector, government must also
continue to address important structural issues to ensure our
country is attractive to private sector investment. Key
requirements include sufficient protections of intellectual
property, tax policies that favor R&D investments, and support
of STEM education to provide a highly trained work force.
In conclusion, we now find ourselves at a time of huge
medical need, but also enormous scientific and economic
opportunity. To retain its preeminence in this golden age of
biomedicine, the United States must pursue the necessary
investments and structural policies. Thank you for your
attention.
[The prepared statement of Dr. Tessier-Lavigne follows:]
[GRAPHIC] [TIFF OMITTED]
Chairman Bucshon. Thank you very much.
I now recognize Dr. Keasling for five minutes to present
his testimony.
TESTIMONY OF DR. JAY KEASLING,
HUBBARD HOWE JR. DISTINGUISHED PROFESSOR
OF BIOCHEMICAL ENGINEERING,
UNIVERSITY OF CALIFORNIA, BERKELEY;
PROFESSOR, DEPARTMENT OF CHEMICAL &
BIOMOLECULAR ENGINEERING,
UNIVERSITY OF CALIFORNIA, BERKELEY;
PROFESSOR DEPARTMENT OF BIOENGINEERING,
UNIVERSITY OF CALIFORNIA, BERKELEY;
DIRECTOR, SYNTHETIC BIOLOGY ENGINEERING RESEARCH CENTER
Dr. Keasling. Chairman Bucshon, and distinguished Members
of the Committee, I thank you for the opportunity to testify at
this important hearing, and for your strong and sustained
support for science and technology. Today I would like to begin
to tell a story of how we engineered a microbial production
process for a much needed drug to combat a deadly disease that
affects millions of children around the world, and how
repurposing that same process allows us to meet needs not only
for health, but also for energy, and the environment.
There are approximately 250 million cases of malaria every
year, causing nearly a million deaths annually. Most of the
victims are children under the age of five. A child dies of
malaria every minute. Conventional quinine-based drugs are no
longer effective. While plant derived artemisinin combination
therapies are highly successful, for many malaria victims, they
are simply too expensive.
To bring down the cost of the therapy and stabilize the
supply, we engineered a microbe, a yeast, to produce a
precursor chemical to the drug. To do this, we transferred
genes responsible for making the drug from the plant to a
microorganism. The process of producing artemisinin is akin to
brewing beer. Rather than spitting out ethanol, the microbes
spit out artemisinin. The microbe consumes that sugar, and
produces the drug from that sugar.
We licensed this microbial production process to Sanofi-
Aventis, who scaled the process to industrial levels. This
year, Sanofi-Aventis produced 70 million doses of artemisinin,
and is on track to produce 100 to 150 million every year for
the next few years, roughly half the world's needs. We predict
that the drug produced by this process could save a large
fraction of the annual one million children that die of
malaria.
Begun in 2004, the artemisinin project was supported by a
$42 million grant from the Bill and Melinda Gates Foundation,
and took roughly 150 person years' worth of work to complete
the project. We were able to complete the project largely due
to readily available, well characterized biological components,
a significant point that I will return to shortly.
The artemisinin story demonstrates the significant medical
benefits of engineering biology, but also reveals how these
benefits extend to chemical manufacturing. Unfortunately,
engineering biology is still time consuming, unpredictable, and
expensive, and many urgent challenges in health, and energy,
and the environment remain needlessly unresolved. Efforts to--
aimed at making biology easier to engineer have come to be
known as synthetic biology.
As was the case with the development of synthetic
artemisinin, synthetic biology represents a convergence in the
advances in chemistry, biology, computer science, and
engineering. Experts in the fields work together to create
reusable methods for increasing the speed, scale, and precision
with which we engineer biological systems. In essence, this
work can be thought of as the development of biological based
toolkits that enable improved products across many industries,
including medicine and health.
About ten years ago, around the start of the artemisinin
effort, several colleagues and I set out to develop these more
generalized approaches to making biology easier to engineer. We
believed that we could engineer microbes to produce virtually
any important chemical from sugar, yet there was a severe lack
of publicly accessible tools for building biological processes
and products, so we went out to the National Science
Foundation, proposed a center dedicated to building these tools
for the research community. In response, NSF granted us the
Synthetic Biology Engineering Research Center, a ten year
multi-institutional research project designed to lay the
foundations for engineering biology.
Now, eight years later, SynBERC has produced a broad range
of toolkits that are being developed in the fields of energy,
agriculture, health, and security, and offer an array of
economic benefits. When SynBERC was established in 2006, it was
the nation's single largest research investment in synthetic
biology.
Eight years later, this, and other federal funding, have
catalyzed the growth of academic research centers around the
country, the production of many synthetic biology enabled
chemicals in the private sector, five startup companies from
SynBERC itself, and a robust private/public consortium that
helps guide the research from lab bench to bedside.
The U.S. model has been so successful that other countries,
particularly China and the U.K. are developing aggressive,
nationally coordinated research programs in an effort to
surpass the U.S. to become the global leaders in biological
engineering. These investments in synthetic biology are already
making their mark on national economies. By some estimates,
domestic revenues from biologically engineered systems was
thought to account for more than 2.5 percent of U.S. GDP in
2012, with a growth rate of 10 percent.
The U.S. has been a leader in this field because of early
and focused federal investment, but we now face stiff
competition from overseas, and uncertainty in our pre-
competitive investments here at home. I believe that now is the
time for federal government to work with academic and
industrial researchers to launch a national initiative in
engineering biology, to establish new research directions,
technology goals, and improve inter-agency coordination. I
thank you for your time.
[The prepared statement of Dr. Keasling follows:]
[GRAPHIC] [TIFF OMITTED]
Chairman Bucshon. Thank you very much.
I now recognize Dr. Venter for five minutes to present his
testimony.
TESTIMONY OF DR. CRAIG VENTER,
FOUNDER, CHAIRMAN, AND CHIEF EXECUTIVE OFFICER,
J. CRAIG VENTER INSTITUTE, SYNTHETIC GENOMICS, INC.,
AND HUMAN LONGEVITY, INC.
Dr. Venter. Chairman Bucshon, distinguished Committee
Members, thank you for the invitation to be here today. I
represent a not-for-profit independent research institute, the
J. Craig Venter Institute, and two biotech companies, Synthetic
Genomics, and Human Longevity, Inc. We have a combination of
funding from the private sector, from donations, from DOE, from
DARPA, from NASA, from NSF, NIH, BARDA, and a range of
interactions that range from 100 percent privately funded to
100 percent publicly funded.
This is a very exciting time in science, as you have heard
from my colleagues. We now have the ability to interchange the
genetic code and the digital code in the computer. We can read
the genetic code, put the data in the computer, and now we have
shown, as my colleague Jay Keasling has discussed, we can go
the other way, and actually write the genetic code. And, four
years ago, we announced the creation of the first synthetic
organism, completely writing the chemical genetic code.
This is having implications in lots of areas. We have had a
great collaboration with BARDA and Novartis for making the
first synthetic vaccine against flu. When H7N9 flu broke out in
China, a team in China sequenced the genome from a patient,
posted it on the Internet. We downloaded it, and within a few
hours synthesized the H7N9 virus. That was immediately started
in development for a vaccine. BARDA has now stockpiled a
substantial amount of the H7N9 vaccine before the first case
has appeared in the U.S. It is the first time in history where
the U.S. is ready for a deadly pandemic before the first case
has reached this country.
We can send vaccines through the Internet. Biological
information now moves around the world digitally. It is not a
matter of sending DNA in clones. We are using this in lots of
different ways. We had recently announced, at Synthetic
Genomics, a collaboration with United Therapeutics to re-
engineer the pig genome, humanizing the pig genome to allow
organ transplantation of hearts, kidneys, and lungs into humans
to meet a huge medical need of lack of organ transplants. This
comes from all these new tools for writing and editing the
genome. You have heard from Jay Keasling how this can be done
to create chemicals. We have engineered a synthetic genomic
algae to produce large amounts of Omega-3 fatty acids that ADM
is taking into extremely large scale production.
The ultimate application of all this is in medicine. We
have recently announced that Human Longevity formed the largest
human DNA sequencing facility in the world. We are scaling up
from 15 years ago, when we sequenced one genome over nine
months for roughly $100 million to doing 100,000 genomes a
year, hopefully within 18 months, with the goal to have one
million human genomes by 2020 in a database to allow this data
driven practice of medicine.
This is a very exciting era, but it is a challenge, as you
have heard from my colleagues, with the changes in government
funding, and the competition from overseas, as Dr. Keasling
talked about. In this same field, the Chinese government
supports their industry to the tune of billions of dollars,
versus competition with industry. These challenges are
important, exciting. Also we deal with the public policy issue.
Bob Friedman, my colleague, is head of policy at the Venter
Institute. We have been asking ethical questions before anybody
else. We have driven them, and the latest iteration of this was
when we announced the first synthetic cell. The Obama
Administration asked their new bioethics commission to take
this on as their number one challenge.
These are exciting times, they are challenging times, but
this science has a chance to revolutionize medicine, and
perhaps be a new industrial revolution. I am pleased to take
any questions. Thank you very much.
[The prepared statement of Dr. Venter follows:]
[GRAPHIC] [TIFF OMITTED]
Chairman Bucshon. Thank you, and I agree. This is an
exciting time in health care. I miss health care. I have been
out of it now for four years. From an overall federal budget
standpoint, usually when I am at a hearing, and we are talking
about discretionary funding programs, I like to say that right
now in Washington, D.C., unfortunately, we are not addressing
the entire piece of the federal spending pie. And--I will. I
recognize myself. Because he pointed--he told me I had to, so I
do, for whatever time I have left.
And that is a challenge, because many people know that 60
or 65 percent of all federal spending right now is mandatory
spending, and the remaining part is discretionary spending,
including Department of Defense, and that is where we start to
see discretionary programs, like research funding, being
pinched in an effort to balance the overall federal budget.
So I am hopeful that in the next number of years, or short
timeframe, that we will begin to address the entire piece of
the pie, and take some of the pressure off the discretionary
spending, particularly research funding, which I think many--
most of us on this panel would agree needs--is extremely
important, and needs to be probably increased to keep up.
I will ask Dr. Venter this question. The return on
investment on R&D, like in the pharmaceutical industry, has
been a subject of recent debate because there are companies
that are adept at R&D, and these returns can be significant
both--from a both clinical and economic perspective. However,
out there there are some forces that are, specifically in the
health care industry, that have maybe the opposite perspective,
people that are controlling companies, and believe that R&D is
no longer productive in the private sector, for example. And
you--seeing this, as some companies are bought and sold, that
some people don't value the R&D that was being done by the
company.
Do you disagree with this? Can we talk about the benefits
of robust R&D, at the same time the potential consequences of
cuts to R&D budget in the private sector, based on the
shareholder investment in the companies?
Dr. Venter. Well, I think the experience that I have, and
if you look at the biotech industry as a whole, it is largely
based on basic research. It is only when you get way past that,
into the manufacture and development of drugs, that I think you
get into some of those conflicts.
What I see is many people turn to biotechnology, and the
robust funding that we have with capital investment, as an
alternative way to fund basic research, because every
breakthrough that we rely upon in the field of synthetic
genomics, we have been doing basic research there for eight
years. With these new efforts to sequence large numbers of
human genomes, and have them impact medicine, these are large
research projects that, in their places, are taken on by
government funding, not by private capital.
So I see it from the opposite point of view. I see much
more private money, private investment, going into supporting
basic research, because it is--I think we all agree, it is the
basic research that drives these breakthroughs in every field.
Chairman Bucshon. Yeah, I would agree. R&D research in the
private sector, you know, is important, and hopefully we can
continue to encourage all of our companies to continue to value
this as a very valuable thing.
Dr. Varmus, in your opinion, do we have the right balance
between basic and applied science research, particularly in the
biomedical science? Do we spend too many resources, or over-
emphasize applied science--sciences at the expense of basic
science research? Do we--where is that balance? Where do you
see that?
Dr. Varmus. Well, thank you for the question, Chairman. It
is----
Chairman Bucshon. Turn on your mike.
Dr. Varmus. --quite difficult--sorry. This is a very
difficult thing to measure, because the definitions of basic
versus applied science, especially in this day and age in which
the approach of basic science to clinical application is very,
very close. I would argue, based on my observations, it is hard
to document numerically that there is, in this moment of
difficulty in obtaining funds for research, a tendency to think
more about how the research that is being done, even in
government supported labs, can be applied to the very real
problems of human disease, and that this creates a situation in
which scientists think their chances of being funded are
augmented, and it may well be, by making specific claims for
how the work they do will be applied in the short run.
We have tried to defuse that somewhat recently at the
National Cancer Institute by announcing a new award, a seven-
year outstanding investigator award, that provides stable
funding for at least 50 percent of an investigator's work, so
they are more willing to take risky approaches to science, to
say, this is an important question. I don't know where it is
going to come out, it may or may not be useful. That is an
element that we need to protect, and I--and we are making an
effort to do that.
I would say one more thing about the previous question you
asked, about research in companies, and I agree with Craig that
the major companies do recognize the importance of research. In
my observation over the last few years, large companies and
small are more willing to come to the NIH to work with us, we
doing more of the more basic work, they bringing in the more
applied approach.
And we see this in the design of our clinical trials,
where--which are increasingly becoming dependent on genetic
analysis of tumors, targeted therapies being provided for tests
by the companies, companies eager to collaborate with us,
either through the NIH Foundation, or through work that we do
at the NCI.
Chairman Bucshon. Thank you very much. I now recognize Mr.
Lipinski for his questions.
Mr. Lipinski. Thank you, Mr. Chairman. I want to start with
Dr. Keasling. And I just want to say, Dr. Keasling, it was--
trying to remember how many years ago, five or six years ago,
that I came out to JBEI specifically at that time mostly to
look at the bioenergy work that was going on there. But I
wanted to ask you about technology transfer.
You successfully co-founded a company, Amyris, to bring
your discovery to the marketplace, so I would like you to talk
about the challenges that you have faced trying to launch your
company, or otherwise transfer your discoveries into commercial
applications, and then talk about what role do you see federal
government can play at helping transfer academic research into
the marketplace, and touch on what--at what stages should the
federal government be involved, and what is the best way for
the federal government to be involved?
Dr. Keasling. All right. So I will start answering that
kind of--the last part first, and that is that the work that
went into the anti-malarial drug was based on basic science
that we did that was funded through the National Science
Foundation to try to understand how microbes produce
cholesterol-like molecules, and how plants produce molecules
that are flavors and fragrances. And we then took that science,
and engineered a microbe, and happened to learn about this
anti-malarial drug.
And that attracted funding from the Bill and Melinda Gates
Foundation that allowed us to both develop this microbe, but
also build Amyris, a company that makes no profit, and neither
does Sinofi-Aventis, on this anti-malarial drug. In fact, they
gave the technology away. It is being used free. And so did the
University of California, which has title to the patents.
What Amyris was able to do was take that same microbe that
produces the anti-malarial drug and swap out a few genes, put
in a few others, and it produces a diesel fuel that is now
running in buses in Sao Paulo and Rio. In fact, they have
clocked about five million miles on that diesel, and is now a
molecule that is in flavors, and fragrances, and cosmetics. In
fact, you can buy cosmetics from these yeast produced
molecules.
Our ability to get that technology out to companies is
critical. Amyris came into the University of California,
licensed that technology, and that allowed them to build the
company. And that--federally funded research, and research
funded by the Bill and Melinda Gates Foundation made all of
that possible.
I think it is critical that the federal government continue
to fund basic science and basic research because, as we heard
in this hearing today, that leads to the development of
companies, and those companies tend to be located near the
science that is being done so they can have access to those
scientists, and build the companies further. Amyris now has
about 400 employees, about 500, actually, in the U.S., and in
Brazil, that are working on producing more molecules like this
that will make the U.S. competitive.
Mr. Lipinski. Thank you. And you had talked about doing a--
the time may be right for some kind of national initiative.
What would--you think that would--should look like?
Dr. Keasling. I think that the U.S. could, and should, make
investments in biomanufacturing. And generally, in this area of
engineering biology, we have been the leader since the
discoveries of genetic engineering in the early '70s. But that
leadership is being challenged by China and many other
countries, and they are building on a lot of the discoveries
here, and the fact that we don't have federally coordinated
effort. An effort that would coordinate all the federal
agencies, so that they are moving in the same direction toward
engineering biology, I think, could have a huge impact on the
field, and also on our national economy.
As I mentioned earlier in my talk, this area is an area
that is growing rapidly, and will continue to grow. We want to
make sure that it grows in the United States, and an effort by
the federal government around engineering biology could ensure
that.
Mr. Lipinski. Do any of the other witnesses have any
comments or suggestions along those lines?
Dr. Tessier-Lavigne. I just want to reinforce the last
point, that the basic science discoveries and their
commercialization leads to--not just to great outcomes, like
the generation of these molecules or new medicines, it also
creates real economic activity locally, as the industry will
locate next to the sites of innovation.
Mr. Lipinski. Thank you. And Dr. Varmus or Dr. Venter,
any----
Dr. Varmus. Well, I just would emphasize that, at the
Cancer Institute, for example, the fundamental tools of genetic
engineering are in use almost every day to change the behavior
of cells, experimental animals that allow us to probe the
secrets of cancer more profoundly, and new developments in this
area are much to be welcomed by us in our experimental
approaches to cancer.
Mr. Lipinski. Thank you. I yield back.
Chairman Bucshon. Thank you. Recognize Mr. Johnson from
Ohio, five minutes.
Mr. Johnson. Thank you, Mr. Chairman, and really appreciate
our witnesses being here today for this hearing. I am an
information technology professional for most of my life before
I came here to Congress, so I am always looking at how advances
in technology affect different industries, particularly yours,
so I would like to go in that direction just a little bit, if I
could.
So, for Dr. Varmus and Dr. Venter, if you would, you know,
we are increasingly seeing the need for big data to help us
decipher scientific problems, including understanding the
genome, and complex diseases, like cancer. What is the future
of cloud computing and big data in biomedical science research,
and what role will they play, do you think?
Dr. Varmus. Thank you. This is a very timely question,
because the NIH, and NCI in particular, are now housing the
largest data sets in the world as a result of the accumulation
of genetic information about cancer. As you may understand,
cancer----
Mr. Johnson. But can't find Lois Lerner's e-mails, go
figure.
Dr. Varmus. No comment.
Mr. Johnson. Go ahead, go ahead.
Dr. Varmus. As you know, cancer is a disease largely driven
by changes that occur during life and genomes, and being able
to understand the patterns which differ from every tumor to
another is critical. We had built, through the exercise I
mentioned, The Cancer Genome Atlas, a huge database that needs
interpretation.
The question about cloud computing is particularly apt for
us at the moment. We now have a--we are about to launch a cloud
pilot exercise in which we will fund three--two or three
competitors to do experiments with cloud computing, to allow
investigators around the world to work with our lab's large
data sets. The NIH more generally has an initiative called Big
Data to Knowledge, BD2K, that was attempting to learn both the
computational rules that will make best use of that data, but
also to do so in the context of privacy, which is important in
medical research, and in a way that allows fair access of our
investigators throughout the world to those data sets.
In addition, there is a movement underway internationally
to create something called a Global Alliance for Genomics and
Health that will--has attracted the attention of literally
hundreds of institutions around the world to be sure that data
sets, initially in the area of oncology, and various genetic
diseases to have access to those data sets, both to understand
the underlying nature of the disease, and to make informed
decisions about prognosis and treatment of those diseases.
Mr. Johnson. Okay. Thank you. Dr. Venter?
Dr. Venter. Thank you for your question. It is--it is, as
Harold said, very timely. There are two thresholds we just
passed that actually allowed us to form Human Longevity. One
was a sequencing technology that just barely passed the
threshold of cost and accuracy.
But the most important changes are in the computer world,
and we are going to rely very heavily on cloud computing, not
only to house this massive database, but to be able to use it
internationally. We will have operations in different parts of
the U.S., and even in Singapore, to allow us to do computation
24 hours a day. The cloud sort of makes that seamless, instead
of trying to transport this massive amount of data.
Trying to move things from my institute in Rockville,
Maryland to La Jolla, we had dedicated fiber, but it is now so
slow with these massive data sets, we use Sneakernet or FedEx
to send discs, because we can't send it by what you think would
be normal transmission. So the use of the cloud is the entire
future of this field.
Mr. Johnson. Okay. All right. Well, Dr. Varmus, in your
written testimony you discussed how supercomputers have created
a powerful tool to analyze massive, complex data sets for
genomics, proteins, and other biological sciences. In my final
30 seconds here, do you think that if the Department of Energy
and National Science Foundation developed the next generation
of computing--supercomputing, moving from petascale to exascale
level, that even more medical breakthroughs would be made
possible, and is supercomputing capabilities a limiting factor
for future medical breakthroughs?
Dr. Varmus. Yes, absolutely, and we--this, in some way,
would--we would obviously capitalize on that for its--the DOE's
agencies. We have, in the past, used DOE beam lines for our
structural biology work. As Craig mentioned earlier, the number
of genomes being sequenced is accelerating very rapidly, and
the ability to sift through all that information, to look for
patterns, to look for common mutations, and different tumor
types, to try to understand the biological events as revealed
by genetic analysis to the clinical events of real life
experiences that the patients had is going to be a tremendous
task that is going to--we have not yet achieved in solving
simply by sequencing these genomes. We need to understand what
those patterns mean, and it is going to require a tremendously
heavy lift in the computer world to do that.
Mr. Johnson. Okay. Well, thank you very much. Mr. Chairman,
thanks for giving me the additional time.
Chairman Bucshon. You are welcome. They are--we are going
to have votes probably in the next five minutes or so, but once
they call the vote, we still have plenty of time. We will be
able to finish our line of questioning, and--so I now recognize
Mr. Peters.
Mr. Peters. Thank you, Mr. Chairman. I want to thank all of
you for being here, particularly my constituent, Dr. Venter.
And we are so proud, and awed, and excited by what you have
accomplished in the genome.
And what I was--what--as I was listening to the testimony,
and looking over some of what you presented, it strikes me that
you, in particular, are someone who has been on both the
private and the public side of this. And we have been talking
for the last year, the model that we followed here with the NIH
is that we provide a lot of funding, and much of it is
competed, so that you have scientists who file these
applications for grants. It is very competitive, it is peer
reviewed, and that has been the basis of a lot of our science.
And what I am inferring from this discussion is that now
there is more a private sector kind of involvement, a lot of
the--it is not the same model. So how should I, as a
policymaker, be thinking about this, and is the old model, the
model that has kind of been our playbook and so successful, is
that still the same, or is that changed?
Dr. Venter. Well, thank you for the question. It is a very
important one to answer--I also spent ten years in government
at the NIH----
Mr. Peters. Right.
Dr. Venter. --so I think I have been institutionalized many
times. So I think the challenge, and the risk I see with
government funding, aside from, as Harold said, the decreased
buying power of it is the increased risk aversion of that
funding. And I am pleased to hear what he says about the seven
year grants. I think that is a step in the right direction.
Finding a way to set aside a certain percentage of NIH
funding to mandate risk is a challenge, and I can tell a story
about it. With a previous NIH director, they started this new
award for high risk research, and I was on the committee with
other successful researchers, and the top 10 people we listed
for this award were rejected because they were too risky.
Mr. Peters. Too risky, right, yeah.
Dr. Venter. So the challenge is how do you legislate risk
taking when it is sort of not built into the fabric of the
people and the government? But somehow we have to take greater
risk with this funding to get more value for that funding.
Mr. Peters. Did that used to happen on the natural because
there was more funding? And one of the things I have heard is
that, because of the reduced buying power, the reduced
investment, effectively, only the safe stuff is getting done,
that if there were more funding, it is alleged that risky stuff
would happen as part of the mix.
Dr. Venter. Well, there was more funding per capita. There
were almost an order of magnitude less scientists when I
started in my----
Mr. Peters. Right.
Dr. Venter. --career. And the funding from the Cancer
Institute, there was much more on reputation of the
investigator versus the sort of negotiated contract of the next
stage of the research. And it sort of had to go that way, I
think, because of fewer dollars per the number of researchers.
So, you know, there is no--I don't have a magic solution for
it, but----
Dr. Varmus. No. I----
Dr. Venter. --we need to change something.
Dr. Varmus. I don't have a magic solution. I would like to
comment briefly on the question, which, of course, is a very
important one. I don't think the model is essentially changed.
I think--and it is important to remember that, while much of
our research is conducted through grants that are given to
competing extramural investigators, we also have other ways of
doing research. For example, through an intramural program,
where there is a lot more stability, and a chance to encourage
risk taking.
And we also, within the NCI, have the privilege of having a
contract laboratory, the national--the Frederick National Lab
for Cancer Research out in Frederick, Maryland, where we can
undertake projects that are extremely risky, like the new RAS
initiative that I mentioned briefly in my testimony.
The question of how we get both investigators and reviewers
to take risks is a tricky one, because everyone recognizes this
is a limited pot of money, and when you have a good proposal
that seems very likely to yield tangible results, everybody's
focus tends to be on funding those first. And we have had to
create programs, like our Outstanding Investigator Award, like
the so-called Pioneer, and other innovation awards that are now
awarded----
Mr. Peters. Right.
Dr. Varmus. --throughout the NIH to try to encourage risk.
But it is not the NIH, it is the whole community that is seized
with this anxiety about how to undertake funding that is most
productive.
Dr. Tessier-Lavigne. If I may just comment briefly also on
the question.
Mr. Peters. We together have 15 seconds. Yeah, go ahead.
Dr. Tessier-Lavigne. The private sector is increasingly
trying to tap into the discoveries in the basic science
community, but they are not generating the knowledge, nor will
they. So there isn't a change in that sense. There is still--
nothing can substitute for the federal support of basic
research.
Mr. Peters. Well, thank you. Mr. Chairman, I appreciate the
hearing. I yield back.
Chairman Bucshon. And, again, we--they have called votes,
but for the first vote, we probably have 20, 25 minutes to get
there to vote, so we are going to continue on with our--with
recognizing Mr. Hultgren for five minutes.
Mr. Hultgren. Thank you, Chairman. Thank you all for being
here. This is a very important hearing. It has been one of my
primary goals on the Committee, to make sure that our
laboratory system is set up, really, to provide the best bang
for the buck, and to better work in our national interest. I
just want to thank you for your work, and for your testimony
here today.
With the great innovation ecosystem in Illinois, I have
seen how labs provide a valuable resource to industry to do
work in facilities that no individual company could build. The
federal government does have a role in this space. Use of
facilities such as the advanced photon source at Argonne have
provided companies such as Abbvie with the unique research
capability to make groundbreaking discoveries.
What would normally take the company weeks on their own can
be done in days with samples spending more in overnight
deliveries than on the lab bench. My scientists at FERMI have
also done key research in the accelerator technology necessary
to finish the Linac Coherent Light Source upgrade at SLAC.
Yesterday I introduced a bill to help modernize the
national labs with my good friend Mr. Kilmer from Washington,
along with Chairman Smith, and other Members from the
Committee. We are looking to make sure that these facilities
are open to partner with industry when it makes sense, ensuring
that discoveries are not stuck in the lab.
Dr. Tessier-Lavigne, how are the goals of pharmaceutical
R&D different from federally funded research projects, and I
wonder if you could explain--but also how can the federal
government help to better accelerate innovation in this field?
Dr. Tessier-Lavigne. Well, thank you. The goals in this
sense are complementary, they are not different, but it is
really a staged process, where the fundamental insights into
what goes wrong in disease, whether it is asthma, or
Alzheimer's Disease, or various cancers, are generated, for the
most part, in the academic sector.
The companies really come in when the discoveries are
breaking, when insights are starting to coalesce, and they sift
through them to try to find the most promising ones, and then
deploy their horsepower, which is really focused around taking
those insights, taking molecular targets, which they believe
will be good targets against which to make drugs, and then
start to make the drugs. That long odyssey of drug making
takes, on average, 13 years, and over a billion dollars. They
do that part of the work.
The--so the research is complementary. It is not identical.
There is some basic research, some fundamental research being
done in the private sector, but very little compared to the
academic sector, and vice versa. Some academic institutions
will actually make drugs, and take them through clinical
trials. Those are the exceptions that prove the rule.
And then at the interface, the small startup companies are
very important in helping sift through the discoveries made in
academia, and move them towards the private sector, with the
big companies then partnering with them as well, and disease
foundations providing an assist. So it is really an ecosystem
with those four components.
How can we facilitate it? There is a lot of effort being
placed right now on that interface. It is really about the
interface. How can we ensure that discoveries in academia don't
lie fallow, that people recognize them and develop them? And
there are a number of initiatives that are being made on those
fronts.
I mentioned in my testimony the Accelerating Medicines
Partnership, which brings together the NIH, the Foundation for
NIH, and 10 companies to focus on very important areas, like
Type II diabetes and Alzheimer's disease, to try to identify
the best molecular targets. What are the best insights from
academia? What are the biomarkers of the disease? What are the
best targets for the biopharmaceutical industry on which to
deploy its horsepower?
So I think it is initiatives at that interface that I think
will yield the biggest bang for the buck. What we are not going
to see is a change where the pharmaceutical industry does a lot
of the basic research, or academia makes a lot of the drugs.
But what we can really help with is that interface.
Mr. Hultgren. Thank you. Dr. Venter, and also Dr. Keasling,
what--are you concerned about any government regulations that
might adversely affect both research and technology transfer of
advances in synthetic biology?
Dr. Venter. Thank you for the question. I have not seen
anything at all. I think, you know, that the whole case of
intellectual property being important in this new field I think
is overplayed. I think, in this new field of applying genomics
to medicine, and the rapid change of events in synthetic
biology, it is first mover effects, and making great advances I
would say are an order of magnitude better than IP is now. It
is like the software industry. The changes are happening so
fast that you can't really protect things with intellectual
property as much as you can by just trying to stay ahead of the
curve. My colleagues may disagree.
Mr. Hultgren. Dr. Keasling, yeah, I wonder if you have any
thoughts on government relations--or, I am sorry, government
regulations that might adversely affect research and
technology.
Dr. Keasling. I don't think there is right now. We have had
a very effective system that started with the dawn of genetic
engineering. That system has changed over the years as the
technology has changed, but it has proven very effective, and I
think we should continue that regulation that works so well.
Dr. Tessier-Lavigne. And if I may just----
Mr. Hultgren. Quickly, I am out of time.
Dr. Tessier-Lavigne. --that is right, comment on Dr.
Venter's point, I think that his point really applies to tools
and technologies, which evolve quickly. I think when it comes
to the pharmaceuticals, there the patent system and IP
protection is absolutely essential. Otherwise, the industry
just won't invest.
Mr. Hultgren. Thank you. I am out of time, and I know we
have got votes, so I will yield back. Chairman, thank you so
much.
Chairman Bucshon. You are welcome. I ask unanimous consent
to allow Mr. Rohrabacher to participate in the questions.
Without objection, the Chair recognizes Mr. Rohrabacher for
five minutes.
Mr. Rohrabacher. Thank you very much, Mr. Chairman, and let
me note, on the last point that was just made, that patent
rights have been considered vitally important to American
progress from day one. In fact, it is the only right that is
written into the body of the Constitution as the word right.
The Bill of Rights came later. And the fact that we have had a
diminishing of patent protection in our country is of great
concern to me, as is the fact that we have had a medical device
tax as a vehicle to try to provide some kind of mechanism.
Seems to me to be showing that perhaps there isn't as much
appreciation for technological advance in the higher circles
that we should have.
Also let me just note that the FDA has recently approved Al
Mann's ten year question to have an inhaler being used as a
substitute for needles for diabetics, and in the treatment of
diabetes. And it took him ten years and a billion dollars.
These are things of great concern. That can't go on. Having
something held off the market for that long, and that
expensive--added to the process are reasons for concern.
But today, Mr. Chairman, I would like to ask the panel
about another flaw in the system. I would like to submit with
a--for the record an article from the New York Times.
Chairman Bucshon. Without objection.
[The information appears in Appendix II]
Mr. Rohrabacher. This article details a real challenge that
has surfaced in California, with a particular company that is
being taken over by a hostile takeover. And it appears to me,
after looking at this, and looking at the details behind this,
that we have a basic flaw in our tax system, and in our basic
corporate structure that we have set up that will discourage
R&D in the private sector by companies.
And what we have here is Allergan, a company that has
hundreds, if not thousands, of employees engaged in research is
being taken over--a hostile takeover by a company who is
actually raising the money for the hostile takeover by a plan
that includes eliminating all the R&D. And thus you have a
profit in eliminating R&D from a company by other companies
wanting to take over.
I mean, this--if this methodology is seen by others, we are
going to have basically a huge reduction--we have made it
profitable for companies, then, to come in and eliminate R&D.
Have any of you gentlemen got any thoughts on that? Or is this
just maybe a new----
Dr. Venter. I will----
Mr. Rohrabacher. --concept----
Dr. Venter. Yes.
Mr. Rohrabacher. --here?
Dr. Venter. This is not the----
Mr. Rohrabacher. I didn't----
Dr. Venter. --a--it is not a new concept to the
pharmaceutical industry.
Mr. Rohrabacher. Okay.
Dr. Venter. CEOs will come in, and think they can greatly
improve the bottom line by getting rid of R&D, and----
Mr. Rohrabacher. Right.
Dr. Venter. --that is true for a very short period of time,
but they basically bankrupt the company very quickly for doing
that. So anybody who takes that philosophy is just----
Mr. Rohrabacher. Well, this----
Dr. Venter. --extremely shortsighted.
Mr. Rohrabacher. Well, then, this is really a--well--
shortsighted. They are not shortsighted for themselves. That is
the whole point. They give themselves a million dollar bonus
and buy a new yacht because they have now given themselves a
profit at the expense of perhaps things--discoveries that could
be made that would improve the lives of all of us ten years
down the line. This is a catastrophe. This is a catastrophe for
people whose lives will now not be helped by the R&D that
Allergan, and other companies like it, are conducting. And we
need to correct this flaw in the system.
All these other things I have heard today are important,
but I am really--Mr. Chairman, I commend you for calling this
hearing. And the fact is that--but what we are--what--this
whole issue that I just brought up, this undercuts so much of
whatever the government's basic research is doing, and all the
other things that have been mentioned, if our own private
companies that invest in it, now we found--we have made it
profitable for other companies to take them over and eliminate
it. We are going to--our people are going to suffer needlessly
in the future because of this.
Mr. Chairman, again, thanks for holding this hearing. All
of the points that were made today are really significant. I
have learned a lot, and I appreciate your leadership in this
issue.
Chairman Bucshon. Thank you, Mr. Rohrabacher. At this point
I would like to thank all the witnesses for your testimony.
This is very valuable testimony, as our Subommittee, and the
full Committee, look to reauthorize National Science
Foundation, and are very important in funding, you know,
research, obviously. And the Members, thank them for their
questions.
The record will remain open for two weeks. There may be
some additional written questions sent to you that didn't get
covered today from the Members, and just please respond to them
as timely as you can. We appreciate your testimony. The
witnesses are excused. The hearing is adjourned. Thank you.
[Whereupon, at 10:18 a.m., the Subcommittee was adjourned.]
Appendix I
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Answers to Post-Hearing Questions
Answers to Post-Hearing Questions
Responses by Dr. Harold Varmus
[GRAPHIC] [TIFF OMITTED]
Responses by Dr. Marc Tessier-Lavigne
[GRAPHIC] [TIFF OMITTED]
Responses by Dr. Jay Keasling
[GRAPHIC] [TIFF OMITTED]
Responses by Dr. Craig Venter
[GRAPHIC] [TIFF OMITTED]
Appendix II
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Additional Material for the Record
Statement submitted by Ranking Member Eddie Bernice Johnson
[GRAPHIC] [TIFF OMITTED]
Letter submitted by Subcommittee on Research and Technology
Chairman Larry Bucshon
[GRAPHIC] [TIFF OMITTED]
Article submitted by Representative Dana Rohrabacher
[GRAPHIC] [TIFF OMITTED]
[all]