[Senate Hearing 113-865]
[From the U.S. Government Publishing Office]




                                                        S. Hrg. 113-865
 
     TACKLING DISEASES OF AGING: WHY RESEARCH COLLABORATION MATTERS

=======================================================================

                               ROUNDTABLE

                               BEFORE THE

                       SPECIAL COMMITTEE ON AGING

                          UNITED STATES SENATE

                    ONE HUNDRED THIRTEENTH CONGRESS


                             FIRST SESSION

                               __________

                             WASHINGTON, DC

                               __________

                            OCTOBER 29, 2013

                               __________

                           Serial No. 113-11

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                       SPECIAL COMMITTEE ON AGING

                     BILL NELSON, Florida, Chairman

RON WYDEN, Oregon                    SUSAN M. COLLINS, Maine
ROBERT P. CASEY JR, Pennsylvania     BOB CORKER, Tennessee
CLAIRE McCASKILL, Missouri           ORRIN HATCH, Utah
SHELDON WHITEHOUSE, Rhode Island     MARK KIRK, Illinois
KIRSTEN E. GILLIBRAND, New York      DEAN HELLER, Nevada
JOE MANCHIN III, West Virginia       JEFF FLAKE, Arizona
RICHARD BLUMENTHAL, Connecticut      KELLY AYOTTE, New Hampshire
TAMMY BALDWIN, Wisconsin             TIM SCOTT, South Carolina
JOE DONNELLY Indiana                 TED CRUZ, Texas
ELIZABETH WARREN, Massachusetts
                              ----------                              
                  Kim Lipsky, Majority Staff Director
               Priscilla Hanley, Minority Staff Director
               
               
                                CONTENTS

                              ----------                              

                                                                   Page

Opening Statement of Chairman Bill Nelson........................     1

                           PANEL OF WITNESSES

Michael W. Hodin, Ph.D., Executive Director, Global Coalition on 
  Aging and Managing Partner, High Lantern Group.................     1
Richard J. Hodes, MD, Director, National Institute on Aging, 
  National Institutes of Health..................................     3
Richard I. Morimoto, Ph.D., Professor, Department of Molecular 
  Biosciences and Director, Rice Institute for Biomedical 
  Research, Northwestern University..............................     5
James L. Kirkland, MD, Ph.D., Professor, Noaber Foundation 
  Professor of Aging Research and Director, Robert and Arlene 
  Kogod Center on Aging, Mayo Clinic.............................     6
John Alam, MD, Head, Therapeutic Strategic Area for Diseases of 
  Aging, Sanofi-Aventi...........................................     9
David Morgan, Ph.D., Chief Executive Officer and Director, Byrd 
  Alzheimer Institute and Director of Neuroscience Research, 
  University of South Florida College of Medicine................    11

                                APPENDIX
                      Prepared Witness Statements

Michael W. Hodin, Ph.D., Executive Director, Global Coalition on 
  Aging and Managing Partner, High Lantern Group.................    28
Richard J. Hodes, MD, Director, National Institute on Aging, 
  National Institutes of Health..................................    31
Richard I. Morimoto, Ph.D., Professor, Department of Molecular 
  Biosciences and Director, Rice Institute for Biomedical 
  Research, Northwestern University..............................    37
James L. Kirkland, MD, Ph.D., Professor, Noaber Foundation 
  Professor of Aging Research and Director, Robert and Arlene 
  Kogod Center on Aging, Mayo Clinic.............................    39
John Alam, MD, Head, Therapeutic Strategic Area for Diseases of 
  Aging, Sanofi-Aventis..........................................    45
David Morgan, Ph.D., Chief Executive Officer and Director, Byrd 
  Alzheimer Institute and Director of Neuroscience Research, 
  University of South Florida College of Medicine................    48


     TACKLING DISEASES OF AGING: WHY RESEARCH COLLABORATION MATTERS

                              ----------                              


                       TUESDAY, OCTOBER 29, 2013

                                       U.S. Senate,
                                Special Committee on Aging,
                                                    Washington, DC.
    The Committee met, pursuant to notice, at 4:09 p.m., in 
Room SD-562, Dirksen Senate Office Building, Hon. Bill Nelson, 
Chairman of the Committee, presiding.
    Present: Senators Nelson, Donnelly, and Warren.

       OPENING STATEMENT OF SENATOR BILL NELSON, CHAIRMAN

    Chairman Nelson. Well, good afternoon. Thank you for being 
here. Thanks to all of you for participating.
    We are going to discuss advancing research on aging and the 
impact on health and chronic disease, and in the next few days, 
NIH, along with the Alliance for Aging Research and the 
Gerontological Society will hold a summit in Washington to 
examine the latest biological research on aging. Five hundred 
attendees will be on hand to produce research recommendations 
to advance aging research. I am pleased that some of the 
brightest attendees came early and they are a part of this 
roundtable. I want to thank Dr. David Morgan from USF for being 
with us and his contributions to Alzheimer's research.
    Medical research on ways to improve health of our nation's 
aging population should be a top priority. The need to increase 
collaboration among researchers has never been more important, 
especially in light of some of the ridiculous political 
environment that we are having to navigate, including 
sequestration, which bring about drastically reduced research 
budgets. This recent showdown, or, shall I say, debacle, 
demonstrated just how critical NIH is to our nation's fiscal 
and physical health, and I want to thank Senator Collins for 
her work in helping getting us out of that catastrophe.
    There is a lot to discuss this afternoon and I want to 
thank all of you again for being here, and I want to turn it 
over to Dr. Hodin to begin our roundtable and take the opening 
statements from the panelists. Dr. Hodin.
    Mr. Hodin.

   STATEMENT OF MICHAEL W. HODIN, PH.D., EXECUTIVE DIRECTOR, 
 GLOBAL COALITION ON AGING, AND MANAGING PARTNER, HIGH LANTERN 
                             GROUP

    Mr. Hodin. Thank you, Senator, and welcome to all. We are 
delighted and I am honored, as Executive Director of the Global 
Coalition on Aging, to open this roundtable session. Let me 
provide perhaps a minute or so of context setting from a 
policy, a political, and economic point of view.
    Population aging is arguably--oh, Senator Collins?
    The Chairman. No, this is Senator Warren----
    Mr. Hodin. Senator Warren.
    The Chairman [continuing]. From Massachusetts.
    Mr. Hodin. Yes.
    The Chairman. Susan Collins is in a markup right now, and 
that is what is preventing her----
    Senator Warren. Right, and I apologize for being late. I 
was doing student loans.
    [Laughter.]
    The Chairman. You are doing great. You just keep it up.
    Mr. Hodin. I thought you were getting prepared for the game 
tonight.
    Senator Warren. Well, we are ready.
    Mr. Hodin. If you would like to say a word or two before we 
continue----
    Senator Warren. No, thanks.
    Mr. Hodin. Thank you, Senator Warren.
    So, population aging is arguably the most seminal topic of 
our day. It is about a shift in society from young to old. 
There are more of us that are over 60 than under 15, and in 
that context, it is about a transformation that we have not 
seen since perhaps the dawn of the industrial age.
    S&P, in their 2010 report, put it this way. Global 
population aging--no other force is likely to shape the future 
of national economic health, social and public finances, as the 
irreversible rate at which the world's population is growing 
older. This is a social phenomenon. It is built on a 
demographic structure that we have before us an historical 
opportunity.
    And I am delighted to be here to help moderate this and 
take remarks from some truly eminent scientists from around our 
great country.
    But, perhaps, Senators, as you lead us in this and we think 
about it, I would suggest that this topic is as much a fiscal 
challenge as any social or health issue. We simply cannot 
afford to continue with public policy the way we invented it in 
the 20th century, in a different demographic time.
    And as I thought about what this means, and particularly 
from a public policy context, it is the notion of thinking 
about spending as an investment rather than a cost, and what 
better investment for the individual and for society as the 
21st century has us living in an era where there are more old 
than young.
    So, I thought a little bit about it historically in this 
great body, and I would suggest to you there are three examples 
that America has before it that could lead us in thinking about 
this in a different way. One is what we did in the 1950s in 
creating the Interstate Highway System. We made a decision. It 
was politically tough, but it was an investment in our future.
    A second is our spending on the children. We do it for 
education and we do it in childhood immunization. In the 21st 
century, it is in our self interest to think of adult 
immunization, for example.
    And thirdly, as you well know, Senator, the space program. 
It is one of the great courageous moments in our time, and at 
the core of it was the notion that we decided to invest and 
think of spending in that way and not as a cost.
    We cannot afford this any different, as one-quarter of our 
total population will be over 60 within the next two decades. 
It is not fiscally sustainable to continue thinking and acting 
as we did in the 20th century.
    I submit to you, this is a big deal. More old than young 
demographically is baked in for the next two next generations, 
and it comes about as a result of two factors. One is 
longevity, we are living longer, but the other are these 
steadily low birthrates. And what America does here will affect 
everyone around the world because this is a global phenomenon.
    The oldest country on the planet is Japan. It is a place we 
will get to. And in 2020, the Japanese will sell more adult 
diapers than baby diapers. This is a place we want to avoid 
here, and if a way to do that is by addressing our NCDs from 
the standpoint of the biology of aging, then we should rethink 
this paradigm, rethink this structure.
    And I commend all of you for being here. We are delighted. 
And I think, at this point, I would like to turn it over to our 
esteemed colleagues, the great scientists who are with us, and 
if you would introduce yourselves as you begin your three- to 
five-minute openings, after which we will then have a 
discussion and some questions among us.
    The Chairman. Why do I not just introduce everybody so that 
we know.
    Richard Hodes, Director of the National Institute on Aging 
at NIH.
    John Alam, M.D., Head, Therapeutic Strategic Area for 
Diseases of Aging.
    James Kirkland, M.D., Ph.D., Professor, Noaber Foundation 
Professor of Aging Research, and Director at the Kogod Center 
on Aging at the Mayo Clinic in Rochester?
    Dr. Kirkland. [Off microphone.]
    The Chairman. Too bad you are not in Jacksonville.
    [Laughter.]
    Richard Morimoto, Ph.D., Professor, Department of Molecular 
Biosciences, and Director, Rice Institute for Biomedical 
Research at Northwestern.
    And David Morgan, Ph.D., Chief Executive Officer and 
Director, the Byrd Alzheimer's Institute, and Director of 
Neuroscience Research at the University of South Florida 
College of Medicine.
    Okay. Please, Dr. Hodin.
    Mr. Hodin. Thank you, Senator.
    Dr. Hodes.

STATEMENT OF RICHARD J. HODES, MD, DIRECTOR, NATIONAL INSTITUTE 
            ON AGING, NATIONAL INSTITUTES OF HEALTH

    Dr. Hodes. Mr. Chairman, members of the committee, thank 
you very much for the opportunity for all of us to join with 
you in this discussion of the basic biology of aging and its 
relevance to age-related diseases and conditions.
    This is really a spectacular and unique time in which there 
is a convergence of imperatives for this kind of effort. One of 
those imperatives has to do with the remarkable advance that 
science has made, and you will be hearing from some of the 
leaders about the areas in which our insight about basic 
biology that underlies aging has advanced.
    The other, Dr. Hodin was alluding to, relates to the 
demography, and there are lots of numbers that express this 
well. Some time during this decade, for the first time, there 
will be more people on the planet--first time in human 
history--age 65 and older than under five. Between now and 
2030, even 2050, it is actually estimated that, worldwide, 
there will be very little growth in the population of 
individuals through age 64. However, there will be a doubling 
or more of those over 65. Those over 100 will increase by four- 
to fivefold. So, we are going to be seeing unprecedented 
societal as well as medical implications of all this. And this 
is itself a remarkable tribute to the advances that have been 
made in medical and public health areas.
    But what comes with it is the challenge of the fact that 
aging is, in fact, a primary risk factor for many conditions, 
and so our attention turns, in addition to the extension of 
longevity, to improving health spans, so we live longer lives 
free of disease with a maximum of health and independence.
    Recognizing this, the NIH has come together, as has the 
scientific community, to advance what has become known as 
geroscience, a new integrative science that explores the 
possibility of the growing insight into the fact that the basic 
processes of aging are related to the risks for many diseases 
and conditions, and so understanding the process of aging will 
help us to identify targets, ways to intervene and prevent 
disease and disability.
    As was noted, together with the Gerontological Society of 
America and the Alliance for Aging Research, NIH will be 
sponsoring a summit that will begin tomorrow and go through the 
end of the week in which scientists from around the world will 
come together to try to explore the most exciting of these 
opportunities and dictate for us what the priorities ought to 
be in pursuing them.
    There will be a number of topics that will be undertaken at 
that summit. Just to give you an idea of some of the 
integrating principles, exploration of the importance of 
inflammation, which we think of in terms of immune response and 
infectious disease but, in fact, is much more than that--
inflammation, which is a growing parameter of aging and also 
appears to be associated with many--most, if not all, chronic 
diseases of aging.
    Adult stem cells, the stem cells in all of us which 
perpetuate the health and integrity of our organs and tissues, 
change with age, and understanding how and why that happens to 
maximize the effectiveness of those cells is important. In 
addition to the cells themselves, the milieu environment in 
which they exist is important, and one striking example 
recently reported here is the identification of a circulating 
factor in the blood of young mice which, when injected into old 
mice, actually reverses cardiac disease that is very similar to 
the cardiac pathology that affects many older Americans.
    Proteostasis, the way in which the proteins of the body 
that are the composition of many of our organs and tissues, the 
way in which it is monitored to make sure that integrity 
sustains itself, changes with age and it also is the heart of 
many diseases of the brain and other organs and tissues. So, 
again, a commonality that is to be seen there.
    It is our hope that what will be achieved at the summit and 
which we can communicate and discuss with you here will lead to 
a growing coordination among the scientific disciplines that 
have focused on specific diseases or organs and tissues to 
recognize that paying attention, as well, to the commonalities 
of aging is a means to maximizing the efficiency with which we 
carry out this research. The Geroscience Interest Group at NIH, 
with leadership provided by some of our guests here, Felipe 
Sierra, Ron Kohanski, Kevin Howcroft, and John Birch, reflect 
now a coalition of some 20 of the Institutes across NIH who 
have come together to sponsor this, recognizing the commonality 
of their own purposes with understanding, a better 
understanding of the aging and aging process.
    So, I look forward to what we will be experiencing in the 
next days in this summit and I look forward to the opportunity 
to share with you and address questions that you will have 
during this hearing. Thank you again for the opportunity to be 
here.
    Mr. Hodin. Thank you, Dr. Hodes.
    Before we proceed, Dr. Morimoto, I would like to recognize 
Senator Donnelly from Indiana. Thank you for joining us. If you 
would care to say anything or----
    Senator Donnelly. I will say that I am a Sox fan, but a 
White Sox fan.
    [Laughter.]
    Mr. Hodin. So, coming from New York----
    Senator Donnelly. So, you and I are on the same team, then.
    Mr. Hodin. Coming from New York, our season ended a long 
time ago, so----
    [Laughter.]
    Mr. Hodin. Dr. Morimoto, please.

 STATEMENT OF RICHARD I. MORIMOTO, PH.D., BILL AND GAYLE COOK 
    PROFESSOR OF BIOLOGY, AND DIRECTOR, RICE INSTITUTE FOR 
          BIOMEDICAL RESEARCH, NORTHWESTERN UNIVERSITY

    Mr. Morimoto. Well, Mr. Chairman, other members of the 
committee, thank you very much for this opportunity.
    So, I am a basic biomedical scientist at Northwestern. I am 
very interested in what is called cell stress and quality 
control. It is an ancient process. Every organism on the planet 
actually can detect changes in the environment and then it 
mounts a response that is protective. When it works well, it 
keeps our cells robust and healthy. The problem is that aging 
and disease challenge the cell stress response. The consequence 
is quality control goes awry.
    Every time our cells divide, it would be just fine if the 
parts replaced were as good or better than the ones that were 
taken away. Unfortunately, what we have learned, at least for 
proteins, which is the major molecule, proteostasis that Dr. 
Hodes talked about, is that the proteins that get replaced are 
imperfect and the system starts to slowly decline.
    The question is, can we detect it early? Can we detect it 
well before it leads to clinical cognitive decline that leads 
to adult onset diabetes, to cancer, to neuro-degeneration? But 
even if we could detect it early, do we have any small 
molecules that we could use to treat people with Alzheimer's 
and Parkinson's and ALS? But I think this emphasis on healthy 
aging, what is it that keeps cells robust, is very important, 
because if we could understand that, that is the underpinning, 
really, for a healthy society and actually pushing back what 
would otherwise be premature aging and disease.
    Senator Warren will appreciate that in 2008, a couple of 
colleagues and I formed Proteostasis Therapeutics on Main and 
Albany in the wonderful town of Cambridge, really to address 
for the first time some of these diseases of aging, to identify 
the molecular biomarkers that occur early, and to actually 
study the course of retinal degeneration, of cystic fibrosis, 
of Alzheimer's and Parkinson's. But I think the key point is 
trying to emphasize what are the molecules that change, when do 
they change, and what can we do about them? Could we even 
restore it so that someone lives a healthier, more productive 
life?
    Thank you.
    Mr. Hodin. Thank you, sir. I might tell you that the kind 
of science that we are dealing with here is very, very 
exciting, and looking at it from a public policy point of view 
and economics, it is the type of future that we will want, so 
thank you very much.
    Dr. Kirkland.

 STATEMENT OF JAMES L. KIRKLAND, MD, PH.D., PROFESSOR, NOABER 
FOUNDATION PROFESSOR OF AGING RESEARCH AND DIRECTOR, ROBERT AND 
           ARLENE KOGOD CENTER ON AGING, MAYO CLINIC

    Dr. Kirkland. Chairman Nelson, Senators Warren and 
Donnelly, and other attendees, thank you very much for having 
me here, and I commend your efforts in looking at ways to 
improve the health span of our aging population.
    I am a clinical geriatrician. I am also a basic scientist. 
And in my career, I have noticed a number of really, really 
exciting changes that have been accelerating over the past 
couple of years. When I went to medical school, I was taught 
that the biggest risk factor for most of the age-related 
chronic diseases, which account for the bulk of health care 
costs, was aging itself. It was chronological aging was the 
biggest risk factor for dementias, for cardiac disease, for 
various cancers, for diabetes, for arthritis and a long list of 
other things. And then we quickly moved own the list to other 
risk factors because we were told, there is nothing you can do 
about aging, so let us mess around with people's blood pressure 
a little bit, their cholesterol, and play around the edges and 
maybe reduce the risk a little bit.
    What has been particularly exciting is in the last few 
years, we have moved from thinking that aging is an inevitable 
risk factor to one that might actually be modifiable in some 
ways. A little bit science fiction at the moment, but it does 
seem, especially since the end of the--around 2009--that we 
have interventions that are pharmacologic that can actually 
manipulate these processes in the same way, to some degree, as 
lifestyle interventions that we have discovered before, things 
like caloric restriction and exercise. And this has accelerated 
to a great degree, and the NIH, and particularly the NIA, are 
really responsible for providing the resources to get to this 
point.
    There is something called the Interventions Testing 
Program, which is a consortium of three centers, and it tests 
drugs that are suggested by the aging community in experimental 
animals, mice, and so far, 16 drugs have been tested and five 
of them so far have increased lifespan in mice, five. And there 
are many others that--approaches that seem to be effective in 
this.
    But, we do not want to increase lifespan at all costs. We 
do not want to live to be 130 and feel like we are 130. What we 
want to do----
    Senator Warren. [Off microphone.]
    [Laughter.]
    Dr. Kirkland. Yes, exactly. What we want to do----
    Senator Warren. [Off microphone.]
    [Laughter.]
    Dr. Kirkland. That is even worse. But the ideal would be 
to--can we figure out a way where we could live to maybe be 100 
and feel like we are 50, as occurs in some centenarians, some 
of the people in our population who have a genetic 
predisposition to live to advanced old age.
    And there might be a chance that we can do this, and there 
does appear a chance that with some of these drugs and genetic 
manipulations that we have been finding recently will affect 
health and lifespan, we are beginning to delay, at least in 
most models and other experimental animals, the onset of age-
related chronic diseases.
    And as Dr. Hodes mentioned, there is a big intersection 
between fundamental aging mechanisms and the genesis of these 
diseases. The prospect that we might be able to target 
fundamental aging mechanisms and delay them as a group instead 
of dealing with them one at a time, only to have another one 
take over a few months later, is extremely exciting.
    So, the basic biologic field has moved from a period of 
description through a period of discerning mechanisms that are 
responsible for age-related processes and now we are at the 
point of developing interventions at least that work in 
vertebrates and lower mammals. We are coming fast to the point 
of translating these things into clinical application. And, in 
fact, some early stage clinical trials with some of these 
agents are, indeed, underway, or are at least contemplated.
    So----
    The Chairman. This is in animals?
    Dr. Kirkland. In humans, very, very early with some of the 
drugs that were found on the intervention testing program and 
other approaches. There are other ways of doing this, as well. 
For example, eliminating senescent cells is one of the things 
which appears to improve health span, and there are potentially 
ways to target these cells and maybe some of these drugs act 
partly through processes affecting these particular kinds of 
cells and other things that are going on.
    So, the field has become extremely exciting. Our students 
are energized. You know, one of the things that I use as a 
bellwether to figure out if an area of science is moving 
forward is whether young students are choosing to put their 
careers on the line and go into this area and it is happening, 
and it is happening big time. We have got a very small medical 
school at Mayo. We have only got six M.D.-Ph.D. students. The 
last time around, four out of the six decided to combine 
geriatrics and basic aging research. So the young people are 
moving into this.
    Now, we have got a lot of challenges. At the moment, as I 
mentioned, this is science fiction with regard to humans. We 
need to test whether these things that we can do in mice are, 
indeed, translatable. We need to expand our discovery pipeline 
so that we can develop more of these agents. We need to know if 
they really do target age-related diseases across species.
    And we need to begin to explore this in a rational way in 
humans. We cannot study lifespan in humans. We cannot even 
study healthspan in humans. So we have to have the right 
clinical trials, paradigms, for doing this, and that means 
having the right kinds of study populations and looking at the 
right kinds of outcomes. We will have to have agents that act 
in people when they are already beginning to feel a bit under 
the weather or at risk. We do not want to develop necessarily 
interventions that you have to give to people in their 20s to 
have an effect when they are 80 because that will not be 
realistic. But I am cautiously optimistic that we are moving in 
this direction.
    A challenge--there are several challenges. One is that we 
do not have many people who are trained in the intersection 
between basic biology and clinical geriatrics. There are 7,000 
geriatricians in the United States. There are around a dozen 
who have basic science grants from the National Institute on 
Aging. That is very small. We need to do a lot of work on 
curricula and training.
    Since we are moving into a period of translation into 
clinical application, that becomes, and I am sure you do not 
want to hear this, but it becomes expensive, and the question 
is, how can we do this and how can we do this without 
cannibalizing the basic research which is so important to keep 
the pipeline going. So I commend what has been happening at the 
NIH with the GSIC initiative, which Dr. Hodes and Dr. Sierra 
and others have formulated where a variety of Institutes--I 
think 20 out of the Institutes or 21--across the NIH have come 
together to look at the intersection between the particular 
disease that that Institute is focused on and aging, and I 
think that is a very good way to go.
    And we have started to emulate that within Mayo, and 
through the generosity of the NIH, we have been able to 
establish now--as of a few weeks ago, we got funding to 
establish a transnational geroscience initiative of aging 
centers across the country so that we can try to coordinate our 
efforts and save costs by approaching things in a rational way.
    I just hope all this can be done. I think it is potentially 
exciting. I think you mentioned potentially transformative 
endeavors in moving our health forward and this is potentially 
one of them. Thank you.
    Mr. Hodin. Thank you.
    The Chairman. Doctor, one of the requirements to be a 
member of the Aging Committee is that you volunteer to offer 
yourself as a guinea pig----
    [Laughter.]
    So I want to offer the Aging Committee, both Republicans 
and Democrats----
    [Laughter.]
    For any of your experiments.
    [Laughter.]
    Dr. Kirkland. I am first on the list, though.

 STATEMENT OF JOHN ALAM, MD, HEAD, THERAPEUTIC STRATEGIC AREA 
             FOR DISEASES OF AGING, SANOFI-AVENTIS

    Dr. Alam. Good afternoon. Thank you very much, Senators 
Nelson, Warren, and Donnelly, for your interest in this very 
important matter, and thank you to everyone in the audience for 
coming today.
    I am a physician scientist who has been, for the last 
almost 23 years now, working in biotech and pharma in R&D of 
novel, innovative medicines, mainly, actually, in my hometown 
of Cambridge, and I am, yes, a Red Sox fan.
    Senator Warren. Go Sox.
    Dr. Alam. I am today head of an R&D group at SANOFI 
dedicated to research in aging and age-related diseases. It is 
actually one of the few units, I believe, across the 
pharmaceutical industry that is focused specifically on aging 
and age-related diseases. SANOFI, otherwise, it is a top five 
global pharmaceutical company that is active in a wide range of 
medical disease conditions--cardiovascular, diabetes, cancer, 
rare diseases, and multiple sclerosis.
    The R&D unit that I lead, which is called TSU Aging, was 
created a little bit more than three years ago with an 
objective of discovering and developing medicines that are 
specifically directed at older individuals and patients with 
chronic disease. We believe that we have been pioneering in 
this approach to aging with a--and moving towards, rather than 
studying diseases in isolation, to the study of a collection of 
certain major age-related diseases in parallel as well as the 
integrated health needs of the elderly with the aim of 
maximizing overall the capacity for independent living with 
aging.
    Today, our R&D activities are attempting to address both 
age-related chronic disease, such as Alzheimer's disease, 
Parkinson's disease, stroke and osteoarthritis, as well as what 
are called age-related geriatric syndromes, such as chronic 
pain, age-related muscle loss, or sarcopenia, and frailty.
    When we set this unit up, our thinking was that along with, 
I think, many of the people around this table, that to approach 
aging and the chronic diseases of aging, that what was required 
was a fundamental shift in the scientific approach to 
discovering and developing innovative medicines for age-related 
diseases.
    In my written statement, I actually give a lot more color 
and detail on the rationale and what makes the chronic diseases 
of aging very different from the more obvious diseases, such as 
infectious disease and cancer, in younger and middle-age 
people, where the basic biologic mechanisms are that much more 
distinct from what is otherwise healthy and normal.
    But for the moment, what I will say is that, based on that 
perspective, we set up the scientific strategy with three 
pillars at the core of the aging group. Number one is in order 
to cross-fertilize ideas and concepts as well as developing 
therapies that address common age-related biologic mechanisms, 
we integrated the scientists working in the major age-related 
diseases and syndromes under one R&D organization and 
leadership.
    Second, we are placing greater emphasis on intervening 
earlier in the disease process rather than intervening late in 
the stage of disease where, particularly in older individuals, 
there may be irreversible damage and loss of function.
    And, third, wherever possible, consider multi-pronged 
strategies and integrated health care solutions that not only 
provide pharmaceutical products, but also address health care 
needs more broadly and integrated solutions that may encompass 
novel technologies and services.
    Otherwise, across global R&D at SANOFI, from an operating 
model standpoint, we have recognized that our internal efforts 
can--for complex diseases, such as a variety of diseases of 
aging, cannot be enough, and so we have adopted over the last 
several years an open innovation model whereby we work in a 
network manner with academia, with governments and other 
players in the biotech and pharmaceutical industry, both 
directly and in one-on-one private collaborations and 
partnerships, as well as in larger public-private consortia.
    Before concluding, I just want to make one comment on the 
article that has been circulated regarding the potential impact 
that the--the potential greater cost impact of extending life. 
In our view, that increased cost might arise from increasing 
life could be an outcome if, in fact, we continued with 
business as usual, that is, developing treatments that 
intervene late in life and extend life only in the context of 
already existing disease and morbidity. However, we believe 
that the opportunity in aging research is that through this 
research, we are able to develop interventions that are early 
enough in the process that they can primarily extend healthy 
life years where, in fact, in the end, we might be able to 
decrease health care costs rather than add to the burden of 
health care costs. In addition, we believe that integrated 
aging solutions that incorporate technology services such as 
nutrition, exercise counseling, and other complements of 
pharmaceuticals have the opportunity to further impact health 
care costs positively.
    In conclusion, by developing novel, innovative medicines 
and integrated health care solutions for the aging population, 
notably through partnerships involving public and private 
stakeholders, we, or SANOFI, is dedicated to finding solutions 
to the problem of this century, the worldwide challenge of 
increasing demand for health care with aging populations. Thank 
you.
    Mr. Hodin. Thank you, Dr. Alam.
    Dr. Morgan, before I turn to you, perhaps I could just 
highlight some points you were just making that are so 
critical, which is that this is about and for the children as 
much as anything else, and the children's children, because 
this is about a demographic historical change in our 21st 
century, and oftentimes, people think of it as a particular 
moment in time related to the baby boomers. That has catalyzed 
this for us, but what it is really about is our demographic 
condition that we will be living with at least over the next 
two to three generations. That is how these things work. And so 
when we think about it as, well, are we going to spend for K 
through eight education or old people, that is not how to think 
about investment in this kind of research.
    Dr. Morgan.

 STATEMENT OF DAVID MORGAN, PH.D., CHIEF EXECUTIVE OFFICER AND 
     DIRECTOR, BYRD ALZHEIMER'S INSTITUTE, AND DIRECTOR OF 
 NEUROSCIENCE RESEARCH, UNIVERSITY OF SOUTH FLORIDA COLLEGE OF 
                            MEDICINE

    Mr. Morgan. Thank you. So, I, first of all, want to thank 
the members of the committee for coming here and listening to 
us today and giving us an opportunity to share with you some of 
our opinions on these issues.
    My name is David Morgan. I have been working on Alzheimer's 
disease for about the last 25 years. But 32 years ago, I 
actually moved from Northwestern University, where--I feel very 
out of place here; I am actually a Cubs fan----
    [Laughter.]
    To the University of Southern California to the Andrus 
Gerontology Center, where I began studying aging and brain 
function, aging and neuroscience, to try and understand not 
necessarily diseases, because at that time, Alzheimer's was 
still really applying to people under the age of 65, not normal 
people in their 70s and 80s who have the same type of 
pathology, but we were trying to understand what were the 
normal changes with brain aging, and it became a very 
interesting topic for me. I developed personally a certain 
perspective on this that may be useful as this geroscience 
community moves forward.
    We have often thought about diseases as having an 
interaction between genes and the environment. It is your 
inheritance and it is your lifestyle and it is what you are 
exposed to and all these things interact to cause--increase 
your risk for heart disease versus diabetes, versus cancer, et 
cetera. But I think the third factor is aging, and it is 
something that often is not considered in any of the models 
that we have about specific diseases.
    And one of the things I noted in going through the 
literature when I started working on Alzheimer's is if you 
looked at people who died from Alzheimer's in their 60s and you 
looked inside their brains and you looked at the amount of 
atrophy and the amount of degeneration and the amount of damage 
that was there, it was always much, much greater than when you 
looked at somebody who died with the same symptoms at the age 
of 90. And part of the reason is that the major change with age 
physiologically is a loss of our reserve capacity, our 
capability of overcoming challenges and insults to our 
physiological well-being.
    You know, even back then, this notion that it would be much 
more beneficial at a population level to slow the aging process 
and, therefore, extend the health span, that this was viewed in 
a very positive way, and if you got rid of heart disease, you 
got a year or two, and you got rid of cancer, you got a year or 
two because something else would come along and be a major 
problem. But that never really seemed to develop and take hold, 
and it is interesting now that after I have shifted into a very 
disease-specific modality in my science that this very simple 
concept is coming forward.
    So, I think it is useful. I think it is valuable. I think, 
as we go through this today, I am going to actually bring up a 
few things that concern me about it. I think there are some 
potential limitations. We have some experience with this 
through the animal system with a thing called caloric 
restriction. It may not be applicable in humans, and certainly, 
I do not know if I would want to live a long time if I had to 
be completely restricted in calories, but I think it gives us 
an example of something that we are pretty convinced can slow 
aging.
    But another feature that I am struck by as I work in 
Alzheimer's disease is how the major risk factors for 
Alzheimer's disease, we think age, you know, too many birthdays 
is the biggest risk factor for Alzheimer's. But beyond that, we 
also noticed that the cardiovascular risk factors are also 
important. The diabetic risk factors are important. And it all 
boils down, ultimately, to lifestyle choices that people have 
made about exercise, about what they eat, about what they 
expose themselves to, about cigarette smoking, et cetera.
    And I think what these are really doing, because they 
affect all these neurodegenerative diseases, is genuinely 
modifying the age process and that some people may get them 
earlier, some people may get them later, but we also have these 
additional influences on our aging. And while genes and the 
environment influence aging, as well, I think they affect 
disease-specific phenomena as well as this general biological 
phenomenon of aging. And finding ways to try and slow that will 
obviously be permitting us to get greater gains in longevity 
than we would have otherwise.
    But, just one caution that I have, and you brought this 
point up. If there is someone who already has dementia and they 
are at the point where they are really not knowing exactly who 
they are or who their relatives are, the quality of life is 
impaired, I do not know if I would want to extend their 
lifespan from that point forward. That would certainly be a 
concern of mine.
    So, I think--I personally believe there is going to be a 
very strong role for disease-specific approaches, as well. I 
think that you have got factors that increase your risk for a 
disease. I think you have factors that increase, or speed up or 
slow down your rate of aging.
    I am a lead representative for an organization called 
Researchers Against Alzheimer's and we are advocating to get 
more and more funding for Alzheimer's because we think it is a 
relatively neglected disease, that the research dollars we are 
investing in it relative to the medical costs are not even 
beginning to be comparable to these other major diseases we 
have discussed.
    But, I do agree. I think that the aging process is a very 
fundamental phenomenon and I think that part of the reason it 
becomes so critical is that the amount of damage you need gets 
less and less as your years get higher and higher.
    Mr. Hodin. Thank you all.
    Senators, did you----
    Senator Warren. Well, I actually am going to have to go 
preside. I just want to say, I wish I could stay for another 
two or three hours. One of the things that happens, I am 
learning, in this job, is we get pulled in a lot of different 
directions.
    But I do want to say on this, I want to commend the 
Chairman. The Aging Committee, my sense is, we want to be your 
partners. Putting this in context, that the challenge we face 
in the 21st century is we are getting old as a--not in this 
room, of course, but, I mean, collectively.
    [Laughter.]
    Mr. Hodin. Well, including this room.
    Senator Warren. Not really.
    [Laughter.]
    In the country, and so it really is the question of how we 
think about the policies that make life possible at the end of 
the 21st century when the fastest-growing age group is those 
over 100 and the next-fastest is those over 90 and those over 
80. And so how we think about dealing with that, and it seems 
to me it is a two-pronged strategy.
    One is we need to treat every child like a gold nugget. 
Polish them up and get maximum value out of them, that each of 
them needs to be able to perform at the height of their 
potential and kind of move that curve forward if we can.
    But the other half is to invest every nickel we can in the 
research that will help us manage our health, our beings as we 
age.
    And so this is just exactly right. I am just sorry I cannot 
stay and take advantage of all you are talking about. You have 
sparked at least 100 new ideas in here. And I just want to 
thank the Chairman for doing this and say that the Leader will 
scold me if I am one minute late, so I just want to thank you.
    Mr. Hodin. Thank you, Senator.
    Senator Warren. Thank you.
    The Chairman. Well, Doctor, it was quite telling, what you 
said, that by a certain year, that we are going to have more 
people in adult diapers than in Pampers. That is kind of 
stunning, but it is the trend. So, to increase that quality of 
life as we continue to age, to be productive and healthy, do 
you have any magic potions, any supplements you want to 
recommend, any brain exercises that I should engage in? I have 
a lot of torment that we have to go through here in this 
political cauldron, but what are some of the things that you 
would suggest?
    Mr. Hodin. Well, thank you, Senator, and adding to Senator 
Warren's point about thanking and congratulating you on calling 
this session today. So, perhaps we can engage in a little 
discussion and maybe even a little controversy.
    Let us start on this basic question of the relationship 
between the biology of aging and the other NCDs that we are 
dealing with. Maybe Dr. Kirkland, Dr. Hodes, others, but we 
have talked a little bit beforehand. You could--by the way, 
this Doctor is the only--I am a political scientist, so I can 
be a layman here. Maybe you can explain this to us and also get 
us through this concern that Dr. Morgan raised about sort of a 
suggestion of one versus the other in the reality of funding. 
How does the biology of aging lead to addressing the NCDs 
themselves?
    Dr. Hodes. I think all of us would be happy to address 
that. As you have heard, there is the strongest kind of 
research evidence to indicate that the aging process itself is 
an underlying factor in common to many diseases and 
pathologies, and maybe I will give you one example. It is a 
little science fictionist, but it is Jim Kirkland's work, so he 
will not dare talk about it too much out of self-consciousness. 
And it is illustrative of the way in which disease-specific 
research has informed the principles we are talking about now.
    And I am thinking about a gene like P16, a gene which was 
described, perhaps first appreciated in terms of its regulation 
of cell division from a cancer point of view. And then the 
observation that in an animal, and probably with some assurance 
all of us, as we age, there is a population of cells, 
relatively small, in every organ and tissue that have become 
what is called senescent. They do not function so well. They do 
not divide so well. And these cells happen to express a high 
level of this gene product P16.
    So through a very ingenious strategy, Dr. Kirkland and 
collaborators generated an experimental mouse by genetic 
manipulation such that at any point in time, they could give a 
drug that would selectively eliminate, kill off, just this very 
small fraction of cells that were senescent. And the outcome, I 
think quite dramatic and surprising to all of us, maybe to 
those who carried out the experiments themselves, were that 
eliminating the small number of cells in an animal that was 
already old, showing the effects of old age, would actually 
reverse in tissues such as muscle the effects of old age. So 
these animals, taking out just these few cells, could now run 
further, run longer, and perform the way younger animals could. 
In this case, although we all understand that prevention is 
likely the more effective treatment than reversal, in this 
case, even reversing the damage in a particular organ, in this 
case muscle and musculoskeletal systems.
    So I cite this as one example on the verge of science 
fiction but coming to reality in which understanding, taking 
advantage of investing in cancer research, understanding the 
basic biology, what regulates cell cycle, and then translating 
that into an intervention that now may be the basis for taking 
it beyond mice and into animal species that could give some 
guidance in humans is one of these examples that I cite.
    The Chairman. Thanks for that. When did you start working 
on those mice?
    Dr. Kirkland. We started working on it a long time ago, the 
original ideas, but it was published in 2011, that particular 
mouse, but there is a lot of other stuff that is equally or 
even more exciting that is occurring around the country and 
across the world, showing related interventions or even other 
kinds of interventions that show this kind of promise.
    It is very early. As Dr. Hodes said, it is still science 
fiction. But there are a lot of groups now working around the 
world on various aspects of the fundamental biology of aging 
that the NIH has largely supported that appear to be beginning 
to bear fruit. At least we can get really, really healthy, 
highly functional mice that are older, you know, and can attack 
your kitchen and things like that.
    [Laughter.]
    Dr. Kirkland. What we--the next really, really big step is 
to--well, there are two things. We need to maintain that 
pipeline. This is extremely important. We cannot cannibalize 
our basic research efforts to pay for the very expensive 
translational efforts that we have to embark on, and we have to 
start the translational efforts and we have to do it the right 
way and a smart way.
    And there are a lot of steps. There are a lot of potential 
red lights going through the tunnel before we reach the end of 
it that have to be addressed. But I am much more cautiously 
optimistic than I was ten years ago that this might--this kind 
of approach, in general, or a related approach, might actually 
work with respect to multiple age-related chronic diseases and 
targeting them together instead of one at a time.
    I think, as Dr. Morgan was saying, it is very, very 
important, also, not to cannibalize disease-specific research 
because it is going to be very important to deal with 
situations once they have gotten out of hand.
    But we need to think of strategies to do this translational 
research and continue the other things or even expand the other 
things that we are currently doing. It is going to take a lot 
of rethinking in medical paradigms and clinical trials 
paradigms and how we go through, interact with regulatory 
agencies and what sort of trial design do we use, what study 
populations do we use. There are a lot of details that have to 
be worked out, and I think this conference that is being 
organized by the NIH is a major stepping stone towards getting 
people to think about some of these strategies around these 
potential obstacles.
    And, similarly, I think the NIH's support of bringing--the 
concept of bringing together the various aging centers around 
the country through a grant that they provided is going to help 
us think collectively and in a competitive way, but not a 
destructive competitive way, how can we achieve these 
milestones in the most economic way possible.
    There is going to need to be an investment, though, and I 
do not know how much of that investment should be public or 
private. I think as the public becomes more and more aware of 
what could potentially be done and they see these old mice 
running around that look pretty healthy, there might be 
increasing support for moving in this direction, and certainly 
industry has recognized this increasingly and is beginning to 
make investments in this area. You are to be commended in 
thinking way ahead of other people in doing some of this, as 
are you.
    Mr. Hodin. Dr. Morimoto, please.
    Mr. Morimoto. One of the remarkable aspects of biology and 
really has contributed greatly to the biology of aging is that 
how all biological systems respond to age turns out to be quite 
similar. And the ability to do these wonderful studies in mice 
and to translate it may come as a surprise to some that the 
discoveries were made in yeast, bakers' yeast, or in a fruit 
fly, or in a nematode, C. elegans. The genes that actually 
regulate aging were not discovered in humans or mice. It was 
actually a little worm.
    But this actually helps us, because unlike many things 
where it is highly specific to a particular organism or a 
particular tissue, it is a fundamental of life on earth at some 
level. And, therefore, as we make these discoveries, there are 
great partnerships, I think something that is very important, 
collaborations across the basic sciences through the clinical, 
and I think here is a very important opportunity. When the 
genes are discovered, the pathways are worked out about how 
aging works, it is really not related to a disease. It is just 
aging. But it becomes a fundamental if we understand that, and 
when it goes away, that is when it then leads us to 
Alzheimer's, Parkinson's, diabetes, and cancer. And I think it 
is when the mismanagement occurs.
    So, I think we have done a good job of investing in very 
good basic science. I would agree and concur with my 
colleagues, we do not ever want to get into a position of 
competing because that is nonproductive. What we have to find a 
way is better partnerships to optimize the resources and, yes, 
certainly see if there are other opportunities, but to now take 
some of these fundamental discoveries.
    There is, however, a real phase shift here. Even though it 
is called the National Institutes of Health, it is really the 
National Institutes of Disease. There is not that much emphasis 
on what is the underlying biology to keep your molecules, your 
genes, your cells healthy. And I think a lot of the emphasis 
here is tied into healthy aging. So, what can we learn to keep 
ourselves more robust and functioning better and longer and 
perhaps by that putting off the early onsets.
    Dr. Hodes. Just reinforcing what has been said, I do want 
to take the chance, as well, to thank you, the Senate, the 
Congress, the administrations that have been enlightened. You 
have heard about the diversity of basic research that has 
ultimately led to important insights, whether it is studying 
yeast or worms, whether it is studying the behaviors of 
organisms that are a single cell. And we have all seen, heard, 
and understood, sadly, even though the present, strong 
criticisms of this kind of research, which, on the face of it, 
unless one understands what their relevance is, do appear to be 
questionable.
    But these examples you have heard today and many more 
converge on this continuing conviction, I think, that we have 
to maintain basic research and the biological and in the 
behavioral side because it ultimately has proven to be the 
grist out of which these great translational opportunities have 
developed.
    So, we thank you and all of the Congressional support we 
have had, bipartisan, over the years for this very important 
perspective.
    The Chairman. Well, you are talking about the amount of 
money that goes to NIH so that you all can give it out in 
grants. That is what you are talking about. There is an 
example. I assume yours was a grant from them, doing what you 
are doing. But you are talking to the wrong person, talking to 
me.
    [Laughter.]
    You need to go and visit with some of these folks that 
continually want to cut, and NIH is a good example. Dr. Collins 
came down here, told us he had to stop 700 grants going out 
because of the sequester in this last fiscal year. And, of 
course, we are facing the potential, if we cannot work it out, 
of another major round of cuts in the sequester come January 
15. So that is part of the problem.
    Mr. Hodin. Well, picking up on, perhaps, this collaboration 
theme, I would like to--Dr. Kirkland, when we were talking 
beforehand, you mentioned--I found it very interesting that our 
friends in Europe, you would suggest, are a little bit ahead of 
us in this. So, I guess I have two sort of related questions. 
One is if you could explain that a little and whether we can--
you know, what this means for American competitiveness and 
America's future, but secondly, in one sense, I mean, this is a 
global challenge. We are all aging, and as we know, it is 
happening across the planet. The emerging markets of Turkey and 
Mexico and, of course, China, due to as much their longevity 
and their low birthrates, are aging even more rapidly than we 
are.
    So, I guess one question is, why is Europe, or how you 
would describe Europe as it were ahead of us, but the second 
related one, Senator, is how do we perhaps collaborate. I mean, 
one thinks of the HIV/AIDS model, which was a collaboration 
globally, and maybe the E.U.-U.S. Trade Agreement might be an 
interesting place.
    Dr. Kirkland.
    Dr. Kirkland. Well, I would hesitate to say or assert that 
Europe is ahead of us in basic aging research. I think the 
United States has really led the world in that, and it is 
because the National Institute on Aging has done such a great 
job amongst--and other organizations who are represented here.
    What Europe has recognized, I think, is that they have, 
because of the single-payer systems, they have older 
populations, they recognize the demographic imperative in a 
very strong way. And one of the things that they have done is 
to focus on creating networks across Europe and funding them 
quite substantially to coordinate and collaborate in aging 
research across centers, which is something we are beginning to 
do here. Regulatory agencies in Europe are also fairly far 
ahead with respect to understanding some of the parameters 
within clinical trials and so forth.
    I would say the United States is heavily represented and 
ahead in a lot of ways when it comes to basic aging research.
    Now, I--so, Europe has different strengths and weaknesses 
than we do and they have chosen to make quite a bit of 
investment into bringing groups together and they are 
accelerating, unlike our situation here, their investment into 
aging research. So they are putting huge amounts into some of 
the universities in Europe that--so, their increments are very 
high. Their fold increase in spending on aging research has 
been high relative to what we have been able to do in the 
United States.
    So, one of the things that various groups around the United 
States have been looking at, we are beginning to come together 
as networks and we are beginning to speak to the European 
networks that are established. And we have had a number of 
discussions, including with leadership at the NIH, about 
potentially finding ways that we can collaborate with European 
networks so that if there are big, expensive projects, we can 
cost share. If there is infrastructure needed for aging 
research, for example, databases or specimen storage kinds of 
paradigms, that we can cost share.
    So, I think we are looking for every possible way we can do 
this kind of research on a collaborative way, not only 
nationally, but internationally.
    Mr. Hodin. Dr. Alam. Oh, yes.
    The Chairman. [Off microphone.] I have to excuse myself for 
a vote. Would you flesh that out for our staff, going through 
the European-U.S. trade route, what it is that you want with 
respect to this shared relationship. I want to thank you all 
very, very much.
    Mr. Hodin. Thank you, Senator.
    So, Dr. Alam was going to say something, and then Dr. 
Morimoto. Please. And then Dr. Morgan.
    Dr. Alam. Well, the comment I was going to make was just 
that I think beyond the science, to translate this into 
clinically actionable outcomes, and particularly as we move 
beyond disease-specific into the geriatric syndromes and 
thinking about aging and how we can impact patients or 
individuals who may not have something we would traditionally 
consider a disease, such as frailty, and that we need to also 
be thinking about in discussing how we can support the 
regulatory pathway and perhaps even the clinical paradigm of 
managing older individuals who have declining function and 
increasing incapacity but do not have a diagnosable disease.
    And I think in that respect, it is actually in that arena 
where Europe is probably further advanced than the American 
system, is because they recognized the function--the impact 
from a financial standpoint of that loss of function and they 
are really starting a whole range of initiatives in public-
private consortia of trying to intervene and in management 
strategies that may not have actually a pharmaceutical around 
it but can have impact in improved function. And they are 
supporting that, I think, both from a regulatory perspective 
and from a reimbursement perspective more actively than we are 
here in the U.S.
    Mr. Hodin. Very interesting. I guess Dr. Morgan, please--or 
Dr. Morimoto. Yes. Sorry.
    Mr. Morimoto. I just wanted to add to what Dr. Kirkland 
said about Europe. It is really different rates of 
acceleration. I think what we are seeing in Germany is a 
tremendous investment of funds. After all, Germany and Japan 
are the two fastest-aging countries on the planet.
    Just to add a little bit more detail, in the past five 
years, the German government invested into a huge countrywide 
Center for Neurodegenerative Disease with 12 centers with the 
headquarters in Bonn. It is a huge investment, nearly 1,000 
scientists. Just, actually, a week ago, I was at the opening of 
the Max Planck Institute on Aging in Cologne, which is an 
extraordinary event focused all around, now, in this case, the 
biology of aging. There is very little translation. This is 
something they are hoping to do. But they have recognized that 
that is where they are going to put their investment.
    I think, by comparison, Japan is aging so fast that they 
are not putting their money into the biology of aging but they 
are putting into robotics to take care of the individuals who 
are aging and other directions like that.
    Dr. Kirkland. Korea.
    Mr. Morimoto. Yes, and Korea. But I think that there is a 
very important opportunity here for the United States to take 
the lead in partnerships. That is something we do well. We are 
good at reaching across to other countries and saying, look, 
how a Japanese, a German ages is the same as an American and 
let us work together because we now have larger populations we 
can study. We can compare the various treatments, the 
modalities. I think that is going to be critical, for us to 
take the lead in the world.
    Mr. Morgan. So, I just have a couple of quick comments. I 
think one of the things about the sequester that we are seeing, 
combined with the increased investment overseas in various 
research, is scientists are talking with their feet. They are 
leaving. They are going back to the countries from which they 
originated. You know, the history of the United States' 
scientific superiority has been the ability to attract these 
people from overseas to come here and I think we are starting 
to see the reverse of that, in part because of reductions in 
funding.
    I think another way to approach some of these things is the 
public-private philanthropy partnership, and I think the best 
example of that I have seen is ADNI, sponsored by the NIA. This 
is an incredibly successful organization where the 
pharmaceutical industry recognizes there is a pre-competitive 
space where they can make investments without necessarily 
worrying about it costing them in competition with the other 
pharmaceutical industry members. And I think your company's 
engagement in this is actually just probably the beginning of 
this, and I think there are opportunities to start considering 
engaging in that type of activity, as well.
    In terms of the international collaborations, there is a G-
8 summit that is coming up and Alzheimer's disease is going to 
be one of the major issues to be discussed there. And I think 
there are some limitations in trying to set up international 
collaborations. Besides the distance, there are restrictions on 
NIH funding to be used overseas. You have to have a special 
justification for it. I think there are ways in which this can 
be made--the regulations regarding these things can be made 
less onerous and more capable of permitting those types of 
interactions in order to support that type of multiple-country 
collaboration.
    Mr. Hodin. Thank you.
    Another point which several of you have touched on and was 
alluded at the very beginning, Dr. Kirkland, you talked about 
your young scientists who are choosing to go into the field. 
How are we doing on skills and competencies? Do we have what we 
need? Do we need to invest in that, as well? Where is that, and 
do we have--I mean, that is going to take a different kind of, 
or a separate kind of funding stream, as well.
    Dr. Kirkland. Yes. From--the field is moving into a new 
realm, and that is a realm of clinical translation. And I am a 
geriatrician and most of us in geriatrics, we have--for a long 
time, we have had nothing fundamental that we could do. We have 
been able to--it is very important work, and I do it as a 
clinical geriatrician. We figure out ways of providing better 
devices, better walkers, better incontinence devices, better 
ways of providing exercise and other kinds of interventions, 
ways of trimming drugs, ways of managing the long list of 
chronic diseases that people have, but we have had nothing 
fundamental, really, really fundamental and transformative, 
that we can do, unlike what has happened in other specialties 
where there are agents and approaches that are novel and 
fundamental and require investigational new drug development.
    So there are very few geriatricians who have had experience 
with translation from the bench to the bedside, with 
investigational new drug work, and this is a real gap. We do 
not have a lot of people who understand the kinds of outcomes 
we need to look at in clinical trials, things like frailties, 
or things like, say, recovery after chemotherapy or surgery or 
treating multiple age-related chronic diseases in a population 
that is elderly with comorbidities and living at home and 
following more than one outcome at a time and doing the right 
statistics. We just do not have people who are trained how to 
do that and understand the basic biology enough to be able to 
do the translation.
    As I mentioned, there are 7,000 board-certified 
geriatricians in the United States, around 12,000 
geriatricians, some of whom have been board-certified in the 
past, but very, very few of them have formal basic science 
training to the kind of level where they are competitive for 
research grants in the basic biology of aging arena.
    It is totally unlike--I am also an endocrinologist. In 
endocrinology, a lot of my colleagues who are in academic 
institutions are quite comfortable walking into a laboratory 
and writing an R01 grant. It is not true in geriatrics. We do 
not have those people trained. So we have got to create 
training programs for these people.
    In the meantime, what we have to do is get groups of people 
working together, basic biologists working with people who are 
experienced with clinical trials. The way we have done it at 
Mayo is by using a lot of people who have been experienced in 
cancer clinical trials and then people with IND experience and 
forming teams. But, eventually, we will need some captains of 
those teams and we do not have them.
    Mr. Morimoto. One of my former hats was as the Dean of the 
Graduate School at Northwestern. So I thought deeply about 
education and training, about the M.D.-Ph.D. programs, about 
the--anything that fell under my umbrella. And I think what you 
bring forth is the necessity for our institutions to be 
creative and create new programs to meet these needs. Often, 
what we do is we take our existing programs and tuck students 
in and just hope it works. But science is more complicated, and 
if you want to train someone who understands aging, it would 
not be a good idea for them to just understand a molecule or 
another one just to be a geriatrician.
    I think what Dr. Kirkland brings forth is that we need to 
train a new breed of, whether you are a Ph.D. or an M.D.-Ph.D., 
actually, it should not make much difference. As a Ph.D., you 
need to understand epidemiology, understand the social 
situation of aged individuals. As an epidemiologist, you really 
should start to understand what is happening to cells. This 
does not happen, even in the best American institutions, 
because they tend to be somewhat Balkanized.
    But I think this is something where NIH has had an 
opportunity. It can stimulate new behavior by calling, you 
know, creating or encouraging people to come up with new 
programs. And it may be that in this area and in this era, that 
we could put forth an idea of developing some new programs to 
cross-train people to meet these needs.
    Mr. Hodin. So as we are, perhaps, coming to a conclusion of 
our discussion, and as you go into the two days of conference, 
maybe, and certainly for the Senate, Dr. Morgan, starting with 
you, what is the one message you want to leave here for the 
Senators that you would like them to address or answer, and 
maybe each of you could conclude on that.
    Mr. Morgan. I do not know that I have a single message. I 
think aging and disease interact in very important ways. I 
personally do not believe that aging is a unitary process. I 
think we are going to find it is just as complicated as all the 
factors that cause disease and we are going to whittle away at 
this phenomenon. It is not going to be one day we will wake up 
and there will be a dramatically reduced rate of aging.
    I think, however, that this is an investment that will be 
something that would benefit us in a long time in the future. I 
do not think it is going to have an immediate impact, but I 
think it is a very worthwhile activity. I think--the one thing 
I have noticed in science is you never really know exactly 
where the most important discovery is going to be made. It is a 
process of serendipity. I think, in some sense, it is actually 
Darwinian. It is random variation and selective retention.
    Nonetheless, I think aging is something that has always 
intrigued me. I think that it is a fundamental research 
question of great interest. There are organisms that do not 
age, interestingly. There is negligible senescence is a number 
of them. But that is kind of beside the point.
    I think----
    Mr. Hodin. Tell me one, just as----
    Mr. Morgan. Organisms that do not ready mature body sizes 
do not seem to show aging, so alligators, for example, is one.
    So, these----
    I never got close enough.
    Ah. Well----
    [Laughter.]
    We count the rings on their teeth when we get really close.
    [Laughter.]
    But I think that the issue of being able to slow aging, 
extending healthspan, and really diminishing the impact of 
these diseases on our society is a very, very worthwhile 
endeavor.
    Mr. Hodin. Thank you.
    Dr. Alam. You wake up 20 years from now. What have we 
achieved as a result from this? Where are we 20 years from now?
    So, I think we are actually--where we are going to be is 
through this, actually, to be able to address the diseases of 
aging by having started in the science of thinking about the 
basic aging processes. And, I guess, in my mind, I do not see 
disease-specific signs versus biology of aging being mutually 
contradictory or exclusive, rather that I think we need to--
perhaps one can start acknowledging that we have been, from a 
science and R&D standpoint, we have struggled in the chronic 
diseases of aging and that maybe scientifically, that we need 
to think about other ways of bringing in actually new thinking 
and new scientific perspectives. And one of the ways, I 
believe, is through focusing on the more fundamental biologic 
processes of aging.
    It is also from a, I believe from a--perhaps this is 1(b)--
that if we are going to address--bring innovative medicines 
that actually do also reduce health care costs, the disease-
specific paradigm inherently seems to keep compounding the 
problem rather than actually being a solution to the problem.
    Mr. Hodin. Very interesting.
    Dr. Kirkland.
    Dr. Kirkland. I think, put simply, we need to put more 
resources into this particular area, the intersection between 
the basic biology of aging and the genesis of age-related 
chronic diseases at the basic level and at the clinical and 
translational level. And I think that particular investment 
could potentially have a major payoff with respect to the 
morbidity and mortality that I see as a geriatrician with my 
patients and could have a huge impact on health care costs, 
especially if it turns out--and we need to test this--if it 
turns out we are able to compress the period of morbidity at 
the end of life or at least increase healthspan while keeping 
lifespan more or less constant and thereby decreasing the 
period of morbidity at the end of life.
    So I think it is an extremely important area. We could be, 
and it is science fiction, but we could be approaching a 
transformative level. It could turn out to be something like--
and I hope it will be--like the space program or these other 
kinds of major endeavors. It has the trappings of that. Who 
knows if it will come to that.
    But I think we need to be moving faster than we are at the 
moment and that involves not only coordination, but it does 
require increased resources, and not only increased resources 
from the private sector and donors but also government, because 
it is going to turn out to be government that is going to be 
spending a lot of the money on dealing with issues with respect 
to our aging population if we do not do something sooner rather 
than later.
    Mr. Hodin. Thank you.
    Dr. Morimoto.
    Mr. Morimoto. Can we control our own inevitable fate? Can 
we separate chronological age from the molecular health of the 
cell? And if we could identify molecules that tell you that you 
are healthy or that there is disruptions of various sorts that 
might lead to risk for a disease, to then be able to apply 
therapeutics or other genetic forms of therapies to change that 
course. So, 20 years from now, if I woke up, I would be happy 
if that happened.
    Mr. Hodin. Dr. Hodes.
    Dr. Hodes. So, I think the way you first raised the 
questions there, what thoughts we might want to leave to this 
committee, to send to the policy makers who view what we do, 
and I guess for me, the starting point I think we would all 
agree upon is that the goal is to maximize the quality as well 
as length of life. This is the obligation we have in pursuit of 
research to that end.
    I think you have heard from the representatives of a 
brilliant group of researchers who have growing perspectives--
we will be hearing more in the next days--as to the specific 
strategies and approaches and priorities for getting there. But 
I would just applaud, again, this committee for bringing us 
here. I think we have an obligation to report back in a way 
that is understandable, compelling, and convincing, and I would 
invite future opportunities to do more of the same with 
individual members, with a committee, because we need to be 
held to the task. I think there is brilliance and commitment up 
to it, but we welcome the scrutiny, the reminder of what the 
goal of all this is, and I think we all have a very common 
sense of that.
    So, my final words would be thanks and a request to please 
bring us before you again for periodic updates and questions 
and a chance to converse with you.
    Mr. Hodin. Thank you, Dr. Hodes.
    I will conclude on the notion of also thanking the Senator 
and the committee for having the foresight and courage to bring 
us together. It has been an honor for me to sit around the 
table with some great researchers, great minds. Thank you for 
that.
    I would offer the thought that really builds on, Dr. Hodes, 
what you just said about being convincing and compelling, and 
it is interesting that during the course of this discussion, 
probably the one word other than ``aging'' that has come up 
more than any other around the table has been Alzheimer's. I 
have seen some maps of the world--I am sure we have all seen 
them--with dots of prevalence, and when you look at this 
movement through the 20th century and then up to 2150, you see 
not just a health challenge or a social crisis, but you see a 
fiscal nightmare. And it is the fiscal nightmare that will get 
the attention around this building and in this political 
milieu.
    And that is why, when I opened up, I attempted to focus on 
the point that sometimes it is important to understand that 
spending might not be as much a cost as it is an investment. 
And I do not have the scientific background to know whether we 
are going to find a cure for Alzheimer's or diabetes through 
the aging process or through a direct approach, but I do know 
that if we do not, we are not going to make it fiscally. And it 
is a global challenge. And so, therefore, I also suggest that 
while this is a part of America's future, it is a part of the 
world's future and there may be some very interesting 
collaborations that we can enable there, as well.
    So, thank you all, and we would like to thank again the 
sponsors and all of those who will be meeting in the next two 
days. Thank you.
    [Whereupon, at 5:29 p.m., the committee was adjourned.]



      
      
      
      
      
      
      
      
      
      
      
      
      
      
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                                APPENDIX

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                      Prepared Witness Statements

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