[Senate Hearing 110-]
[From the U.S. Government Publishing Office]


 
  DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND 
          RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2008

                              ----------                              


                          MONDAY, MAY 7, 2007

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 1:31 p.m., in room SD-116, Dirksen 
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
    Present: Senator Harkin.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF DR. JEREMY BERG, DIRECTOR, NATIONAL 
            INSTITUTE OF GENERAL MEDICAL SCIENCES

                OPENING STATEMENT OF SENATOR TOM HARKIN

    Senator Harkin. The Committee will come to order.
    This is the subcommittee's fourth hearing on the National 
Institutes of Health this year. We've heard from nine 
institutes, today we'll hear from four more: The National 
Institute of General Medical Sciences, the National Human 
Genome Research Institute, the National Library of Medicine, 
and the National Institute of Biomedical Imaging and 
Bioengineering.
    We asked these four Institutes to appear together because 
they're all involved in expanding the frontiers of science. 
Unlike many of the institutes at NIH, none of these are charged 
with attacking a particular disease. Instead, they develop 
cutting-edge tools and resources that benefit research on all 
diseases--things like sequencing the human genome, combining 
huge, easily searchable databases, developing new imaging 
technology or basic research training.
    What I'd like to ask is if each of you could speak for 5 to 
7 minutes. Summarize the research that you've overseen over the 
past year or so, and give us a look ahead at the initiatives 
that you are planning for fiscal year 2008 and beyond.
    Senator Specter cannot be here today, but I will keep the 
record open for his opening statement, and any questions that 
he might want to submit.
    At the outset, I just want to thank each one of you for the 
work that you do in the Institutes that you direct, all that 
you're doing to improve people's health. We are grateful for 
your dedication and skill, each and every one of you, for so 
many years.
    I started these forums--these hearings, like this--I don't 
know if you've talked to any of your fellow Institute 
Directors, but I feel it's good to be able to get into these in 
a little bit more depth. Actually, the first person that 
started these in this room, and having them in this manner was 
Senator Lowell Weicker, and I was a freshman Senator at the 
time. I just thought they were great sessions for us to learn 
more in depth about what the Institutes are doing, and that's 
why we're doing it in this manner again.
    So, I've had, basically, four at a time, like this, and try 
to group them in some kind of a semblance of rationality of 
what the Institutes were doing.
    So, I'd like to, again, just kind of get into it. I'll have 
some questions when you finish, but I'd like to just go 
through, perhaps all the Directors once, I may even ask you a 
question in between, so we have kind of a free-flow, more than 
any structured kind of a presentation.
    So, I will start first with Dr. Jeremy Berg, Director of 
the National Institute of General Medical Sciences since 2003. 
He received his M.S. in Chemistry from Stanford, his Ph.D. in 
Chemistry from Harvard. His own research focuses on the way 
that proteins regulate gene activity.
    Dr. Berg, welcome and please proceed. By the way, all of 
your statements will be made a part of the record in their 
entirety.

                  SUMMARY STATEMENT OF DR. JEREMY BERG

    Dr. Berg. Well, thank you very much, Senator Harkin, both 
for your leadership and for this opportunity.
    NIGMS, the National Institute of General Medical Sciences, 
is often referred to as the ``basic science institute,'' 
because we support research on fundamental biological 
processes. As one measure of how successful this approach has 
been, NIGMS has supported a total of 62 Nobel Prize winners 
over the 45-year history of the Institute, including three this 
past year.
    The research that NIGMS has supported has also done things 
like enabling the Human Genome Project and contributed 
substantial, to the technology that led to the biotechnology 
industry, which current estimates indicate has created about 
200,000 jobs in the United States and has an annual revenue 
base in the United States of about $40 billion.
    The research that we support really depends on scientists 
working on the advances that others have made in the past, as 
all of our research does. One illustration of this, there's a 
handout which I think you have a copy of----
    Senator Harkin. Or, do I have it?
    
    

                                Figure 1

    Dr. Berg. Figure 1 reveals the so-called ``Central Dogma'' 
of molecular biology. This goes back to the 1960's, and shows 
the information flow from DNA, where the genetic information is 
stored, through RNA, and converted into proteins, which are the 
molecules that do most of the work in the body.

                             RNA VERSUS DNA

    Senator Harkin. What's the difference between RNA and DNA?
    Dr. Berg. Chemically, there's a very minor difference, 
there's one extra hydroxyl group in RNA. The major difference: 
is that DNA is very stable, and is present in the cell very 
robustly. RNA is used much more as a signal or a messenger, so 
the DNA information is translated to RNA, that's then used, and 
the RNA is degraded, in general, very rapidly. It is a way of 
sending a message out, and then the message is destroyed, so 
the new messages can----
    Senator Harkin. So, RNA exists for short periods of time?
    Dr. Berg. Most RNAs exist for just seconds or a few 
minutes, some much longer than that.
    But, as you'll see in one of the examples I've described, 
RNA is also very actively involved in many processes, some of 
which we're just beginning to understanding.
    Even though this idea has been around for 50 years or so, 
there are still lots of new discoveries, both bolstering it and 
adding new loops to this simple information diagram.
    The Nobel Prize last year in chemistry went to Roger 
Kornberg for determining the structure of RNA polymerase. This 
is something that's been known since the late 1960s, and is 
exactly how the information in DNA is converted into RNA. It 
was known that there was this very important and very 
complicated protein enzyme, RNA polymerase, that converts the 
information in DNA into RNA. See figure 2.



                                Figure 2

    It was known to be very complicated, and starting about 20 
years ago, Dr. Kornberg made it one of his missions in life to 
figure out what this enzyme looked like, in order to understand 
how it works. It is the key protein which collects information 
and figures out which genes should be turned on and which ones 
should be turned off.
    He was funded for a long period of time when he started on 
this quest, and I must say, personally, that I think a lot of 
people regarded it a sort of a Don Quixote-esque quest to go do 
something very important, but that had a very small chance of 
ever succeeding.
    Starting in 1999, he got the first real glimmers that he 
was going to succeed. Subsequently, he has been reporting more 
and more interesting structures, revealing the overall 
structure, which is incredibly complicated, and how it works--
both the chemical mechanism, and now more and more information 
about how it collects information from the outside, and from 
the other things within the cell.
    This really sets the stage for a much deeper understanding 
of gene regulation, a process that is fundamental to many 
aspects of health, and also a mechanism that is regulated in 
diseases like cancer and many others as well.
    The other Nobel Prize that we supported was in physiology 
and medicine to Andrew Fire and Craig Mello for something that 
was really much more of a discovery, something that was 
completely unanticipated, which is that RNA actually regulates 
itself. The discovery was the result of an experiment that 
turned out very differently than they thought, and they were 
clever enough to realize that there was something very 
interesting going on. It was an experiment that was predicted 
not to work, that worked. They followed that up, and discovered 
this process which we call RNA interference, or RNAi, which 
allows small pieces of RNA, that are either present in the 
cell, or introduced into the cell, to shut down genes in a very 
specific way. Again, this was something that was completely 
unanticipated.
    One measure of how important it is, is Fire and Mello's 
discovery was reported in 1998, and they won the Nobel Prize 
only 8 years later, which is incredibly fast on the Nobel Prize 
timescale. One, RNAi is a fundamentally important discovery, 
second, it's a very powerful research tool. See figure 3.



                                Figure 3

    As investigators are building on the work from the Human 
Genome Research Institute, one of the questions they are 
pursuing is, what does each gene do? RNAi gives a way for 
scientists to specifically go through and turn off one gene at 
a time in a given cell type, then see what happens. The tool 
just didn't exist before, and it has dramatically cut down the 
cost of doing this type of gene-by-gene analysis.
    The second really exciting thing about RNAi, is that it's 
immediately adaptable to new therapeutics, and there are a 
large number of different therapeutics being developed using 
RNAi. The most advanced is a treatment for macular 
degeneration, which is now in Phase II clinical trials. 
Basically, there's a specific RNA molecule that can be injected 
directly into the eye to shut down the expression of a 
particular protein, which blocks the process that underlies 
macular degeneration.
    There are many other areas that are being advanced with 
RNAi. One particularly exciting area is pandemic influenza. 
With RNAi, one of the challenges of planning for pandemic 
influenza is the virus has not yet--thank goodness--been 
transferred from birds into humans to a very large degree. If 
we have to wait for that to occur to develop medicine, or 
develop a vaccine, that puts in a lag-time which could be very 
devastating to the human population. With RNAi, we already know 
a lot about influenza viruses, and can find things which are 
common to all of the different influenza viruses, and 
potentially develop a therapy or a sort of a vaccine-like 
treatment that will be completely independent of the strain, 
some sort of a universal flu vaccine.
    Again, this is still very much in development, and there 
are lots of problems to be solved. The RNAi approach opens up a 
new avenue, which has the potential to save hundreds of 
thousands of lives, and billions of dollars to the world 
economy.
    In terms of the future, there are two important aspects. 
First off, although we can't anticipate and predict what new 
discoveries will be made, we can anticipate that they will 
occur. If you look at what's happened since the Central Dogma 
was first coined, on average about, every 5 years there's some 
new, revolutionary discovery that no one anticipated and that 
really changes the landscape of biomedical research. We still 
don't think we know all there is to know by any stretch of the 
imagination, so there will be new discoveries. I can't tell you 
what they will be, but I can tell you that they will exist.
    To foster those sorts of discoveries, NIGMS has been 
involved in two new programs: one is the NIH Director's Pioneer 
Award, which was started a few years ago as part of the NIH 
Roadmap; and more recently, the NIH Director's New Innovator 
Award, which was started this year, thanks to the funds that 
were provided in the joint resolution.
    The idea of these awards is really to encourage the 
scientific community to send forth their most creative ideas, 
really out of the box sorts of things, and have a home for 
funding some of those ideas. We want to push the sort of 
creative things that might be difficult to fund in the 
relatively conservative environment that we find ourselves in.
    The second thing that we're sure we're going to have to 
deal with is complexity. If you look at the last handout, even 
though the Central Dogma is relatively simple, it's occurring 
with, about 20,000 genes. There are many other modifications to 
the Central Dogma that we know occur, and all of these things 
take place in concert in each of thousands of different cell 
types in our body and respond to interactions from other cells 
and environmental signals. We need to find the sort of 
conceptual frameworks for dealing with systems that are this 
complicated. We know what the parts are now, but trying to 
understand systems or machines, this is complicated, really a 
daunting challenge.

                           PREPARED STATEMENT

    We have a program, Centers for Systems Biology, which is 
bringing together biologists, computer scientists, and other 
people who are accustomed to dealing with this sort of 
complexity to try to take the first baby steps to address this. 
Not only do we have to deal with complexity, but also 
variations from individual to individual, which are key to 
health and disease. With the information that's coming from 
NHGRI and other Institutes, we now are starting to know more 
and more about what sort of variability there is, and we're 
trying to stay ahead of the curve in developing conceptual 
frameworks and tools that will help us interpret this 
information when it becomes available.
    So, with that, thank you very much.
    [The statement follows:]
                 Prepared Statement of Dr. Jeremy Berg
    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2008 President's budget request for the National 
Institute of General Medical Sciences (NIGMS). The fiscal year 2008 
budget includes $1,941,462,000.
    Throughout its 45-year existence, NIGMS has been a wellspring of 
discovery. The fundamental knowledge generated by NIGMS research 
impacts every other NIH component and has broad applications in the 
pharmaceutical and biotechnology industries. NIGMS contributes to the 
health of the biomedical research enterprise in other important ways, 
as well. A prime example is our cutting-edge research training program, 
which produces a substantial number of well-prepared new scientists. 
Their ideas and talents contribute to our growing knowledge base, 
allowing continued progress toward treatments and cures for countless 
diseases that rob us of friends, family, and years of productive life.
                     nurturing intellectual capital
    When discussing science and medicine, we often focus on compelling 
research advances and medical breakthroughs. But behind every ``what'' 
is a ``who,'' a creative individual asking and answering a crucial 
question--the brainpower driving scientific progress. NIGMS is 
steadfast in its commitment to nurturing and maintaining this 
intellectual capital through its significant support of investigator-
initiated research and research training.
    In the context of this opening statement, it has become habit to 
reference the past year's NIGMS-supported Nobel Prizes. Of course, this 
is a ritual I am extremely proud to continue by reporting that the 2006 
prizes in the two areas most relevant to biomedicine, physiology or 
medicine and chemistry, went to three NIGMS grantees. But I would like 
to go further, using the prize-winning research to show you how NIGMS 
support creates opportunities for major discoveries to happen.
    Two geneticists, Andrew Fire and Craig Mello, received the 2006 
Nobel Prize in physiology or medicine for their discovery of a gene-
controlling mechanism called RNA interference. Their breakthrough came 
about by surprise, when they had the keen insight to figure out why an 
experiment failed. Fire and Mello's seminal finding, made relatively 
recently in 1998, has dramatically transformed biomedical research and 
has already led to new treatments that are being tested in the clinic 
for a range of diseases.
    The 2006 Nobel Prize in chemistry is a very different story. In 
this case, the achievement resulted from painstaking persistence on a 
fundamentally important question. The prize went to a biochemist who 
refused to give up on a problem that even today would be perceived as 
ferociously difficult. Combining biochemical research with novel 
biophysical methods, Roger Kornberg captured a detailed, three-
dimensional snapshot of the enzyme that reads our genes. This work has 
deeply enriched our understanding of one of the most fundamental life 
processes: how DNA gets copied into RNA. While the mindset, creativity, 
and acumen were Kornberg's, decades of unwavering NIGMS support enabled 
him and a talented set of coworkers to pursue this groundbreaking 
accomplishment, which has had a significant impact on biomedical 
research.
                         tools breed innovation
    To capitalize on creative ideas, scientists need tools as well as 
funding. These tools can take many forms, from new technologies to 
model organisms. Research with bacteria, yeast, insects, worms, and 
rodents continues to confirm that the basic operating principles are 
nearly the same in all living things, and that studies in other 
organisms yield important knowledge applicable to human health.
    Thus, we are no longer surprised to learn that a gene or a process 
in a mouse, a worm, or a fruit fly is the same, or very similar, as 
that in a person. Examples of high-impact research done using model 
organisms abound, including the 2006 Nobel Prize-winning discoveries, 
which were made in roundworms and yeast. A more recent study in 
roundworms showed how early cell damage contributes to the development 
of Huntington's disease. The researchers who did this work discovered 
that an error in how proteins fold leads to the massive protein 
clumping inside cells that typifies Huntington's disease. Because 
protein clumping is also linked to other neurological conditions such 
as Alzheimer's and Parkinson's diseases, it is likely that this work 
will have far-reaching implications.
    Along with essential new knowledge about life processes, health, 
and disease, basic research can yield technologies with direct medical 
relevance. A case in point is an unexpected discovery by bacteriologist 
Yves Brun. While studying bacteria to better understand cell division, 
he found that the organisms produce a remarkable, natural form of 
``superglue.'' Additional studies revealed that the bacterial glue is 
the strongest biological adhesive ever measured, capable of holding 
nearly 5 tons per square inch. What's more, it doesn't dissolve in 
water. Brun is now working to learn more about the properties of the 
natural glue, which could be an ideal candidate for a surgical 
adhesive.
    For a further demonstration of uncharted exploration as a powerful 
engine of discovery, consider the study of the three-dimensional 
structures of biological molecules. This research, which relies heavily 
on tools and expertise from the physical sciences, has been a prime 
source for the development of life-saving medications like those used 
to treat AIDS, many types of cancer, asthma, and several other health 
conditions. NIGMS has provided significant support for structural 
studies and other research at the interface of the biological and 
physical sciences. In addition, we continue to communicate and 
collaborate with Federal agencies focused on the physical sciences to 
maximize the benefit of our funding activities to the scientific 
community.
    Of course, technology is only useful if it is available and 
affordable to many bright minds across the country. Every investment 
NIGMS makes has this end goal in mind, and currently the Institute is 
supporting several databases, materials repositories, genetic and 
genomic tools, and other shared resources that provide vital 
information and equipment to thousands of biomedical researchers. The 
Institute's team science efforts in such areas as high-throughput 
protein structure determination (the Protein Structure Initiative), how 
genes affect individual responses to medicines (the Pharmacogenetics 
Research Network), and new approaches to significant and complex 
biomedical problems via collaborations among scientists from diverse 
fields (``glue grants''), have all matured to a level where the fruits 
of progress are being shared widely with scientists everywhere.
                        investing in the future
    Perhaps the most important element in determining the future of 
biomedical research is providing young people with opportunities to 
develop an understanding of the scientific process and to become 
fascinated with the challenges and opportunities that scientific 
careers present. Who will make the discoveries that will drive research 
in the future? If we went back in time, could we have known that Fire, 
Mello, Kornberg, and many other unnamed scientists would have gone so 
far in advancing our understanding of key life processes?
    Some individuals can hardly avoid catching the science bug. Roger 
Kornberg grew up in a household dominated by science: His father, 
Arthur (also a long-time NIGMS grantee), shared the Nobel Prize in 
physiology or medicine when Roger was 12 years old. Roger took 
advantage of the many opportunities available to him and began learning 
about science at a very early age.
    Most people, however, do not grow up in such a rich scientific 
environment. Take Ryan Harrison, who caught the science bug a few years 
ago, while attending a Baltimore City public high school that has a 
large population of underrepresented minority students. Ryan, the son 
of a teacher and a former corrections officer, met Jeffrey Gray, a 
biophysicist at Johns Hopkins University, through an outreach program. 
Ryan spent 2 years working in Gray's laboratory and then came in 5th 
place in the Intel Science Talent Search, the most prestigious high 
school science competition in the country. He continues to pursue 
research as an undergraduate at Johns Hopkins, and we look forward to 
following his progress and achievements.
    In order to address the health needs of our Nation, we must tap the 
full diversity of the talent pool of our country to attract the best 
minds into research. NIGMS has been a pioneer in this arena through its 
programs that provide opportunities for underrepresented minorities to 
pursue scientific careers. We recognize that underrepresentation is a 
challenging and complex problem. Single interventions are unlikely to 
effect lasting, multidimensional changes in diversity. As these 
programs mature, we are committed to conducting and rigorously 
evaluating the effectiveness of a broad range of biomedical workforce 
diversity programs.
    Once scientists have embarked on their careers, we must continue to 
provide opportunities for them to contribute fully to biomedical 
research. An effort to do just that is the new NIH Pathway to 
Independence award, which facilitates the transition of highly 
promising postdoctoral scientists from mentored to independent research 
positions. NIGMS was delighted this year to receive, and fund, a 
healthy number of applications for this unique program. In addition, we 
continue to give special consideration to regular research grant 
applications from new investigators as another way to help them get a 
solid start.
    We also realize the need for scientists to be able to test 
unconventional, potentially paradigm-shifting hypotheses and use novel, 
innovative approaches to solve difficult technical and conceptual 
problems that impede scientific progress. Toward this end, we are 
developing a new grant program based primarily on the innovativeness 
and potential impact of a scientist's ideas. We will launch the program 
later this year and anticipate that it will serve as a model for other 
NIH institutes and centers. The design of this program has benefited 
from our experience with the NIH Director's Pioneer Award program, an 
intriguing experiment on how to fund scientific research that is part 
of the NIH Roadmap for Medical Research.
    Through the efforts I have described today, we hope to continue our 
strong record of identifying and supporting the talented and creative 
scientists whose work paves the way for future medical advances.
    Thank you, Mr. Chairman. I would be pleased to answer any questions 
that the Committee may have.

    Senator Harkin. Thank you very much, Dr. Berg. I've got 
some follow on things, but we'll move on through here.
    Dr. Francis Collins, has served as Director of the National 
Human Genome Research Institute since 1993, received his Ph.D. 
from Yale University, and his M.D. from the University of North 
Carolina School of Medicine. Dr. Collins has discovered 
numerous important disease genes, and is well known for his 
leadership from the beginning to the end of the Human Genome 
Project.
    Again, my thanks for your leadership in that area, but I 
continue to hear just glowing comments, last week, about your 
presentation to our group about a week and a half ago. It was 
just a great presentation.
    Welcome, again, Dr. Collins, to the committee, and please 
proceed.
STATEMENT OF DR. FRANCIS S. COLLINS, DIRECTOR, NATIONAL 
            HUMAN GENOME RESEARCH INSTITUTE
    Dr. Collins. Thank you, Senator Harkin, thank you for those 
kind comments about the event 10 days ago.
    I'm very happy to be here with my colleagues, as part of 
this hearing on Frontiers of Science, and ever since this 
Congress--led by your vision, Senator Harkin--got the Human 
Genome Project off the ground, we've had the privilege of 
working at that frontier. I'm pleased to report, we've made a 
lot of progress in the 4 years since the Human Genome Project 
completed all of its goals, in April 2003, famously ahead of 
schedule, and famously under budget--we've used that foundation 
to build a real future for personalized medicine.
    You're going to hear a lot more about exciting developments 
in that regard in the coming weeks and months, describing 
dramatic genetic discoveries for common diseases, with 
important public health consequences.
    Let me tell you about one that's particularly exciting for 
me. Just last week in Science magazine there were two reports 
about identifying genetic risks for heart disease, for heart 
attacks, specifically. These funded--one of them by the Heart, 
Lung and Blood Institute--are very important, because they scan 
the entire genome and identified a region that confers a 
substantial increased risk of heart attack in an area of the 
genome we had no idea was involved in this disease before.
    But stunningly, just a week before, my team and two other 
teams, who had been studying Type II Diabetes, the adult-onset 
form of diabetes, reported also in Science magazine, the 
identification of a total of 10 genes involved in that 
important disease, where as previously, only three had been 
known.
    Stunningly, one of the regions of the genome identified in 
the diabetes study appears to be the same one that is involved 
in heart attack. Nobody expected this. This is like winning the 
lottery 2 weeks in a row by picking the same number. It just 
shouldn't happen. After all, the genome is a big place. But 
instead, we've zeroed in on this place on chromosome 9, which 
must be a very important part of the genome in terms of its 
role in human health, and identified ways in which it can 
influence risk of diabetes on the one hand, and heart attack on 
the other. Everybody involved in these studies is scratching 
their heads, not having expected this outcome, but clearly 
we're onto something pretty important.
    Now this kind of discovery can open new doors to prevention 
and treatments. Take diabetes, for instances, where we sorely 
need that. Estimates are we spend $132 billion a year in the 
treatment of diabetes and its complications, as well as the 
consequences to the 21 million Americans who have this disease, 
as far as loss of work, and premature mortality and morbidity. 
Yet, we don't really understand that disease nearly as well as 
we need to, in terms of the precise molecular basis of what's 
going on.
    With this outpouring, now, of these 10 new gene variants, I 
would say, only three of which you might have guessed at, and 
the others are complete surprises--we can finally shine a light 
on this mysterious disease in a way that should, both offer us 
the chance to do better prevention, and we know prevention can 
work for diabetes. We know that if you identify the people at 
high risk, and get them into an exercise program, you can 
reduce their chance of becoming diabetic by as much as 58 
percent.
    We can also use these new discoveries to pinpoint pathways 
for which new drug therapies could be designed, instead of 
continuing the same process we have up until now, based upon 
what we knew about the disease, now we know so much more.
    How did this come about? Well, in the little handout, 
figure 4 and I hope it's somewhere there in your little pile. 
Okay, so this is a simple diagram that shows what it is that 
geneticists are doing now with common diseases, which we 
couldn't do before. 



                                Figure 4

    It looks very simple in this cartoon--basically, you 
identify people with the disease, the affecteds, as it were, 
and you identify controls, that is, people who clearly don't 
have the disease--and then you want to check, across the entire 
genome, places where there are difference in the spelling, 
``variants'' as we call them, and see, are there any out there 
that look like Variant B--where, in my color-coding here, the 
orange spelling of Variant B is more common in the 
``affecteds'' than the ``unaffecteds'' and that will tell you 
that Variant B may be a risk factor for that disease.
    Most of the variants in the genome aren't going to look 
like B, they're going to look like A, where there really isn't 
any difference, because most variation doesn't affect diabetes.
    But, the problem with this strategy was, until very 
recently, we didn't have the power to do this. Because, while 
this cartoon looks very simple, to do this right, you need 
1,000 or more affected individuals, and 1,000 or more 
unaffected individuals, and we thought you might have to check 
as many as 10 million different places in the genome in order 
not to miss the answer.
    Well, the HapMap came along, a project which I had the 
privilege of leading, as a natural follow-on the Human Genome 
Project, which basically built a catalogue about all of these 
variants, and figured out how they traveled in neighborhoods, 
so that you didn't have to check all 10 million if you chose 
wisely, you could choose a much smaller set, and they served as 
proxies for the ones that you didn't actually look at. That 
made it possible to do something which, 5 years ago, would have 
cost $10 billion, the study of diabetes that I just mentioned. 
Now we can do that for less than $1 million. I don't know too 
many areas of science where costs have come down by that kind 
of curve, in just 5 years.
    If you look at the next image figure 5, the next thing in 
your little packet, you can see what the consequences of this 
are starting to be, in terms of this are starting to be, in 
terms of discovery, so above the line are, in fact, major 
common diseases for which we have been learning about genetic 
factors involved, and you can see, as we sort of blow up the 
scale here, in the last 2.5 years, a lot of findings coming 
along, prostrate cancer, lupus, macular degeneration, 
inflammatory bowel diseases, Type 2 Diabetes, psoriasis, heart 
attack.




                                Figure 5

    I put bipolar disease on here, because in a publication 
tomorrow in a major journal, there will be a description of 
what happened to a group at the NIH, led by Dr. McMahon that 
applied this same strategy to looking at manic-depressive 
illness, and came up with a very surprising finding of a gene 
that appears to be involved in that disease, that maybe is even 
involved in the lithium pathway, which makes a certain amount 
of sense, but it's not a gene that anybody would have guessed 
that. I hear through the rumor mill, there are other studies of 
bipolar disease, also using this same new, very powerful 
strategy, discovering similar findings.
    So, this is really the year, where all of a sudden, we're 
going to learn a great deal about the genetics of common 
disease, with many consequences, and if you go to the last 
picture here, it's an attempt to show how that's going to play 
out in terms of the practice of medicine.
    The top part of the diagram, figure 6, which says, 
``Accelerated By Human Genome Project,'' is what's now 
happening--the ability to identify these genetic risk factors 
using the tools that have come out of this effort.




                                Figure 6

    What happens next, in the clinic, is going to be the 
ability, diagnostically, to predict who's at risk, and if you 
have an intervention that will reduce that risk, people will 
probably be interested, especially now that we're seeing the 
Genetic Information Nondiscrimination Act getting close to 
passage, finally----
    Senator Harkin. Finally.
    Dr. Collins [continuing]. Which will mean that people won't 
be afraid to take advantage of that information, as they have 
been in the past.
    We'll also be able to use these same tools for 
pharmacogenomics, this effort to identify the right drug at the 
right dose for the right person, knowing that we're all a 
little different there, too, the same tools can be used to 
figure out why that is.
    Perhaps most importantly in the long term, these gene 
discoveries shine a bright light on pathogenesis that gives you 
the chance to develop treatments that will be more efficacious, 
because they're really targeted towards the primary problem, 
and perhaps, if we do this right, also less likely to cause 
side effects, because you are going right to the primary 
problem.
    So, it's a very exciting time for this kind of strategy. 
How are we able to do that? I should bring along my show-and-
tell here, I brought you a couple of chips to indicate the kind 
of technologies that have come out of this sort.
    Senator Harkin. What am I looking at?
    Dr. Collins. The one in the little plastic case, here, is 
an Affymetrix Gene Chip, this one chip can be used to detect 
50,000 different variable places in the genome in one 
experiment. This particular company, Affymetrix, was actually 
founded on an NIH SBIR grant from the Genome Institute, about 
14 years ago, and has now become a major contributor to the 
revolution in genomic medicine that we see.




    The other one, called Illumina, is a separate company, what 
you're looking at there is a microscope slide, and you see 
stripes on it, each one of those stripes has about 60,000 
different DNA spelling detectors, so it is basically a 
detector, and so with the whole slide, you can then look at a 
very large number of variations in a single DNA sample, and 
test those extremely reliably, and for a cost of about an 8th 
of a penny per particular genotype, per particular DNA 
spelling. Again, that's come down dramatically in cost, over 
the last 5 years.



    So, these are exciting times, not only are we focused on 
this approach to look at those variants in the genome, I might 
mention, we're also pushing hard, Senator, to get to the point 
of being able to sequence anybody's complete genome, all of the 
letters of their 3 billion letter code, for $1,000.
    Senator Harkin. I read that in your testimony.
    Dr. Collins. Yeah, that's ambitious, isn't it?
    Senator Harkin. Yeah.
    Dr. Collins. A couple of years ago, it would have cost $10 
million, we are now probably on the brink of a totally new 
technology, really turning out to work in high throughput that 
will bring that cost down to, perhaps, $100,000 for human 
genome. So that's three orders of magnitude--I'm sorry, two 
orders of magnitude in a fairly short period of time.
    To get down to $1,000, we've got two more orders of 
magnitude to go, but that's an explicit goal of our Institute, 
working with other collaborators, and we are putting a lot of 
our own technology development money into that. So, imagine 
what that's like, that you get your entire genome set?
    Senator Harkin. What makes you think you can do that?
    Dr. Collins. We don't have to----
    Senator Harkin. That's a big order.
    Dr. Collins. It is. We don't have to violate any laws of 
physics, though, it is quite possible to do this, so investing 
in various technologies, and Dr. Pettigrew has some of these 
same approaches in his portfolio, particularly using 
nanotechnology, one of the more promising ideas, is you take a 
nanopore, a tiny little pore in a membrane, and you thread DNA 
through it in a way that there's a change in the electrical 
current as each base goes by, whether it's an A, or a C, or a 
G, or a T, it gives you a slightly different signal. People are 
seriously looking at that, as a way to read out--very fast--
because DNA would just fly through this pore, from a single 
molecule of DNA--a very large amount of DNA sequence.
    Whether that's actually going to work in practice? I guess 
I'd give it about a 50/50 chance right now, but there are other 
kinds of technologies right behind it, that are also lining up 
to do this. I'm counting on the ingenuity of the investigators 
that have already pushed this envelope so far, that I would 
think it would be a mistake for anybody to bet against it, and 
we do expect that the $1,000 genome will be a reality, sometime 
in the next 10 years.
    One of the areas, just to conclude, that we're specifically 
focused on, in terms of applying all of these technologies, is 
cancer.
    So, working with the Cancer Institute, we have gotten 
together in a partnership called the Cancer Genome Atlas, where 
we are applying, not only DNA sequencing technology, but also a 
host of other ways of looking at what's going on in cancer, in 
terms of which genes are turned on or turned off, which parts 
of the genome are duplicated or deleted.
    We have a large number of investigators all working 
together, initially on brain tumors, on ovarian cancer, and on 
lung cancer. But, if this pilot looks as promising as we expect 
it to, we hope to expand that to perhaps as many as 50 
different cancer types, after the pilot concludes in a period 
of 3 years. That's a very exciting project, and all of the data 
is being placed into a database, where any qualified 
investigator can see it right away, following up again on our 
premise that data access is really important, for speeding up 
this kind of research.

                           PREPARED STATEMENT

    So, in this brief time, I'm just scratching the surface of 
some of the things that are happening now in the field of 
genomics. Having been at NIH for 14 years, people are 
occasionally asking me, ``Well, aren't you getting tired of it? 
Isn't it time to move on?'' My only answer is, ``This is the 
best part.'' This is the part that we really worked to get to, 
where we have the foundation, and now we can apply it in ways 
that are really going to transform medicine.
    Thank you, Senator, I'd be glad to answer your questions.
    [The statement follows:]
              Prepared Statement of Dr. Francis S. Collins
    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2008 President's budget request for the National Human 
Genome Research Institute (NHGRI). The fiscal year 2008 budget included 
$484,436,000.
    The theme of this hearing is ``The Frontiers of Science.'' In 
leading the Human Genome Project, we at NHGRI have had the privilege of 
working at the frontiers for many years. And the projects I will 
describe today demonstrate how research at NHGRI is advancing ever more 
rapidly to catalyze a true revolution in medicine.
    In February 2006, the Department of Health and Human Services 
announced the creation of two related groundbreaking initiatives in 
which NHGRI is playing a leading role. The Genetic Association 
Information Network (GAIN) and the Genes, Environment and Health 
Initiative (GEI) will accelerate research on the causes of common 
diseases such as asthma, schizophrenia, the common cancers, bipolar 
disease, diabetes, and Alzheimer's disease and help develop strategies 
for individualized prevention and treatment, thereby moving towards the 
possibility of personalized medicine.
    GAIN is a public-private partnership among the NIH, the Foundation 
for the NIH, Pfizer, Affymetrix, Perlegen, the Broad Institute, and 
Abbott. GEI is a trans-NIH effort combining comprehensive genetic 
analysis and environmental technology development to understand the 
causes of common diseases. Both GEI and GAIN are powered by completion 
of the ``HapMap,'' a detailed map of the 0.1 percent variation in the 
spelling of our DNA that is responsible for individual predispositions 
to health and disease. Beginning in fiscal year 2007, GAIN will produce 
data to narrow the hunt for genes involved in six common diseases and 
GEI will provide data for approximately another 15 disorders. 
Additionally, GEI will develop enhanced technologies and tools to 
measure environmental toxins, dietary intake and physical activity, and 
an individual's biological response to those influences.
                       ongoing nhgri initiatives
Use of Comparative Genomics to Understand the Human Genome
    NHGRI continues to support sequencing of the genomes of non-human 
species because of what they say about the human genome. The honey bee 
genome was published in the journal Nature in October. This bee's 
social behavior makes it an important model for understanding how genes 
regulate behavior, which may lead to important insights into 
depression, schizophrenia, or Alzheimer's disease. The genome of the 
sea urchin was sequenced and analyzed in November, revealing unexpected 
sophistication among its sensory and immune system genes.
Medical Sequencing
    When it becomes affordable to sequence fully any individual's 
genome, the information obtained will allow estimates of future disease 
risk and improve the prevention, diagnosis, and treatment of disease. 
NHGRI is particularly interested in having a sequencing program that 
both drives technology and produces data useful to biomedical research. 
To this end, NHGRI has developed a medical sequencing program that 
utilizes DNA sequencing to: identify the genes responsible for dozens 
of relatively rare, single-gene diseases; sequence all of the genes on 
the X chromosome from affected individuals to identify the genes 
involved in ``sex-linked'' diseases; and survey the range of variants 
in genes known to contribute to certain common diseases.
Sequencing technology advances, on the way to the $1,000 genome
    DNA sequencing enables a detailed ordering of the chemical building 
blocks, or bases, in a given stretch of DNA, and is a powerful engine 
for biomedical research. Though DNA sequencing costs have dropped by 
three orders of magnitude since the start of the Human Genome Project 
(HGP), sequencing an individual's complete genome for medical purposes 
is still prohibitively expensive. However, bold new advances in 
sequencing technology developed by NHGRI-funded researchers promise to 
reduce this cost greatly. NHGRI's ultimate vision is to cut the cost of 
whole-genome sequencing to $1,000 or less. This could potentially 
enable sequencing of individual genomes as part of routine medical 
care, providing health care professionals with a more accurate means to 
predict disease, personalize treatment, and preempt the occurrence of 
illness.
New findings in genetics of common disease
    Technology development and new research approaches enabled by the 
HGP, the HapMap, and related NIH initiatives have led to important new 
understanding of the role of genetic factors in a number of common 
diseases. For instance, the Hap Map made possible research that 
recently identified two major genes that influence risk for developing 
adult macular degeneration, a leading cause of vision loss, with those 
at lowest risk having <1 percent chance of developing the disease, and 
those at highest risk a 50 percent chance (Klein et al., Science 2005; 
Yang et al., Science 2006). Other similarly derived recent discoveries 
include that variations in the genes TCF7L2 (Helgasson et al., Nature 
Genetics 2007) and SLC30A8 (Sladek et al. Nature 2007) elevate risk for 
developing type 2 diabetes, variations in the genes IL23R (Duerr at 
al., Science 2006) and ATG16L1 (Hampe et al., Nature Genetics 2007) 
affect risk for Crohn's disease, a gene on chromosome 8 plays a role in 
prostate cancer, and the gene SORL1 (Rogaeva et al., Nature Genetics 
2007) plays a role in Alzheimer's disease. Each of these discoveries 
opens a new door toward prevention and treatment.
Knockout Mouse Project
    The technology to ``knockout'' or inactivate genes in mouse 
embryonic stem cells has led to many insights into human biology and 
disease. However, gene knockout cells in mice have been made available 
to the research community for only about 10 percent of the estimated 
20,000 mouse genes. Recognizing the wealth of information that mouse 
gene knockouts cells provide, NHGRI coordinated an international 
meeting in 2003 to discuss the feasibility of a comprehensive project. 
These discussions have now resulted in a trans-NIH, coordinated, 5-year 
cooperative research plan that will produce gene knockout cells in mice 
for every mouse gene and make these mice available as a community 
resource.
Chemical Genomics and the Molecular Libraries Roadmap Initiative
    The NHGRI has taken a lead role in developing a trans-NIH chemical 
genomics. Part of the NIH Roadmap, this project offers public-sector 
researchers access to high throughput screening of libraries of small 
organic compounds that can be used as chemical probes to study the 
functions of genes, cells, and biological pathways. This powerful 
technology provides novel approaches to explore the functions of major 
cellular components in health and disease. In its first year, the ten 
centers in the Molecular Libraries Screening Centers Network entered 
screening data from 45 assays in the PubChem database at the National 
Library of Medicine. The team also published a new high-throughput 
screening approach that is speeding the production of data to be used 
to probe biological activities and identify leads for drug discovery.
                      new and expanded initiatives
Population Genomics
    To promote application of genomic knowledge to health, NHGRI 
recently established an Office of Population Genomics. The mission of 
the office is to stimulate multi-disciplinary epidemiology and genomics 
research and develop new resources for the study of common disease. It 
will take on challenges such as developing standards for genetic and 
phenotypic data and improved analytic strategies for relating them, 
stimulating novel research approaches, and supporting cross-
disciplinary training to prepare researchers for new opportunities to 
improve health made possible through programs such as GEI and GAIN. 
This February, NHGRI's Advisory Council approved two new initiatives in 
this area. One funds development of a ``basic tool set'' for phenotypic 
and environmental exposure measurements in large-scale genomic 
research; the other supports existing biorepositories to conduct 
genome-scale studies with phenotype and environmental measures in 
electronic medical records. In the tradition of the HGP, the Office 
will promote widespread sharing of data, to stimulate the broadest 
possible application of knowledge and maximize public benefit.
The Cancer Genome Atlas (TCGA)
    The Cancer Genome Atlas (TCGA) is a joint NCI-NHGRI effort to 
accelerate understanding of the molecular basis of cancer through 
application of genome analysis technologies. Technologies developed by 
the HGP and recent advances in cancer genetics have made it possible to 
envision mapping the changes in the human genome associated with all 
forms of cancer. TCGA began in 2006 with a 3-year, $100 million pilot 
project to determine the feasibility of a full-scale effort to explore 
the universe of genomic changes involved in all human cancers. Over the 
3 years, NCI and NHGRI each plan to contribute a total of $50 million. 
The first diseases being explored are glioblastoma multiforme, ovarian 
cancer, and squamous cell lung cancer. TCGA will provide (1) new 
insights into the biological basis of cancer; (2) new ways to predict 
which cancers will respond to which treatments; (3) new therapies to 
target cancer at its most vulnerable points; and, (4) new strategies to 
prevent cancer.
The Human Microbiome
    There are more bacteria in the human gut than human cells in the 
entire human body. Furthermore, gut microbes have a profound effect on 
many human physiological processes, such as digestion and drug 
metabolism, and play a vital role in disease susceptibility and even 
obesity. The human microbiome project represents an exciting new 
research area for NHGRI, which, except for the bacterium E. coli, has 
focused its large-scale sequencing program on higher organisms rather 
than bacteria. Sequencing the genomes of 100 microorganisms that 
represent a significant, but unknown, fraction of all microbes in the 
human gut should provide a more complete picture of this aspect of 
human biology than has been available previously.
                        other areas of interest
The U.S. Surgeon General's Family History Initiative
    The family medical history is an effective and inexpensive means to 
determine more accurately an individual's risk for specific diseases; 
however, it is underutilized in health care. The U.S. Surgeon General's 
Family History Initiative was established to focus attention on the 
importance of family history, and NHGRI has taken a lead role in this 
initiative. To further the effort in 2006, NHGRI selected the 12,000 
employees at Brigham and Women's Hospital for a 1-year demonstration 
project to educate and engage the health care community about the 
family history. To spread the importance of family history to the 
public, the software tool, ``My Family Health Portrait,'' was enhanced 
for easier use, and resource materials were distributed to chronic 
disease and genetics experts in the State health departments of every 
U.S State and territory.
Genetic Discrimination
    NHGRI remains concerned about the impact of potential genetic 
discrimination on research and clinical practice. A wealth of research 
has demonstrated that many Americans are concerned about the possible 
misuse of their genetic information by insurers or employers. The 
Genetic Information Nondiscrimination Act of 2007, S. 358, and its 
companion House bill, H.R. 493, are presently under consideration by 
the Congress. In 2005, the administration supported S. 306, the Genetic 
Nondiscrimination Act of 2005. In January of this year, President Bush 
visited the NIH and reiterated the administration's desire to see 
Congress pass a bill to protect Americans from genetic discrimination.
    Thank you, Mr. Chairman. I hope I have offered you an informative 
view of the newest frontiers of science from the front lines of genomic 
science. I would be pleased to answer any questions that the Committee 
might have.


    Senator Harkin. Thank you, Dr. Collins. I want to come back 
to this knock-out project. I don't understand it, but I want to 
understand it a little bit more, but we'll get to that later.
    Dr. Donald Lindberg has served as the Director of the 
National Library of Medicine since 1984. He has an M.D. from 
Columbia University. Dr. Lindberg is a noted pathologist and a 
pioneer in applying computer technology to health care.
    Dr. Lindberg, welcome again to the committee. You've been 
here many, many times over the years. Good to see you again.
STATEMENT OF DR. DONALD A.B. LINDBERG, DIRECTOR, 
            NATIONAL LIBRARY OF MEDICINE
    Dr. Lindberg. Thank you, Senator Harkin.
    Senator Harkin. Please proceed.
    Dr. Lindberg. Since 1836, the National Library of Medicine 
(NLM) has been extremely fortunate to have received good help 
and consistent funding from the Congress. Thanks for this, and 
for today's opportunity to be present, again, before the 
committee.
    What does NLM do? Libraries, we too, are really part of 
science infrastructure. For much of our history, it was 
sufficient for NLM to acquire, organize and disseminate 
biomedical knowledge from the world for the benefit of the 
public health. But, biomedical knowledge has radically changed, 
both in volume and in form, and now, in addition to doctors and 
scientists, we also serve the public directly.
    To do this work, we now spend a lot of time, money, effort 
and space in creating and maintaining the electronic networks, 
databases, and information technology standards. These are 
essential now to support both new discoveries, and the use of 
these in good patient care. The number of papers we're indexing 
has gone up roughly 100-fold, database entries 1,000-fold. In 
addition, we now link genetic data directly online to the 
formulary and even the three-dimensional structures of the 
small molecule and protein products, pretty different from the 
old days.
    These, and over 40 highly specialized NCBI databases are 
important to researchers exploring the questions, how genes 
work, and how genomic medicine can help us. In some ways, the 
task of helping patients and families to understand their 
medical situations, is as difficult--maybe more difficult--as 
helping the scientists.
    Taking both groups together, we responded by computer to a 
billion online inquiries last year. They tell me that--
petabytes and all of that doesn't mean too much to most 
people--but basically every 3 days, we download an amount of 
data totally equivalent to the contents of the Library of 
Congress. So, this information is really used.
    NLM is the largest medical library in the world and, by 
far--more than even an ordinary modern library. Since our 
beginning, Congress added a number of explicit 
responsibilities, and I'll mention some. The two large ones, of 
course, are the Lister Hill Center for communications research, 
and more recently, NCBI for biotechnology information.
    In addition, we have responsibility for collection of 
information on toxicology, environmental health, healthcare 
technology, and most recently, for the establishment of a 
national--speedily becoming international--clinical trials 
registry.
    So, we're infrastructure. As such, we note that scientific 
infrastructure responsibilities, and hence, expenses, must 
increase faster than the growth of the experimental science we 
serve. This is because all of the Institutes share Dr. Collins' 
infectious belief that molecular biology and whole genome 
studies are science's best bet. I do, too.
    Thus, more experimental data needs to be acquired, 
organized and made available online to investigators. 
Successful databases grow in size, and in the number of users, 
and the costs go up, even with increases in our efficiency.
    We are most grateful to the committee for increases in 
funding, specifically for that which it provided for this 
purpose this year.
    Some might think that infrastructure role a bit dull, but 
for us, with the current growth of insights and discoveries 
stemming from use of our information service, it's more like a 
great roller coaster ride on a sunny day.

                       ELECTRONIC HEALTH RECORDS

    I want to mention very briefly, we have an interest in the 
full deployment of electronic health records. Across the United 
States, this is one of our top priorities. It's one of the 
Department's top priorities. It's important for two major 
reasons.
    First, long experience has shown that quality control 
warnings, clinical guidelines, best practices are simply so 
numerous and complex that they are not helpful when left to 
either doctors or patients alone to remember and use. We need 
computer-based medical informatics support. NLM does, in fact, 
support informatics research and training in the universities. 
We ourselves produce and disseminate information technology 
standards nationally, and as an official HHS function.
    Electronic health records are key for a second important 
reason, namely to get family and genomic studies into the 
patient record.

                    ACCESS TO SCIENTIFIC LITERATURE

    Briefly, the future now holds new discoveries that will 
come from new directions and new measurements, such as the 
genomic work that Dr. Collins describes. These will be based on 
ready access to full text sources of scientific literature and 
scientific databases, but new discoveries will also come from 
reexamination of some old ideas.
    The following shows Barry Marshall and Robin Warren on 
October 4, 2005, receiving their telephone call from the Nobel 
Prize Committee in Stockholm; lifting a glass, of course, on 
the occasion.

               [From The New York Times, October 4, 2005]

 Two Win Nobel Prize for Discovering Bacterium Tied to Stomach Ailments

                        (By Lawrence K. Altman)


     Barry Marshall and Robin Warren, celebrating their Nobel Prize

    . . . ``made an irrefutable case that the bacterium Helicobacter 
pylori'' causes ulcers and other diseases. . . .
    . . . A famous experiment Dr. Marshall conducted on himself. . . .
    . . . Dr. Marshall said that information he obtained from the 
National Library of Medicine, a part of the National Institutes of 
Health in Bethesda, Md., aided his discovery. . . . Dr. Marshall worked 
in a hospital in Port Hedland, in the Australian outback about 1,000 
miles from Perth. . . .
    . . . bundles of references . . . ``a whole lot of literature 
showing that many patients with ulcers had gastritis that the ulcer 
experts in the 1980's had forgotten about.''

    The prize honored their discovery that--and proof--that 
peptic ulcer is actually caused by infection by a bacterium, 
Helicobacter pylori--not by neurosis, stress, spicy food or all 
the other nonsense we used to be taught about.
    Now, when he received the call, Marshall immediately said 
to the press, ``Information from the National Library of 
Medicine aided my discovery.'' Dr. Marshall himself worked in a 
hospital in Port Hedland, Australia in the outback, 1,000 miles 
even from Perth, but he got what he described as ``bundles of 
references'' showing that many patients with ulcers had 
gastritis that the ulcer experts had forgotten about.
    So, of course, we're grateful for this discovery, and for 
the acknowledgement. But frankly it makes one hope that 
whatever else in medicine is not true will also get re-examined 
by some doubters with library cards.

                         NLM FUTURE PRIORITIES

    Now, for the next year, just three areas we have great 
interest in. Dealing with the space problem, which we're 
seriously at NLM and the committee has helped us with that in 
the past by providing money for planning. We are also very keen 
on the outreach to consumers, patients' families and the 
public, and the NIH MedlinePlus magazine, which again, you 
helped us with a Capitol Hill launch. That was great.
    Senator Harkin. Yeah, I remember that. Yep, yep.
    Dr. Lindberg. Mary Tyler Moore. Then we think we ought to 
be doing something more in our Long-range Planning Committee 
from the Board of Regents thinks that we ought to be doing more 
to try to be involved in helping the country with disaster--at 
least health information management. So those are our hopes and 
desires.
    Senator Harkin. Yeah, it was, a nice event. How often do 
you come out with that?
    Dr. Lindberg. Quarterly.
    Senator Harkin. Quarterly. Online also?
    Dr. Lindberg. Online also. Anyone can actually request it 
online and get it free.
    Senator Harkin. Yeah, oh, I understand. Yeah.

                           PREPARED STATEMENT

    Dr. Lindberg. Lance Armstrong was on the cover of the first 
edition, as you remember. He was helpful, too.
    Senator Harkin. Oh yeah?
    Dr. Lindberg. Mary Tyler Moore was on the cover of the 
second edition.
    [The statement follows:]
             Prepared Statement of Dr. Donald A.B. Lindberg
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the National Library of Medicine 
(NLM) for fiscal year 2008, a sum of $312,562,000.
    The National Library of Medicine has a remarkable track record of 
preserving the past while serving the present and preparing for the 
future. A just completed Long Range Plan done by the Library's Board of 
Regents lays out in broad terms the challenges the Library will face 
over the next decade and charts a course for action to successfully 
meet these challenges.
    Prominent among the challenges is the need to create the 
information resources essential to achieving the goal of ``personalized 
medicine,'' in which prevention and treatment strategies are tailored 
to an individual's specific genetic make-up. The first step is to 
provide huge linked databases and software tools that allow scientists 
to correlate clinical, genomic, and chemical compound data with 
published research findings to determine how genetics and a person's 
environment interact to cause disease and to identify potential new 
therapies. Such resources, now being developed by NLM, will speed 
scientific discovery and can ultimately transform medical care by 
allowing clinicians to customize treatments to a patient's genetic 
characteristics.
    In an era of increasing chronic disease, a related challenge is the 
need to empower people with the knowledge and motivation to improve 
their health and play a more active role in their health care. The 
information that pours out of the Nation's laboratories--and often 
finds its way into the public media--has the potential of improving the 
health status of our citizens. The National Library of Medicine has 
created heavily used Web-based information services aimed at the 
public. These services transmit the latest useful findings in lay 
language and provide guidance that can be easily understood by the 
public. NLM works with libraries and community-based organizations to 
increase public awareness and use of these valuable resources.
    Electronic health records with advanced decision support 
capabilities will be essential to achieving personalized medicine and 
will also help people manage their own health. Much of the seminal 
research work in this arena was supported by the National Library of 
Medicine or undertaken by people who received NLM-funded informatics 
education. This work builds on two decades of research and development 
of the Unified Medical Language System (UMLS) resources which help 
computer systems behave as if they ``understand'' the language of 
biomedicine. The NLM also serves as an HHS coordinating center for 
standard clinical vocabularies and supports, develops, or licenses for 
U.S.-wide use key clinical vocabularies.
    No information source is useful if it is unavailable. A third major 
challenge facing the National Library of Medicine is ensuring 
uninterrupted access to critical information resources in the event of 
disaster or other emergency, natural or man-made. As recent hard 
experience demonstrated, this requires careful advanced planning, 
strong inter-organizational arrangements, and skillful management of 
information during the emergency, in addition to robust technical 
backup arrangements for computer and communication systems. NLM's new 
Long Range Plan specifically recommends that the Library establish a 
new Disaster Information Management Research Center and ensure 
effective recognition and use of libraries as a major and largely 
untapped resource in the Nation's disaster management efforts.
    This opening statement is built around these three themes--
scientific information resources that can lead to personalized 
medicine, information services that enable greater personal involvement 
in health and health care, and marshalling the Library's resources to 
assist the country's in emergency situations.
          scientific information resources--near and long term
    Fueled in part by funding from the National Institutes of Health, 
the pace of discovery in today's world of biomedical research is 
amazing. The NLM is now at the center of much biomedical research--not 
only receiving, storing, and disseminating published research results, 
but actually serving as a crossroads for the genomic and other data 
coming from laboratories around the world. NLM databases and systems 
are essential tools in all aspects of biomedical research. Users 
conducted more than 1 billion searches of them in the last year.
    The core of the National Library of Medicine is its expanding 
collection of more than 8 million books, journals, and other materials. 
The Library subscribes to more than 20,000 periodicals of which some 
5,000 are indexed for Medline/PubMed, the immense online database of 
the journal literature. From the more than 16 million records in 
Medline/PubMed one may link to a tremendous variety of relevant Web-
accessible online resources at NLM and elsewhere. NLM's National Center 
for Biotechnology Information (NCBI) has already begun building the 
Medline/PubMed of the future by redesigning its displays and interfaces 
to make it easy for users to see important links and retrieve 
information they might not otherwise have noticed.
    The NCBI is the source of GenBank, the genetic sequence databank 
that contains all publicly available DNA sequences. GenBank is produced 
from thousands of sequence records submitted directly from researchers 
and institutions prior to publication. NCBI has also created PubChem, a 
repository for what are called ``small molecules'' that are crucial in 
drug development. Small molecules are responsible for the most basic 
chemical processes that are essential for life and they often play an 
essential role in disease.
    The NCBI's effective performance on these and other trans-NIH 
priorities has earned NLM a prominent role in the important new Genome-
Wide Association Studies (GWAS) project. GWAS is an NIH-wide initiative 
directed at understanding the genetic factors underlying human disease. 
It involves linking genotype data with phenotype information in order 
to identify the genetic factors that influence health, disease, and 
response to treatment. NCBI is building the databases to incorporate 
the clinical and genetic data, link them to the NLM's molecular and 
bibliographic resources and, for the first time, make these data 
available to the scientific and clinical research community. dbGaP 
(database of Genotype and Phenotype) debuted in December 2006 to 
archive and distribute data from Genome-Wide Association Studies.
    PubMed Central, a Web-based archive of biomedical journal 
literature also developed by the NCBI for the NIH, provides free access 
to the full-text of peer-reviewed articles. PubMed Central is also home 
to full-text journal articles submitted by scientists with NIH funding 
under the NIH Public Access policy.
    NLM's Lister Hill National Center for Biomedical Communications 
also produces important tools for biomedical and informatics research, 
including digital image libraries--sets of image data that can be used 
in research, clinical care, and training. In one example, NLM is 
currently collaborating with NIH and other researchers to develop 
advanced imaging analysis tools for research in human papillomavirus 
infection and cervical neoplasia. The tools will allow effective 
analysis of some 100,000 images of the uterine cervix and they will 
become the primary resource for professional training and testing in 
this field. Another set of imaging tools being widely applied in the 
scientific community, for education and other purposes, is related to 
the ``Visible Humans.'' These two enormous data files (one male and one 
female) were created under the guidance of the Lister Hill Center and 
provide detailed image data sets that serve as a common reference for 
the study of human anatomy, for testing medical algorithms, and as a 
model for image libraries that can be accessed through networks.
                  information services for the public
    The audiences served by the Library have multiplied in recent 
years. In addition to providing researchers and health care providers 
with access to scientific information, the NLM also now has services 
for the public--from elementary school children to senior citizens. The 
Library's main portal for consumer health information is MedlinePlus, 
available in both English and Spanish. Much of this information is 
based on research done or sponsored by the NIH Institutes. In addition 
to more than 700 ``health topics'' (main entries on diseases and 
disabilities), MedlinePlus has interactive tutorials that are useful 
for persons with low literacy, medical dictionaries, a medical 
encyclopedia, directories of hospitals and providers, surgical videos 
that show actual operations, and links to the scientific literature. 
Just last September we launched here in the Congress a major initiative 
to put into doctors' offices and share with the public good health 
information in the form of a new publication, the NIH MedlinePlus 
Magazine. We were joined in unveiling the publication by Senator Tom 
Harkin and Congressman Ralph Regula.
    Several databases for consumers are byproducts of research in NLM's 
Lister Hill Center. One of these is the ClinicalTrials.gov database, 
which describes clinical research studies funded by NIH and others 
around the world. The site contains information on more than 37,000 
federally and privately supported trials and is searched daily by some 
30,000 people. Another Lister Hill Center database is the Genetics Home 
Reference, a Web site for consumer-friendly information about genetic 
conditions and the genes or chromosomes related to those conditions.
    NLM's toxicology and environmental health program also produces 
heavily used consumer information resources. The Household Products 
Database provides easy-to-understand data on the potential health 
effects of more than 2,000 ingredients contained in more than 6,000 
common household products. The colorful Tox Town looks at an ordinary 
town and points out many harmful substances and environmental hazards 
that might exist there. ToxMystery, an unusual interactive Web site for 
children between the ages of 7-10, provides an animated, game-like 
interface that prompts children to find potential chemical hazards in a 
home.
    Of inestimable help to the NLM in meeting its varied 
responsibilities--both to the scientific community and to the public at 
large--are the 5,800 member institutions of the National Network of 
Libraries of Medicine. The Network comprises eight Regional Medical 
Libraries, 120 ``resource libraries'' primarily at schools of the 
health sciences, and thousands of hospital libraries and community-
based organizations. Together they form an efficient way to ensure that 
the published output of biomedicine is easily accessible by scientists, 
health professionals, and the public. They cover the critical ``last 
mile'' to familiarize researchers, health professionals and the public 
and to develop sustainable partnerships with community organizations to 
improve access to health information for underserved populations.
            managing vital information in times of disaster
    A number of NLM's advanced information services and tools are 
designed for use by emergency responders when disaster strikes. The 
Library has a history of providing assistance in such cases, for 
example the gas leak disaster in Bhopal, India, in the eighties, and 
Hurricane Mitch and the earthquakes in Central America in the nineties. 
NLM's TOXNET, a cluster of databases covering toxicology, hazardous 
chemicals, toxic releases, environmental health and related areas, 
provides a foundation for services to first responders, such as WISER 
(Wireless Information System for Emergency Responders). Used in 
Louisiana after Hurricane Katrina, WISER provides information via 
handheld mobile devices to help identify unknown substances.
    Among other such projects, the Library: (1) supported pioneering 
work on automated biosurveillance, self-healing wireless networks, and 
smart tags to track patients during emergencies; (2) built the 
Influenza Virus Resource with the National Institute of Allergy and 
Infectious Diseases to provide vaccine researchers access to genomic 
data of many influenza strains; (3) developed OSIRIS (Open Source 
Independent Review and Interpretation System), a software package to 
assist in identifying 9/11 victims' remains via DNA; (4) worked via the 
National Network of Libraries of Medicine to re-establish and maintain 
a level of health information services in the Katrina-affected region; 
and (5) developed the Radiation Event Medical Management (REMM) system, 
in collaboration with the HHS Office of Public Health Emergency 
Preparedness, the National Cancer Institute, and the CDC.
    In summary, the National Library of Medicine is well positioned to 
make a maximum contribution to the Nation's health--by making 
increasing amounts of scientific data available to researchers and 
health practitioners, by contributing to the national effort to improve 
the information infrastructure of the health care system, by providing 
to the public access to authoritative information for use in 
maintaining their personal health, and by enabling health sciences 
libraries to make substantial contributions of disaster information 
management. All of these activities will depend on a strong and diverse 
workforce for biomedical informatics research, systems development, and 
innovative service delivery. To that end, the National Library of 
Medicine will continue its longstanding support for post-graduate 
education and training of informatics researchers and health sciences 
librarians and redouble its efforts to improve the diversity of these 
fields.

    Senator Harkin. Right, right.
    Thank you very much, Dr. Lindberg.
    Now we turn to Dr. Roderic Pettigrew, first appointed as 
the first Director of the National Institute of Biomedical 
Imaging and Bioengineering in 2002. He received his M.S. in 
Nuclear Medicine and Engineering from Rensselaer Polytechnic 
Institute and a Ph.D. in Applied Radiation Physics from 
Massachusetts Institute of Technology and an M.D. from 
University of Miami School of Medicine. His own research has 
focused on imaging of the heart using MRI. Interesting.
    Welcome, Dr. Pettigrew. Please proceed.
STATEMENT OF DR. RODERIC I. PETTIGREW, DIRECTOR, 
            NATIONAL INSTITUTE OF BIOMEDICAL IMAGING 
            AND BIOENGINEERING
    Dr. Pettigrew. Thank you, Senator Harkin. It is my pleasure 
to report to this committee, the remarkable advances that have 
been made in another frontier of science, that of medical 
technology. This field claims the top ring advance in clinical 
medicine of the last quarter century, three-dimensional human 
imaging via magnetic resonance imaging, or MRI, and computed 
tomography, or CT.
    In addition, the U.S. medical technology industry has grown 
to be a $90 billion enterprise with positive trade surplus, and 
perhaps more importantly, these technologies have significantly 
improved the Nation's health care.
    My Institute, the National Institute of Biomedical Imaging 
and Bioengineering is the youngest at the NIH and leads the 
development of a broad range of emerging biomedical 
technologies. It was created to focus on the science of 
technological innovation, create new tools that will improve 
our understanding of disease, and translate these types of new 
knowledge into practical solutions.
    Our research domain is the interface of the physical and 
the life sciences, and our vision is one of disease detection 
on a personalized basis, sufficiently early to pre-empt serious 
consequences of many illnesses, such as heart disease and 
cancer.
    When therapies are needed, these too, will be personalized, 
and targeted to the offending biologic process. I offer from 
our young, but broad, portfolio illustrative examples, and you 
have a handout.
    Senator Harkin. Got it here.
    
    

                                Figure 1

    Dr. Pettigrew. See figure 1.
    These are three examples, or from three areas that are 
already transforming modern healthcare. We have just heard 
about the tremendous advances being made in understanding the 
genetic basis of disease, such as diabetes and heart disease 
from Dr. Collins. The use of DNA sequences and genetic 
variations, as determined in HapMap studies, combined with 
advanced bioengineering technologies is beginning to be used 
for routine diagnostics at the first point of physician 
contact, and this, we term the point of care. A practical 
example of a very recent development of a DNA-based 
electrochemical sensor that can quickly identify the specific 
bacteria responsible for an infection is shown here.
    This is actually similar to the type of chip that Dr. 
Francis Collins gave you. Normally, identifying bacteria 
responsible for urinary tract infections or infections in 
general, takes about 2 days. But, with the euro-sensor that you 
see there, this can be accomplished in about 30 minutes. This--
--
    Senator Harkin. What you mean, is the specific type of the 
bacteria can be identified.
    Dr. Pettigrew. Yes.
    Senator Harkin. Within 30 minutes.
    Dr. Pettigrew. That's right.
    Senator Harkin. Okay.
    Dr. Pettigrew. Thank you for clarifying that, the bacteria 
specifically responsible for the urinary tract infections can 
be identified in 30 minutes, from the normal panoply of 
bacteria that are commonly responsible for this type of 
infection.
    This also allows for a more personalized prescription of 
the most specific and effective antibiotic treatment, and helps 
reduce the growing problem of antibiotic resistance caused by 
non-specific use of antibiotics.
    Perhaps more importantly, Senator, this type of device as 
indicated, is indicative of the type of exciting technological 
innovation that is leading to tools for personalized 
diagnostics on a routine basis. These systems, like the one you 
have on the board there, obviously are portable, they employ 
nanotechnologies that are ultimately responsible for this type 
of portability, and as a result of the portability, these can 
be available in all communities, including the rural and 
underserved areas.
    Another example of an engineered point of care diagnostic 
device is figure 2, a contact lens that senses the glucose in 
tear fluid, and shows a level of glucose simply by changing 
colors.



                                Figure 2

    A second area of transformative technology supported by my 
Institute is tissue engineering and regenerative medicine. 
This, as you heard from the National Institute of Arthritis and 
Musculoskeletal Disease, in the earlier testimony session, is 
an emerging technology in which tissues are grown to repair or 
replace diseased or damaged tissues or organs. 



                                Figure 3

    Figure 3 shows a subject who has a ruptured Achilles tendon 
in the upper left quarter panel. You can see the defect which 
was completely re-grown after placing a matrix material seeded 
with biologically active molecules. In the bottom right quarter 
panel, you can see the placement of this matrix material, on 
which normal Achilles tendon tissue was re-grown. Six months 
after this particular procedure, this individual patient had a 
normal tendon repair.



                                Figure 4

    Figure 4, the innovation is on a larger anatomic scale. 
This example illustrates the additional modern advances of 
image-guided interventions, or also team or inter-disciplinary 
science, as it has been referred to in the recent past.
    These are areas that we also specifically promote at our 
Institute. The problem being addressed in that particular 
handout that you have is identifying in the brain the very tiny 
site responsible for epileptic seizures, while also identifying 
surrounding normal critical structures. The goal is to show all 
of this structural, metabolic and electrical information in 
three dimensions to the surgeon with live updates while he or 
she is operating, so as to affect a successful removal of the 
offending tissue with minimal damage to the normal brain 
tissues.
    The team involved in this study is truly inter-
disciplinary. It involves a neurosurgeon, mechanical engineer, 
radiologist, computer scientist, bioengineer and so forth, all 
who have worked together to dramatically transform the way in 
which brain surgery will be performed.
    Specifically, this team already reports being able to treat 
up to 60 percent more patients with epilepsy, and in doing so, 
they've also been able to reduce the operating time by 1.5 
hours, and perhaps even as importantly, if not more so, they 
accomplish this with no neurologic deficits after the operative 
procedure.

                           PREPARED STATEMENT

    In the future, the vision of an even earlier, preemptive 
identification of disease will be achieved, as will less 
invasive approaches to treatment, which will target disease at 
the cell, and molecular, level. The NIBIB is working to create 
more of these types of transforming technologies, that will 
help realize this vision and improve the Nation's health.
    I thank you for this opportunity to present this overview, 
and also will be delighted to respond to any questions that you 
might have.
    [The statement follows:]
             Prepared Statement of Dr. Roderic I. Pettigrew
    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2008 President's budget request for the National 
Institute of Biomedical Imaging and Bioengineering (NIBIB). The fiscal 
year 2008 budget included $300,463,000.
                bridging the physical and life sciences
    The mission of the NIBIB is to improve human health by extending 
the frontiers of biomedical science, through the development and 
application of innovative biomedical technologies. A major focus of 
NIBIB is bridging the physical and life sciences in order to develop 
new biomedical technologies and methodologies that have a profound, 
positive impact on human health. Translating these technological 
breakthroughs from the bench to bedside is also a very important aspect 
of the NIBIB mission, and is demonstrated in some of the examples given 
below.
            translating emerging technologies into practice
A Quantum Project to Treat Stroke
    Ultimately, NIBIB seeks to translate technological advances into 
solutions that improve human health by reducing disease burden and 
enhancing quality of life. To accomplish this goal, NIBIB must be well-
positioned to utilize ideas and techniques that are at the cutting edge 
of science. Also, NIBIB must be bold and far-reaching in generating 
some of its initiatives in order to more rapidly facilitate discoveries 
and translate them to clinical practice. NIBIB recently launched the 
Quantum Grants Program, which supports very high impact, high risk, 
interdisciplinary and transformative research focused on major 
biomedical problems. The goal of this program is to solve or 
dramatically improve a major, previously intractable medical problem 
through the development and application of new and/or emerging 
technologies. Interdisciplinary teams of scientists will conduct 
collaborative research resulting in a prototype product, technology or 
procedure that promises to solve a significant healthcare problem, and 
that can be translated into clinical practice in an accelerated time 
frame. The first grant, awarded in September 2006, aims to develop a 
novel treatment for stroke, based on implantable units that will lead 
to neurovascular regeneration of cerebral tissue. This is the first 
application that has as its target, a treatment for stroke that seeks 
to restore functional tissue.
Seeing and Treating Heart Arrhythmias
    Heart arrhythmias are a major health problem. In particular, atrial 
fibrillation, a disorder found in about 2.2 million Americans, is a 
significant cause of stroke. This occurs when a blood clot forms in the 
fibrillating heart chamber and then breaks loose and travels to the 
brain. Minimally invasive surgery can be used to treat atrial 
fibrillation. However, the procedure is complicated and lengthy, often 
lasting many hours. NIBIB investigators are developing new imaging 
techniques that permit the abnormal electrical activity to be 
identified and mapped onto a patient-specific image of the heart. This 
potentially permits the procedure to be done in one hour instead of 
six. Beyond the time saving, this approach has the potential for lower 
cost, decreased exposure to x-rays, greater success rates, and fewer 
complications. The effort involves collaboration between radiologists, 
computer scientists, bioengineers, and cardiologists.
    Addressing heart diseases of a medically underserved population is 
the central focus of the Jackson Heart Study. The National Heart, Lung 
and Blood Institute, the National Center for Minority and Health 
Disparities, and NIBIB co-fund this study to assess risks factors for 
cardiovascular diseases, including diet, exercise, and co-morbidity 
factors such as diabetes and obesity.
Help for the Paralyzed
    Paralyzed or ``locked in'' individuals who retain normal cognitive 
function but are unable to move parts of their bodies to communicate 
now have a means of using the computer, based on an interface 
technology developed by NIBIB grantees. Brain waves, detected by a 
skullcap with attached electrodes, are decoded and used to communicate 
with a computer. By simply thinking of the letters, the user can spell 
words on the computer. No interaction with a keyboard or mouse is 
required. Over the past year, a team of neuroscientists has worked 
intensively to move this system from the laboratory to home use. For 
one NIH-funded neuroscientist with late-stage amyotrophic lateral 
sclerosis (ALS, or Lou Gehrig's Disease), this device has enabled him 
to continue his research. ``I couldn't work independently without it,'' 
he wrote recently for an article posted on the NIBIB web site entitled 
``Brain-Computer Interfaces Come Home.''
       nanotechnologies for personalized and preemptive medicine
Point-of-Care Systems
    Empowering clinicians to make decisions at the bedside, or the 
point-of-care, has the potential to profoundly impact health care 
delivery and to help address the challenges of health disparities. The 
success of a potential shift from curative to predictive, personalized, 
and preemptive medicine will rely in part on the development of 
portable diagnostic and monitoring devices for near-patient testing. 
The NIBIB has contributed to advances in this area by funding the 
development of sensor and platform-based microsystem technologies. 
These instruments combine multiple analytical functions into self-
contained, portable tabletop devices that can be used by non-
specialists to rapidly detect and diagnose disease, and can enable the 
selection of a definitive therapy at the time of the visit to the 
physician. A prototypic example under development and funded by NIBIB 
can identify, from a single drop of urine, the DNA of the specific 
bacteria responsible for a given urinary tract infection. Moreover, 
this test can be completed in just a few minutes, compared to the 2 
days often required by standard culture techniques.
    A second example is in the area of improved diabetes control 
through non-invasive continuous glucose monitoring. Several NIBIB-
funded researchers are working to engineer such a device. One has 
developed a contact lens that changes colors in response to the 
concentration of glucose in tears. The lens wearer can compare the 
color of the contact lens to a chart in order to determine his glucose 
concentration. If indicated, medications to control blood glucose, such 
as insulin, can then be administered.
            next generation minimally-invasive technologies
Restoring Touch in Robot-assisted Surgery
    Robot-assisted surgery is expanding the applications and reducing 
the complications of minimally invasive surgery. Nonetheless, this 
expansion has been inhibited due in part to the lack of a sense of 
touch. When surgeons operate on their own, their hands provide 
important tactile feedback. Although all fields of surgery could 
benefit from tactile feedback, cardiac surgery is among the fields that 
have the most to gain. Because of the large number of sutures used, the 
delicate tissues involved, and the need for precise work, tactile 
feedback is essential in cardiac surgery. An NIBIB-funded research team 
is working closely with a cardiac surgeon to create a robotic system 
that delivers required touch sensitivity. Use of this system could 
result in fewer broken sutures, more consistent application of force to 
tissues during surgery, and suture knots with superior ability to stay 
together. This system is now in development, and it could also serve as 
an important teaching tool for surgical residents. Rather than the 
current practice of teaching students exclusively on live patients, new 
surgeons could obtain more extensive practice in the lab before 
performing live surgery. Using computer algorithms that recognize 
motion, a trainee's movements can also be compared to an expert's 
performance and assessed.
     non-surgical biopsy through new approaches to optical imaging
    The diagnosis of many conditions such as cancer depends on 
microscopic evaluation of tissue samples. Typically these samples go 
through a process of fixation and staining before they are looked at 
under a microscope in the pathology laboratory. NIBIB researchers have 
made significant progress in developing techniques to image tissue in 
place without the need for surgical biopsy, fixing, and staining. This 
new imaging approach makes use of the different fluorescent 
characteristics of normal and diseased tissue, and offers the potential 
for examining the tissue at the point of care, in the operating room or 
medical office. Many potential human applications exist, including 
imaging tissues that form as a sheet such as the bladder or bowel 
lining. Physicists, biophysicists, imagers, engineers, biologists and 
clinicians are working together to advance this technology.
         feeding and sustaining the scientific talent pipeline
Interdisciplinary Training Programs
    An important goal of the NIBIB is to train a new generation of 
researchers equipped to meet the modern needs of interdisciplinary and 
transdisciplinary research. The Institute's proactive approach is to 
develop creative and flexible opportunities that will fill critical 
gaps in the career continuum while also enhancing the participation of 
underrepresented populations. As examples, the NIBIB has a program to 
co-train basic and clinical investigators, a Residency Supplement 
Program to provide research experiences to clinical residents and 
fellows, and postdoctoral support programs for interdisciplinary 
training to individual postdoctoral fellows.
    The NIBIB also supports and participates in a number of programs to 
address gender and diversity issues in biomedical imaging and 
bioengineering. The NIBIB partners with the NSF in the University of 
Maryland, Baltimore County, Meyerhoff Scholarship Program alliance. 
This has been an exceptionally effective diversity honors program. 
Eighty-five percent of the 511 students who have graduated since 1993 
have earned a science, technology, engineering, or math doctoral 
degree.
    The NIBIB has also partnered with the Howard Hughes Medical 
Institute to support the HHMI-NIBIB Interfaces Initiative, a program to 
develop new curricula to train Ph.D.-MD level scientists at the 
interface of the physical and life sciences and give them the knowledge 
and skills needed to conduct research. Collectively, these programs 
will help to train a new generation of researchers equipped to better 
meet the challenges of the 21st Century.
    Once trained, it is critical that we encourage those who aspire to 
be great scientists to pursue research careers. New investigators are 
the innovators of the future and their entry into the ranks of 
independent researchers is essential to the health of the research 
enterprise. In addition, the recent closure of the Whitaker 
Foundation--a catalyst in the evolution of bioengineering as a 
forefront discipline--has left many in the scientific community 
concerned about new and early career investigators. For these reasons, 
the NIBIB is specifically targeting new investigators for special 
funding consideration. This policy has proved to be successful; in 
fiscal year 2006 nearly one-third of the NIBIB-funded traditional 
research grant investigators were new NIH investigators. The NIBIB also 
participates in the trans-NIH ``Pathways to Independence'' program 
which will support recently trained scientists conducting independent, 
innovative research.

    Senator Harkin. Thank you very much, Dr. Pettigrew.

                           NIH COLLABORATION

    You know, it just seems like, every one of you, in your 
written testimony that I read, and sort of what you were saying 
here, you're all involved in this sort of personalized 
medicine. I guess I'm curious about that, and how that is 
proceeding, and whether or not there's enough correspondence, 
or I think, overlap--what's the word I'm searching for, when 
you talk together?
    Multiple Speakers. Collaboration.
    Senator Harkin. Collaboration, thank you, that's the word--
is there enough collaboration going on among you and other 
people at NIH on this? Is this a direction that's sort of, 
something new at NIH that I'm picking up on? Is there enough 
collaboration? I just throw it out there for anybody.
    Dr. Lindberg. I think it's endorsed by all.
    Senator Harkin. Yeah?

                         PERSONALIZED MEDICINE

    Dr. Collins. If you've seen Dr. Zerhouni's presentations--
and I know you have because he's been in front of this 
committee, he has very articulately, I think, put forward this 
notion of the four P's--of personalized, preemptive, predictive 
and participatory--as the emblems that need to be applied to 
medicine of the future, if we're going to move away from 
treating advanced disease in a direction that, in fact, 
prevents that disease in the first place, because clearly we 
can't sustain the curve we're on right now, as far as 
healthcare costs.
    I think we are all very much attached to that vision as the 
promise of the future. You know, you wouldn't go to a shoe 
store and just pick up a pair of shoes without noticing what 
size it was, and carry it off to the cashier. But, for 
medicine, we've been doing the one-size-fits-all approach, most 
of the time, because it was the best we could do, we didn't 
have enough information about how to personalize the prevention 
strategy, so everybody kind of got told to do the same thing, 
and most of the time they ignored us. Or the treatment 
strategies, because, you know, you had a diagnosis, well, 
here's what you're supposed to do, but that might not be the 
right drug for that person.
    We now have, I think, a golden opportunity to really change 
that perspective into one that is much more individualized, 
recognizing that while we're a lot alike, we're also different 
in really important ways that affect our chances of getting 
sick, and our abilities to prevent that. I do think--to answer 
your question about collaboration, this is one of the major 
topics the Institute Directors have gotten together on, the 
road map the common fund, has provided opportunities to bring 
projects of this sort more to the forefront, even when no 
single institute could do.
    So, certainly for me, after being at NIH for 14 years, I've 
not seen an atmosphere more in favor of collaboration and 
sharing of initiatives and willingness to not worry too much 
about which Institute gets the credit than what I see right 
now. Of course, in times of budget constraints, it's even more 
critical to do that, it's critical at any time. But now, with 
things being so tight, I don't think any of us want to let an 
opportunity go by that we might be able to get together and do.
    That also extends to collaborations outside of NIH. One of 
our big projects to look at the genetics of common disease is a 
public/private partnership where a good deal of the costs of 
the project are being covered by a pharmaceutical company, even 
though they get no benefit from it, other than the assurance 
that it's going to get done right, and the data will be 
accessible to them and everybody else and everybody else at the 
same time.

                           NIH COLLABORATIONS

    Senator Harkin. Anybody else on that?
    Dr. Collins. Just on pharmacogenetics, pharmacogenomics, 
are the differences in responses to drugs, that's actually a 
trans-NIH program that's been in place before the Roadmap, the 
pharmacogenetics research network and then now involves, I 
think, 10 or 11 different Institutes and Centers, working on 
different diseases and different drugs, but sharing a common 
knowledge base, and sharing expertise in how to design trials 
appropriately, and, I mean, use the available technology. I 
think it's very much a collaborative effort that's much more 
than the sum of the parts, because it's been so well 
coordinated from the get-go.
    Senator Harkin. In the back of my mind in all of this is 
that the cost of healthcare keeps going up and up and up and 
up. It seems like every time we come up with new discoveries, 
it just costs more money. So, should we quit discovering 
things?
    Dr. Lindberg. I'd like to comment on the collaboration, 
because----
    Senator Harkin. Oh, okay. Because I want to follow-up on 
this idea that I was, just a--but, go ahead, go ahead, on the 
collaboration, go ahead.
    Dr. Lindberg. Well, often we've been asked, ``Do you ever 
collaborate with anyone?'' I always come prepared with, 
starting to make a list, and it's--it always is a very, very 
long list for NLM----
    Senator Harkin. Yeah.
    Dr. Lindberg [continuing]. Because it's natural to 
collaborate.
    But, I think in this list that I made for this particular 
moment, in case you asked, I was surprised to find that we're 
actually, there's more collaboration within HHS than I've ever 
seen in 23 years.
    For example, we work with FDA now, you know, when you get a 
medication, there's a little tiny thing in there that tells you 
all the things that could happen, and if you can, got eyesight 
good enough----
    Senator Harkin. You need a 50 power magnifying glass, 
that's for sure.
    Dr. Lindberg. Yeah, I mean, it's a totally ridiculous 
thing.
    But anyway, we have a team that has worked to produce a new 
thing through a RX Norm that's a new way to identify those 
drugs, and it was done with VA and with FDA, surprisingly 
enough, and FDA now sends us, every day, 300 or 400 new sort of 
packaging of that stuff, so it can go up online, and an 
ordinary person can read and halfway understand it.
    That's--that's sort of amazing. We're working with the 
Office of the Secretary on a Radiation Event Medical Management 
little, a chippy, like this one, and--for toxicology with the 
National Institute of Environmental Health, and also the CDC, 
so actually, there's more collaboration in the health agencies 
than I've seen in past years. Of course, lots at NIH, as well.
    I think you'd--I think you actually can be sure that that's 
happening.
    Senator Harkin. That's good, that's reassuring.
    Dr. Berg. Senator, can I comment, briefly on your point 
about costs going up?

                           HEALTH CARE COSTS

    Senator Harkin. Yes.
    Dr. Berg. With improved diagnostics--and actually knowing 
what disease it is that you're treating, and treating the right 
people--I think there's a real hope that the costs will go 
down. One example is breast cancer treatment. One of the first 
personalized medicine products that's out there is a gene chip 
that looks at expression patterns and is reasonably good at 
predicting whether or not someone is likely to benefit from 
chemotherapy.
    Senator Harkin. Yeah.
    Dr. Berg. The potential consequences of this is that you do 
this test early on and only treat the people who are likely to 
benefit from the very expensive treatment. Don't treat in the 
same way, people who aren't going to benefit from the expensive 
treatment anyway.
    Senator Harkin. Well, it was said to me once, you know, if 
you took the money that goes into health care now, how many 
trillion is it now? Whatever it is. I don't think people would 
mind so much the expenditure, in terms of percentage GDP if, in 
fact, that money went for preventative medicine, early 
detection, so that people didn't have to go through these 
excruciating illnesses, and have to go through chemos and 
radiation and all of the other things you go through--we've 
done pretty well there, in terms of patching and fixing and 
mending later on, but that costs a lot of money.
    In fact, it ought to be shifted, now, to an earlier point 
in time for identification, risk factors, and then getting 
people on the right course of action as they go through their 
life to prevent the onset of illness--I don't think there would 
be that much consternation on the spending of money. Most of 
the people just see it as just going for the same old, you 
know, patch and fix me up once I get in trouble.
    So, I'm encouraged that, what you're all talking about here 
is moving that point of interaction with the patient earlier on 
some point in time. That's going to cost money. It's going to 
cost money, but hopefully as we reach--as we develop these new 
research regimes, and new techniques, new interventions, that 
some of the other stuff will start coming down. That's our 
hope, anyway. I hope it's not a false hope.
    Dr. Collins. No, I think that's a very wise vision, and one 
that could be achieved, it really does require a change in 
mindset, and of course, it requires a change in reimbursement 
also----
    Senator Harkin. That's true.
    Dr. Collins [continuing]. In terms of how health care is 
paid for in this country.
    Senator Harkin. That's the ticket.
    Dr. Collins. Which is a big issue.
    Senator Harkin. Is how we reimburse.
    Dr. Pettigrew. If I could just interject here, and follow-
up on an earlier question--what you just described, Senator, is 
the paradigm that we currently operate under in health care, 
and that is a curative paradigm.
    Senator Harkin. Sure.
    Dr. Pettigrew. Where the response is after there's a 
symptom, and an obvious problem. And, what you also described 
is, where we're headed and going as a preemptive paradigm, in 
which technologies--like the one we've talked about, that we've 
all talked about--will be able to provide an indication that 
there is a developing disease, early enough so that we can 
intervene at a time where the technologies that we have to 
prevent serious consequences, are effective.
    You notice that all of us sounded the same tone of 
personalized health care. I think the reason for that, is that 
the more that we learn about disease, the more we appreciate 
that a disease that has a given name can be quite different in 
different people, and typically is quite different in different 
people. So, Dr. Berg mentioned breast cancer as an example, and 
we know that there are significant differences in the gene 
expression patterns associated with breast cancer, and 
consequently, the treatment should be different--it's not a 
one-size-fits-all-type of paradigm or approach. That is 
certainly where we're headed.
    I think all of the technologies that we certainly support, 
really are aimed at being able to see things when they are 
earlier in the disease process, and in addition to that, 
developing therapies which are very targeted, specifically to 
the offending biologic process.

              NIH GENES, ENVIRONMENT AND HEALTH INITIATIVE

    Dr. Collins. Senator, can I add one other thing to this 
discussion, because I think it's a really important one, and 
that is the importance of paying attention to the environmental 
contributions, as well as the genetic ones. I think sometimes 
people get the sense that we're so excited about genetics--and, 
believe me, some of us are--that we're ignoring the fact that 
common diseases like heart disease and diabetes and cancer, are 
some interplay between hereditary predisposition, and some 
environmental trigger, and we need to understand both.
    We particularly need to understand the environment, because 
that's the part we might be able to change in somebody who's at 
high risk, in order to reduce that risk.
    In that regard, and this also plays into your question 
about collaboration, there is this initiative called the Genes, 
Environment, and Health Initiative, which has now participation 
by virtually all of the NIH Institutes, and for which $40 
million a year have been allocated for the current year, and 
three more years after this, assuming the budget allows for 
that.
    This is explicitly an intent to both identify what 
hereditary factors are involved in common disease, but also to 
develop new and more accurate technologies for assessing 
environmental exposures--in the air, in the water--and also 
what the effect of those exposures are on the individual. So, 
you not only want to know what's out there, and you not only 
want to know what the body burden is, you want to know what the 
response was, biologically, of that person. Because it might 
have been that a particular substance was handled just fine by 
one person, was actually quite dangerous for another.
    David Schwartz, the Director of NIEHS, and myself, are co-
leading this effort, this Genes, Environment and Health 
Initiative, and already a large number of scientists have 
gotten engaged in helping to lead this, and we will fund, in 
the next few months, a substantial number of new proposals to 
try to accomplish this hand in hand, not studying genes in 
isolation, or environment in isolation, but really getting 
those two fields together, in a cohesive way. And, I think 
that's a very exciting and timely effort, at the present time, 
where we could finally really begin to get our minds around 
what are the causes of these common disorders, and what we 
could do about it.

                         KNOCKOUT MOUSE PROJECT

    Senator Harkin. One other thing you mentioned in your 
written testimony, you didn't mention it here, was this--tell 
me about this Knockout Mouse Project, I just don't understand 
it.
    Dr. Collins. All right, I'm happy to, Senator. That's 
another example of a wonderful collaborative effort, because 
this involves 19 Institutes that have gotten together to 
support this.
    So, what's a Knockout Mouse? Probably conjures up images of 
people in a boxing ring punching a little rodent, that's not 
quite what we had in mind.
    Senator Harkin. Or just rubberstamping the same mouse or 
something, I don't know.
    Dr. Collins. No, the idea here is, the mouse remains our 
best laboratory research model for trying to understand human 
disease, and mice have about 20,000 genes, just like humans do. 
If you can find a human gene and look at it, you can almost 
certainly find the mouse homologue of that gene, and it will 
have a similar sequence. Many times, what we've learned about 
human diseases, in terms of exactly what's wrong when a gene is 
misspelled, we've learned first by looking at what happens when 
that gene is misspelled in the mouse, because there we can do 
breeding, we can do careful examination in ways that we can't 
with people.
    So, about 2000 or so, mouse genes have been systematically 
knocked out, that is, inactivated, to see what the consequences 
would be. That has been a major part of NIH-funded research 
now, for more than 20 years. But, it's been done in an 
individual laboratory way. Many of the papers in the medical 
literature describe the consequences of these knockouts, and 
it's taught us a prodigious amount about biology and disease.
    But, we think we've reached a point where this kind of 
cottage industry knockout is maybe not the way to go forward. 
We want to see what happens, now, systematically, if you were 
to knock out, one at a time, all 20,000 genes, and do it in a 
sort of Genome Project mindset where you would do it with high-
efficiency, low-cost, and easy access to the outcome. That's 
been another problem, some of the mouse knockouts have been 
made multiple times, because people haven't been willing to 
share, and we want to make sure that this time these are all 
made in a way that anybody with a good idea can get access.
    So, all of the institutes got together--even in a tough 
budget time--and agreed to donate parts of the budget here to 
make this happen, and we also joined up, quite vigorously, with 
the Europeans, who have a similar interest in this, and the 
Canadians, who have a similar interest. Just this past March, 
we had an international meeting in Brussels, where we pulled 
together an International Knockout Mouse Consortium, with all 
agreeing to work together to get this done, as quickly as 
possible, at low cost as possible, with high quality, and to 
make all of these mice accessible to any investigator who wants 
it.
    So, basically, what we're going to end up doing here, is 
saving the NIH a ton of money.
    Senator Harkin. Help me understand this, you're going to 
knock out one gene----
    Dr. Collins. At a time.
    Senator Harkin [continuing]. At a time.
    Dr. Collins. Yes. These days that can be done in a sort 
high through-put way.
    Senator Harkin. So then you've got a mouse with a gene 
knocked out.
    Dr. Collins. Yes.
    Senator Harkin. What are going to do with that mouse?
    Dr. Collins. So, basically, those will be available as 
frozen embryonic stem cells to anyone who then wants to 
investigate that one, and see, ``Okay, what happens when that 
gene is knocked out?'' We, at the present time, we don't have 
the funds to take all 20,000 and put them through a very 
elaborate set of measurements to see, ``Well, is there a 
problem with the nervous system, is there a problem with the 
blood system, do they have some birth defect of some sort?'' 
We're going to count on the community to, one by one, as they 
get interested in a particular knockout, to do that, and then 
put that information in the public domain. But, what we won't 
expect them to do, is to actually go and do this tricky thing 
of knocking out that specific gene, which people have been 
doing, but at a very inefficient sort of basis.
    Senator Harkin. How long will it take you to do this?
    Dr. Collins. Five years is the estimate, to get all 20,000 
of these knocked out and available, I hope we can do it sooner.
    Senator Harkin. They're done in different places around the 
globe?
    Dr. Collins. So we at NIH, we're funding two major centers 
to do this, but in Europe, there's a major center, in Canada, 
there's a major center. We are all now working together to make 
it clear that we don't duplicate the effort--each center has 
their own list of which genes they're responsible for, we watch 
closely to see what progress is being made, we'll reassign some 
if people fall behind in one place, and get the centers that 
are going faster to pick up the slack, just like the Genome 
Project, it's international, it requires a lot of careful 
management and tracking, but it's very achievable.
    Senator Harkin. That's interesting. The one thing that 
comes to mind is that if I'm not mistaken, genes interplay. So, 
if you knock out one gene, maybe that doesn't do much. But, 
maybe if you knocked out one 10 notches down, it might have 
another effect.
    Dr. Collins. It's a very good point, Senator, and in fact, 
if you have them all generated as knockouts one at a time, by 
mouse breeding, you can make any combination you would then, 
like, to look at the interactions.
    Senator Harkin. Yeah, I guess that----
    Dr. Collins. That's the beauty of being able to figure out 
who mates with whom--which you can do in the mouse cages.
    Senator Harkin. I guess that just comes about through 
various studies and things, and looking at different genes that 
have an effect on one thing or another, and matching those up. 
Yeah, I can see how that would work.
    Dr. Collins. So, take for cancer, for instance, what we're 
learning about these ``tumor suppressor'' genes, that is, genes 
that normally keep cells from growing out of control when 
they're not supposed to. A lot of what we've learned is to 
knock those genes out in the mouse, those mice generally do 
develop a cancer of some sort, you can then understand by 
breeding in other kinds of mouse genetic changes, is there some 
way to suppress that cancer, by activating some other part of 
the pathway--exactly like you say. It's a very powerful system. 
You can do some of these things by cells growing in laboratory 
dishes, but there's no substitute, really, for having an intact 
animal, where you have complete control over the whole system.

                         EXPLANATION OF HAPMAP

    Senator Harkin. Explain that HapMap to me again.
    Dr. Collins. Yeah, what is this thing?
    Senator Harkin. My question is, cost reduction on studies?
    Dr. Collins. Yes.
    Senator Harkin. Detailed map of the one-tenth percent 
variation--tell me about that?
    Dr. Collins. All right, sure, I'm happy to, this is one of 
my favorite topics, Senators.
    So, your DNA and mine are 99.9 percent the same, that would 
be true if I picked anybody else to compare myself to, we're 
all that similar. But, that point .1 percent is still a lot of 
differences, because the genome is such a big place, with 3 
billion letters in the genome, .1 percent of that, well, that's 
still 3 million changes between you and me, and if we looked at 
the whole room, and asked, ``How many places are there in the 
genome where, as a roomful of people, we have common 
differences?'' I'm not going to talk about the rare ones that 
you might find only once, but the common ones, because those 
are the ones that often drive the risk of common diseases--
there would be about 10 million of those in the whole genome.
    So, in that collection of 10 million variants, there are 
some we really want to discover, that play a role in diabetes 
risk, or heart disease or cancer or asthma or schizophrenia. 
Yet, finding which one is a real needle in a haystack.
    What HapMap set out to do, was two things. One was, first 
of all, to build that catalog of those 10 million variations, 
because when HapMap started in 2002, we only knew of about 2 
million, and we clearly needed a more thorough look.
    But, the other thing that HapMap did, which turned out to 
be an incredibly useful shortcut, was it figured out that these 
variations in the genome are not traveling independently of 
each other. They're basically traveling in neighborhoods. So, 
if there's a neighborhood on a chromosome where you have 30 or 
40 SNPs, there's a good chance if you check two or three of 
those, and see what their variation is--a SNP, by the way, is a 
Single Nucleotide Polymorphism which is just a fancy word for 
saying a ``difference in DNA spelling.'' If you check two or 
three out of those 30 or 40, you can probably predict what the 
others are going to be without even looking at them, and that's 
a reflection of the fact that we're a young species, and these 
segments of the chromosomes, neighborhoods, if you will, have 
been traveling in unbroken form since our common ancestors.
    Well, you see how that's valuable. That means, if you're 
looking for a variant that plays a role in asthma, for 
instance, you don't have to check all 10 million. If you check 
a carefully chosen 300,000, it turns out, is about the number--
and I say carefully chosen because you've got to know what the 
boundaries of these neighborhoods are, some of them are little, 
some of them are bigger, what HapMap did was to tell you how 
those neighborhoods are organized--then for a fraction of the 
effort, you can actually look at the entire genome, and you 
won't miss the answer, you'll find the neighborhood where the 
culprit is hiding. That saves about a factor of 30 or 40 in the 
amount of work you have to do.
    That, plus these technologies, like these chips that I 
brought to show you--which have greatly cut down the laboratory 
costs, mean that we got from this $10 billion price tag for 
doing a diabetes study, to less than 1 million, and that is a 
profound change in the space of just 5 years.
    So, HapMap plus technology forward is a magnitude drop in 
cost. Phenomenal.

                           INTRAMURAL PROGRAM

    Senator Harkin. All right, nice explanation.
    Dr. Berg, I want to ask you some--I was reading over your 
testimony, you mentioned Jeffrey Gray and Ryan Harrison, caught 
the bug, he was in high school, he met a person at Johns 
Hopkins through an outreach program, he spent 2 years working 
in his laboratory, came in fifth place in the Intel Science 
Talent Search, et cetera, et cetera--what outreach program got 
him interested?
    Dr. Berg. There's a program he attends at the Baltimore 
Polytechnic Institute that has a program of scientists from 
around the area who can come and just give talks about what 
careers in science. I think it was when he was in 10th grade he 
went to one of these, and thought this sounded, he didn't----
    Senator Harkin. It wasn't an outreach program from you?
    Dr. Berg. It wasn't supported by NIH, no. Although we do 
have programs--not at the high school level--but at other 
levels that try to do the same sort of thing.
    Senator Harkin. I guess that was my question. Is there a 
specific program for high school kids to intern with scientists 
in labs that's backed by NIH? Is there such a thing?
    Dr. Berg. We have a diversity supplement program for high 
school kids. If someone has a lab and wants to have a high 
school kid come in and work in their lab, there's a way of, to 
get some support through that program for a particular person. 
But it's an NIH-wide program.
    Senator Harkin. What do you mean, it's NIH-wide, I mean, 
don't you handle it?
    Dr. Berg. Every Institute has their own version of it. For 
us, it's a supplement to a grant. So if they have a grant from 
NIGMS, they can apply, but if they have a grant from any other 
institute, they can apply as well, and that particular grant is 
supplement.
    Dr. Collins. The other big program we have is summertime 
internships in the intramural program at NIH, we have hundreds 
of high school students who compete avidly for the opportunity 
to come and spend 10 or 12 weeks in a laboratory. Generally, in 
my lab, I take one or two each summer. They are full of talent, 
it's a very competitive program----
    Senator Harkin. High school? High school?
    Dr. Collins. High school kids. We also take college kids, 
but the high school program is very hotly sought after.
    Senator Harkin. How about--that would be a limited number, 
I mean, these come here for your intramural program.
    Dr. Collins. Right.
    Senator Harkin. But, I mean, this kid was at a lab at Johns 
Hopkins?
    Dr. Berg. Yes, he is now an undergraduate at Johns Hopkins, 
and working.
    Senator Harkin. How about when he was a high school 
student, he worked in a lab?
    Dr. Berg. Right.
    Senator Harkin [continuing]. At Johns Hopkins?
    Dr. Berg. Right.

                         ADOPT A SCHOOL PROGRAM

    Senator Harkin. How much of this is done around the 
country? We've got labs all over the country that are funded by 
NIH. Do we have any program, that you know of, do you know of 
any program at NIH where high school students, who have 
exhibited an interest in science, and would like to spend an 
internship, a summer, testing out whether or not they really 
want to get into this kind of research, and do that? Is there 
a----
    Dr. Lindberg. This is a little bit harder to do than it 
sounds like, but we're trying to get at that.
    I should say, first of all, that many of the Institutes at 
NIH have an Adopt-A-School Program. We, for instance, have 
adopted, in Series Two inner-city high schools in The District 
of Columbia and that's pretty successful, so there's a lot of 
movement back and forth there. But, I mean, high school kids 
are young, so they can't just drop out and tool around, they 
might get a summer. But, anyway, we're trying hard to do that, 
we've had several outreach programs with high school--large 
numbers of high schools, five or six together, for instance, 
New York we just did, with NYU being the host.
    You can get them for a day, and that's about it. We tried 
one in Chicago, and they, the schools let us down on the 
transportation with busses, and we had--so we had those kind of 
basic problems.
    I would say the best program that I know of is in Houston, 
and it's the, now-called the Michael DeBacky High School for 
Science, and it's associated with Baylor. It's taken them over 
25 years to get the thing really working, it took 20 years 
before they even called it the Michael DeBacky School, but he 
and the other Baylor faculty have pitched in, and it is, again, 
an inner-city school, but it's got something like 98 percent of 
the kids going into college, and most of those going into 
science. So, it's a very intense activity, but a very 
successful one.
    We're trying to follow that model, of course.
    Dr. Berg. Let me add one other program, so, another way 
that we try to influence early science education is we have a 
series of curriculum supplements that are developed that we 
make available to teachers from around the country, and NIGMS 
developed one less than 2 years ago on doing science, so it's 
not on any particular disease, but it's about the scientific 
process, curiosity, and designing experiments and controlled 
experiments, intended for 7th and 8th graders, and that is--was 
developed in partnership with the NIH Office of Science 
Education. We went through all 25,000 copies of it in, I think, 
a little less than a year, I think it's the first--most widely-
distributed supplement that they've done. So, this gives tools 
for the, for teachers to develop strong programs.
    Senator Harkin. How many students come out to NIH every 
summer for this?
    Dr. Collins. I don't know the exact numbers, it's in the 
hundreds.
    Senator Harkin. Oh, yeah?
    Dr. Collins. Yes, and every university I know----
    Senator Harkin. These are high school kids, they've got a 
place for them? I'm getting into the weeds now, on this, but 
I'm really curious as to----
    Dr. Collins. I can get you those numbers, Senator. I don't 
actually know how many high school, how many college are there 
in the summer, but the place is crawling with summer trainees, 
which makes it a great place to be in the summertime, all kinds 
of irreverent questions being asked about science.
    Every university that I've ever been involved in has a 
similar program in the summer in their own location to try to 
bring students in.
    One thing we do, on April 25, which is DNA Day every year, 
because of the publication of Watson and Crick's paper in 1953 
on April 25--we send all of our post-docs and graduate students 
out to high schools, and they spend the day, all over the 
country, talking about the excitement about the science that's 
happening as a consequence of our understanding of DNA. That's 
been, this has been the fifth year we've done that, this year. 
It is both great for the students, and it also activates the 
post-docs to take this on as part of their own professional 
future, that they're going to spend some part of their time 
reaching out to high schools in their own vicinity, and trying 
to teach about what they do.
    Senator Harkin. I'm looking for, I just, ideas, ways of 
which we get high school students interested, provide access to 
post-docs and people like that who can kind of bring them along 
a little bit.
    Dr. Lindberg. I can give you another number, because every 
summer we bring a dozen to 15 students from this inner-city 
school, and we used to bring six faculty. So that we were, we 
thought, helping them. I would say that the net results of that 
is that the students are fantastic, they're really good, and I 
think they make progress even in the course of one short 
summer, and the faculty flunk.
    We've stopped--we think that's throwing good money after 
bad, and we stopped supporting it. We still bring the students. 
But, they have different things to learn, I mean, for instance, 
the first bunch we brought through, we gave them--like you're 
giving us--5 minutes to say something about what do they 
accomplish in the course of the summer, and two actually passed 
out, I mean, this was a tremendously threatening thing. You 
know, a board room, and all of these adults, and you know, it 
was awful. So, we decided that, you know, one of the top things 
they've got to learn over the course of the summer, is stand up 
and make a presentation, look in the eye and tell you, and that 
is top of the list, and they do very, very well. Now, they're 
actually doing multi--they're doing Power Point and Keynote and 
all of these kinds of things.

                             PUBLIC ACCESS

    Senator Harkin. Yeah, sure.
    There's a lot of talk about publication of research 
articles, and how soon it should be done. We're getting input 
from private publications and others, I don't know the answer, 
but I just want to know--if Congress were to require that all 
NIH-funded research articles be deposited in the PubMed Central 
Database, which is the public access plan that NIH has 
proposed--how would that improve scientists' ability to conduct 
research?
    Dr. Lindberg. Well, I think it probably would improve it 
quite a bit. I mean, one of our tests, probably, is from PubMed 
Central right now, and that is the place that these things 
would go and the proposals that we've described. The number 
that are coming in voluntarily is way less than 5 percent of 
the amount that should come in, but lots of other sources are 
putting in articles, that are free forever, the publishers and 
so forth--there's a million articles now in that three set, and 
it's very, very heavily hit, something like 12 million per 
month get looked at.
    If you looked at it another way, like, ``Are all of those 
of any interest?'' Well, 75 percent are of interest. This 
includes many that we're scanning in from, well, the old 
issues, let us say, when one publisher says, or society, ``You 
may have this thing,'' then we say, ``Okay, if at our expense 
you would allow us to go and scan in all of these old ones, 
back to Volume 1, Number 1, you know, which you have copyright 
to,'' so they have a right to say yes or no, would you do that, 
and then we'll do that if it can be made freely available 
forever.
    Well, lots have said yes, and the Wellcome Trust in England 
has partnered with us on that, I mean, they, it's dollar for 
dollar, although actually the pound is going up faster than the 
dollar has, so we've made a little money on the deal, and so 
that's going forward very, very well, and that's part of this 
experiment, in which I said, David Lipman is here, he can 
confirm all of this for me, but he tells me that 75 percent of 
those articles do get used right away, so they are of real 
interest. I think it would make a big difference.

                         MEDLINE PLUS MAGAZINE

    Senator Harkin. Well, I appreciate that for the record. We 
don't really know exactly what we're going to do yet.
    But, I wanted to ask you about MedLine Plus magazine.
    Dr. Lindberg. Great, I love it.
    Senator Harkin. Again, I've felt for a long time that----
    Dr. Lindberg. There's a new one.
    Senator Harkin [continuing]. That NIH--yeah, you just 
showed it to me.
    Dr. Lindberg. Yeah, okay, good.
    Senator Harkin. I've got it right here, I have it right 
here. I have felt for a long time that NIH had to be more 
aggressive in getting their stuff out to the general public, 
both at basic science base, but also in translation, so people 
can understand it. That's why I was happy to join you when you 
started putting this magazine out, because this is readable. I 
mean, you know, even I can understand some of this stuff.
    So, I think it's a great resource. And, again, I'd like to 
see copies of this in every doctor's office around the country. 
People ought to come in, and they ought to have access to it, 
and online, you say they can get access online now.
    Dr. Lindberg. Yeah, but most people don't yet have 
computers and access.
    Senator Harkin. I understand that.
    Dr. Lindberg. I'd like to see it, just as you say, sitting 
in that waiting room, when they're so boring.
    Senator Harkin. Well, how many copies are you putting out?
    Dr. Lindberg. Well, we're putting out around 50,000 right 
now, between 40,000 to 50,000, and that's being financed partly 
by the Friends of NLM found the money to do this, some 
contributions from the NIH Institutes on a passing-the-hat 
basis. In order to do what you said, we think that we probably 
could do it by--there are around 500,000 doctor's offices, so 
if you schedule, say, three per office, that would be 1.5 
million each quarter, 6 million per year, would cost around 
$3.6 million.
    Senator Harkin. $3.6 million per year?
    Dr. Lindberg. Yeah, and we have about $.4 million, so we're 
lacking $3.2 million. How to get it, obviously would be 
childishly simple, to get it through advertising, but that 
would defeat the purpose, we think, of the whole operation, 
so----
    Senator Harkin. Yeah, true.
    Dr. Lindberg [continuing]. We've just sworn we're not going 
to do that. So, we've got to get it either by private 
contributions, or appropriations.
    Senator Harkin. Well, would doctor's offices subscribe to 
it? I mean just, you know, would they pay for it out of their--
--
    Dr. Lindberg. I don't know, we could try it. We haven't 
tried it, I must say. But we could try it.
    Senator Harkin. There's some good stuff in here.
    Dr. Lindberg. Actually, it would be--it is the only case in 
which NIH is delivering information, publications, directly to 
patients. I mean, of course, there's lots of information on all 
of the Institutes' websites, just as ours, but that's a little 
different, that's not a publication, often it's as much for 
scientists as for patients, but this is aimed right at, between 
the eyes of the patient.
    I must say, I was interested in the conversations we've 
just had, because some of the things Dr. Collins spoke about 
are really, the doctors and the researchers. You're 
communicating with them magnificently, even if you've got to go 
to poor old Belgium to do it.
    But, a lot of the other things you spoke about first just 
won't happen, at all, unless the patients understand it, and 
agree to it. Including this environmental thing. Because, I 
mean, who knows where the exposure is, the patient is the 
expert on the exposure. Unless they believe in this, and 
participate and understand it, you know, maybe through this 
kind of a magazine, maybe through everyone else's efforts, none 
of this stuff will happen. First of all, if they don't trust 
us, I mean, you have now your Federal legislation pending, that 
would be a big help. But, I think they have to understand, as 
well.
    I mean, if this whole genetic experiment runs up against 
stem cells, that's, that we don't want to put up with, we don't 
want to have it stopped, we want it understood and welcomed.
    Senator Harkin. I missed that, if it's up against what?
    Dr. Lindberg. Well, if people were to conclude that the 
genetics, the experiments you're talking about have any sort of 
a political or religious bias, or----
    Senator Harkin. Oh.
    Dr. Lindberg [continuing]. Obstacle, that would be very, 
very bad. It would be incorrect, we don't want that to happen, 
but it would be an obstacle to getting this work done, this 
personalized health experiments. So, I think these magazines, 
this effort is an important one.
    Senator Harkin. Well, I'm just saying----
    Dr. Lindberg. I appreciate your help.
    Senator Harkin [continuing]. Is there, what more can we do? 
I mean, $3.2 million, that gets it to every doctor's office, 
now you want to get it also out to community health centers. I 
suppose maybe your doctor's offices include community health 
centers----
    Dr. Lindberg. Yeah.
    Senator Harkin [continuing]. Maybe.
    Dr. Lindberg. Well, I think the higher the volume, the 
less, you know the prices decrease. These things are about a 
dollar apiece, I think they can get it now for something like 
50 cents, that would give us our 6 million, if you get that, 
maybe we can drive it below that, find some other way to get it 
done. Because they can download them right now, free, and copy 
it themselves.
    Senator Harkin. I thought you said I could download this.
    Dr. Lindberg. You can, yes, yeah, sure. But, I don't know 
how many people would do it, maybe we can more people doing it, 
maybe that's what the doctors could do, instead of paying a 
fee.
    Senator Harkin. Yeah, still, people like to pick up stuff, 
and read it.
    Dr. Lindberg. I agree, I agree, I agree. But, I think the 
volunteer agencies, for instance, the alliances have been 
wonderful to work with, you have lots of work with them and----
    Senator Harkin. Which one can I get the money from?
    What are your budgets here?
    Dr. Berg. Senator, let me give you one other thing we've 
been doing, in terms of trying to communicate the basic science 
messages. It's an electronic newsletter called Biomedical Beat, 
where we go through the press releases for the investigators 
that we support, and write one- or two-paragraph, plain 
language, understandable, hopefully, descriptions of some of 
the advances. It's been growing for a little bit more than a 
year now, and the number of people who actually subscribe has 
increased.
    Senator Harkin. Let's take a look at that $3.2 million, 
huh?
    Dr. Lindberg. Yes, sir.
    Senator Harkin. All right.
    Dr. Lindberg. The price is good until midnight.

                       HUMAN MICRO BIOME PROJECT

    Senator Harkin. We'll see what we can do about that.
    Let's see, what else did I want to go over here?
    Dr. Collins, you mentioned the new effort called Human 
Micro Biome Project, trillion of microbes in the human gut, you 
went to talk about obesity and intestinal--could we also find 
out what causes irritable bowel syndrome and things like that, 
too? It seems to be an exponential rise up.
    Dr. Collins. So, this Micro Biome opportunity is another 
example of something we couldn't have dreamed of doing as 
recently as 3 or 4 years ago.
    You know, our bodies are both populated by microorganisms 
in various body cavities and orifices, some not proper to 
mention in a Senate hearing, and there are also, of course, 
many microorganisms in our skin. It's clear that we coexist 
with those organisms, happily most of the time, in fact it's 
clear they contribute to our health. But if something goes awry 
and the balance is off or you get the wrong microorganism in 
the wrong place, then one can result in an unfortunate disease 
situation.
    Yet, we don't know nearly enough about this. We've been 
limited in our understanding of microbiology by what kinds of 
bacteria we can actually culture in the laboratory. It's clear, 
that's only a tip of an iceberg. There's lots of other 
microbes, particularly in our GI tract, that you can't grow. 
Yet, they're there, and many of them are probably helping us 
and some of them have the capacity to hurt us. So, how would we 
get at those?
    Well again, the promise of being able to do very high 
through-put, very cheap DNA sequencing comes to mind, because 
these microbes have DNA also. DNA is their instruction book, 
just like ours. So, even if you can't culture them, you can 
determine what their DNA is by simply doing a--what we call a 
metagenomic experiment, where you make DNA from a whole 
collection of microbes and you read out the sequences and you 
piece together what must have been there.
    Again, because this would have been prohibitively expensive 
until 3 or 4 years ago, it hadn't been approached in a very big 
way.
    A very recent experiment that I think got everybody's 
attention about this, done by Jeff Gordon at the Washington 
University in St. Louis, relates to obesity. Where he was able 
to show--initially in mice, and then in people--that the 
particular collection of microbes in the gut have a lot to do 
with whether that mouse is going to be obese or not obese.
    In fact, you can take an obese mouse and put the microbes 
into that animal that had previously been in a skinny mouse, 
and the fat mouse starts to get skinny too, without any other 
change. So, there's something going on there, in terms of an 
interaction between the host and the bacteria that live in 
their intestinal tract. That's been possible also now to show 
with people, that a change in body weight can be accomplished 
by a change in microbes.
    Now, imagine what a wonderful circumstance that would be, 
if we could figure out how to help people lose weight or not 
gain weight, simply by altering their intestinal flora. It's 
not unimaginable that might not be the case.
    So, we have, in fact, again as a collaborative effort 
involving lots of institutes, come up with a plan, which we 
hope will be funded as part of the Common Fund--because this is 
one of those that touches upon all of the institutes you see 
here and many that you don't--to enable a really organized 
effort to try to characterize what bacteria are present in 
these various parts of the body. How variable are they from 
person to person? What happens when you take antibiotics for an 
ear infection? Does it just throw everything off? How long does 
it take it to recover?
    If you looked at identical twins, do they have the same 
microbes, or are they different? If they're different, why are 
they different? Particularly, what happens with inflammatory 
bowel disease or with vaginitis or with a particular kind of 
dental problem like periodontitis, that changes those microbial 
flora in a way that we currently really don't understand, that 
might lead you into a pretty good idea about how to correct the 
situation.
    So, it's very exciting. Again, another international 
opportunity here, because the Europeans are very interested in 
this and I think you're going to hear a lot about this in the 
course of the next 3 or 4 years as the amount of data we can 
generate really goes up very quickly. This instrument, this 
sensor that Dr. Pettigrew told you about, could, of course, be 
a way in which whatever we learn about microbes could be 
quickly translated into a diagnostic, yes, once you know what 
to put on that diagnostic in order to access what particular 
thing is there that you want to know about right away.
    Senator Harkin. Well, that's all well and good. I hope you 
don't mind if I remain skeptical.
    Dr. Collins. Don't mind at all.
    Senator Harkin. I mean come on, look, I mean, calories in, 
calories out. More calories in, less calories out, it's stored, 
it's stored as fat.
    Dr. Collins. We used to think it was just that simple. To 
first approximation it is, but clearly the microbes in your gut 
are a big part of your digestive process.
    Senator Harkin. It has to do with the rate of how fast you 
burn up your energy, too.
    Dr. Collins. Also, whether you're really efficient at 
absorbing what you take in, or whether some of it doesn't 
actually get absorbed. That has a lot to do with what goes on 
in the distal small intestine, and particularly the colon, and 
the microbes apparently have a bigger part of that. I think we 
were all surprised. I was skeptical too, until I saw this paper 
in Nature from Dr. Gordon. It looks quite compelling.
    It only takes a tiny change in your efficiency of absorbing 
what you eat over the course of many weeks to have a 
significant effect on what happens with body weight. It doesn't 
mean that it has to be this drastic difference based on what 
microbes are there. A little bit makes a big difference over 
the course of a long period of time.
    Senator Harkin. I, again, I remain skeptical. I just find 
that, it seems to me that we just need to change some diets and 
habits and what we consume as kids in this country, in terms of 
carbohydrates and fats and starches and sugars and everything 
else that we consume too much of. We get in these habits and 
habits are hard to break.
    Dr. Collins. Senator, I think you're absolutely right. This 
may be a modification of that fundamental principle that might 
make it a slightly easier case for somebody who's really 
struggling, but you're basically correct.
    Senator Harkin. That is true. Some people have different 
rates of metabolism. People have to exercise and eat less than 
other people in order not to become obese. I understand that, I 
understand.

                          MACULAR DEGENERATION

    I want to ask about macular degeneration. Dr. Berg, you 
talked about macular degeneration in a way--and I wrote this 
down--reverse damage. Is what you're doing, is it at the point 
of stopping it from progressing, or can you actually reverse 
the damage?
    Dr. Berg. This is not something that we're directly 
funding. The idea is that it does not reverse the damage, but 
stops the progression.
    Senator Harkin. Yeah.
    Dr. Berg. The way that the pathways contribute to the 
progression of a disease are understood, to some degree, you 
can block them with this RNA interference-based therapy.
    Senator Harkin. Where are we in that? I mean, are we in 
human trials right now?
    Dr. Berg. Yes, the phase one trials were successfully 
completed, the phase two trials are underway now.
    Senator Harkin. It actually stopped the degeneration?
    Dr. Berg. That's my understanding. The initial trials are 
just safety related, but they're into the phase two trials now 
and the expectation is that this therapy, if all goes well, 
will be on the market, I believe, in 2009.
    Dr. Lindberg. I think even before that, though, the eye 
guys have reported that, you know, once they've--well, first of 
all, the important thing is that a single gene could be seen as 
responsible for this disease, which was thought in the past to 
be one of these complex things that must be complicated, but 
wasn't.
    So, once having found that that has to do with capillary 
growth, the ophthalmologists just reached out and took a 
syringe full of Avastin and injected it in the globe. If you do 
this every 10 days for four or five times, you know, 
metaphorically, they give you back your driver's keys, you 
know, that you can go from those big things to those small 
things and you can drive a car again. So I mean, it's a pretty 
enthusiastic kind of response.
    Senator Harkin. Fascinating.
    Dr. Collins. This is really a wonderful success story and 
comes from several directions, Senator. So, basically, macular 
degeneration, particularly the wet type, does seem to be 
something that's gone awry, in terms of capillaries. But the 
treatment that Dr. Lindberg's referring to actually came out of 
the study of cancer, where we realized, particularly from the 
work of Judah Folkman, that cancer seems to have the ability to 
grow, particularly because it recruits blood vessels. Of 
course, if you can block the blood vessels, you can starve the 
tumor and it might be a very effective approach.
    That's what this drug Avastin is all about, it's an 
antibody against a particular factor, VEGF, which is what blood 
vessels need in order to proliferate. So, you're blocking that 
proliferation. It's a very powerful scheme.
    But, it turns out that this same strategy works quite 
nicely for this wet form of macular degeneration because, there 
again, your goal is to try to block the proliferation of these 
blood vessels that are causing the blindness issue. In fact, 
there is a fragment of Avastin that's called Lucentis, I think 
it is, which was approved by the FDA for treatment, which is 
just as effective but I gather, has some economic 
disadvantages.
    So, here we are in a circumstance where a disease that we 
considered to be both untreatable and probably not possible to 
understand, in the space of a short period of time, we've come 
a long way.
    The mention of genetics has also been a big surprise. Most 
people thought this disease, which comes on in your 70s, 80s, 
or sometimes even 90s, was not going to have anything to do 
with genetics. But it turns out there are a couple of genes 
which play the major role, along with smoking. If you basically 
can put those together, you can make a very strong prediction 
about who's at risk. Here's a chance to do prevention. Coming 
back to our idea about focusing on preventing the disease, 
instead of waiting until it happens.
    If we now know what the pathway is that causes risk here, 
which has something to do with inflammation, then perhaps by 
blocking inflammation in the eye, which we have drugs that are 
pretty good as anti-inflammatory agents, we might be able to--
with those people at very high genetic risk, to prevent them 
getting the disease in the first place. The Eye Institute is 
investigating that vigorously right now.
    Dr. Lindberg. But Avastin's pretty cheap.
    Dr. Collins. It is pretty cheap.
    Dr. Lindberg. It's an off-label use, of course, but, and I 
think the ophthalmologists are amazingly gutsy to do it. They 
impress me.
    Dr. Berg. The potential advantage of the RNA-based therapy, 
is the same pathway. What this RNA molecule does, it blocks the 
expression, not of VEGF, but the receptor, what VEGF docks 
into. As I understand it, what the trials have indicated is it 
might be longer lasting, so you wouldn't need to get these 
injections as frequently.

                          RNA AND FLU VACCINE

    Senator Harkin. You mentioned RNA also, in terms of 
pandemic flu virus. I've had different people in my office 
talking about, you know, producing the vaccines. You're right, 
we really have to wait until we find out exactly what strain it 
is that is going from human to human. Once you do that, then 
you can develop the vaccine, but it takes a while to develop 
the vaccine, obviously, ape-based, long time. Then there was 
another process. Cell-based.
    Then, someone came out and said, ``Oh, there's an RNA-based 
method and it's even quicker than anything.'' But you were 
talking about it in terms of, excuse me, getting all these 
different strains and finding some RNA-based system of covering 
them all, but that was different than what I had heard. What I 
had heard, you'd wait until you found out exactly what the 
strain was, then you would develop an RNA-based vaccine to that 
exact strain and you could do it in just a couple months or 
something like that. What am I not understanding here?
    Dr. Berg. Because we now have sequences of many flu 
strains, we can see which parts of the viral RNA genome are 
conserved. Those are things which presumably the virus can't 
change to avoid, without damaging itself. Because RNA 
interference is so general, you can target the RNA molecules 
anywhere you want. We can go after regions in the viral genome 
which don't vary from strain to strain. This concept has the 
potential to be something which I was very skeptical about, 
sort of a universal flu vaccine.
    Senator Harkin. Universal flu vaccine. Is that being 
pursued right now? Is that----
    Dr. Berg. It is. There's a company that's been developing 
it in partnership with Novartis (it originally started with an 
SBIR grant from NIH). Again, it's early stage, but----
    Senator Harkin. So how come they were talking to me about--
again, I'm just, I don't know much about this, everyone on my 
staff does, but I was led to believe that RNA could only be 
used to develop a vaccine for a specific strain, not for a 
universal vaccine. That's why I don't, I'm having a hard time 
understanding this.
    Dr. Berg. Right. This is a whole new world of therapeutics 
and, again, the macular degeneration example is the one that's 
most advanced. This requires a whole new pharmacology. We still 
don't know very much about how to deliver these RNA molecules 
as drugs.
    Senator Harkin. So it's possible----
    Dr. Berg. It's possible.
    Senator Harkin [continuing]. To get a universal flu 
vaccine, no matter what strain comes out.
    Dr. Berg. That's the promise. Again, this is very early----
    Senator Harkin. But again, should we be putting more energy 
and effort and money into that, or into building facilities 
that, when the strain comes out we can put people to work right 
away developing the vaccine on an RNA basis?
    Dr. Berg. For the time being, I would say, you absolutely 
need to continue to invest in the technology to make the 
vaccine available. The whole concept of this technology is only 
a few years old. There are lots of potential problems, such as 
how do you deliver RNA molecules? How do you keep them stable 
enough so that they work? There are lots of hurdles to be 
overcome, but advances in any one area have the potential to 
impact the whole field.
    Senator Harkin. My gosh, if you could develop a universal 
vaccine, that would be the answer to everything.
    Dr. Berg. Absolutely. We're investing, and NIAID is 
investing very heavily in moving this forward.
    Senator Harkin. When is Dr. Fauci here?
    Mr. Fatemi. May 21.
    Senator Harkin. Anyone here talk to the Doctor, tell him 
I'm going to ask him that.
    Dr. Berg. I will warn him.
    Dr. Collins. I have a feeling he'll hear about this.
    Senator Harkin. Warn him I'm going to tell him, ``Dr. 
Berg's got a different approach.''
    Dr. Berg. Well, they're the ones who are supporting it, so 
it really just stems from this discovery of RNA interference, 
which opened up this whole new approach and that's obviously an 
area where, if we could do it, it would have a huge impact.

                             NANOTECHNOLOGY

    Senator Harkin. Dr. Pettigrew, I didn't much get into it 
with you, but this whole area of nanotechnology that I know a 
little bit about, we hear it being applied in all different 
areas of physics and material sciences and things like that, 
nanotechnology, but I don't hear too much about it in health. 
Most of what I read about nanotechnology as to material 
sciences, physics, that type of thing, but--computers, but not 
too much in health. So what is there in nanotechnology that I 
don't know about? What implications does it have for health and 
health research?
    Dr. Pettigrew. Well, it's actually quite involved in 
health, and much of the technology that I refer to in my 
testimony regarding the ability to detect diseases at the 
cellular and molecular level would, in fact, involve devices 
that are constructed at the nanometer scale. As you know, a 
nanometer is a billionth of a----
    Senator Harkin. The delivery mechanism?
    Dr. Pettigrew. As a delivery mechanism, and also, as a 
mechanism for observing the response to a therapeutic 
intervention.
    For example, we've talked several times now about breast 
cancer and heart disease and so forth. One might envision--in 
fact, there is considerable work already under way in this 
area, to develop a probe that consists of a nanometer-sized 
particle, which carries three components on this particle. The 
first component is a homing agent that delivers the particle to 
the specific target, such as the HER2 receptor in breast 
cancer. The second component on this particle would be an 
imaging agent that allows you to see that, in fact, it went 
there. It also allows you to see how much went there, and the 
size of the tumor, in the case of cancer. The third thing would 
be to deliver a therapeutic agent, such as a gene that codes 
for vascular cell death, apoptosis, which actually has been 
demonstrated in some early studies.
    So, you'd have this one particle that is target-specific, 
goes directly to the target of interest, say a cancer cell, or 
the vascular supply to the cancer cell, as Francis mentioned 
about angiogenesis and the role that that plays, in which the 
goal is to destroy the antigenic activity.
    The gene is delivered specifically, by way of this targeted 
nanoparticle, to the cells that make up the lining of these 
tiny blood vessels, kills them, and destroys the vascular 
supply.
    So, I think that nanotechnology is very much involved. I 
don't know if you've had the NCI participate in the hearings 
yet, but when you talk with them, you'll hear about their large 
nanotechnology research effort aimed at developing just these 
kinds of probes. My Institute, as well, is very involved. We 
have a substantial part of our funding, is active in this, in 
this area. These devices are termed biosensors, in the sense 
that they send out a signal when they interact with the 
particular biologic process you're trying to discover.
    Another example would be to identify tumors on the basis of 
the enzymes that they produce, such are protease, which lyses 
proteins. You have a structure that's constructed in such a 
way, and this is nanometers in size, that it has two components 
linked chemically by a bridge. The two components are such that 
one emits light and the other one absorbs light.
    When they're closely constructed, the emitted light is 
absorbed by the counter-component, but the bridge is 
constructed in such a way that is it lysed specifically by the 
enzyme that the cancer produces. So, when this nanostructure 
reaches the cancer, and is tailored to be lysed by a specific 
protease, that lyses, breaks these two components apart and, as 
a result of that, you can see it and you see the light.
    So, the detection of light means that you've found the 
cancer. This allows you to identify cancer at an early stage, 
this is where the preemption comes in, is because you can 
identify it at the cellular stage. Also, monitor the response 
to various therapies. So----
    Senator Harkin. This is part of translating what you're 
doing into actual?
    Dr. Pettigrew. Yes. Yes. Absolutely. So again, just to 
emphasize, I mean, much of the work that's going on now in 
developing innovative new technologies that will allow you to 
identify disease early on, this happens at the nanometer scale, 
one. Then two, deliver therapy specifically targeted to that 
expression of the disease in that individual, also done by 
nanotechnology.

                  GENE THERAPY RESEARCH IN EYE DISEASE

    Senator Harkin. Anything else, Dr. Collins, about gene 
therapy--what was that dog's name?
    Lancelot, the dog. I met Lancelot the dog a few years ago 
and Lancelot was blind and they did gene therapy and the dog 
sees. I understand that's now been done, replicated on a number 
of other dogs. I think the last I heard they were now going to 
primates.
    Dr. Collins. Going to primates called people.
    Senator Harkin. Oh, I thought we were just going into----
    Dr. Collins. So, there is a clinical trial about to get 
underway, which is supported by NIH. Yeah, this is a really 
fascinating story. So, the condition here is Lever's congenital 
amaurosis.
    Senator Harkin. That's it.
    Dr. Collins [continuing]. Which causes blindness.
    Senator Harkin. Exactly.
    Dr. Collins. In this case, different than macular 
degeneration, it's a degeneration of the retina.
    Senator Harkin. Right.
    Dr. Collins. This particular version of it is caused by 
mutations in a gene called RPE65, which doesn't mean very much, 
but it turns out the briard dogs have this same genetic 
problem, which is why Lance was such a good model to try it 
out. I've also seen the films of these dogs before and after 
treatment, which are really dramatic----
    Senator Harkin. It's dramatic.
    Dr. Collins [continuing]. Going from bumping into 
everything to clearly having a good grasp of what's around them 
through their corrected vision.
    So, this is a circumstance where gene therapy injected into 
the eye, carrying in the gene therapy vector, the right version 
of this gene to make up for the fact that the one that the 
patient has is not working, shows a lot of promise. In fact, I 
don't know whether, in fact, they've enrolled the first 
patients. This must be about the time where they were getting 
ready to do so, and I think I just saw last week, there's also 
a study getting underway in Europe for the same condition also 
using the same gene therapy vector. So, I think we all wait 
with bated breath to see if what worked so nicely for the dogs 
is going to work for people as well, with, I think, a good 
reason for optimism.
    Senator Harkin. That's great. That's great. That would be 
under probably the National Eye Institute I assume, right?
    Dr. Collins. Yeah.
    Senator Harkin. But you, obviously know about it since it 
has to do with genes and everything.
    Dr. Collins. Yeah, exactly, but Dr. Sieving could tell you 
even more.
    Senator Harkin. Exactly.
    Well, thank you all very much, thank you again for your 
leadership, all that you're doing at NIH.
    Does anybody have any last thing for the record, before 
we----
    Dr. Pettigrew. Yeah, I just wanted to comment on the 
earlier question regarding training for students.
    Senator Harkin. Yeah.
    Dr. Pettigrew. While I think it is more of a challenge to 
get high school students at the NIH, we do have two programs 
directed at undergraduate students, both on the NIH campus 
where we bring in a group of undergraduate students, and train 
them specifically in bioengineering, and we also have a 
program, in conjunction with the National Science Foundation 
where we establish 10 sites around the country at 10 
universities, where students at the undergraduate level, and 
early graduate level, come and work specifically in these areas 
of new technologies.
    Senator Harkin. Mm hm.
    Dr. Pettigrew. We have a third program that we've recently 
created in partnership with the Howard Hughes Medical 
Institute, to develop a new training curricula, focusing 
specifically on team science and interdisciplinary sciences, as 
I mentioned before, which is very much one of the waves of the 
future, where you bring together scientists of multiple 
disciplines.
    We think that these will be the scientists of the future, 
and that in order to really make that a reality, that the 
curricula that exists today need to be modified, so that the 
languages of these different disciplines--mathematicians, and 
biologists and physicists talk in different languages and know 
different things--are brought together and understand human 
biology and disease, as well as a physical science world, so 
that once they finish school, the can serve and function more 
effectively in a team science situation.
    Dr. Collins. Senator, if I could----
    Senator Harkin. Yeah.
    Dr. Collins [continuing]. Just as one final comment, 
express thanks from all of us, to you and Senator Specter for 
the leadership that you've shown through these years in 
supporting NIH. In my 14 years at the Institution, I've never 
seen more scientific opportunity, more excitement, more young 
scientists champing at the bit to jump in and solve problems 
that are going to have profound implications on human health. 
It is really a remarkable time.
    Yet, we are caught in this dilemma where, we're not limited 
by ideas, we're not limited by talent, we're not limited by 
potential for transforming medicine, we're really limited by 
the ability to take the resources that we've got and try to 
stretch them as far as we can. We really appreciate the way in 
which you and Senator Specter have led this process to try to 
make it possible for us to do as much as we can.
    This diabetes discovery that I'm so excited about, just in 
the last 2 weeks, opens up a whole new set of opportunities in 
terms of prevention and treatment----
    Senator Harkin. Sure.
    Dr. Collins [continuing]. Yet when I look and see that we 
spend the equivalent of one latte per year, per American, on 
diabetes research--not a venti, mind you----
    More like a grande--it does seem sort of discordant, we 
could do so much more.
    Senator Harkin. Well, thank you all very much, thanks, Dr. 
Collins. Well, it's been a great partnership with Senator 
Specter and with me, and over all of these years, and we've 
seen some great things happen, and right now we're really 
concerned about the budget crunch, and the fact that we've 
doubled the funding at NIH, but now it's been leveling off and 
it's going back, and we never, ever intended for that to 
happen. We wanted to get it on a higher plateau, and then keep 
going up. We're both very dismayed by this, and we're going to 
try to everything we can to get a better allocation this year 
for NIH.
    But, that's just another battle we'll have to fight, I 
guess, on the budget.
    But, I agree with you, there's just a lot of exciting 
things out there. I mean, this is why I really talked about 
these young people, getting young people enthused and excited 
about a career in science, and getting them when they're young. 
I think during that period when we were doubling it, I kept 
asking questions about it, because young people now see that 
they could have a career in research, and I don't want to 
destroy that, I don't want to have them say, well, maybe yes, 
maybe no.
    Dr. Lindberg. Now they're stranded.
    Senator Harkin. Yeah.
    We've floated them out there, now they're stranded out 
there. So, hopefully we can fix that, with better budgets and 
that kind of thing.
    Dr. Lindberg. Many thanks for all you've done.

                     ADDITIONAL COMMITTEE QUESTIONS

    Senator Harkin. There will be some additional questions 
which will be submitted for your response in the record.
    [The following questions were not asked at the hearing, but 
were submitted to the Department for response subsequent to the 
hearing:]
               Questions Submitted by Senator Tom Harkin
                             nlm facilities
    Question. Dr. Lindberg, I understand that NLM faces increasingly 
stringent space constraints stemming from the continued expansion of 
its collections, the growing need for computing infrastructure for 
storage, search and retrieval of electronic media and the successful 
implementation of its many important programs. Can you provide some 
examples of how space limitations affect the Library's ability to 
fulfill its many functions for information services, research and 
training?
    Answer. Space limitations affect a range of NLM operations and 
services.
    NLM's onsite space for new manuscript collections, such as the 
papers of eminent biomedical scientists and the records of important 
professional societies and foundations is at capacity. It is 
anticipated that the Library may be completely out of space for all 
collections, including printed books and journal volumes, films, 
pictures, and electronic collections, by 2010, even projecting a yet-
to-be seen decline in hard copy publications. NLM serves as an archive-
of-last-resort for the health community, provides access to materials 
that are not available elsewhere in the world and preserves materials 
that other health sciences libraries discard. Due to space limitations 
NIH no longer maintains on-campus training facilities used to teach NIH 
researchers and other staff to use NLM's search and retrieval systems. 
The rate of expansion NLM's National Center for Biotechnology 
Information (NCBI) has been partially governed by the speed with which 
NIH can locate and reconfigure office and work space for NCBI staff in 
other on-campus facilities.
    NLM's Go-Local service provides consumers and physicians with links 
from Medline search results to facilities that provide related health 
care services within their geographic regions. Existing facilities 
support 17 Go-Local sites, which cover one-quarter of the U.S. 
population. Additional space would be needed for servers that would 
allow expansion of Go-Local to cover the entire U.S. population. Space 
is also one factor that could delay the addition of servers and storage 
devices needed to house the molecular sequences data key trans-NIH 
research initiatives, such as whole genome association studies and 
metagenomics projects.
    Question. Can you tell us what steps NLM and NIH are taking to 
address these concerns and what more is needed?
    Answer. NLM is implementing a number of steps to provide additional 
space for its collections and operations. NLM currently leases space in 
other buildings, both on- and off-campus. As of spring 2007, NLM leased 
approximately 33,000 square feet of space in other on-campus facilities 
and approximately 23,000 square feet of office space off-campus. These 
figures compare to 312,000 square feet of space in the two NLM 
buildings (Bldgs 38 and 38A). In coming months, NIH has arranged for 
NLM to take occupancy of additional on-campus space to house staff of 
the NCBI. In addition, NLM plans to lease off-campus space for the 
expansion of NLM's computer facilities. To make additional space for 
its physical collections, NLM also plans install additional compact 
shelving in building 38. This will require structural reinforcement of 
the building to support the additional load of more densely packed 
books and manuscripts.
    Question. How cost-effective is it to lease additional space/
facilities?
    Answer. On campus, administrative space can be leased at a rate of 
approximately $19 per square foot, compared to approximately $37 off 
campus. Rental of on-campus space involves additional costs associated 
with moving NLM staff to the new site and relocating displaced NIH 
staff to other--typically off-site--facilities. Other costs must also 
be taken into account. In evaluating options for expanding its computer 
facilities, NLM found local expansion considerably less expensive than 
off-site locations due in no small part to the lower cost of 
electricity on campus.
    Question. What is the status of plans to construct the new building 
at the National Library of Medicine for which planning funds were 
appropriated several years ago?
    Answer. Architectural plans were completed in 2003 for a building 
that would provide additional space for Library collections and 
collaborative workspace for NLM's expanding research and development 
capabilities, in particular those of the NCBI. NIH did not request 
funding for construction in the fiscal year 2008 Budget.
                                 ______
                                 
            Questions Submitted by Senator Daniel K. Inouye
                       basic behavioral research
    Question. Dr. Berg, over the past 8 years, this subcommittee and 
our colleagues in the other body have pressed the NIH to find or assign 
a home for basic behavioral research at your institute. The NIH has not 
responded to positively to this matter even though this same request 
was a recommendation of the National Academy of Sciences and of 
Director Zerhouni's advisory committee. It is also a part of the NIGMS 
statute. Basic behavioral research needs dedicated leadership at the 
NIH in this important field of science. When will it be possible for 
NIH to respond favorably to this request?
    Answer. Basic behavioral research, like basic biomedical research, 
is supported throughout the NIH, both in disease- and stage-of-life-
specific institutes and in the institutes and centers with more general 
missions. An analysis performed by the working group of the Advisory 
Committee to the Director, NIH, indicated that nearly $1 billion in 
basic behavioral research is supported across NIH, including support 
within NIGMS. There is, and should be, basic behavioral research 
supported by each of the Institutes that relates to its mission.
    The authorization language for NIGMS states: ``The general purpose 
of the National Institute of General Medical Sciences is the conduct 
and support of research, training, and as appropriate, health 
information dissemination, and other programs with respect to general 
or basic medical sciences and related natural or behavioral sciences 
which have significance for two or more national research institutes or 
are outside the general area of responsibility of any other national 
research institute.'' In response to congressional inquiries and in 
keeping with this mission, NIGMS has initiated two programs recently. 
The first, ``Collaborative Research for Molecular and Genetic Studies 
of Basic Behavior in Animal Models,'' is intended to facilitate 
research involving basic behavioral scientists and investigators with 
expertise in modern molecular biology and/or genomics. The second, 
``Predoctoral Training at the Interface of the Behavioral and 
Biomedical Sciences,'' will support institutional training grants that 
provide new scientists with rigorous and broad training in behavioral, 
biological, and biomedical sciences. These new programs reflect the 
potential high impact of integrating behavioral and biological 
approaches to advance fundamental understanding and yield new 
approaches to promoting human health and treating disease.
    The NIH Office of Behavioral and Social Sciences Research (OBSSR) 
was established by Congress to stimulate research in behavioral and 
social sciences research throughout NIH and to integrate these areas of 
research across the NIH institutes and centers. Coordination across NIH 
is also enhanced by the establishment of the Division of Coordination, 
Portfolio Analysis, and Strategic Initiatives by the NIH Reform Act of 
2006. NIGMS and the other institutes and centers are working with OBSSR 
and the new division to ensure that NIH supports a broad portfolio of 
basic behavioral research to further the broad NIH mission. This broad 
base of support provides a wide range of opportunities for behavioral 
scientists to find support for their research that is relevant to the 
NIH mission. In addition, basic behavioral research, just like basic 
biological and chemical research, that underpins the NIH mission at a 
deeper level, can find support at the National Science Foundation.
                  information resources for hawaiians
    Question. Dr. Lindberg, last year you visited one of our native 
Hawaiian programs at Papa Ola Lokahi. I am most appreciative of the 
National Library of Medicine's continued interest in increasing access 
to health information and health resources for Native Hawaiians. What 
were your impressions of the Native Hawaiian programs at Papa Ola 
Lokahi?
    Answer. An NLM team visited Hawaii in July 2006 and came away 
impressed with the effectiveness of Papa Ola Lokahi in working with 
Native Hawaiian communities and health providers.
    Question. How can the National Library of Medicine and Papa Ola 
Lokahi work together to increase access to healthcare information in 
Hawaii?
    Answer. The National Library of Medicine and Papa Ola Lokahi are 
working together in a variety of ways to improve access to healthcare 
information in Hawaii. Working with Papa, NLM has supported two pilot 
projects--one to strengthen the community library at Miloli'i so that 
residents have online access to health information; a second to install 
a computer in the waiting room of the Waimanalo Health Clinic so that 
patients can access health information. Both projects have made very 
good progress and are nearing completion. Also, with NLM support, Papa 
organized a one-day meeting in July 2006 to discuss needs and options 
for preserving and strengthening the collections of Native Hawaiian 
Health materials. The meeting was attended by various Hawaiian museum, 
archival, academic, and community organizations with an interest in 
this topic. NLM was pleased with Papa's work to arrange and conduct 
this meeting, and is exploring possible follow up. NLM has also 
provided support to Papa for improvement of Papa's web site, and, 
earlier, for participation of two Papa staff persons in NLM's Native 
American Internship Program. Additionally, Papa is represented on the 
NLM-supported Health Information Task Force of the National Congress of 
American Indians. And a Papa staff person was invited to participate in 
the NLM-sponsored Tribal Outreach Conference held in July 2006 in 
Albuquerque, NM. NLM will continue its multi-dimensional relationship 
with Papa Ola Lokahi in order to enhance access to healthcare 
information throughout Hawaii.
                                 ______
                                 
              Questions Submitted by Senator Arlen Specter
                             public access
    Question. Dr. Lindberg, please provide the following information on 
eligible articles deposited with NIH under the NIH Public Access 
Policy. Please include all articles that are eligible for deposit under 
the policy, including manuscripts and final published articles 
submitted by authors and publishers:
    (1) The total number of articles that have been deposited with NIH 
since the May 2, 2005 implementation date and the overall percentage of 
deposits to date. Please describe how you arrived at the total number 
of eligible articles.
    (2) The month-by-month deposits of articles, shown as a percentage 
of eligible articles available for deposit, and as a monthly total of 
the number of deposited articles from May 2005 to April 2007.
    Answer. (1) Total articles deposited with NIH under the NIH Public 
Access Policy, May 2, 2005 to April 30, 2007
    Articles deposited under the Public Access Policy: 6,196
    Total articles eligible for deposit under the Public Access Policy: 
142,000
    Percent Deposited: 4.4 percent.
    Using 2005 publication data as a baseline, we estimate that 71,000 
articles per year (or 5,916 per month) should have been deposited as a 
direct result of the Policy. This is a conservative baseline because of 
a general upward trend in publication rates from year to year.
    (2) The month-by-month deposits of articles, shown as a percentage 
of eligible articles available for deposit, and as a monthly total of 
the number of deposited articles from May 2005 to April 2007.

        TABLE 1.--AVAILABLE ARTICLES BY MONTH, AS OF MAY 31, 2007
------------------------------------------------------------------------
                                    Articles      Eligible    Percent of
             Month               deposited \1\    articles      target
------------------------------------------------------------------------
May 2005.......................           110         5,916          1.9
June 2005......................           107         5,916          1.8
July 2005......................           186         5,916          3.1
August 2005....................           146         5,916          2.5
September 2005.................           146         5,916          2.5
October 2005...................           156         5,916          2.6
November 2005..................           143         5,916          2.4
December 2005..................           161         5,916          2.7
January 2006...................           208         5,916          3.5
February 2006..................           172         5,916          2.9
March 2006.....................           175         5,916          3.0
April 2006.....................           166         5,916          2.8
May 2006.......................           231         5,916          3.9
June 2006......................           220         5,916          3.7
July 2006......................           160         5,196          2.7
August 2006....................           168         5,916          2.8
September 2006.................           252         5,916          4.3
October 2006...................           302         5,916          5.1
November 2006..................           317         5,916          5.4
December 2006..................           482         5,916          8.1
January 2007...................           746         5,916         12.6
February 2007..................           651         5,916         11.0
March 2007.....................           639         5,916         10.8
April 2007.....................       \2\ 152         5,916          2.6
                                ----------------------------------------
      Total....................         6,196       142,000          4.4
------------------------------------------------------------------------
\1\ Articles that are approved for release in PubMed Central, including
  articles that may not actually be released until 12 months after
  publication, as specified by the author.
\2\ Authors of articles submitted in April 2007 have only had a few
  weeks to review and approve them after conversion to the PubMed
  Central archival format. We expect the number of approved articles for
  April to rise in the coming weeks to the same level as for previous
  months, as authors have time to respond.

    At the request of publishers, NLM deployed a mechanism in December 
2005 (http://www.nihms.nih.gov/publishers.html#q2) to allow publishers 
to deposit author manuscripts on behalf of their authors. The welcome 
growth in deposits from September 2006 forward has been due mostly to a 
large publisher, Elsevier, beginning to use this system. As of April 
2007, Elsevier is submitting all of its author manuscripts based on NIH 
funded research.
    Author manuscripts need to be converted to an archival format for 
posting on PubMed Central. This conversion must be verified by the 
author. When author manuscripts are submitted by the authors 
themselves, the authors almost always complete this verification step. 
However, NIH is only able to post a portion of bulk deposits being made 
by Elsevier to PubMed Central, because many authors do not follow up 
with the necessary verification and approval. Author participation is 
voluntary under the policy.
    In previous reports on the Policy, we counted the initial 
submissions of files as the number of manuscript deposited. (The actual 
number of articles that could be publicly released was slightly lower, 
but the difference was not significant as long as the majority of 
deposits were made by individual authors.) However, because of the 
large dropout rate associated with Elsevier's bulk deposits in recent 
months, it is more accurate to count as deposits only those articles 
that have the author's final approval for release in PubMed Central. 
These numbers include author manuscripts that may not actually be 
released until 12 months after publication, as specified by an author.
    This more accurate measure of compliance applies to all of the 
articles reported in Table 1. As a result of this change in metrics, 
the deposits for 2005 and the first half of 2006 will be slightly lower 
than the corresponding numbers in earlier reports to Congress.
    For reference, Table 2 shows the total number and percent of author 
manuscripts sent to NIH via bulk deposit, made by Elsevier between 
September 2006 and April 2007. The right column shows the number that 
received the author's final approval for release to PubMed Central and 
is included in Table 1.

     TABLE 2.--ELSEVIER BULK DEPOSIT SUBMISSIONS, AS OF MAY 31, 2007
------------------------------------------------------------------------
                                               Manuscripts
                                  Manuscripts    approved
              Month               sent to NIH   for public     Percent
                                    via bulk    release by
                                    deposit      authors
------------------------------------------------------------------------
September 2006..................           77           52         67.5
October 2006....................           76           42         55.3
November 2006...................          204          120         58.8
December 2006...................          521          251         48.2
January 2007....................          711          398         56.0
February 2007...................          796          419         52.6
March 2007......................          810          389         48.0
April 2007......................        1,012          106     \1\ 10.5
                                 ---------------------------------------
      Total.....................        4,207        1,777        (42.2)
------------------------------------------------------------------------
\1\ Authors of articles submitted in April 2007 have only had a few
  weeks to review and approve them after conversion to the PubMed
  Central archival format. We expect the number of approved articles for
  April to rise in the coming weeks to the same level as for previous
  months, as authors have time to respond.

    We should note that Bulk Deposit is only one method by which 
publishers can submit content to PubMed Central. Under the Public 
Access Policy, two scientific societies have signed agreements to 
deposit all of their final published articles based on NIH funded 
research to PubMed Central. These PubMed Central (NIH Portfolio) 
agreements will result in 100 percent of their deposited articles 
posted on PubMed Central without author involvement.
    Independent of the Policy, a number of journals routinely deposit 
their complete contents in the PubMed Central archive. Many, including 
the Proceedings of the National Academy of Sciences and the eleven 
journals of the American Society for Microbiology, have been doing so 
since 2000 or 2001, years before the Public Access Policy took effect. 
Authors who publish in these journals do not have to deposit their 
manuscripts based on NIH funded research under the Policy, because a 
copy of the journal's published article is already available to the 
public through PubMed Central. These articles were not included in the 
baseline total of articles eligible to be deposited under the Policy 
(71,000 per year or 5,916 per month) and, therefore, are not included 
in Table 1. Approximately 700 articles based on NIH-funded research 
come into PubMed Central each month from regularly participating 
journals.

                          SUBCOMMITTEE RECESS

    Senator Harkin. Well, thank you all very much, and thanks 
for taking the time to come down here today, and your 
expertise, and wish you the best, and keep on doing what you're 
doing.
    May 21 will be our next NIH hearing.
    Thank you very much. The subcommittee will stand in recess 
to reconvene at 2 p.m., May 21, 2007, in room SD-116.
    [Whereupon, at 3:29 p.m., Monday, May 7, the subcommittee 
was recessed, to reconvene at 2 p.m., Monday, May 21.]
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