[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


                                     ______

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       Available via the World Wide Web: http://science.house.gov
       

              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

                              ----------                              


                   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

                              ----------                              


                   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]