Touching every life, every day
Annual Review
2005/06
The Medical Research Council (MRC) is the UK’s leading
publicly funded biomedical research organisation.
Our mission is to:
●
Encourage and support high-quality research with the aim
of improving human health.
●
Produce skilled researchers, and to advance and
disseminate knowledge and technology to improve the
quality of life and economic competitiveness in the UK.
●
Promote dialogue with the public about medical research.
IN THIS REVIEW
1 Welcome
2 MRC touching every life
6 You and your genes
Molecular and cellular medicine
10 You and your body
Physiological systems and clinical sciences
14 You and your immunity
Infections and immunity
12 page supplement: Living longer, living healthier
18 You and your mind
Neurosciences and mental health
22 You and your lifestyle
Health services and public health
26 You and your treatment
MRC Technology
28 You and your life
Conclusion
MRC Annual Review 2005/06
1
Welcome
Our 2005/06 Annual Review shows how every day
the achievements of MRC scientists are making a real
difference to the lives of people of all ages everywhere.
This year our researchers once again made pioneering discoveries that will
benefit millions of people, both in the UK and throughout the world.
At the MRC National Institute for Medical Research, the development of a
mouse model of Down syndrome, for example, provides us for the first time
with an experimental tool that could revolutionise treatment of a disability that
affects one in 1,000 babies.
The MRC Cancer Cell Unit’s work on developing a new diagnostic test for
pre-cancer of the oesophagus is an example of high-quality translational
research – taking laboratory findings and turning them into new healthcare
interventions that will benefit people worldwide.
And a study by scientists working at University College London, which showed
that adults with autistic spectrum disorders don’t recognise people’s faces in the
same way as other people, marks a major breakthrough in our understanding
of this condition.
Meanwhile, at the MRC unit in The Gambia, the introduction of a vaccine
against Haemophilus influenzae type B has wiped out a deadly form of
meningitis that infects three million children – mainly African – each year.
To make sure that MRC research continues to improve people’s lives, we have
been building up our capacity for clinical research and have reinforced our
commitment to experimental medicine, which brings together laboratory and
patient-based research. To this end, we are working – with the Wellcome
Trust, the Wolfson Foundation, the English and Scottish Health Departments,
the British Heart Foundation and Cancer Research UK – to build new clinical
research infrastructure with state-of-the-art equipment and other sophisticated
diagnostic tools.
Undoubtedly the biggest challenge to human health this year was avian (bird)
flu, a disease with the potential for global impact. We have been at the
forefront of efforts to meet the challenge of a possible pandemic, leading a
delegation to South East Asia to look at surveillance facilities and to discuss
future scientific collaboration. We have set aside an additional £10 million for
flu research and have already awarded the first £4 million to ensure solutions
are developed as quickly as possible.
These are all examples of how our commitment to the best quality research
creates tangible results for people all over the world. The Government’s
recent proposal to create a single fund of more than £1 billion for health
research offers the potential for even closer working collaboration in medical
research across the public sector. We very much welcome this new initiative
and are optimistic that it will strengthen further the UK’s outstanding record
in medical research.
Professor Colin Blakemore, MRC Chief Executive
2
Touching every life, every day
Touching every life
MRC-funded scientists have made far-reaching
contributions across the whole spectrum of medical
research this year.
Many discoveries that lead to new diagnostics and treatments start with investigating
the action of the body’s 30,000 or so genes and the 250,000 odd proteins that
regulate our cells’ behaviour. Hundreds of MRC scientists are trying to identify and
determine the structure and function of genes and proteins – both when they are
working properly and when they go wrong. In “You and your genes” on pages 6–9
you can read about how their discoveries are providing a better understanding of
pathways that lead to cancer, which could ultimately result in individually tailored
treatments designed to halt or control it.
Other MRC scientists are studying how organs and tissues work and how factors
such as diet, lifestyle and environment, even before birth, can affect their functioning.
This provides valuable information that could help in the development of medical
interventions for major health problems such as obesity, diabetes, high blood
pressure, heart disease, stroke and osteoporosis. You can read about their work in
“You and your body” on pages 10 –13.
Our body’s ability to identify and destroy foreign invaders – be they viruses, bacteria,
parasites or other infectious agents – is one of the bedrocks of good health. The
increasing globalisation of infectious disease, however, poses a serious threat.
Uppermost in everyone’s mind is bird flu, which is why scientists at the World
Influenza Centre (based at the MRC National Institute for Medical Research) are
working around the clock to detect and combat any flu virus with the potential to
cause a human pandemic. Turn to “You and your immunity” on pages 14 –17 to learn
about their progress, as well as other advances that could lead to new medicines,
vaccines and ways of preventing infectious disease.
“Developments in science
can be found in every aspect
of our daily lives.”
Alan Johnson, Secretary of State for the
Department of Trade and Industry
MRC Annual Review 2005/06
“Infectious diseases are not
only a health issue; they
have become a social
problem with tremendous
consequences for the
wellbeing of the individual
and the world we live in.”
World Health Organization
3
Despite the progress we have made over the last 50 years or so, the workings of the
human brain and mind remain a mystery. In “You and your mind” on pages 18 –21
you can see how MRC scientists are using research techniques ranging from cuttingedge brain imaging tools to clinical studies involving people of all ages to gain a better
understanding of how the brain works. Their findings are helping advance
understanding of common mental disorders such as schizophrenia, depression and
anxiety, substance abuse, neurodegenerative diseases such as Alzheimer’s and
Parkinson’s disease, as well as conditions affecting children such as attention deficit
hyperactivity disorder (ADHD).
Public health research, which looks at the impact on health of socio-economic factors
such as education, work, housing and income, is one of our key priority areas,
reflecting its increasing national importance. Our Public Health Research Overview
Group was set up to help us build on past successes and aid the development of new
strategies to advance research in this important area. You can read about the group’s
work in “You and your lifestyle” on pages 22–25.
We want to ensure that the discoveries of MRC scientists are turned into new
treatments to benefit human health as quickly as possible. Our affiliate company MRC
Technology (MRCT) works with industry to achieve this. Turn to “You and your
treatment” on page 26 to see the progress MRCT has made this year.
4
Touching every life, every day
Global impact
Lab-based research has always been a major MRC strength and the results of our
scientists’ discoveries are responsible for many of the healthcare improvements we
are now witnessing worldwide. These include, to name but two, magnetic resonance
imaging (MRI), the most powerful and sensitive diagnostic technology currently
available, and monoclonal antibodies, which now form the basis of a third of all new
drug treatments for a variety of major diseases.
“We are rightly proud of
the past achievements of
the MRC and we want to
build on those.”
Lord Sainsbury of Turville,
Parliamentary Under-Secretary
of State, Department of Trade
and Industry
WHAT DOES IT MEAN?
To ensure our work continues to have a global impact on health it is vital that
discoveries made in the laboratory are turned into new methods of prevention,
diagnosis and treatment quickly. This so-called translational research demands
close teamwork between scientists at different points of the research spectrum.
The university-based research centres we have established this year to look at
asthma, child health, brain disease, and diet and cancer are four new examples of
how we are tackling major healthcare challenges through collaboration and
multidisciplinary working.
We have also begun to recruit the first 3,000 volunteers for the UK Biobank, which
has been set up to track the genetic and lifestyle factors influencing the health of
500,000 people aged 40–69 over the next three decades.
The project, which we are funding with the Wellcome Trust, the Department of
Health and the Scottish Executive, will have a major impact on our understanding of
some of the world’s biggest killers, including heart disease, diabetes and cancer.
Medical interventions
Drugs, surgical procedures, devices,
behavioural treatments and healthcare
processes used to change the course of
a disease for the better.
Monoclonal antibodies
Laboratory-produced antibodies that can
be engineered to home in on specific
protein molecules.
Neurodegenerative diseases
Disorders caused by the deterioration
and death of certain nerve cells in the
brain (neurones).
Public health
The health of the whole population as
opposed to the health of individuals.
MRC Annual Review 2005/06
INFANCY
Professor Faraneh Vargha-Khadem’s
pioneering images of children’s
brains (page 21) will help increase
awareness of the long-term
outcome of medical treatments on
memory, learning and self-esteem.
LATE OLD AGE
CHILDHOOD
Led by Professor Nancy Rothwell,
Professor Anita Thapar’s discovery
of how genes and birthweight
interact in young children showing
signs of antisocial behaviour
(page 20) could be of huge
social significance.
the first safety trial of IL-IRA
(page 13), a drug that dramatically
reduces brain injury after stroke,
could benefit hundreds of
thousands of older people who
have strokes worldwide.
OLD AGE
Professor Simon Thompson’s finding
that ultrasound screening can halt
deaths from abdominal aortic
aneurysm (page 12) will save the
lives of many men over 65.
Lifelines
Highlighting how our
research is touching
people at every stage of
life all over the world
YOUTH
Professor Sarah Rowland-Jones’s
study of a remarkable group of
orphaned Kenyan teenagers who
have resisted HIV (page 15) could
lead to vaccines and new forms of
treatment for HIV/AIDS.
MIDDLE AGE
ADULTHOOD
Professor Roger Cox’s discovery of
a gene involved in insulin secretion
(page 11) holds great promise for
better diagnosis and treatment of
type 2 diabetes.
Dr Nicholas Coleman’s discovery of
a key step in the development of
cervical cancer (page 6) could help
save thousands of women from
having unnecessary treatment.
5
6
Molecular and cellular medicine
You and your genes
Your body is made up of billions of tiny building
blocks or cells, inside each of which are genes that
guide your development and physical appearance.
But genes – and the proteins they
Nearly 7,500 people in the UK and
encode – are about much more than the
462,000 people worldwide develop
Refining treatment for
cervical cancer
colour of your eyes or the texture of
cancer of the oesophagus (gullet) each
The cervical smear, which detects pre-
your hair. Cancers, and indeed most
year. The disease has a poor survival
cancerous changes in the cells of the neck
diseases, are the result of changes in one
rate – around eight per cent in the UK.
of the womb (cervix), has led to a
or more cellular proteins. MRC
But if diagnosed and treated early this
dramatic drop in cervical cancer. Not all
scientists are engaged in a huge number
rises to 80 per cent. Dr Nicholas
women who have an abnormal smear,
of studies designed to find out more
Coleman and Dr Rebecca Fitzgerald
however, will develop cancer. So what
about how these work and what
of the MRC Cancer Cell Unit,
determines who will and who won’t?
happens when they go wrong.
Cambridge, have now developed a
promising new test for detecting early
Cancer counts
All of us become more susceptible
to cancer as we get older. MRC
discoveries are leading to the
development of new approaches to
diagnosis and more effective treatments
with fewer side effects.
Innovations in diagnosis
Early diagnosis of cancer offers the best
hope of successful treatment and
pioneering discoveries in the basic
biology of cancer cells are now leading
to new screening methods that could
result in earlier detection.
or pre-cancerous cells.
Cervical cancer, which mainly affects
young women, is caused by the human
papilloma virus (HPV). For cancer to
Current tests for oesophageal cancer
occur, Dr Nicholas Coleman discovered
are expensive and highly labour-intensive
that a part of the genetic material of HPV
because they involve the analysis of cell
– its viral DNA – must combine with the
changes through a microscope.
DNA of the cervical cells. Dr Coleman has
The new patented test, which involves
now found that the remaining part of the
swallowing a spongy capsule with a
viral DNA actually prevents cells from
string attached, could easily be
turning cancerous. It is only when cells rid
automated, making it possible to screen
themselves of this in an effort to protect
large numbers of people here and
themselves from damage that they become
abroad. It identifies tell-tale marker
cancerous.
molecules called minichromosome
maintenance proteins, in scrapings of
cells taken from the oesophagus. The
research was funded jointly by the MRC
and Cancer Research UK.
The finding could form the basis of followon tests to help decide which women
infected with HPV should receive further
treatment to prevent cervical cancer.
Knowledge of how cervical
cancer develops could lead to
tests that could help women
to avoid unnecessary surgery.
MRC Annual Review 2005/06
Diagnosing breast cancer
in women at high risk
the development of ‘targeted’ treatments
Around one in a hundred women carry
path to cancer and so halt the disease in
the gene mutations BRCA1 and BRCA2 that
its tracks.
– drugs designed to block key steps on the
increase their risk of breast cancer by
around 70 per cent.
WHAT DOES IT MEAN?
These women often have regular screening
DNA (deoxyribonucleic acid)
Molecule that carries genetic
information in our cells.
to help detect early signs of breast cancer.
But mammograms (breast X-rays) do not
always identify breast tumours, especially
in women under 50, because their breast
tissue is so dense. Professor Martin Leach
Steps on the road to cancer
and colleagues at the Institute of Cancer
All cancers start with a fault in a cell’s
Research have now discovered that
genes. If a gene that regulates cell growth
magnetic resonance imaging (MRI) is twice
is damaged it becomes permanently
as sensitive as mammography alone in this
altered, as do the cells copied from it
group of women. It detected 77 per cent
when it divides and new cells grow.
of tumours, whereas mammograms found
Because the cells can no longer keep their
only 40 per cent. When researchers gave
growth in check, cancer occurs.
women both tests, they found 94 per cent
of the tumours. The research, part of the
multi-centre Magnetic Resonance Imaging
Breast Screening Study, was carried out in
partnership with the Royal Marsden NHS
Foundation Trust.
7
It takes more than one genetic fault for a
cell to turn cancerous, but as we age we
accumulate an increasing number of these
faults. Our scientists are part of a global
DNA replication
The process by which the DNA double
helix unwinds and makes a copy of itself
as cells divide.
Free radicals
Reactive molecules that can cause
the tissue damage linked with many
diseases, including cancer, and
with ageing.
Genes
Units of hereditary information that
contain instructions for the production
of proteins.
Mutation
A change or alteration in a gene that
stops it working in the normal way.
effort to find out more about different
pathways along which such genetic
mistakes can occur. In time this could aid
Cancer is mainly a disease of
later life, with 64% of cases
diagnosed in people aged
65 and older.
8
Molecular and cellular medicine
Rare results
In another study Professor Ashok
DNA damage is a first step in cancer
Venkitaraman of the MRC Cancer Cell
development, so understanding how
Unit, Cambridge, discovered that a protein
cells repair DNA can help throw light
that is defective in families with another
on how cancer occurs as well as why
rare inherited disease, Rothmund-
some cancers become resistant to
Thomson syndrome, is needed to trigger
treatment. Certain rare inherited diseases
the cell copying process. Sufferers of
increase the risk of cancer because of
this syndrome are at particularly high
faults in genes involved in DNA repair.
risk of bone cancers.
Identifying which genes are involved can
provide clues to how non-inherited forms
Red alert
Have a heart
of cancer develop.
The genetic damage that leads to cancer
Stem cell therapy holds enormous promise
can be caused by a number of
for treating heart failure and recent
environmental factors such as cigarette
research has shown that adult stem cells
smoke, viruses, sunlight or diet. Dr Sheila
might help repair a damaged heart. The
Bingham of the MRC Dunn Nutrition Unit,
advantage of adult stem cells is that they
Cambridge, previously discovered that a
can be obtained from patients themselves
diet high in red meat increases the risk
rather than being harvested from embryos
of bowel cancer. Following on from this
so the patient’s immune system is less
Dr Bingham’s team examined cells from
likely to reject them. But the future
volunteers eating different types of food.
success of such therapy depends on
They discovered that a diet high in red
resolving key issues such as how to select
meat raises levels of compounds in the
the best cells, how to inject them into the
large bowel that can alter DNA, making it
heart and how to make sure they behave
more susceptible to the changes leading to
as they should.
Dr Kevin Hiom and Dr KJ Patel of the
MRC Laboratory of Molecular Biology,
Cambridge, have discovered two genes
that seem to be responsible for DNA
repair in one such disease called Fanconi
anaemia.
bowel cancer. This is the first definite link
between eating red meat and the early
stages of bowel cancer.
A group of scientists led by Dr Ken Suzuki
of the Harefield Heart Science Centre,
Imperial College London, has been using
sophisticated techniques to study how
grafted adult stem cells survive, grow,
Studying rare genetic diseases
that increase the risk of cancer
can help scientists learn more
about the origin and development
of non-inherited cancers.
MRC Annual Review 2005/06
change into specialised heart cells, and
muscle cells but these cells, in turn, were
communicate with patients’ own heart
able to generate new muscle tissue. The
Currying favour
cells. They are also using tissue and gene
finding is a step towards potential new
engineering to try and improve the ability
treatments for muscle-wasting diseases
of donor stem cells to repair the heart as
such as muscular dystrophy.
How do antioxidants found in food
work? When scientists examined their
effects on blood cells in the test tube
they found that the compounds trigger
cells to generate their own antioxidants.
Curcumin (found in the curry spice
turmeric), epigallocetechin (found in tea)
and alpha lipoic acid (found in meat
and vegetables) were especially effective.
Surprisingly, vitamins C and E, which
are well-known as antioxidants, did not
work in this way. The research, led by
Dr Maria O’Connell at MRC Human
Nutrition Research, Cambridge, could
ultimately lead to supplements or
‘functional foods’ to help protect
against disease.
well as developing new ways to deliver
stem cells to the heart.
First ever Down mouse
One in 1,000 children is born with Down
Muscle power
syndrome, which causes learning and
Scientists have long suspected that stem
memory disabilities and congenital heart
cell-like satellite cells, which adhere to
defects. People with Down syndrome have
mature muscle fibres, are responsible for
three copies of chromosome 21 instead
building new muscle tissue. However it has
of the normal two. Now scientists have
never been confirmed. Professor Terence
developed a mouse model with these
Partridge of the MRC Clinical Sciences
features by introducing about 90 per cent
Centre, London, has now conclusively
of the 250 genes on human chromosome
proved that this is indeed the case by
21 into its cells. Previously it was only
grafting some mouse satellite cells into
possible to place small fragments of
degenerating muscle. Not only did the
human chromosomes into mouse cells.
cells generate many thousands more new
The research, co-funded by the Wellcome
Trust, was led by Dr Victor Tybulewicz
of the MRC National Institute for Medical
Research and Professor Elizabeth Fisher
of the Institute of Neurology, University
College London. It is a major breakthrough
which will accelerate the development of
treatments for Down syndrome and other
chromosomal disorders.
Scientists have identified the
first definite link between
eating red meat and the
genetic damage that can lead
to bowel cancer.
Mammoth discoveries
Some 10,000 years after woolly
mammoths walked the earth a sensitive
new technique has enabled researchers
to crack their genetic code. The
technique – single molecule analysis –
was developed by Dr Paul Dear at the
MRC Laboratory of Molecular Biology.
It has allowed scientists at the Max
Planck Institute for Evolutionary
Anthropology in Leipzig to read the
complete genetic alphabet of DNA
extracted from the mitochondria – the
‘power plants’ of cells – of a fragment
of mammoth bone. The tools used could
be put to widespread use in analysing
other ancient DNA samples.
9
10
Physiological systems and clinical sciences
You and your body
Your environment, even in the womb and during
childhood, can cause biological changes in your
body that may affect your future health and
wellbeing.
MRC scientists are examining the links
other tissue in the body? Dr Ulf Ekelund
between our external environment and
of the MRC Epidemiology Unit in
what goes on inside our bodies in an
Cambridge found that babies who gained
attempt to find out more about
weight rapidly between birth and six
common diseases such as diabetes,
months and between the ages of three
osteoporosis and heart disease.
and six were fatter and taller when they
were 17 years of age.
Weighty matters
Low birth weight babies who gain weight
rapidly in their early months are more
likely to become obese and develop
diabetes and heart disease in later life.
But is there a particular point at which
this ‘catch-up’ weight gain tips the scales
in favour of later obesity? And what
effects does it have on the relative
percentage of fat, muscle, bone, and
In another study researchers examined
the medical records of 8,760 Finns.
Those who had heart attacks in middle
age tended to have been small at birth,
thin at two years of age and to have put
on weight rapidly between the ages of
two and 11. This growth pattern was
Obesity: all in the genes?
linked to insulin resistance, when the
Early diet and lifestyle aren’t the only
body produces but cannot use insulin,
determinants of obesity. Professor Stephen
which is an early stage in the
O’Rahilly at the University of Cambridge
development of type 2 diabetes. The
has spent over a decade looking at the
research, which was led by Dr Clive
part played by genes. His latest research
Osmond and Professor David Barker of
has discovered that children with early-
the MRC Epidemiology Resource
onset obesity are 10 times more likely
Centre, Southampton, lends weight to
to possess a mutation in the gene
the idea that being undernourished in
responsible for a pituitary gland hormone
the womb causes permanent
called beta-melanocyte stimulating
physiological changes that increase the
hormone (beta-MSH). A related hormone,
risk of heart disease in later life.
alpha-MSH, is already known to control
appetite and satiation, or the feeling of
being full. Until now, however, it was not
known that beta-MSH plays a similar role
in the body’s weight control system.
The best start in life. A mother’s
diet during pregnancy can affect
her child’s health and wellbeing
for the rest of his or her life.
MRC Annual Review 2005/06
11
Insulin control clue
Building strong bones
Calcium counts
Every time you eat insulin is released. This
Research led by Professor Cyrus Cooper
During the second half of pregnancy over
vital hormone, secreted by your pancreas,
from the MRC Epidemiology Resource
300mg of calcium a day crosses the
encourages your tissues to absorb glucose
Centre in Southampton suggests that
placenta to be added to the unborn baby’s
from the bloodstream after eating. A lack
vitamin D supplementation during
bones. In The Gambia women only
of insulin or an inability to use it properly
pregnancy could help improve children’s
consume around this amount themselves
causes diabetes. Scientists have identified a
peak bone mass and reduce the risk of
per day, so MRC researchers wanted to
protein called nicotinamide nucleotide
osteoporosis later in life.
find out whether giving Gambian mothers
transhydrogenase (Nnt) that could throw
light on the origins of defects in insulin
secretion and diabetes. Although Nnt was
previously known to deactivate free
The scientists found that children whose
mothers had higher levels of vitamin D
during pregnancy had stronger bones
a high-dose calcium supplement had any
effect on their bones or their babies’
bones compared to those given a placebo.
when they reached age nine. Vitamin D,
Remarkably they found that calcium
which is found in foods such as oily fish
supplementation of 1500mg a day had no
and made in the skin after exposure to
significant effect on babies’ birth weight,
sunlight, plays a major role in helping the
growth or the calcium content of their
The scientists found that mice lacking Nnt
body to absorb the calcium needed for
bones. This suggests that changes in the
displayed early signs of type 2 diabetes.
healthy bones.
mother’s body enable unborn babies
radicals, harmful molecules that damage
cells, it was not known to play a role in
insulin secretion.
They surmised that this was because a lack
of Nnt resulted in increased free radical
damage to the insulin-producing cells of
the pancreas. The discovery could
eventually lead to the development of new
treatments for type 2 diabetes. The
research was led by Professor Roger Cox
of the MRC Mammalian Genetics Unit,
Harwell, and Professor Frances Ashcroft
of Oxford University.
New insights into genetic control
of insulin secretion could
eventually lead to new
treatments for type 2 diabetes.
12
Physiological systems and clinical sciences
to take what calcium they need –
WHAT DOES IT MEAN?
What a trial
irrespective of their mothers’ intake.
New treatments are not always better
Aorta
The body’s largest artery, which
carries blood from the heart to all
your vital organs.
The team are now examining what
than tried and tested ones, as the results
effect supplementation had on the
of a randomised controlled clinical trial
mothers’ bones.
carried out by Professor Tony Green of
Randomised controlled trials
Studies in which equal numbers of
patients are randomly allocated either a
new therapy or a dummy treatment
(placebo) and the results compared.
The research is one of a number of
Type 2 diabetes
The most common form of diabetes,
which usually appears in mid to later
life. Patients either do not make enough
insulin or their bodies are unable to
use it properly.
studies led by Dr Ann Prentice of MRC
Human Nutrition Research, Cambridge,
that are attempting to define the calcium
the University of Cambridge and
Addenbrooke’s Hospital show. The trial
compared a new drug, anagrelide, with an
older drug, hydroxyurea, in patients with
essential thrombocythemia, a condition
needs of mothers and babies.
that increases the risk of blood clots,
The team is also investigating the effects
heart attacks and strokes. Surprisingly,
of calcium intake in pregnancy on mothers’
those prescribed the older treatment
and children’s blood pressure. Extra
developed fewer blood clots and
calcium may be important to protect
experienced fewer side effects, a finding
against pre-eclampsia, the potentially fatal
that could save taxpayers up to
high blood pressure disease of pregnancy.
£22 million every year.
It’s also thought that low calcium intake in
pregnant women might predispose
Saving lives worldwide
offspring to high blood pressure.
The incidence of abdominal aortic
aneurysm (AAA), progressive weakening
of the wall of the body’s main artery, is on
the increase globally, partly as a result of
the world’s increasingly ageing population.
More than one in 50 UK men aged over
65 die of an AAA each year. Many of these
deaths could be prevented by early
diagnosis and preventive surgery. The
problem is that AAA is often symptomless.
Trials of a new compound
designed to halt inflammation in
the brain could lead to better
treatment for stroke.
MRC Annual Review 2005/06
The MASS trial, which the MRC has
Stroke hope
funded for 10 years, has shown that a
Each year 100,000 people in England
and Wales have their first stroke and
30,000 go on to have further strokes.
Nine out of 10 cases occur in people
aged over 55. At the moment there is
no cure and most patients are left with
some degree of disability. But research
led by Professor Nancy Rothwell of the
University of Manchester, could change
this. The study established the safety
of a naturally occurring protein, IL-1RA,
that blocks the action of the
inflammatory chemicals that trigger
brain damage in stroke.
painless ultrasound scan can detect AAA
so that preventive action can be taken.
As a result, the UK’s National Screening
Committee has now recommended that
a national AAA screening programme
should be set up. The trial was co-led by
Professor Simon Thompson of the MRC
Biostatistics Unit, Cambridge.
Genes and chips
A pioneering new method that combines
classic gene-hunting techniques with
microchip technology is allowing scientists
to study whether individual genes are
switched on in a cell at a particular time.
The method, developed by Professor Tim
Aitman’s team at the MRC Clinical
Sciences Centre, London, has already
enabled scientists to identify key genes
involved in high blood pressure and insulin
resistance, both risk factors for heart
ABCA1 had previously been implicated in
the risk of heart disease. The finding, made
This is the first clinical trial of the
compound in patients who have had
a sudden stroke.
by Professor Chris Higgins and Dr John
McVey, throws new light on the way the
body controls blood clotting and breaks
down blood fats. This is a good example of
how clinical observation can feed into
basic research to increase knowledge of
how disease develops.
disease. Many labs across the world are
In a study at the MRC Protein
now using the method to advance
Phosphorylation Unit, Dundee, Professor
understanding of other common diseases.
Dario Alessi and his team has worked
out the action of a gene that is mutated
From patients to lab
and back
in patients with a rare inherited condition
Other scientists at the centre found that
WNKI, contains the instructions for making
ABCA1, a protein that carries fats around
an enzyme that is involved in controlling
the blood stream, was altered in a patient
the uptake of salt into organs such as
with a rare inherited bleeding disorder.
the kidneys.
that causes high blood pressure. The gene,
Backstop
An intensive exercise programme
combined with cognitive behavioural
therapy is as effective at relieving back
pain as spinal surgery. These are the
findings of the MRC Spine Stabilisation
Trial led by Mr Jeremy Fairbank,
Consultant Orthopaedic Surgeon at the
Nuffield Orthopaedic Centre and the
John Radcliffe Hospital, Oxford.
During the trial patients underwent a
supervised programme of individually
tailored exercises. These included
stretching and flexibility exercises for
the spine together with general muscle
strengthening, spine stabilisation
exercises and aerobic activities such as
walking on a treadmill, step-ups, cycling
and rowing.
13
14
Infections and immunity
You and your
immunity
Your immune system uses a highly sophisticated
series of defence mechanisms to protect your body
against infections.
MRC scientists are working hard to
Sir John Skehel and a team at the World
As yet, H5N1 cannot pass easily from
understand exactly how infectious
Health Organization (WHO) World
person to person. The fear is, however,
agents invade cells and how the immune
Influenza Centre, which is based at the
that its genes might mutate and gain this
system responds, taking us a step nearer
MRC National Institute for Medical
ability, or that its genes could mix with
to discovering new ways to defeat
Research, London, have been analysing
human flu virus genes to create a new
threats to health such as bird flu, AIDS,
the genetic make-up of viruses
strain of flu that could spread from
malaria, variant CJD and the hospital
recovered from people with bird flu.
person to person.
Their analysis of one of two fatal cases
Scientists led by Dr Ten Feizi of Imperial
in Turkey showed an alteration in a
College London have developed new
protein previously observed in human
technology to test for sugar-type
cases in Hong Kong and Vietnam. The
molecules found on the surface of flu
viruses were also found to be sensitive
viruses. These provide a kind of molecular
to the antiviral drug Tamiflu™ and to an
‘footprint’ that could potentially be used
older drug called amantadine, suggesting
to identify new strains of H5N1. In the
that a cocktail of antivirals might be an
event of a flu pandemic this knowledge
effective treatment.
could be vital not just for people in the
superbug, MRSA.
Flu progress
The H5N1 strain of influenza, otherwise
known as bird flu, has been in and out of
the headlines this year amid predictions
that it may be the first pandemic of the
21st century. MRC research is playing a
major role in preparations to meet this
threat if and when it arises.
UK but also throughout the world.
MRC researchers are
leading efforts to combat
a possible flu pandemic
should the H5NI virus find
a way to jump easily from
birds to people.
MRC Annual Review 2005/06
15
Dr Áine McKnight of University College
London that HIV-2 is lazier. More
WHAT DOES IT MEAN?
specifically, although HIV-2 is able
CD4 cells/T helper cells
White blood cells that helps to
orchestrate the immune response by
signalling to other immune cells to do
their jobs. In HIV their number declines
over time leaving the body open to
opportunistic infections.
to get into the immune cells and infect
the body just as efficiently as HIV1, it
then lies low, with the result that the
person does not develop full-blown AIDS
for 20 years or more.
Monkey business
In a joint study with scientists at Harvard
Focus on AIDS
One of the many puzzles surrounding the
HIV virus is why some people succumb to
infection rapidly and why some resist it for
many years. Without treatment, most
HIV-positive children die by their third
birthday. But a remarkable group of HIVinfected Kenyan orphans have survived
into their teens with no signs of HIVrelated disease or suppression of their
immune system. Research led by Professor
Sarah Rowland-Jones of the MRC Human
Immunology Unit, Oxford, reveals that the
secret of their resistance seems to lie in
the vigorous response of their ‘CD4’
immune cells. Further studies of immune
mechanisms in people who resist the virus
could provide information that could aid
the design of an HIV vaccine for use in
developing countries.
University, USA, Sir John Skehel’s team at
the MRC National Institute for Medical
Research has established the molecular
structure of simian immunodeficiency virus
(SIV), the AIDS-like virus that infects
monkeys. Studies such as these can help
scientists learn more about how cells
respond to HIV infection, which could
aid vaccine design.
Vaccine hope
Many of the millions of people with HIV
worldwide do not have access to
treatment, which is why the best hope of
Gene sequence
The precise order in which the ‘letters’
of the DNA alphabet are arranged to
form a ‘sentence’ for a particular gene.
Emerging infections
Infectious diseases that are either new
to humans, new to a geographical area
and/or no longer controllable by
previously effective drugs.
Pandemic
A worldwide outbreak of an
infectious disease.
Prion (Proteinaceous infectious
particle) A unique type of infectious
agent made only of protein.
Species barrier
The inability of infectious agents to cross
easily from one species to another.
controlling the AIDS epidemic may lie in a
preventive vaccine. Scientists led by
taking anti-retroviral drugs, to see whether
Professor Andrew McMichael and
it boosts their immune system sufficiently
Dr Tomás Hanke, of the MRC Human
to enable them to stop taking medication.
Immunology Unit, Oxford, have developed
The research is supported by the MRC
a potential vaccine tailor-made for a strain
and the International AIDS Vaccine
of HIV-1 found in central and east Africa.
Initiative (IAVI).
HIV-1 is responsible for the current
This has now been tested in several
pandemic of AIDS. HIV2, a second type
hundreds of healthy volunteers and HIV
Antiviral drugs have transformed
of the virus found mainly in West Africa,
patients and found to be safe and to
HIV/AIDS from a death sentence into a
seems to weaken the immune system
trigger an immune response against HIV-1
long-term but manageable illness, at least
more slowly. The question is why?
in most of those vaccinated. The next step
in developed countries. But worryingly,
A clue may lie in the discovery made by
is to test the vaccine in infected patients
MRC research suggests that people in the
16
Infections and immunity
Take my breath away
More than 300 million people
worldwide have asthma and the number
is rising. Professor Stephen Holgate at
Southampton General Hospital has
found that levels of a powerful immune
system chemical, tumour necrosis factor
(TNF) alpha, are present in high levels
in the bronchial tubes and lungs of
people with severe asthma. When 15
patients were treated with etanercept, a
TNF alpha-blocking drug, they
experienced a significant improvement
in symptoms. This research presents a
potential new approach to treating
severe treatment-resistant asthma.
Targeting superbugs
The hospital superbug, methicillin
resistant staphylococcus aureus (MRSA)
particularly affects the elderly and those
with lowered immunity. Current
treatments are toxic, expensive and not
always effective. Professor Paul Williams
of Nottingham University has found that
signalling molecules produced by
another bacterium block communication,
toxin production and the growth of
staphyloccocus.
UK are now becoming infected with HIV
one such protein, apical membrane antigen
strains that are already drug-resistant.
(AMA1). The team also pinpointed a small
Of 2,357 HIV-positive individuals studied
subregion of the protein that could
by Dr David Dunn and team at the MRC
potentially be targeted by antimalarial
Clinical Trials Unit, London, 335 (14 per
drugs. The finding helps increase
cent) had some level of resistance to at
understanding of how AMA1, which is
least one drug before they began therapy.
currently in trials as a vaccine, works.
Parasite attack
Four out of 10 people in the world live
in malarial areas and malaria claims more
than three million lives each year. There
is widespread resistance to most antimalarial drugs and, as yet, no vaccine.
Dr Michael Blackman of the MRC National
When the malaria parasite invades red
blood cells a number of important
proteins – including AMA1 – need to
be shed from its surface. In another
study Dr Blackman has identified an
enzyme, PfSUB2, that enables this
shedding to occur.
Institute for Medical Research has spent
According to the findings of other
the past 15 years trying to find out how
researchers from the same unit, the
proteins on the surface of malaria
process of cell invasion in malaria is
parasites help them invade red blood cells.
driven by a minute molecular ‘motor’,
Recently, in collaboration with scientists
which uses molecules similar to those
from the Netherlands and France, he has
that power our muscles. The research,
succeeded in establishing the structure of
which was led by Dr Tony Holder,
provides further insights into how malaria
parasites get into the bloodstream.
In another study Dr Steven Gamblin of
the MRC National Institute for Medical
Research, London, discovered the
structure of metallo-beta-lactamases,
a ‘superfamily’ of enzymes involved in
the development of antibiotic resistance.
These findings are aiding the ongoing
search for new antibiotics to stand up
to superbugs.
MRC research could lead to new
drugs and vaccines for malaria,
which affects between 270 million
to 480 million people a year – 90%
of whom live in Africa.
MRC Annual Review 2005/06
17
The life of prions
Creutzfeldt Jacob Disease (CJD) and
variant (v)CJD, the human versions of
‘mad cow disease’, are caused by
molecules called prions. The hallmark of
these diseases is that normal harmless
prion proteins (PrPc) change shape,
transforming them into dangerous prion
proteins (PrPSc). Two studies from the
MRC Prion Unit, London, are helping
increase our understanding of how this
happens and how it may be prevented.
In the first study Dr Sarah Tabrizi
developed a model that suggests that
clumps of abnormal prion protein inside
brain cells trigger them to commit suicide.
Thanks to a vaccine pioneered by MRC scientists Hib meningitis has been wiped
out among Gambian children
In the second investigation, Dr Azadeh
Kahlili-Shirazi created monoclonal
of destroying prions on surgical
Cambridge, has recently discovered that
antibodies capable of distinguishing
instruments and medical equipment. The
the inner core of the hepatitis B virus
between PrPc and PrPSc. When injected
discovery could help reduce the risk of
(HBV) changes shape as it replicates,
into infected mice the antibodies
accidental transmission of vCJD to other
opening a pocket on the virus molecule.
protected against disease progression.
patients. The team is now collaborating
This could provide a potential target for
with the chemical company DuPont to
drugs to treat hepatitis B, which is a major
All washed up
produce a commercial product and has
cause of cirrhosis, liver failure and liver
Prion proteins are resistant to
submitted details to the Government’s
cancer throughout the world.
conventional sterilisation because they
health watchdog, the National Institute for
cling to steel, plastic and rubber. In a third
Health and Clinical Excellence (NICE).
Meningitis success
A deadly form of meningitis has been
study from the unit, Dr Jonathan
Wadsworth has identified prion proteins
Pockets of resistance
wiped out in The Gambia as a result of the
in the guts of patients with vCJD at levels
In order to design antiviral drugs scientists
introduction of a vaccine pioneered by
of up to one per cent of that found in
must first identify target viral proteins or
MRC scientists. According to Dr Richard
their brains. This suggests that the disease
parts of proteins that could potentially be
Adegbola, Head of the Bacterial Diseases
could be transmitted through
disabled at different points in the virus’s
Research Programme at the MRC
contaminated surgical and diagnostic
life cycle. Once a target has been
Laboratories in The Gambia, since the
equipment in the gut.
identified, ‘candidate’ drugs can be selected
Haemophilus influenzae type B (Hib)
– either from existing medications or new
vaccine was introduced the number of
drugs designed with the aid of computers.
cases dropped from over 200 to 0 per
Dr Tony Crowther of the MRC
100,000 in babies under a year old, and
Laboratory of Molecular Biology,
from 60 to 0 cases per 100,000 in children
Meanwhile, a fourth researcher, Dr
Graham Jackson, has developed an
enzyme-based detergent similar to a
biological washing powder that is capable
younger than five.
18
Neurosciences and mental health
You and your mind
Even the most sophisticated computer cannot
perform the many complicated operations that your
mind carries out every minute of every day.
MRC scientists are helping to unravel
for schizophrenia, a gene called
The research, which was led by Professor
the mysteries of the mind by working
phosphodiesterase 4B (PDE4B). The gene
Alex Thomson of the School of Pharmacy,
out the mechanics of mental processes
was already known to play an important
London University, focused on
such as attention, perception and
role in how we think and remember but
connections between cannabinoid
memory and studying the origins of
until now was not linked to mental
receptors (so called because they are the
problems such as addiction, attention
health problems.
keyholes used by cannabis to enter brain
deficit hyperactivity disorder, depression
and schizophrenia.
Understanding
schizophrenia
One in 100 people in the UK – that’s
around 500,000 – have schizophrenia,
and worldwide it’s estimated that as
many as 51 million people are affected.
The illness is among the top 10 causes
of disability in developed countries and
approximately one in 10 people with it
commit suicide.
PDE4B was also found to be linked to a
previously discovered gene, ‘disrupted in
schizophrenia’1 or DISC1, which increases
the risk of both schizophrenia and
bipolar disorder (manic depression). The
researchers discovered that DISC1 helps
control the action of PDE4B, revealing a
potentially important relationship
between the two genes.
Cannabis connections
Heavy cannabis use can lead to anxiety,
personality disturbances and depression
cells) and a family of nerve cells called
interneurones. These cells, which are
involved in controlling anxiety and panic
attacks, are also implicated in the
development of schizophrenia.
Change in thinking
The long-held view that schizophrenia and
bipolar affective disorder are separate
illnesses with their own underlying disease
processes and treatments is becoming
increasingly untenable in the light of recent
gene research, according to Professor
Nick Craddock of Cardiff University.
Scientists co-led by Professor Miles
and even trigger schizophrenia in some
Houslay from the University of Glasgow
susceptible people. Research suggests
Studies of genetic variation co-led by
have now identified a new ‘biomarker’
that this may be due to the blockage of
Professor Craddock reveal that, at a
certain chemicals at a junction on one of
genetic level at least, there is no clear-cut
the busy networks of pathways used by
distinction between schizophrenia and
brain messenger chemicals.
bipolar disorder. He argues that a change
of thinking to reflect this fact could aid
new approaches to diagnosis. In turn, this
could help in the development of better
management and treatment options for
serious mental illness.
Studying the genes of families
with schizophrenia could in time
lead to new screening and
diagnostic techniques as well as
targeted treatments for the illness.
MRC Annual Review 2005/06
Tackling addiction
High time
Addicts crave drugs and suffer relapse
The chemical messenger dopamine, which
not just because of the alluring high they
is responsible for feelings of pleasure, is
bring, but also because they are compelled
known to play a key role in addiction.
by the powerful memory associations
Cocaine, for example, blocks the action of
surrounding their drug-taking.
dopamine transporter proteins (DAT) that
Treatments to eliminate memories
normally ‘hoover up’ dopamine and carry
triggered by these cues could therefore
it into the cells. This leads to dopamine
prove effective in helping addicts give
overload and causes the high experienced
up their habit for good.
by cocaine users.
Scientists from the MRC- and Wellcome
Dr Gerome Breen, at the MRC Social,
Trust-funded Behaviour and Clinical
Genetic and Developmental Psychiatry
Neuroscience Institute at the University of
Centre, London, has discovered that
Cambridge have shown that it is possible
cocaine abusers are more likely than non-
to knock out selectively the memory
abusers to have mutations in DAT. This
associations connected with taking
suggests that some people are genetically
cocaine. They did this by inactivating a
predisposed to become addicted to the
gene, zif268, in the amygdala, a part of the
drug more quickly.
brain where emotional memories are
formed and stored.
A team led by Dr Andrew Lawrence, from
the MRC Cognition and Brain Sciences
The aim of the researchers, Professor
Unit, Cambridge, has unearthed a new
Barry Everitt and Dr Jonathan Lee, was to
clue to how drug addiction works in the
test the effects of the treatment on
brain, while investigating what happens
memory ‘reconsolidation’. This is a
when some Parkinson’s disease patients
process by which every time we call a
misuse their medication.
memory to mind it becomes changeable.
The ability to disrupt the memories
activated by exposure to drug cues
provides a potentially powerful and new
approach to treating addiction.
Parkinson’s disease occurs when
dopamine-producing cells in the brain die.
It is treated by the drug L-dopa, which the
remaining brain cells use to make more
dopamine available. Patients who overuse
this drug often become addicted to
gambling, food and sex. The researchers
found that Parkinson’s drugs triggered a
greatly enhanced release of dopamine in
circuits in the brain concerned with
reward. The finding suggests that drugs of
abuse work by hijacking the brain’s natural
reward system.
WHAT DOES IT MEAN?
Attention deficit hyperactivity
disorder (ADHD)
A syndrome characterised by inattention,
distractibility, impulsivity and
hyperactivity that generally starts before
age seven.
Antisocial behaviour
Any activity that affects other people in
a negative way.
Biomarker
A biological characteristic that can aid
the prediction, identification, diagnosis,
and treatment of a particular disease or
disease risk.
Dopamine
A brain chemical that regulates
movement, emotion, motivation and
feelings of pleasure.
Interneurone
Nerve cells found within the central
nervous system that acts as a link
between sensory neurones and
motor neurones.
Neurotransmitter
A chemical found in the brain that
carries messages from one nerve cell
to another.
Psychopathy
Lack of empathy and remorse.
19
20
Neurosciences and mental health
Antisocial origins
they grow up. Dr Essi Viding of the
The research has involved tracking large
What causes antisocial behaviour? A study
MRC Social Genetic and Developmental
groups of people for 30 years and could
of 240 children with attention deficit
Psychiatry Centre, London, led the
help in the development of genetic tests to
hyperactivity disorder (ADHD) suggests
research, which was co-funded by the
determine the prognosis of children with
that a combination of genes, brain
MRC, the Department of Health and
the disorder.
chemistry and environmental factors
the Home Office.
Facing up to autism
may play a role. The children who were
antisocial had a mutation in a gene
What’s stopping you?
People with autistic spectrum disorders
encoding a brain enzyme, catechol
Lack of impulse control is one of the
(ASD), often don’t make much eye contact
O-methyltranferase (COMT). Children
biggest problems for people with ADHD
and find it difficult to recognise faces. Now
with this gene mutation were also more
and their families. But what stops us
Professor Uta Frith of the Institute of
likely to be antisocial if they had been of
blurting out the first thing that comes into
Cognitive Neuroscience at University
low birth weight. The research, which was
our heads, jumping red lights or rushing in
College London may have discovered an
led by Professor Anita Thapar at Cardiff
front of cars without looking? The answer,
important reason why. She scanned the
University’s Neuropsychiatric Genetics
according to Dr Samuel Chamberlain of
brains of normal adults and adults with
Co-operative, was co-funded by the MRC
the University of Cambridge School of
ASD as they looked at pictures of faces
and the Wellcome Trust.
Clinical Medicine, is the brain hormone,
or houses. In healthy adults attention
noradrenaline. Giving atomoxetine, a drug
increased the brain’s response to both
which raises levels of noradrenaline, to
faces and houses, but in those with ASD
healthy volunteers helped them to put a
it only increased response to houses.
brake on their impulses. Atomoxetine is
This was found to be due to poor
licensed to treat ADHD. The study was
communication between brain areas
co-funded by the Wellcome Trust.
involved in facial recognition.
tendencies was mainly influenced by
About half of all children with ADHD
The study, the first of its kind, provides an
environment. These findings are in line
recover, but for others problems persist
insight into the mechanism that may
with previous research showing that
into adulthood. Professor Terrie Moffitt,
underlie one of the most characteristic
children with psychopathic tendencies are
of London’s Institute of Psychiatry, has
symptoms of ASD, which affects 535,000
at risk of continued antisocial behaviour as
now revealed that two genetic variations
people in the UK.
In another study, involving nearly 4,000
pairs of seven-year-old twins, researchers
discovered that a tendency towards
psychopathy and antisocial behaviour was
strongly inherited. By contrast, antisocial
behaviour in those without psychopathic
in the part of the brain that produces
dopamine predict which children with
ADHD will continue to suffer problems.
Research has revealed genetic
variations that could help
determine which children with
autistic spectrum disorders will
continue to suffer them as adults.
MRC Annual Review 2005/06
How heroin damages
the brain
Say what?
injecters with brain tissue from 16 non-
Antibiotics such as streptomycin used to
treat serious bacterial infections such as
tuberculosis can cause permanent hearing
loss and now we know why. According to
Professor Corné Kros of the University of
Sussex, the drugs enter cells in the inner ear
that are involved in hearing. They do so
through a one-way valve which then closes,
trapping them inside.
drug users. The drug abusers’ brains
Baby it's you
showed a level of brain damage normally
Research carried out by Professor Mark
Johnson from the Centre for Brain and
Cognitive Development at Birkbeck College,
London, confirms the popular view that
newborn babies can identify and prefer
looking at their caregivers’ faces. The study
was part of ongoing research looking into
the development of social thinking. The next
step is to extend it to babies at risk of
Young drug abusers are up to three times
more likely to sustain brain damage than
non-drug users, according to Professor
Jeanne Bell from Edinburgh University.
Researchers compared brain tissue
samples from 34 heroin and methadone
only seen in much older people, which was
similar to the early stages of Alzheimer’s
disease. The finding adds to previous
research showing that drug abuse causes
low-grade brain inflammation and suggests
that intravenous drug abuse may cause
21
autism, which could, in time, help pinpoint
early signs of the condition.
Origins of amnesia
Babies born very early, children with
congenital heart problems and children who
have been put on heart-lung machines are
all at risk of hypoxia (lack of oxygen) and
ischaemia (lack of blood flow) to the brain.
These can lead to subsequent problems
with memory and learning called
developmental amnesia (DA). Professor
Faraneh Vargha-Khadem has now begun
to examine what causes DA and to develop
ways to diagnose and help children at risk.
The study, the first large-scale one of its
kind, is being carried out at the University
College London Institute of Child Health
and Great Ormond Street Hospital for
Children NHS Trust, London.
premature ageing of the brain. The study
was co-funded by the MRC and the US
National Institute on Drug Abuse.
Read my lips
Nearly nine million people in the UK –
that’s about one in five of us – have some
degree of hearing loss and many use lip
reading to help in communication. It is,
however, a complex skill to learn and even
when mastered may involve a certain
Dr Sharon Thomas of the MRC Institute
different regions of the brain concerned
of Hearing Research, Nottingham, showed
with sound and language processing are
that training can help improve the ability
involved in lip reading, suggesting that skill
to distinguish between sounds such as ‘b’
reflects the efficiency of the brain circuitry
and ‘p’ that look similar on the lips and, in
linking these areas.
another study, found that observers can
use visual cues to discriminate language
and accent. In a third study at the institute,
Dr Deb Hall found that a number of
amount of guesswork.
Studies from the MRC Institute
for Hearing Research are aiding
the development of better training
programmes for people who use
lip reading.
22
Health services and public health
You and your lifestyle
Health and wellbeing depend on many factors,
including our level of education, where we live,
our work, diet and lifestyle and, not least,
the political environment.
MRC scientists are exploring how these
Researchers looking at the effects of the
Grains of truth
and factors such as IQ and young
opening of a large superstore in Scotland
What we eat in childhood can have a long-
parenthood may affect health. Their
found that, contrary to expectation, its
lasting impact on our health. A diet rich
discoveries are invaluable in helping us
presence had little effect on residents’
in unrefined cereals, such as wholemeal
as individuals to make healthier choices,
fruit and vegetable intake. The fact is
bread, wholewheat pasta and brown rice,
and in providing the foundations for
supermarkets provide opportunities for
which contain more fibre, vitamins and
evidence-based healthcare policies.
both healthy and unhealthy food choices.
minerals than refined foods, may help
We now need to discover what other
protect against heart disease, diabetes
Market forces
factors determine what people put in
and some cancers. This is why, although
Many public health experts argue that
their shopping trolleys.
there are no official UK guidelines for
practical obstacles to healthy eating
faced by people who don’t own a car
and who live in less affluent areas
without a nearby supermarket are
partially responsible for their poorer
diet and health. Policymakers have even
suggested that the development of food
superstores in deprived communities
could improve the diet and health of
The study, which was led by Dr Mark
Petticrew, was the first of its kind to use
a controlled design involving an
intervention area where the new store
was built and a nearby matched control
area. Its results could help inform future
policy on urban regeneration.
wholegrain consumption, the US
Department of Health and Human Services
recommends that adults should eat three
16 gram servings a day. One serving is
equivalent to one Weetabix or one slice
of wholemeal bread. Only a quarter of
adults meet this level, however, and
research has now revealed that few
children and young people do either.
residents. But it may not be that simple,
as shown by an innovative pilot study
from the MRC Social and Public Health
Sciences Unit in Glasgow.
In an analysis of the dietary habits of 1,583
young people aged between four and 18,
Dr Susan Jebb and colleagues from MRC
Human Nutrition Research and colleagues
at the University of Newcastle found that
less than a third consumed even one
serving of wholegrain food a day. This was
especially true of youngsters whose
parents held manual jobs.
The dietary data were collected as part of
the 1997 National Diet and Nutrition
Survey. The results will be used to help
develop nutrition policy and to contribute
to government advice on healthy eating.
MRC Annual Review 2005/06
Lowering the risk of
diabetes
initiatives and health education messages
Even small changes in lifestyle could help
highest risk but that everyone should be
lower your risk of diabetes, according to
encouraged to make small changes to slow
research by Dr Simon Griffin, a GP at the
the rapid rise in the numbers of people
MRC Epidemiology Unit, Cambridge, and
with diabetes.
colleagues. They analysed the lifestyle of
middle-aged participants in a study
assessing the impact of diet, exercise and
other lifestyle factors on a number of
different diseases.
None of the participants who were
Few children and young people in the
UK eat enough wholegrains for health
according to a large survey part-funded
by the MRC.
23
physically active and ate a high-fibre, lowfat diet, and hence were not overweight,
developed diabetes during a five-year
period. Applying this finding to the whole
population, if more of us adopted similar
healthy habits fewer of us would develop
diabetes. This suggests that government
A healthy lifestyle that includes
regular physical activity can help
protect us against developing
diabetes in later life.
should be aimed not just at those at
The findings are helping to inform the
NHS National Screening Committee’s
development of a strategy to identify who
might benefit from testing for undiagnosed
disease or from measures to reduce their
risk of disease.
The research was part of the EPIC-Europe
study, which involves over half a million
people in ten countries.
24
Health services and public health
Bottling up obesity
babies solids until six months. It was
Bottle-fed babies who start solids early are
carried out at the MRC Epidemiology
more likely to become obese as children,
Unit, Cambridge, as part of the Avon
according to research led by Dr Ken Ong.
Longitudinal Study of Parents and
Researchers tracked around 1,000
Children funded by the MRC and the
mothers and their babies born in the early
Wellcome Trust.
1990s. They discovered that bottle-fed
babies who began solids before the age of
Cycle of disadvantage
four months consumed more calories and
A lot of attention is focused on the poor
had a greater risk of being overweight or
academic achievements of children of
obese at ages three and five. By contrast,
teenage parents, which in turn has an
breast-fed infants appear to compensate
effect on their opportunities in life.
when starting solids early by reducing their
But, at a time when most women put off
milk intake. The research reinforces the
having children until their late 20s, 30s or
‘breast is best’ message, as well as the
even 40s, children born to mums in their
current government recommendation that
early 20s could be at even more of a
it is healthier for parents to delay giving
disadvantage than those born to teenagers.
Professor Dale Hay of Cardiff University
Children born to mums in their early 20s
may be at more of a disadvantage than
those with teenage mothers, due to them
receiving less support.
tracked the children of women who
attended antenatal clinics in 1986 up to
grades A* to C and most failing to get
age 16. Those born to teenage mums and
even a single GCSE. Professor Hay
mums in their early 20s had poorer
surmises that teenage mums and their
literacy and numeracy skills by the end of
children may receive more support from
primary school. By age 16, however, the
sources such as government and social
children of teenage mums had improved
services than those who have babies in
their skills. This was not true for children
their early 20s. This MRC-funded research
born to mums in their early 20s, with only
was part of the South London Child
a fifth gaining five or more GCSEs at
Development Study.
MRC Annual Review 2005/06
Bright idea
It’s long been known that the less well-off
Dementia does not
discriminate
experience greater levels of illness and are
Many diseases that affect us as we age are
likely to die earlier than their wealthier
linked to poverty. In the case of dementia,
peers. But we still don’t completely
however, it seems that this is not the case.
understand how poverty might actually
When researchers examined the incidence
‘get under the skin’.
of dementia in over 13,000 people in
England and Wales they found that those
In one study researchers measured
living in affluent areas were just as much at
traditional socio-economic aspects of
health as well as IQ and processing speed,
risk as people in poorer areas.
an important component of intelligence,
The research showed that the risk of
in a group of 1,347 56-year-olds from the
developing dementia increased with age,
west of Scotland. Those with higher IQs
with one in 70 people aged 75 to 79 and
who processed information faster were
one in 15 of those aged 85 and over
less likely to experience ill health and
developing the condition. This is contrary
die early.
to previous studies suggesting that the
incidence of dementia declines in older age
Traditionally, studies have examined
groups. Dementia affects around 550,000
differences between rich and poor in the
people in England and Wales, with around
light of behaviours, such as smoking and
163,000 new cases diagnosed each year.
diet, and physical risk factors, such as
More research is now needed to find out
blood pressure or obesity. This study
whether the incidence of dementia in the
shows that a lower IQ is yet another
UK is rising or falling. The research was
reason why some people who are less
led Dr Fiona Matthews of the MRC
well-off experience poorer health. The
research was led by Dr David Batty of the
Biostatistics Unit, Cambridge.
MRC Social and Public Health Sciences
Unit, University of Glasgow.
MRC research into risk factors
for dementia will aid the
planning of services to meet
current and future care needs.
WHAT DOES IT MEAN?
IQ (Intelligence quotient)
Score achieved on an intelligence test
that identifies learning potential.
UK National Screening
Committee (NSC)
A body that advises government on all
aspects of screening policy, drawing on
the latest research evidence.
Unrefined cereals
Cereals which have not been processed
to remove the husk, such as brown rice,
oats, wholegrain breakfast cereals and
wholegrain bread.
25
26
MRC Technology
You and your treatment
In the future, your doctor will be able to refer to your genetic
makeup to prescribe ‘personalised’ medication. Tailored to your
body’s unique needs, this radical new approach will ensure that
you receive the most effective drug for you, at the right dose,
from the start.
Our affiliated company, MRC Technology (MRCT), bridges the gap between the scientist’s
laboratory and your doctor’s surgery, helping to turn groundbreaking MRC discoveries
into new drugs and other interventions.
The road to discovery
MRCT’s new state-of-the-art laboratories in north London opened in February 2006. Its
scientists, many of whom have come from the pharmaceutical industry, are now using
highly sophisticated techniques, including high throughput screening involving robots, to
sift through tens of thousands of compounds to identify those with the potential to be
developed into new drugs. In addition to possible new treatments for major diseases such
as cancer and Alzheimer’s, they are also looking for new therapies for diseases of poverty,
such as tuberculosis and malaria, which have traditionally been neglected. “It is very
exciting to be tackling such a breadth of unmet medical need,” says Dr Roberto Solari,
MRCT’s chief executive.
“Improving our connections
with industry is vital to
harness the power of
medical science to drive
productivity and growth in
the British economy.”
Dr Roberto Solari,
MRCT Chief Executive
MRC Annual Review 2005/06
Well-connected
This year MRCT has been involved in the start-up of Raindance Technologies Inc, a
biotechnology company devoted to discovering, developing, and commercialising
‘microfluidic’ devices thousands of times smaller than a drop of water with a variety of
uses in medical research.
MRCT also has a new collaboration with the Chinese National Centre for Drug Screening
(NCDS), which arose out of an MRC mission to China in autumn 2005. Through this it
will have the opportunity to hunt through the NCDS chemical library, which includes
many unique extracts from traditional Chinese herbal medicines.
And MRCT is also in the process of setting up ‘showcase’ days, designed to highlight the
work of MRC scientists both from our own units and institutes and from MRC-funded
research in universities, with a view to enhancing our collaboration with the
pharmaceutical and biotechnology industries.
License to cure
Licensing from MRCT this year amounted to a spectacular £142 million, £108 million of
which came from royalties on the monoclonal antibody-based drug, Humira®, which helps
reduce pain and slow down joint damage in rheumatoid arthritis. All licensing revenue
that the MRC receives through MRCT is used to fund yet more research, leading
eventually to more medical breakthroughs by our scientists.
WHAT DOES IT MEAN?
Basic research
Research usually carried out in the
laboratory designed to expand scientific
knowledge of biology and disease
mechanisms and processes, as well as
to understand how drugs work.
Drug discovery
The research process that identifies
molecules which have promise as new
medicines for humans.
Microfluidics
Study of the behaviour of fluids at
volumes thousands of times smaller
than a drop of fluid and the design of
systems in which such small volumes of
fluids will be used.
License
Legal authorisation to market drugs,
devices and other products used in
healthcare. In the UK licensing is the
responsibility of the European
Medicines Evaluation Agency and
the Medicines and Healthcare
products Regulatory Agency.
RESEARCH
IDEA
PATIENT
BENEFIT
POLICY/
PRACTICE/
WEALTH
HEALTH
SERVICES
RESEARCH
BASIC
RESEARCH
EXPERIMENTAL
MEDICINE
CLINICAL
TRIALS
Medical research is not a
simple linear process but a
continuous circle that
involves many different
stages that culminate in
benefits to human health
and national wealth.
27
28
Conclusion
You and your life
In this annual review you have read about some of
the hundreds of discoveries made by MRC scientists
this year and seen how our work is helping people
throughout the world to lead healthier lives.
The next time you, or someone close to you, visits a doctor or
goes to hospital, there is a very high chance that some of the
methods and medications used to diagnose and treat you
originated from a discovery made in an MRC laboratory. And
much of the advice on diet and lifestyle we are now given also
derives from MRC research.
But some of the discoveries that are touching your and other
people’s lives today will have been made many years, or sometimes
decades, ago. It is important to remember that even today, with
all the sophisticated methods at our disposal, it still takes an
average of 10 years for a new treatment to reach clinical practice.
This is why it is so vital that medical research continues to be a
high priority.
Funded by the UK taxpayer, the MRC is committed
to ensuring that both now and in the future, we
will continue to touch every life, every day.
Image credits:
Cover: Photograph by Tim Barker.
Inside covers and pages 6–9 (background): Computer
artwork of double helix of DNA. Alfred Pasieka/Science
Photo Library.
Page 8: Light micrograph of a transverse section through
cardiac muscle. Astrid & Hanns-Frieder Michler/Science
Photo Library.
Pages 10–13 (background): Red blood cells.
Getty Images (UK) Ltd.
Pages 14–17 (background): Computer models of oxygen
molecules. Russell Kightley/Science Photo Library.
Page 15: Particle of AIDS virus. Copyright MRC.
Pages 18–21 (background): Light micrograph of a
section through the cerebellum of the brain.
Innerspace imaging/Science Photo Library.
Pages 22–25 (background): Computer artwork of
molecular structure of a protein (cytochrome C550).
Phantatomix/Science Photo Library.
Medical Research Council
20 Park Crescent, London W1B 1AL
Tel: 020 7636 5422
Fax: 020 7436 6179
www.mrc.ac.uk
© Medical Research Council 2006
Live longer,
live healthier
A look at our scientists’ work on
health and disease in later life, and
your views on medical research
into ageing
What is ageing?
We start to age the moment we are
born and throughout life our cells are
constantly repairing and renewing
themselves. As we get older, however,
this process becomes less efficient.
Our skin becomes less elastic, our hair
greyer, our eyes less sharp and our
joints less flexible.
This ageing process happens to
everyone. But the speed at which it
occurs varies from person to person
and even from organ to organ within
the same person. Ageing need not
always spell poor health or loss of
ability but the older we get the greater
our risk of them.
But ageing is not just about these
obvious signs. As we age, the genes
and proteins inside our cells may also
become irreparably damaged and our
cells’ energy-producing machinery
may fail, leaving us vulnerable to
age-related diseases.
“In all countries, and in developing
countries in particular, measures to
help older people remain healthy
and active are a necessity,
not a luxury.”
The World Health Organization
MRC Annual Review supplement
1
Age research in perspective
‘Improving quality of life’ is the most important factor in deciding what ageing
research is funded, according to a consultation commissioned by the MRC and
the Biotechnology and Biological Sciences Research Council (BBSRC).
The initial survey involved three one-day
workshops with around 60 people in total, aged 16
to 82 from a wide range of different backgrounds.
This was followed by an omnibus survey of over
2,000 members of the UK public.
We commissioned Ipsos MORI to help us learn
more about how Britons view scientific research
into ageing. The results offer a unique snapshot of
public views, which we will use to help shape our
future funding decisions. The study examined
questions about the importance of scientific
research, both personally and for society as a
whole. It also asked what criteria are important in
deciding which research projects are most
worthwhile and should be funded.
Perceptions of ageing
During the workshops, many participants thought
of ageing primarily as ‘age-related problems’ rather
than a process that happens throughout life. They
were broadly aware of scientific research into
ageing, assuming research would be conducted into
health conditions linked to ageing such as cancer,
heart disease, Alzheimer’s and ‘general mental
decline’, but had little awareness of individual
research programmes. Participants placed much
higher value on this medical research than on
research into cosmetic ways to hold back the clock
such as anti-ageing creams. And they showed a
clear preference for a combination of organisations
funding research, including the Government and
charities, as well as industry.
The workshops identified public benefit and value
for money as overriding criteria for allocating
taxpayers’ money. They viewed scientific
excellence as an important consideration, but
one they would presume was a precondition
for receiving any funding.
Balancing need and benefit
Participants tended to think that research that
benefited the maximum number of people was
most important, but they recognised that a balance
should be struck between the level of need and the
benefit for the greatest number. There was a
feeling among participants that funding currently
tends to be targeted at conditions that are
‘curable’ whereas conditions that can only be
‘managed,’ such as arthritis, receive less funding.
In the quantitative survey, more than twice as
many of the 2,000 British adults interviewed said
that research into prevention was more important
than finding cures. To find out more about
research into ageing, half of the national sample
said they would look on the internet and/or speak
to their doctor or look in the doctor’s waiting
room. Other relatively popular information
sources were ageing-related charities, chosen by
three in ten, or family and friends, the television or
a newspaper, all chosen by around one in six.
You said . . .
Most important to you personally
48%
said research into preventing age-related
conditions was most important to them personally.
29% said research into managing these conditions
and how best to support and care for someone
with them was most important.
18% said research into curing these conditions
was most important.
Most important factors when deciding how
taxpayers’ money should be spent
•
•
•
Improving quality of life (56%)
Preventing future problems (35%)
Looking for cures (34%)
2
Live longer, live healthier
Cell lines
The ten trillion cells that make up
our bodies are constantly dying and
being replaced to keep us strong and
healthy. The process of cell death,
known as apoptosis, ensures that
cells that are old or damaged beyond
repair ‘commit suicide’.
As we grow older, however, the mechanisms
controlling this are more likely to go wrong.
Many age-related diseases are a result of faults in
apoptosis. If too rapid, it plays a role in heart
disease and degenerative brain disorders such as
Parkinson’s and Alzheimer’s. Cancer, on the other
hand, is caused by cells failing to die. MRC research
into apoptosis is providing valuable clues as to how
we can tackle these diseases.
A cell component called the proteasome,
sometimes known as the ‘master controller’ of
the cell, plays a central role in apoptosis. The
proteasome gets rid of abnormal proteins and
breaks down and recycles others. If a protein’s
time is up the proteasome ‘tags’ it to be destroyed.
And one tag it often uses is a small molecule called
ubiquitin, which latches on to the marked
protein and carries it to the proteasome to
be sliced up and disposed of.
Before a cell divides, it has to copy the
genetic information contained in its
DNA molecules. If the DNA is
damaged, for example by UV
rays from the sun, the
normal copying enzymes,
called DNA polymerases,
are blocked. Cells then
use special enzymes,
called translesion
polymerases, which
can copy DNA even
when it is damaged.
MRC-funded scientists at the University of Sussex
Genome Damage and Stability Centre have
discovered that the ability of translesion
polymerases to stick to ubiquitin enables them to
slip past damaged DNA. As research team leader
Professor Alan Lehmann observes: “This provides a
long-sought clue to how cells get round DNA
damage. It is an important way to protect us from
cancer and may inform future drug discovery.”
Radical solutions
Scientists have determined the structure of a key
energy-producing enzyme, Complex 1, which may
provide a clue to how we age. Complex 1 is one of
five enzymes found in mitochondria (the
powerhouses of cells) that work together to
create the energy our cells need to function.
Complex 1 generates almost half this energy, but
as a by-product produces harmful free radicals
which are thought to possibly be involved in ageing
and diseases such as Parkinson’s. Research leader
Dr Leonid Sazanov of the MRC Dunn Human
Nutrition Unit, Cambridge, says: “The discovery
may suggest ways to minimise production of free
radicals, with implications for dealing with ageing.”
MRC Annual Review supplement
Around the
arteries
Blood clotting is a normal protective
mechanism our bodies use to
prevent excessive blood loss if we
injure ourselves. Problems can occur,
however, if blood clots in the wrong
place at the wrong time.
The vast majority of heart attacks and strokes, for
example, happen when a narrowed and furred
artery is blocked by a clot. MRC scientists are
trying to find out more about the clotting
mechanism, which could lead to new treatments
and ways to prevent these diseases.
When blood vessels are injured, cells that line the
walls of the arteries (endothelial cells) release a
protein called Von Willebrand’s Factor. This
consists of long sticky strings that catch platelets
(the blood cells involved in clotting) and glue them
together. If they become tangled, however, their
ability to glue platelets together is hindered, which
impedes clotting. The protein strings are stored in
unique cigar-shaped structures also found in the
endothelial cells. Although scientists have known
about them for 40 years, the reason for their
structure remained a mystery until now.
Research by Professor Dan Cutler of the MRC
Cell Biology Unit, Cambridge, reveals that the
cigar shape enables the strings to be stored in
coils to prevent tangling.
Statins: the results
Millions of middle-aged and older people in the UK
take statins to lower their cholesterol. This is a
direct result of trials funded by the MRC and the
DID YOU KNOW?
In the UK there are now 30 million
prescriptions a year for statins and
other cholesterol-lowering drugs.
3
British Heart Foundation that showed that statins
protect against the risk of premature death from a
heart attack or stroke. Currently, however, you
are only likely to be prescribed a statin if you have
high cholesterol. But new MRC research suggests
that even if your cholesterol level is not raised you
may be able to benefit from a statin if you have
other risk factors for heart attack or stroke.
A fishy story
Oily fish, such as herring, mackerel, sardines,
salmon and swordfish, are a major source of
omega-3 fatty acids, which help to protect against
heart disease. And now Dr Susan Jebb of the
Nutrition and Bone Health Group at MRC Human
Nutrition Research, Cambridge, may have found
the reason for their protective effect. Two groups
of people were asked to eat either oily fish or
white fish for a week. At the end of the study
those who put oily fish on their menu had lower
levels of harmful blood fats called triglycerides.
High blood levels of triglycerides are linked with
diabetes, high blood pressure and heart disease.
Through the keyhole
Ruptured abdominal aortic aneurysms, caused by
weakening and ballooning of the main artery
leading from the heart to the abdomen, claim
4,500 lives a year. Eighty per cent of those with a
ruptured aneurysm die before reaching hospital.
Of those who undergo emergency surgery, a
further 50 per cent die after the operation. This
could now change as a result of insights gained
from the Multi-centre Aneurysm Screening Study
(MASS) trial, which the MRC has funded for the
past 20 years.
The study shows that a minimally invasive
(‘keyhole’) technique called endovascular
aneurysm repair (EVAR), halves the risk of death
from aortic aneurysm repair. Traditional surgery
involves a general anaesthetic and a large cut in
the abdomen. But EVAR involves making just two
small cuts in the groin and can often be done
under epidural anaesthetic.
4
Live longer, live healthier
Courtesy of Dr Nick Fox, National Hospital for Neurologyand Neurosurgery
Nerve centres
A hallmark of brain disorders such
as Parkinson’s disease, Alzheimer’s
disease and other types of dementia,
which are caused by the premature
death of our brain cells, is the
build-up of clumps of toxic proteins.
MRC scientists led by Professor David Rubinsztein
of the University of Cambridge have revealed that
clumping occurs when transporter proteins called
dyneins are faulty or missing. Dyneins carry toxic
waste out of cells for disposal, so if for some
reason they cannot do this, waste builds up.
MRC researchers from the University of
Cambridge, meanwhile, have identified another
feature that may encourage deposits of toxic
proteins. Most of the proteins in our bodies are
made up of smaller protein units. Each of these in
turn is composed of strings of hundreds or
thousands of amino acids. The researchers, led by
Dr Jane Clarke and Professor Chris Dobson,
suggest that when proteins have 70 per cent of
their amino acid sequences in common they are
more prone to aggregate.
Protein clues
In a study at the MRC National Institute for
Medical Research, researchers have worked out
the 3-D structure of a protein called Ataxin 3.
Mutations in this protein are associated with an
inherited nerve disorder, Joseph-Machado disease,
which causes clumping very similar to that of
Alzheimer’s disease. The research, led by Dr
Annalisa Pastore, could provide clues to the origins
of Alzheimer’s disease.
Another research team has identified a new gene
called chromatin modifying protein 2B or CHMP2b
that when mutated causes early-onset dementia.
The protein encoded by this gene is involved in
moving proteins around the cell. Research leaders
Professor John Collinge of the MRC Prion Unit and
Scan of Alzheimer’s patient’s brain
Professor Elizabeth Fisher of University College
London say: “The finding brings us closer to new
therapies and new ways in which we can prevent
the onset and progression of dementia.”
A snip in time
Current drugs for Alzheimer’s disease slow or
delay the onset of symptoms, but now MRC
researchers at Liverpool University have created
compounds that could target its underlying causes.
The compounds, which are based on modified
forms of the blood-thinning drug heparin, work by
blocking an enzyme called beta-secretase whose
job it is to snip a protein called amyloid precursor
protein (APP) into smaller fragments. This action is
thought to be the key first step in the protein
build-up that characterises Alzheimer’s. As lead
scientist Professor Jeremy Turnbull says: “These
compounds have the potential to be developed
into a completely new class of drugs, which for the
first time could act directly to treat the underlying
cause of Alzheimer’s disease.”
Spotlight on Parkinson’s
Parkinson’s disease happens when brain cells that
produce dopamine, a messenger chemical that
controls our muscles, die. Doctors still don’t know
why this occurs, but there is some evidence that
MRC Annual Review supplement
certain garden pesticides or contaminants present
in some designer street drugs may sometimes
be involved.
MRC scientists have now found that some people
with Parkinson’s disease possess a mutated form of
a protein found in the mitochondria of cells called
HtrA2. Dr Miguel Martins of the MRC Toxicology
Unit, Leicester, explains: “Parkinson’s has long
been linked to mitochondrial damage, but until two
years ago there were no straightforward links
connecting mitochondrial protein mutations and
Parkinson’s. We think that proteins like HtrA2 and
another protein called PINK1 are involved in
protecting mitochondria from the natural damage
that occurs as a result of the cell’s normal energy
generation process. If damage is exacerbated by
certain toxic insults, such as those mentioned, the
absence of HtrA2 or PINK1 might prevent
mitochondria from coping with this damage. These
mitochondria will then fail, leading to the death of
brain cells that normally cannot be replaced.”
The traditional treatment for Parkinson’s disease is
the drug L-dopa. Long-term use, however, can
cause severe involuntary movements, tics and
hallucinations. Scientists at the MRC Clinical
Sciences Centre at Hammersmith Hospital,
London, have performed safety trials on what
5
could become a completely new treatment for
Parkinson’s disease. It involves pumping a protein
called glial cell line-derived neurotrophic factor, or
GDNF, into the brain to encourage dopamineproducing cells to grow. In an early safety trial in
patients the treatment improved both symptoms
and quality of life – without any serious side
effects. More recently, the team has found that the
treatment stimulated regrowth or ‘sprouting’ of
dopamine nerve endings in the brain of one of the
five trial patients.
Lead researcher, Professor David Brooks
comments, “If GDNF does promote sprouting, it
may be possible to reverse disability in Parkinson’s
disease patients while avoiding the treatment
complications of current medications.”
DID YOU KNOW?
Alzheimer's disease and dementia affect
more than a million people in the UK.
This figure is set to double in the next
25 years as the population ages.
6
Live longer, live healthier
Tackling
diabetes
Diabetes is not only a leading cause
of premature death – especially from
cardiovascular disease – but also a
major cause of blindness, stroke,
amputation and kidney failure.
The disease is caused by lack of insulin, a hormone
produced by the pancreas that enables the body
to use blood glucose for energy. Most people with
diabetes in the UK have type 2 diabetes, which
usually develops after the age of 40. In this type
of diabetes, the pancreas still makes insulin but
the body cannot use it properly.
Insulin clue
Scientists have recently identified a protein called
nicotinamide nucleotide transhydrogenase, or Nnt,
that could throw light on the origins of defects in
insulin production. Nnt was previously known to
deactivate free radicals – harmful molecules that
damage cells. Until this discovery, however, it was
not known to play a role in insulin secretion. The
scientists found that mice lacking Nnt produced
less insulin and had higher blood glucose levels –
both early signs of type 2 diabetes in humans.
The scientists surmised that this was because a lack
of Nnt resulted in increased free radical damage in
the pancreas.
Co-leader of the research, Professor Roger Cox
from the MRC Mammalian Genetics Unit, Harwell,
says: “This increases our understanding of how
insulin is secreted and could open up exciting
possibilities for treating type 2 diabetes in people.
It may even turn out that defects in Nnt can cause
human type 2 diabetes.”
Preventing diabetes
The good news is that even if you are at risk of
developing diabetes – for example because of a
family history of the disease – you may be able to
protect yourself against it. MRC research carried
out as part of the European Prospective
Investigation into Cancer and Nutrition (EPIC)
found that exercise, a high-fibre, low-fat diet and
not being overweight protected against diabetes
developing in those with a high risk of it.
This suggests that such measures could protect
us all against diabetes, which could in turn help
reduce the incidence of a disease that is today
increasing dramatically.
DID YOU KNOW?
Around 150 million people have
diabetes worldwide. This could
double by 2025 as a result of
the ageing population.
MRC Annual Review supplement
Bone truths
Our bone cells are constantly being
broken down and renewed. And,
until around our mid-20s, they are
replaced faster than they are lost.
From our 40s onwards, however,
both men and woman start to lose
more bone than they make as part
of the natural ageing process.
Calcium is known to help build bone, but in
recent years there has been growing interest in
the potentially bone-protective effects of other
nutrients. One MRC study, for example, showed
that vitamin D supplements could reduce fractures
in older people by a fifth. And researchers from
MRC Human Nutrition Research, Cambridge, have
now also found that adolescents and older women
with high intakes of fruit and vegetables have
heavier, more solid, bones. The results add weight
to the five-a-day campaign and proposals to
improve school meals.
DID YOU KNOW?
One in two women and one in
five men over the age of 50 in the
UK will break a bone, almost
always as a result of osteoporosis.
Joint action
More than half of all people aged 65 or older have
visible signs of osteoarthritis on X-ray, and 10 per
cent experience significant pain and disability.
At the MRC Health Services Research
Collaboration in Bristol, a research programme
is underway examining major questions relating
to joint replacement.
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8
Live longer, live healthier
Tracking
health
How long we live and how healthy
we are as we age is largely a result
of the interplay between our
unique genetic make-up and our
environment. However, the effects
are often not fully evident until
we get older.
Long-term studies of large groups of people
(cohorts) are one way in which MRC scientists
are learning more about how these key factors
keep us fit and well or make us more liable to
illness later in life.
Although it may be many years before the results
of such research are known, they are the only
reliable way of analysing the combined effects of
behaviour, upbringing, lifestyle and genetic make-up
on the health of the population. The discovery of
the link between smoking, lung cancer and heart
disease, made by MRC researcher Sir Richard Doll,
is just one example of the far-reaching impact this
kind of research can have on public health
messages and behaviour.
DID YOU KNOW?
500,000 people aged 40 – 69
will contribute DNA and health
information to the UK Biobank.
Bank it
To learn more about the links between genes,
lifestyle, health and disease in middle age we are
funding the word’s largest biological databank, the
UK Biobank, with the Department of Health, the
Wellcome Trust and the Scottish Executive. The
information contained in the bank will help in the
development of new ways to prevent, diagnose
and treat conditions such as Alzheimer’s disease,
cancer, diabetes and heart disease. We have
recently started collecting DNA samples and
health and lifestyle information from the first
3,000 volunteers whose health will be tracked
for up to 30 years.
MRC Annual Review supplement
9
The womb effect
Improving daily life
A host of studies have now unearthed the
effects of life before birth on later health. MRC
research – much of it carried out at the University
of Southampton – has shown that poor nutrition
in the womb, for instance, significantly increases
our likelihood of developing heart disease, high
blood pressure, stroke, diabetes and osteoporosis
in later life.
As we age and our hands become less nimble,
tasks such as opening jars and doing up buttons
can become harder. We may start to rely on aids
such as glasses for computer work or watching TV,
while gradual loss of hearing may affect our ability
to take part in conversations in noisy places.
MRC-funded research is looking at a range of
factors including treatments and therapies that
could help improve our daily lives as we age.
Another study, the Avon Longitudinal Study of
Parents and Children, is tracking the health of
14,000 children born in the Bristol area in an effort
to learn more about how genes and the
environment affect lifelong health.
A third large study, Whitehall II, has been teasing
out the effects of workplace stress, job security,
change in the workplace and the work-life balance
on the health of civil servants at work and after
they retire.
The MRC National Survey of Health and
Development, meanwhile, which began in 1946, is
tracking the health of more than 5,000 people born
in a single week of that year. Their findings provide
a fascinating picture of the effects on health of
social changes such as the introduction of the NHS
in 1948, the Clean Air Act of 1956, and changing
trends in baby feeding, diet, smoking and drinking.
The study has shown, for instance, that small
babies, especially first-born boys, are more prone
to high blood pressure in midlife. It has also
revealed that less well-off men and women who
weigh more, have poorer health and an inactive
lifestyle, do less well in tests of joint mobility and
function. Another finding was that the risk of
breast cancer, especially in premenopausal women,
was increased by being heavy at birth and growing
fast after birth.
For instance, a large survey of more than 50,000
people aged 75 or older from 100 GP surgeries
throughout the UK showed that many were not
receiving help for treatable conditions such as
blurred vision and cataracts. The survey also
showed that many older people with severe
hearing loss did not possess a hearing aid, or if
they did, still could not hear properly.
Professor Astrid Fletcher of the London School of
Hygiene and Tropical Medicine, who led the
research, observes: “The findings highlight the need
to make specialist eye-testing more accessible to
older people and to improve the provision of
modern hearing aids.”
MRC researchers from Cambridge have developed
a test that gives more accurate information about
individual patterns of hearing loss at different
frequencies. The research will help to identify
more accurately those who need hearing aids and
also guide the choice of hearing aid. Research being
carried out at the MRC Institute of Hearing
Research in Nottingham, meanwhile, is looking at
various aspects of lip reading.
Other MRC research has focused on identifying
the causes of bladder problems, which affect 35
per cent of us, especially women, as we age. The
research included a large survey of 280,000 men
and women aged over 40 in Leicestershire, which
examined the incidence of bladder problems and
the impact of these on their lives. Other studies
have looked at different ways of managing such
problems, from specialist continence advisory
services to drugs and surgery.
Participants’ comments during a public consultation by
the MRC and the BBSRC on attitudes towards medical
research into ageing
“People in their 90s don’t seem
to be that old”
“Now I understand how important
understanding cells is”
“Nobody knows what old is anymore”
“Ageing isn’t a problem,
it’s part of life”
“Genetic research is very important”
“Scientists are giving us better
knowledge about what to do and
what not to do”
“There should be a balance between
the benefits to younger people versus
older people”
“It’s our money that’s being spent
so we should have a say in how it
is being used”
“The public don’t know as much as
the experts. They [the experts]
should have the final say”
“The key word is prevention”
“I didn’t realise there was so much or
so many ways of looking at ageing”
“You can feel old at 21”
“Cell research and genetics will
keep people healthier and prevent
debilitating disease”
“Will it benefit health and mobility?
Will it help maintain quality of life?
Is it cost-effective?”
“Research is essential”
“It would have to increase the
quality of life for the majority of
the population”
Technical note
The Ipsos MORI Social Research Institute conducted this research for the MRC and the
BBSRC. It comprised three workshops (with around 60 participants) in March 2006 and
in-home face-to-face interviews with 2,162 UK adults aged 15+ in May 2006 (with data
weighted to the profile of the UK population). For further information about Ipsos
MORI’s research visit www.ipsos-mori.com
Find out more
For further information on MRC-funded research into ageing, email
[email protected] for a copy of our booklet Ageing and Health
or download a copy at www.mrc.ac.uk