APPENDIX 5: NOTE OF THE VISIT TO WASHINGTON
DC
54. The Sub-Committee visited Washington DC, Bethesda
and Baltimore on 18 and 19 January 2005. Members present
were Lord Oxburgh, Lord Sutherland of Houndwood (Chairman), Lord
Soulsby of Swaffham Prior and Baroness Walmsley. They were supported
by Michael Collon (Committee Clerk), Jonathan Radcliffe (Specialist
Assistant) and Michael Norman (Committee administrator). They
were accompanied by staff of the British Embassy: Phil Budden
(First Secretary, Science and Technology), Joshua Mandel (Senior
Adviser, Science and Technology) and Matt Bricken (Research Assistant,
Global Issues Group).
55. The purpose of the visit was to study the organisation
and conduct in the United States of research into matters related
to ageing, both publicly and privately funded, and to hear about
some of the research projects being undertaken.
Ellison Medical Foundation
56. The Committee first visited the Ellison Medical
Foundation. The Foundation was established as a non-profit
corporation in the latter part of 1997 through the generosity
of Lawrence J. Ellison, founder and CEO of Oracle, "for the
purpose of positively affecting scientific discovery by funding
basic biological and biomedical research, with the expectation
that the research would significantly impact people's lives".
57. A Scientific Advisory Board was established in
1998 to guide the Foundation in the fields of research that would
benefit from financial support and have an important impact on
public health. The Foundation initially focused on funding research
that addressed the basic biological components of ageing, including
its processes, related diseases and disabilities. The first awards
on ageing research were presented in 1998.
58. The Committee met Dr Richard Sprott. Dr Sprott
was previously the Associate Director of the National Institute
on Aging, but in 1998 was recruited to become the first Executive
Director of the Ellison Medical Foundation.
59. Dr Sprott told the Committee that Mr Ellison
had taken the view that public funding of research was too much
orientated towards research into diseases, to the exclusion of
basic scientific research. He felt that public funds allocated
to research by the National Institutes of Health (NIH), and in
particular the National Institute on Aging (NIA), did not allow
for sufficiently high risk research to be carried out. He was
content himself to take risks with his own money, and to fund
twenty projects even if it was likely that only one of them would
be successful.
60. New Scholar awards of $50,000 a year for 4 years
were made to young researchers for the sort of creative research
for which they would not get public funds. The funding was for
good people with good ideas, rather than for projects. Applications
were limited to 4 pages, though a number of referees were required.
A small outside review group decided which applications should
succeed.
61. A number of Senior Scholar awards were also made
each year, consisting of grants of $150,000 a year for 4 years
made to established researchers, together with grants of the same
order for administration costs. The total value of Senior Scholar
awards was therefore of the order of $1 million. Applications
for these were only 2 pages long. They went before a panel of
6 reviewers who read all the applications and listed the top 6
in order of priority. Applications listed by all the reviewers
were automatically granted; those listed by none were automatically
refused. Those whose applications were listed by some but not
all reviewers might be asked to make a further 3-page application.
62. On the basis of such brief applications, the
Foundation had been putting $20 million a year into aging
research. It would not be possible for public funds to be allocated
on the basis of such a process. The Chairman contrasted this with
the position in the UK, where researchers spent a substantial
proportion of their time completing applications for grants.
63. Dr Sprott explained that only 4% of the funds
were spent on administration. The work depended entirely on the
will of the benefactor. It was open to Mr Ellison at any
time to review the direction of the funding, and to terminate
projects. He and the Scientific Advisory Board had recently independently
reached the conclusion that funding work on infectious diseases
was not worth continuing, and that more funds should be put into
ageing research.
64. The Foundation drew a sharp distinction between
the biology of ageing and diseases of ageing. Its funds were applied
to basic biology, not to cures for diseases or, for example, to
vaccines. Its objective was not extension of life expectancy,
but improving the quality of the terminal third of the lifespan.
Its interest was in understanding the basic processes of ageing.
Until recently the Foundation had contributed 20% of the funds
spent on basic research into ageing; now the NIA was contributing
more, but the proportion funded by the Foundation was still 10%.
65. As an example of work currently funded, Dr Sprott
gave an outline of the work on cell senescence and the shortening
of telomeres. $20 million spent on this was well worthwhile.
66. Internationally, in the 1980s, investments in
ageing research had been made by the UK, France, Italy and the
Netherlands. After putting a great deal of money into the field
over 5 years, France and the Netherlands had decided that this
work was unproductive, and ceased to fund it. But Italy had persevered
with the education of new scientists in basic molecular science.
67. The key was to attract the brightest young scientists
and direct them towards pure research into ageing. The effect
was that after 4 years they were committed to this research, which
resulted in some of the best young scientists being in this field.
This raised the profile of ageing research, which in turn attracted
the best scientists. Until a few years previously ageing had,
apart from nutrition, been the least highly regarded field of
research. The position now was very different.
68. The Foundation was not afraid of controversy.
Much of the work it funded involved experiments on animals, and
it might soon consider funding stem cell research.
69. Funding was also provided for conferences and
developing infrastructure. For example, the Foundation supported
the "Science of Aging Knowledge Environment" (SAGE KE)an
online resource for researchers hosted by the American Association
for the Advancement of Science.
70. Asked how the position in the UK might be improved,
Dr Sprott said that he did not see any value in a bricks and mortar
institute dedicated solely to ageing research; this tended to
isolate researchers on ageing from other researchers. The UK could
have great influence on sharply focussed basic research with an
investment of $20 million. The problem was to get the best scientists
to leave existing posts in other institutions. A measure of success
was whether the work achieved what the application for the funding
grant had said hoped to be achieved.
71. It was noted that in the US, not many researchers
were medically qualified. Dr Sprott was not convinced that
research carried out by MDs was of particularly high quality.
National Institute on Aging, Washington DC
72. The Committee next visited the headquarters of
the National Institute on Aging (NIA). The NIA is one of the 27
institutes of the National Institutes of Health (NIH) based in
the Washington suburb of Bethesda. Congress granted the authority
for the setting up of the institute in 1974. The purpose is to
provide leadership in ageing research, training, health information
dissemination, and other programmes relevant to ageing and older
people. Subsequent amendments designated the NIA as the primary
federal agency on Alzheimer's disease research.
73. The NIA sponsors research on ageing through extramural
and intramural programmes. The extramural programme funds research
and training at universities, hospitals, medical centres, and
other public and private organisations nationwide. The intramural
program conducts basic and clinical research on the NIH campus
in Bethesda, and in Baltimore.
74. Over lunch, the Committee met Dr John Hardy,
Chief of the Laboratory of Neurogenics, and were shown around
his laboratory. Originally from the UK, he had moved to the US
in the 1990s. He still retained close ties with British academe,
and had recruited several researchers from research groups in
the UK. Dr Hardy felt that the UK had become over-restrictive
in its regulation of human tissue samples; it was increasingly
difficult to obtain specimens for research. It was his opinion
that stem cell research would not benefit his particular field.
75. The Committee met Dr Richard J. Hodes, the Director
of the NIA; Dr Huber Warner, associate director with responsibility
for the Biology of Aging Program; Dr Miriam Kelty, associate director
for Extramural Affairs; Dr John Haaga, deputy associate director
of the Behavioral and Social Research Program; and Dr Tamara Jones.
76. Dr Hodes explained that there had been considerable
resistance to the setting up of the NIA, including two Presidential
vetoes. However it now had an annual budget of $1billion. It had
a considerable intramural research facility, but most of the funds
went on extramural research. There were four extramural research
programmes:
- the Biology of Aging Program, headed by Dr Warner;
- the Behavioral and Social Research Program;
- the Neuroscience and Neuropsychology Program;
and
- the Geriatrics and Clinical Gerontology Program.
77. The primary task of the NIA was the funding and
supervision of research projects in each of these four programmes.
A distinction was drawn between research into the ageing process,
the impact of the process on individual diseases especially prevalent
among older people, and research on those diseases. It was easier
to fund research into specific diseases than research into the
ageing process.
78. Asked about the accountability of the NIA, Dr
Hodes said it was responsible to Congress for the use of the funds
voted for it. The mission of the Institute was very broad, and
the appropriation came with little specificity as to the use to
be made of it. However the legislation establishing the NIA had
been amended to designate the NIA as the primary Federal agency
for Alzheimer's disease research, and it was expected that at
least half the NIA budget would be spent on research into Alzheimer's.
79. There was no requirement to provide an annual
report to Congress, or to the Department of Health and Human Services
(DHHS). There could however be Congressional hearings; normally
these were for the purposes of information, but they could occasionally
become confrontational.
80. Dr Jones added that in 2004 the NIA had attended
a record of nine hearings on, inter alia, appropriation, Alzheimer's,
longevity, frailty, retirement, the Older Americans Program 2004,
and meals on wheels. The House of Representatives had done away
with its committee on aging, but the Senate had two committees
with interests in the topic. The NIA was not allowed to lobby
Congress, but there was a daily process of contact, and regular
provision of information.
81. Continuing, Dr Hodes said that accountability
for the quality of NIA research was ultimately to the National
Advisory Council on Aging (NACA), which advised the Secretary
of the DHHS, the Assistant Secretary for Health, the Director
of the NIH, and himself as Director of the NIA. The Council met
three times a year to consider applications for research and training,
and to recommend funding for those applications that showed promise
of making valuable contributions. The Council also made recommendations
to the Director of the NIA regarding research conducted at the
Institute. There was a simple test for success: had research improved
the quality of life of older people?
82. Dr Hodes said that the NIA did not have a great
deal of contact with the Ellison medical foundation. Each was
aware of and respected the other's work, but the Foundation's
work was almost entirely concentrated on young researchers. Dr Warner
added that they had to be careful to avoid overlap with funding
of research by private foundations. There was not yet much overlap
in the field of ageing because there was not much such research.
However nearly every Ellison senior scholar was also funded by
the NIA. He was more worried about the balance between programmes
than about overlap.
83. Dr Kelty explained that the scientific community
trusted the NIA because research grants were not made by policy-makers,
while the reason administrators trusted the allocation of research
funds by the NIA was because peer review demonstrated that the
research was of value.
84. An example of a project to which large funds
had been allocated was biomarkers. Fifteen years earlier, the
Biology of Aging Program had set aside funds for research into
biomarkers, but ultimately it had not proved useful. The research
had been attempting to find predictive indications of ageing,
but the technology was not ready for it.
85. Dr Warner said that a contrast was the programme
on the genetic and molecular basis of ageing. The first five years
had not proved promising, but they had persevered, and the second
five years had been spectacular. Research based on fruit flies
had shown that selecting the offspring of older mothers for two
or more generations could lead to an increase in life expectancy
of up to 75%. A number of scientists working on different but
interrelated aspects of this had had relatively little contact,
and the NIA initiative had brought them all together.
86. Dr Haaga spoke about demographic issues. The
Behavioral and Social Research Program had made a number of grants
on work designed to measure objectively people's fundamental well-being.
Measurement of healthy life expectancy (HLE) was a hot area of
research. In the US, unlike the UK, HLE had been rising at the
same rate as life expectancy over previous years, but currently
obesity had the potential to reverse this.
87. Asked what datasets the UK should start building
now as a basis for future research, Dr Haaga explained that the
health care system in the UK provided a single database which
facilitated research. In the US, by contrast, there were problems
about access to Medicare data and medical records. They had now
brokered access to that information, and to information about
income for research on the social aspects. But, as in the UK,
there was more concern about protecting privacy, at the expense
of making data available for research.
88. One of the most profound discoveries of the last
50 years had been the impact of social status on health. This
dwarfed differences between the sexes. Much of the data had come
from the Baltimore longitudinal study. This had been going for
forty or fifty years. Subjects came back every year for two days
of tests. The results were good, but the study was expensive.
Data from other countries where health statistics were well documented
were also used. Dr Haaga cited the 2002 English Longitudinal Study
of Ageing.
89. The US had no tolerance for discrimination by
age, and would not countenance the NHS view that a person could
be too old for treatment to be cost-effective and worthwhile.
But there was considerable discrimination by social status.
90. The Chairman explained that the Committee had
concerns about the disparate nature of research activity in the
UK, and the apparent lack of coordination. Dr Hodes agreed
that there were also coordination problems in the US, both between
all the institutes comprised in the National Institutes of Health,
and also with other researchers looking at different parts of
the life-span, including child health.
91. Training was an important part of the NIA's work:
not only training researchers for such projects, but also training
those to support research. They were at that time training an
outstanding economist to work on the ageing process. Dr Haaga
explained that, although there were country-wide variations, there
was a general shortage of gerontologists, and of nurses with specific
training in gerontology. The NIA was funding programmes to insinuate
gerontology into the training programmes of all medical staff.
92. Asked what he felt were promising long-term areas
of research, Dr Warner instanced research into the replacement
of cellspossibly but not necessarily stem cell research.
The most important thing the Biology of Aging Program could do
was increase the mobility of over-70s. Dr Haaga suggested that
it was important to persuade people to do what was good for them,
rather than just lecturing them about it.
Fogarty International Center
93. The Committee briefly visited the Fogarty International
Center, the smallest of the NIH institutes, which supported the
NIH through international partnerships and addressed global health
challenges through collaborative research and training programmes.
The Director explained the international work of the NIH.
National Institute on Aging Intramural Research
Program, Baltimore
94. On Wednesday 19 January the Committee visited
the NIA Intramural Research Program in Baltimore. The Committee
met Dr Michele Evans, Deputy Scientific Director of the NIA; Dr
Vilhelm Bohr, Chief of the Laboratory of Molecular Gerontology;
Dr David Schlessinger, Chief of the Laboratory of Genetics; Dr
Donald Ingram, Acting Chief of the Laboratory of Experimental
Gerontology; Dr Linda Fried, Director of the Division of Geriatric
Medicine and Gerontology at Johns Hopkins Hospital (who is also
a member of the National Advisory Council on Aging); and Dr Mark
Mattson, Chief of the Laboratory of Neurosciences.
95. The Committee was welcomed by Dr Michele Evans.
96. Dr Will Bohr explained that he was also a professor
at Aarhus University and had worked in Europe, so that he was
in a good position to compare funding in the US and in Europe.
Only 10% of the NIA research budget funded intramural research;
the remaining 90% funded extramural research. This could be and
was used to fund research in other countries. This was in contrast
to EU funding, which could be used only to fund research in the
Member States.
97. Dr Bohr was strongly of the view that a research
centre was necessary. A virtual centre was inadequate. A real
centre with walls had the advantages of being able to attract
top-quality research scientists by paying them competitive salaries.
It provided a training ground for new researchers, and created
a good working environment.
98. Molecular biology of ageing was now top-tier
science. The goal was to add life to years, rather than years
to life. The laboratory did not attempt to cover the whole subject,
but focused on those areas at the cutting edge at molecular level.
He thought that the NIA attempted to cover too much ground, and
suggested that if the UK set up a national research institute,
it should not have too wide a remit, but should concentrate on
a small number of matters specific to ageing. The advantage of
an intramural programme was that it had the resources for high-cost
research like the Baltimore longitudinal study. In the past, the
programme had dealt with high-risk research which could not be
done privately. Now however the NIA had to compete with other
researchers.
99. Dr Bohr saw environmental effects as being at
least as important as genetics on ageing. However, there were
some rare genetic diseases that allowed scientists to understand
the ageing process, especially Werner's syndrome, which led to
premature ageing, and Bloom's syndrome, sufferers of which had
a much higher incidence of cancer. The effects of low-level radiation
were also being studied. His view in general was that some environmental
stress was beneficial, as it conditioned the body.
100. Dr Evans was asked about the relationship between
the intramural and extramural research programmes. She replied
that there was discussion between the two, but that traffic was
mainly one-way. The intramural programme had more latitude to
get people to work on long-term research which did not necessarily
look as if it might have an immediate impact on ageing. An example
was Dr Schlessinger's work on genetics. When the laboratory
was set up 5 years ago, its major impact on ageing could not have
been predicted.
101. The intramural programme obtained resources
without competing for them, and was held accountable mainly through
informal peer review. Its programme was often adjusted in the
light of external evaluation. It was possible to tell researchers
about a change in direction, and easy to recruit any necessary
new researchers; but less easy to dispense with those no longer
necessary.
102. Asked what the critical mass might be for a
similar establishment in the UK, Dr Evans replied that it would
not have to be as large as the NIA. Work could be done with fewer
researchers, but would have to be restricted to fewer topics.
Examples might be 5 years on molecular biology, followed by 5
years on translational work. It was a question of picking out
the key areas scientists would want to work in. The work might
be done in partnership with UK universities. University researchers
had the advantage of being able to contact researchers in pharmaceutical
companies; NIA researchers were not allowed any such contact.
103. Dr David Schlessinger gave an overview of the
work on Genetics. His field of statistical genetics, which lay
between epidemiology and pure genetics, was a relative newcomer
to gerontological research. His work looked at multiple causality,
trying to distinguish the effects of specific genes. The laboratory
was studying the extent to which phenomena previously associated
solely with ageing might have genetic origins. An example was
the menopause. This occurred at about age 50 in most women of
whatever ethnic group. However in the case of 3% it occurred in
the low 30s or early 40s. This had found to be for genetic reasons:
they were born with too few oocytes to enable them to support
a full reproductive life-span. For them the menopause, though
age-related, was determined at birth.
104. The Committee was told that geneticists were
critical of the UK biobank because the level of self-reporting
was too high. Many genetic studies had been carried out in Sardinia.
The founder population had all arrived at about the same time,
and until recently there had been little inter-marriage with other
groups. Studies had taken place in four towns among people who
had themselves, their parents and grandparents all been born there.
105. Dr Donald Ingram explained that the Laboratory
of Experimental gerontology was the newest arrival at the NIA.
Current experiments included animal modelling; attempting to identify
genes with effects on ageing; cognitive enhancements which might
have a direct effect on Alzheimer's; and nutrition and the effect
of calorie restriction. This was monitored by the Aging Intervention
Testing Program (AITP), and there had been requests for access
to it from all over the world.
106. Dr Ingram was critical of advertisements for
dietary supplements and hormone replacement therapies which promoted
their ability to increase longevity. They had no basis in fact.
He felt that regulations were lax in the case of natural ingredients.
107. Dr Linda Fried gave an overview of the work
at Johns Hopkins University. They had fifty researchers working
solely on ageing. This required a different mindset and different
financing to single researchers working on single projects. The
work was focused on frailty, seeking to answer why older people
became frail. This needed a multi-disciplinary team. The university's
work also gave high priority to training, and to translating research
into public health practice.
108. Dr Fried said that if a topic excited colleagues,
they would want to work together to get funding for it. An alternative
was where in the case of a number of related projects the whole
could be said to be greater than the sum of the parts. Usually
a number of related projects were funded from different sources.
It was not essential for all the projects to be funded from the
same source, but it was helpful.
109. There was a need to articulate the benefits
of an ageing population. Society had abandoned the notion that
the elders were the natural governors. This needed to be reconsidered.
The use of the experience and wisdom of older people was good
socially and good for their own health, and it enabled them to
feel they were putting something back into the community. Age
cut-offs were arbitrary, and there should be more flexible ways
of culling older people. We should not throw away the investment
in the education of 20% of the population; the academic world
in particular was not making use of their knowledge and experience.
110. Dr Mark Mattson gave an outline of the work
of the Laboratory of Neurosciences on Alzheimer's, Parkinson's
and Huntingdon's diseases, and of his work on calorie restriction.
It was now clear that overeating had a major impact on cardiovascular
disease, diabetes, stroke and some cancersand possibly
also Alzheimer's and Parkinson's. Experiments with rats and monkeys
had shown that calorie restriction led to increased lifespan.
Rats on restrictive diets lived 30% longer, and showed the effects
of improved memory. However, there were questions over whether
the artificial experimental conditions gave a real control group
against which to compare the effects. A pilot calorie restriction
experiment was underway with human volunteers, though still in
the preliminary stages.
111. Asked about the distinction between ageing and
age-related diseases, Dr Mattson said that it had at one
time been his opinion that there was no such distinction, and
that the two were interrelated, but this was no longer his view.
It was not the case that we would all get Alzheimer's if only
we lived long enough.
Acknowledgement
112. In addition to those to whom we have specifically
referred, the Committee met a large number of other people on
this visit. All were extremely welcoming, helpful and generous
with their time. We thank them all. We especially thank Dr Sprott,
Dr Bohr, Dr Jones and the Embassy staff for their work in arranging
our visit.
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