WellcomeNews ISSUE 56 OCTOBER 2008

Happy returns
Career Re-entry Fellows profiled
Heart of the matter
Ethnicity and cardiovascular disease
Striking a chord
Guitarist’s recovery from brain tumour
The Glasgow Spy
A tale from the Wellcome archive
 Wellcome News
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WellcomeNews | Issue 56
editorial
Other researchers are using scanners to
identify the parts of the brain that become
activated when we perform particular tasks.
Such approaches have shown that the ventral
striatum encourages us to be adventurous
– it becomes activated when we choose
unfamiliar options – and that the brain
regions responsible for stopping habitual
behaviour are underactive in people with
obsessive–compulsive disorder and their
unaffected close relatives.
The challenge for neuroscience – as in all
areas of biomedical science – is to find ways of
taking basic research forward to help people.
Some areas have seen considerable success:
for example, a modern look at psychology
has been developed by a cadre of talented
researchers into highly successful cognitive
behavourial therapies for mental illnesses
Biology is always fascinating, but there is
such as bulimia nervosa, post-traumatic stress
a particular mystery to neuroscience that
disorder and panic disorder.
captivates and charms. Watching a real-time
But in other areas there is still much
video of a nerve cell growing, sending out
to do, particularly for dementia and
its tiny growth cones as it searches for the
neurodegenerative diseases. Indeed,
correct path to take, gives us a glimpse at how
as reported on page 10 of this issue,
the remarkable wiring of the nervous system
previous estimates of levels of dementia in
is laid down during development. When a
developing countries may have substantially
bee works out the best route to take as it flies
underestimated the problem – the 10/66
between flowers with just 1 million neurons,
Dementia Research Group has found that
it is solving problems that a supercomputer
the prevalence of dementia in urban settings
could take a week to answer. And yet such
in Latin America is comparable with rates in
delights are tempered by brain images from
Europe and the USA.
people with Alzheimer’s disease – seeing
As part of our commitment to invest
the destruction wreaked in the brain by this
in this area, in October 2007 we awarded
neurodegenerative disease brings home the
£1.3 million funding to a collaboration
devastating impact it has on the lives of those
of leading UK experts to investigate the
afflicted and on their relatives, friends and
genetics underlying late-onset Alzheimer’s
society at large.
disease. The team is scanning the entire
At the Wellcome Trust, we are fortunate
human genome in search of the genes that
to be able to fund so many talented
predispose people to or protect them from
neuroscience researchers in the UK and
developing the disease.
internationally. We fund research that
Now, in a joint activity with the Medical
includes molecular and cellular neuroscience,
Research Council, we have launched
cognitive, neuropsychological and imaging
a new scheme of Strategic Awards in
studies, and clinical studies investigating
Neurodegenerative Diseases. Such diseases
neurological and psychiatric conditions.
take several different forms, and include
And, as a browse through the news section
Alzheimer’s disease, frontal temporal
of our website (www.wellcome.ac.uk/news)
dementia, Parkinson’s disease, Huntington’s
shows, this research is bringing many new
disease, amyotrophic lateral sclerosis
insights.
and multiple sclerosis. We hope that this
In the last few months, for example, we
£30m scheme will help to bring greater
have seen studies of the chemicals that send
understanding of the biological processes
messages between nerve cells showing that
underlying these diseases, and will catalyse
acetylcholine is vital for our brain cells to
the development of early diagnostic
pay attention to a demanding task, and that
approaches and new, effective therapies.
serotonin plays a critical role in regulating
emotions such as aggression during social Mark Walport
decision making. Meanwhile, new retinal Director of the Wellcome Trust
ganglion cells have been discovered that
control our levels of sleepiness according to
the brightness of our surroundings.
in this issue
news 2–4
funding 6–8
research 10–14
features
Back to the bench 5
Vive la différence 9
Finding Pat Martino 15
The Glasgow Spy 16
noticeboard 17

Unravel the strange case

of the Glasgow Spy (top),
learn about the relationship
between maternal diet and
child health (above left),
discover how jazz guitarist
Pat Martino regained his
music after losing it to
amnesia (above right), meet
Liverpool’s lambanana
leishmaniasis sculpture
(right), and more…

WellcomeNews | Issue 56
news
Flu fighters
Wellcome Trust-funded researchers are
to examine what is preventing the H5N1
avian influenza virus from causing a human
pandemic, and what mutations are required
to realise its deadly potential. The research
could hold the key to early identification
of a potential influenza pandemic, and to
developing drugs and a vaccine.
Professor Ten Feizi at Imperial College
London believes one reason that H5N1 has
not yet evolved into an effective pathogen
capable of widespread transmission between
humans lies in how the virus attaches itself
to the respiratory tract. She is leading an
international research project, which has
received over £720 000 from the Trust, to
identify the receptor molecules in the human
respiratory tract to which viruses attach.
The researchers will also look at how changes
in the binding protein on the surface of the
virus might increase its ability to attach to the
tract and cause infection.
For this project, Professor Feizi will work
with Professors Menno de Jong and Jeremy
Farrar from the Wellcome Trust South-
east Asia Programme in Vietnam, Dr Alan
Hay and Dr Steve Gamblin at the Medical
Research Council National Institute for
Medical Research, London, and Dr Mikhail
Matrosovich at the Philipps University of
Marburg, Germany.
H5N1 avian flu has not spread from birds
to cause a human pandemic. iStockphoto
2 | WellcomeNews | Issue 56
Wellcome to India
We are launching a new partnership with
the Government of India’s Department of
Biotechnology to fund biomedical research
in India.
Operated as an independent, public
charitable trust based in New Delhi, the new
alliance will deliver a programme of research
fellowship schemes aimed at supporting
current and future leaders of Indian
biomedical science.
Both partners have committed £40 million
over the next five years to the venture,
through which three new fellowship schemes
– at the early, intermediate and senior
stages – will be administered. The early and
intermediate awards will be launched in late
2008, the senior in spring 2009.
Jimmy Whitworth, Head of International
Activities at the Trust and one of the
venture’s founding trustees, says: “India
produces thousands of talented young
biomedical researchers with PhDs each year,
but the opportunities for them to continue
postdoctoral work in their home country
is limited, with many only returning to fill
research leader roles far later in their careers.
The aim of the new funding is to build
credible career pathways in India for Indian
scientists at all stages.”
www.wellcomedbt.org
On the record
We have been working with GPs to create
guidance for the use of patient records
in research. These guidelines should
outline best practice for how patient data –
invaluable for guiding research to develop
tomorrow’s treatments – can be used by
researchers without compromising patient
confidentiality.
International news
The remit of our biomedical ethics funding
in developing countries has recently
broadened, and now includes support for
research on the ethical issues arising at any
point in the development and delivery of
healthcare in developing or restructuring
countries. Prospective applicants are
invited to discuss any ideas for funding in
biomedical ethics with the grants team
(email biomedicalethics@wellcome.ac.uk;
tel. +44 (0)20 7611 8536). We have also
launched our International Engagement
Awards, which fund projects that encourage
public engagement with health research in
developing countries. After an impressive
response to the first round, 15 awards have
been made.
www.wellcome.ac.uk/
internationalengagement
Improved access
As part of our open access policy,
grantholders are required to make their
research papers available through UK
PubMed Central (UKPMC) within six months
of publication. Now, we and other UKPMC
funders have announced further support
for UKPMC over the next three years, to
enhance information retrieval, provide access
to additional content, and develop grant-
reporting functionality.

War and Medicine
Don’t miss War and Medicine, the third
major special exhibition at Wellcome
Collection, which runs from 22 November
2008 to 15 February 2009. Devised in
collaboration with the Deutsches Hygiene-
Museum, Dresden, the exhibition will assess
the impact and influence that war and
medicine have had on one another.
www.wellcomecollection.org/
warandmedicine
A military radiographer in protective gear.
Photograph by H J Hickman, c.1918.
London’s medical history
November 2008 sees the
launch of Medical London,
a unique publication that
charts the role of disease,
treatment and cure in
London’s history.
Written by historian and
poet Richard Barnett and edited by author
Mike Jay, the publication comprises three
elements. Sick City is a book of essays that
explores 2000 years of life and death in
London and the role of medicine in the
city’s life. Anatomy of the City is an illustrated
gazetteer that guides you around London’s
medical landscape and the tales that lie
behind it. Lastly, there are six elegantly
designed maps for self-guided walks on a
range of topics – from Daniel Defoe’s Plague
Year wanderings to the naval surgeons of
maritime Greenwich.
This stunning guide to London’s medical
past is published by Strange Attractor Press, in
association with Wellcome Collection, host
to a series of events celebrating the book’s
publication. It is also being marked by a series
of walks based on the sites featured in Medical
London, taking place during October. To find
out more see www.wellcomecollection.org
and www.medicallondon.org.
Literarily speaking
Launched at the 2008 Cheltenham Literature
Festival, the Wellcome Trust Book Prize is a
new annual competition to recognise and
reward the best in fiction and non-fiction
writing centred on medicine.
The £25 000 prize will be awarded for
high-quality literature that explores the
human experience of health or illness,
or else promotes interest in medicine.
An independent panel of judges – chaired
for this year by comedian Jo Brand – will
decide on a shortlist of six books for the
prize, from which the winning title will be
chosen in 2009.
Among other events at the 2008
Cheltenham Literature Festival was ‘Writers
and Remedies’. These five events explored
the part played by medicine in the lives and
works of writers from the 18th, 19th and 20th
centuries, including Jane Austen, Charlotte
Brontë, Marcel Proust and Thomas Mann.
Building on the success of the ‘Writing
Medicine’ events at last year’s festival,
‘Bodies’ was a series of six events for the
2008 festival that were funded through a
Wellcome Trust People Award. This series
united medical experts and contemporary
writers to examine how the two groups
consider biomedical issues and how these
issues are expressed on the page.
Top draw
The Big Draw 2008, the national campaign to
get people drawing, was launched at a unique
festival, ‘Drawing on Life’, at Wellcome
Collection and University College London
on 26–28 September. Over 1000 venues are
expected to get involved in The Big Draw,
which runs throughout October.
www.thebigdraw.org
news
In perspective
The first of a series of
perspectives on UK
science education,
Perspectives on Education:
Primary Science, was
published in September.
In it, leading voices in
primary education look at
primary science in England over the 20th
century and give their views on its place
in the National Curriculum and on trends
in attainment, attitudes and teaching
approaches. Download the PDF at
www.wellcome.ac.uk/perspectives.
Picture perfect
Harriet Foyster, 15, who attends The
Priory LSST in Lincoln, is the winner of
the Wellcome Image Awards competition,
in which entrants described their favourite
image from the 2008 Awards in fewer than
100 words. Her choice was an image of a
ruptured blood vessel by Anne Weston,
which can be seen (along with the other
images) at www.wellcome.ac.uk/en/
wia. Harriet wins prints for herself and her
school, and the chance to be a judge for
next year’s Awards.
One of
Steven Appleby’s
cartoons for
The Big Draw.
WellcomeNews | Issue 56 | 3
news
Superlambanana
Liverpool School of Tropical Medicine played
host to a very special visitor over the summer:
Super‘kalazar’banana, one of 118
‘lambanana’ sculptures on
display across Liverpool as
part of the Capital of
Culture celebrations.
The statue’s distinctive
decoration was designed
and painted by LSTM staff and
is an interpretation of the lifecycle
of the Leishmania parasite, which is
responsible for 60 000 deaths per year.
On the statue, images to represent the
parasite, the sand flies that transmit the
parasite and human hosts were fused with
symbols inspired by Australian aboriginal
art. The rear and side of the statue show the
insects’ stomachs containing a blood meal
with the purple parasites flowing out. The
front features a woman, and the white wings
and brown eyes of the deadly insect rise in
the tail. Super‘kalazar’banana recently sold
for £6000.
www.liv.ac.uk/lstm/lambanana
Building on broadcast
As part of our broadcast activities, a series of
‘Crossover Labs’ are planned for late 2008
and early 2009. These week-long, intensive
events bring together professionals from
audiovisual production (including TV, web
and games) with professionals from other
Charles Darwin, by Franz Carl Muller.
4 | WellcomeNews | Issue 56
The Liverpool
Super‘kalazar’banana.
Shape by Taro Chiezo, design
by Rod Dillon and Ektor Diaz.
Prizes for grantholders
Funded through a Broadcast Development
Award, the film Fireworks by Jonathan
Hall and Hannah Robinson was the grand
prize winner at the 11th Annual American
Screenwriters’ Association International
fields to develop new media projects. We are
Screenplay Competition.
funding three Crossover Labs – the first to
involve scientists – which will be themed
Professor Harold Cook, director of the
around games, documentaries and content
Wellcome Trust Centre for the History of
for children.
Medicine at University College London,
This programme follows on from the
has won a gold medal in the 2007
success of another unique collaborative
ForeWord Magazine Book of the Year
project: Science on Film. Taught by leading
Awards for his book Matters of Exchange.
broadcast professionals and scientists, and
run in partnership with the Documentary
Also at UCL, Professor Eleanor Maguire,
Filmmakers Group, this project brought
Senior Research Fellow at the Wellcome
together eight film makers and eight
Trust Centre for Neuroimaging, has
biomedical scientists on an intensive film
won the 2008 Royal Society Rosalind
production and training scheme. You can
Franklin Award, given in recognition
watch the resulting films online at
of an individual’s contribution to
www.wellcome.ac.uk/scienceonfilm.
the promotion of women in science,
A number of broadcast projects to celebrate
engineering and technology.
Darwin 200 (the bicentenary of Charles
Darwin’s birth) are also in development.
Dr Daniel Freeman from the Institute
These include Evolution Matters, two
of Psychiatry, King’s College London,
programmes about good practice in teaching
has received the 2008 May Davidson
evolution in primary and secondary schools.
Award from the British Psychological
We have joined with Channel 4 to fund an
Society’s Division of Clinical Psychology.
alternate reality game for 14- to 19-year-olds
This award is given in recognition of
around genomics and evolution. Finally, we
a clinical psychologist who has made
are commissioning a four-minute animated
an outstanding contribution to the
fly-through of the Tree of Life to form part of
profession within his or her first ten
David Attenborough’s BBC1 special on
years of qualifying.
Darwin’s birthday.
Wellcome Trust Career
Re-entry Fellowships
provide support for
postdoctoral scientists
who want to resume
their research career
after a break of two years
or more. Chrissie Giles
meets two of the three
scientists awarded
fellowships this year to
find out what they’ve been
doing away from science,
and how it has been for
them getting back to
the lab.
Back to the bench
Dr Wendy Gaisford is a research scientist
working on autoimmunity and type 1 diabetes
at the University of Cambridge. She returned
to the lab in March 2008 after 14 years out
of science.
“I took a break from my job in immunology
at the National Institute for Biological
Standards and Control to have children.
While they were growing I had a number of
jobs, including freelance medical writing
and working for a science-based computing
company. I realised that I didn’t want to be
sitting at a computer for the rest of my life
and that I wanted to be in the lab again.
“I started looking around and found that
it was virtually impossible to get back into
science – people just don’t want you if you’ve
been out for a while. Science moves on very
quickly and so the longer you’re out, the
harder it is for you to prove that you can get
back up to date.
“I had been applying for jobs but got
rejection after rejection. Then I did an Open
University course, T160, which helps women
to return to technical jobs. They put me in
touch with Cambridge AWISE [Cambridge
Association for Women in Science and
Engineering], who recommended the
Wellcome Trust grant. This grant was the
best option, particularly as it pays both
the researcher and the lab expenses.
“The biggest change since I last worked in
science is the technology – it’s just amazing,
particularly the way you can identify and sort
particular cells. It’s all so much easier now
that everything is automated.
Dr Wendy Gaisford, research scientist at the University of Cambridge.
“I don’t know where I’m going next but I “Coming back to the lab was hard –
know this grant has given me the chance now I was really rusty. All the things I knew,
either to stay in academia or get into industry I’d forgotten, and it took almost a whole
– it’s been brilliant coming back to the lab.” year to get back into everything.
“In my spare time I write, and I’ve recently
Dr Jennifer Rohn is a postdoctoral researcher got a book deal for my first novel, so I know
working on cell shape at the MRC Laboratory if it all went horribly wrong I’d be OK, but
for Molecular Cell Biology at University I really hope I get a permanent lab position.
College London. I don’t regret anything though. My time on
“I got my PhD at the University of the ‘other side’ in science publishing has been
Washington in Seattle and came to London really useful. Now colleagues come to me for
to do a postdoc. After that I joined a small help with journal submissions – it’s great
biotech start-up company in The Netherlands. being a scientist who knows how to write a
I was there for about four years and it was paper and get it published.”
going really well, but after 9/11 the whole
biotech industry in Europe collapsed. I ended For more on our Career Re-entry
up stuck in Amsterdam on the dole for nine Fellowships, see www.wellcome.ac.uk/
months, doing freelance science writing and careerreentry.
unable to find a research position. I ended up
returning to Britain to go into scientific
publishing.
“I worked at BioMed Central for 18 months
and then moved on to a society journal. I
really loved the work but the whole time I had
the feeling that I had only left science because
I was forced out. The job market was looking
better but I didn’t think it was possible to go
back to science as I’d been out for four years.
“At a party I met Buzz Baum, who runs the
lab I’m working in now. He said there might
be something in his lab I could do, but could
offer only one year’s salary. So I left my cushy,
permanent job in publishing and took this in
the hope I would get something. I was really
lucky to get the Wellcome Trust grant.
Dr Jennifer Rohn, postdoctoral researcher at UCL.
WellcomeNews | Issue 56 | 5
funding
Unravelling neurodegeneration
Digital artwork representing Alzheimer’s disease. Adrian Cousins
In partnership with the Medical Research
Council, we are calling for proposals for
Strategic Awards in Neurodegenerative
Diseases. The £30 million strategic initiative
aims to stimulate high-quality, collaborative
research that will advance knowledge
of neurodegenerative diseases through
interdisciplinary approaches.
By addressing key gaps in our knowledge of
these debilitating and distressing diseases, this
initiative should catalyse the development
of much-needed new approaches for early
diagnosis and effective therapies.
Consortia of leading research groups
from the UK and the Republic of Ireland
are invited to apply for five years’ funding
(up to £5m), which will support the
development of collaborative and innovative
Research evidence in policy making
We understand the importance of
using evidence from health research in
policymaking. As part of our commitment
to build capacity in this area, we are making
a joint call for proposals with the Alliance for
Health Policy and Systems Research (HPSR)
for a new initiative, on enhancing capacity to
apply research evidence in policy making.
6 | WellcomeNews | Issue 56
interdisciplinary research programmes
to investigate the biological processes
underlying neurodegenerative diseases,
including Alzheimer’s disease, frontal
temporal dementia, Parkinson’s disease,
Huntington’s disease, amyotrophic lateral
sclerosis and multiple sclerosis. Partners may
include international researchers and those
from the pharmaceutical industry.
Preliminary applications must be received
by 12 December 2008. More details of the
call can be found at www.wellcome.ac.uk/
neurodegen/wn. Prospective applicants
should contact Dr Shewly Choudhury
(s.choudhury@wellcome.ac.uk)
or Dr Joanna Latimer (joannalatimer
@headoffice.mrc.ac.uk).
Teams based in low-income countries are
invited to make brief expressions of interest
to the Alliance for HPSR by January 2009.
We and the Alliance will then fund the most
promising proposals. In total, US$1 million
(£550 000) is available for the scheme.
For more details see
www.who.int/alliance-hpsr/en/.
Enhanced funding
for clinicians
New support for clinicians, particularly those
in the early stages of their careers, comes in
the form of several new funding schemes we
have launched in September 2008.
In collaboration with the Academy of
Medical Sciences (who will administer the
scheme), we are supporting research-active
clinical lecturers who have recently
completed their MD or PhD through funding
that will allow them to maintain research
momentum. The crucial pilot data that will
be generated should ensure that this
important group of investigators enhance
their competitiveness for applications for
longer-term funding. Starter Grants for
Clinical Lecturers will provide between
£15 000 and £30 000 over two years, to
contribute to the costs of research
consumables.
Our Postdoctoral Training Fellowships for
MB/PhD graduates provide a unique
opportunity for the most promising newly
qualified MB/PhD graduates to make an early
start in developing independent research
careers. The fellowships, which are for up to
four years, are open to individuals who have
graduated as an MB/PhD or who have
achieved a high-quality PhD in a relevant
subject either during or before commencing
their initial medical, veterinary or dental
degree.
As part of our commitment to supporting
and nurturing excellence in clinical research
across disciplines and at all career stages, we
have changed our eligibility criteria, meaning
that clinical psychologists are now welcome
to apply for our range of clinical schemes.
www.wellcome.ac.uk/Funding/
Biomedical-science/Grants/Fellowships-
and-personal-awards/
Clinical scientists can apply for a range of Trust schemes.

Technology Transfer
Translation Awards provide funding
for applied research and development
projects that address an unmet need in
healthcare.
Who can apply? Wide eligibility –
open to both academic researchers and
companies.
What’s available? Funding to develop
the project to the point where there is a
realistic expectation that the innovation
will be developed further by the market.
What's the deadline? Preliminary
applications should be received by
17 November 2008.
More info: www.wellcome.ac.uk/
Funding/Technology-transfer/Awards/
Translation-Awards/
Seeding Drug Discovery awards are made
as part of a five-year, £91 million initiative
to develop drug-like small molecules in an
area of unmet medical need.
Who can apply? Wide eligibility –
open to both academic researchers and
companies.
What’s available? Funding for two to
three years to develop early-stage small
molecules to the point where they are
attractive to third-party funders – typically
at the stage of selection of an optimised
pre-clinical candidate.
What's the deadline? Preliminary
applications should be received by
7 November 2008.
More info: www.wellcome.ac.uk/
seedingdrugdiscovery
Neuroscience
and Mental Health
Three grants have been made through
our Neuroscience and Mental Health
stream. At the Institute of Education,
Professor Ian St James Roberts has
been awarded a project grant to explore
the relationship between crying and
sleep–wake patterns in infants in the first
18 months of life. Professor Philippa
Garety and colleagues at the Institute of
Psychiatry, King’s College London will
use project grant funding to explore how
jumping to conclusions and anxiety-related
processes are linked in psychosis. Lastly, an
equipment grant has been made to Professor
Brian Day at the Institute of Neurology,
University College London. This funding
will be used to upgrade and expand a
3D motion analysis system.
Infectious ideas
Penicillium mould.
David Gregory and Debbie Marshall
Two project grants have been awarded to
researchers at Imperial College London
through the Immunology and Infectious
Disease stream. Dr Maria-Gloria Basanez
will explore how the differences in cattle
and human density affects the spread of
onchocerciasis (river blindness), which
is transmitted by a black fly. Dr Matthew
Fisher and colleagues will study Penicillium
marneffei, the only Penicillium fungus to cause
serious disease in humans, to find out what
makes this particular fungus pathogenic.
New research will relate babies’ crying to their
sleep patterns. Anthea Sieveking
funding
South Africa demographic
surveillance support
Professor Stephen Tollman at the University
of Witwatersrand, South Africa has received
core funding for his research at the Agincourt
demographic surveillance site. This funding
follows earlier Wellcome Trust support for
the research, which focuses on the health
and socioeconomic changes affecting a rural
population in transition, near South Africa’s
Mozambican border.
Large Arts
We have made three large Arts Awards. One
goes to Bridget Nicholls of Animal Alchemy
for the 2009 International Arts Pestival, a
festival to celebrate insects in art and the art
of being an insect. Anna Ledgard has received
funding for ‘For the Best’, a performance
project with young people attending the
Evelina Children’s Hospital Renal Unit
at Guy’s and St Thomas’, London. Simon
Pummell will work on ‘Shock Headed Soul’,
a project to create a film and publication
based on Daniel Paul Schreber’s 1903 book
Memoirs of my Nervous Illness.
Gaining knowledge
At the Wellcome Trust Centre for
Neuroimaging at University College London,
Dr Dharshan Kumaran has been awarded
an Intermediate Clinical Fellowship. The
neurologist and chess grandmaster will study
knowledge acquisition in the human brain.
Henry Wellcome
Fellowships
The prestigious Sir Henry Wellcome
Postdoctoral Fellowship scheme is
now taking applications for its third
year of awards.
Who can apply? Talented researchers
who are in the final year of their PhD
or who have less than one years’
postdoctoral experience.
What’s available? £250 000 for a
four-year, full-time fellowship to develop
an independent research career in the best
labs in the UK and overseas.
What’s the deadline? Preliminary
applications must be received by
3 November 2008.
More info: www.wellcome.ac.uk/shwpf
WellcomeNews | Issue 56 | 7
funding
Humanities resources
We have made three significant awards
to support the interdisciplinary field of
medical humanities.
King’s College London will receive
about £2 million over five years, and
Durham University around £1.8m.
The grants will be used to establish centres
of excellence in medical humanities.
At King’s, Professor Brian Hurwitz and
colleagues will study ‘The Boundaries of
Illness’, looking at personal and cultural
representations of health and illness and
the boundaries between them. Professor
Martyn Evans and colleagues at Durham
University will examine ‘Medicine and
Human Flourishing’ – a programme of
research aimed at understanding the
human side of medicine.
A man seeks medical help after “going rather too far in the Pursuit of Pleasure and Amusement”.
Lithograph by George Cruikshank.
Malawi renewal
We have renewed funding for the
Malawi–Liverpool–Wellcome Trust
Programme for Research in Tropical
Medicine, one of our four Major Overseas
Programmes. The £8.8 million award includes
£800 000 for a new training and learning
centre. The Programme also has a new
Director, Professor Rob Heyderman from
the University of Liverpool.
8 | WellcomeNews | Issue 56
The Glasgow Centre for the Social History
of Health and Healthcare – a joint venture
between the University of Strathclyde
and Glasgow Caledonian University – has
received the largest award ever made for the
history of medicine in Scotland. The £375 000
Enhancement Award will be used to employ
new researchers over the next five years and
assist with outreach activities.
Dr James Mills, Director of the Centre,
said: “Many of the illnesses we associate
with today – binge drinking, obesity and
non-prescription drug use – are nothing new.
By looking at the policies of the past, we
can help inform how we can deal effectively
with the same problems now, and just as
importantly, which policies should
be avoided at all costs.”
Road to discovery
A Strategic Award of £4.7 million has been
made to the European Molecular Biology
Laboratory’s European Bioinformatics
Institute (EMBL-EBI) to make a number of
databases from the drug discovery company
Galapagos NV part of EMBL-EBI’s open access
resources. The databases contain details of the
properties and activities of drugs and drug-like
small molecules, and should prove invaluable
for researchers developing new drugs.
Fruit fly. Audio Visual, LSHTM
In development
Among the awards made through the
Molecules, Genes and Cells stream is
a programme grant to Wellcome Trust
Principal Research Fellow Professor Elizabeth
Robertson at the University of Oxford to
study the networks of genes that control
development in the early mammalian
embryo. Meanwhile, at the University of
Glasgow, Dr Stephen Goodwin plans to use
a genome-wide approach to explore how a
gene called fruitless acts with other genes in
male fruit flies to coordinate events that lead
to sex-specific behaviours and physiology.
Sound approach
A Technology Development Grant has
been awarded to Professor Brian Derby
and colleagues at the University of
Manchester. The team will optimise scanning
acoustic microscopy, a technology usually
used in engineering, for use in medical
applications, matching tissue features
to its mechanical properties.
Glasgow grants
Funding for the Wellcome Trust Centre for
Molecular Parasitology at the University
of Glasgow has been renewed. Also at the
Centre, malariologist Professor Andy Waters
was awarded a Principal Research Fellowship.
Translational research
Dr Jillian Baker and colleagues at the
University of Nottingham have received a
Seeding Drug Discovery award to develop
highly selective ß1-antagonists. Unlike other
ß-blockers, which cause airway narrowing
and so can’t be given to patients with
respiratory diseases, these drugs would be
suitable for patients with both heart and lung
diseases. Dr Liam Marnane and colleagues
from University College Cork have been
given a Translation Award to develop a signal
processing system, based on EEG and ECG,
to help medical staff to identify seizures
in newborn babies without the need for
complicated equipment.

The SABRE study will examine links between health and ethnicity. SABRE
Vive la différence
Ethnic differences seem to play a major role in a
person’s susceptibility to cardiovascular disease.
Chrissie Giles talks to Professor Nishi Chaturvedi,
who has been at the forefront of this research for
over 20 years, about a major new study, SABRE.
Some 20 years ago researchers scouring
routine mortality statistics from the UK came
across something strange. They found that
first-generation migrants of Indian Asian
descent had significantly more heart attacks
and strokes than white European people. In
contrast, African Caribbean people, although
also at higher risk of stroke, seemed to be at
a significantly lower risk of coronary heart
disease – particularly men, whose risk was
half that of their European counterparts.
Nishi Chaturvedi – now Professor of
Clinical Epidemiology at the International
Centre for Circulatory Health, part of
Imperial College Healthcare NHS Trust – was
intrigued. To try to unpick this apparent
ethnic aspect to susceptibility to heart
disease, she and her colleagues performed
two surveys of 4000 Londoners between 1989
and 1991: the Brent study, which looked at
an African Caribbean population, and the
Southall study, which looked at an Indian
Asian group.
These studies found that, although both
ethnic minority groups had higher rates of
original participants from the Southall and
Brent studies, a unique and large population
that has been followed for a long period of
time. “We’re trying to explore the idea of
‘diabetes toxicity’,” says Professor Chaturvedi.
“Why does diabetes seem to be particularly
bad for an Indian Asian or African Caribbean
in terms of cardiovascular disease?”
The researchers have begun seeing the
individuals from the original studies again,
a process expected to take three years. The
Southall and Brent studies captured only
mortality data since the baseline studies,
so now the researchers are studying the
participants’ medical records to see what
cardiovascular events have occurred since
the first studies. They are also looking at early
signs of cardiovascular disease that are not
apparent to the individual.
Professor Chaturvedi hopes that
understanding these risk factors better will
lead to a change in the way that people are
diagnosed and treated for cardiovascular
diseases. “We know a lot about how to
prevent disease occurring in the first place
if you’re European, and we know a lot about
how to treat people who are at high risk of
cardiovascular disease,” she says. However,
the story isn’t so clear for Indian Asians and
African Caribbeans. “Given the differences in
risk, we don’t think the same cut-off points
should apply,” she says. This kind of research
should benefit everyone, not just those
from the populations studied. For example,
understanding how African Caribbean men
are ‘protected’ from heart disease could
provide information relevant to the health of
people in other ethnic groups.
diabetes than Europeans, the profiles of fats
What are the ethical implications of this
(lipids) in the bloodstream varied. Indian
kind of work? “Sometimes there are criticisms
Asians tended to have ‘unhealthy’ blood lipid
that you’re compartmentalising groups that
profiles, which are linked to an increased risk
can’t be compartmentalised,” says Professor
of heart disease, while the African Caribbeans
Chaturvedi. “People ask, ‘What do you mean
had ‘healthy’ lipid profiles.
by “Indian Asian” or “African Caribbean”? Is
Although the variation in lipid profile
this a genetic or a racial thing?’”
appeared to be behind the ethnic differences
She explains that ‘ethnicity’, the definition
in susceptibility to heart disease, it was not
they use to group individuals, may appear
clear why diabetes affected lipid profiles
somewhat heterogeneous, being based
differently in the two groups. The study
on a number of factors including lifestyle,
follow-up confirmed that adverse lipid
religion, language, cultural beliefs and
profiles and diabetes contributed to the
behaviour – which can differ substantially
high rate of heart disease in Indian Asians,
between groups. “Nevertheless, whether
but did not explain it completely.
you’re talking about a Punjabi Sikh, a Muslim
In addition, the studies also showed that
or a Bangladeshi, all those groups share a
the greater risk of stroke in both ethnic
predisposition to heart disease and diabetes…
groups was strongly related to their higher
It does go back to an underlying biological
rates of diabetes, even though blood pressure,
explanation rather than one based on
the most important risk factor for stroke,
lifestyle,” she says.
differed substantially.
“In order to reduce that risk you have to
So, in 2008, Professor Chaturvedi and
appreciate why it occurs in the first place.
colleagues embarked on SABRE (Southall and
This comparative epidemiology will help us
Brent Revisited). This study, funded by the
to understand that difference.”
British Heart Foundation and us, revisits the
www.sabrestudy.org.uk
WellcomeNews | Issue 56 | 9
research
Switching off to sound
Children with autism pay less attention to speech sounds. Don Bayley/iStockphoto
Oxford researchers have shown that children
with autism ‘switch off’ to repeated speech
sounds.
Findings such as these could ultimately
help to guide how people teach and
communicate with children affected by the
disorder, although the researchers stress that
more research in this area is required.
In autism, children often don’t pay
attention to speech sounds, but it is not
clear why. Professor Dorothy Bishop and
Dr Andrew Whitehouse from the University
of Oxford studied 15 children with autism
and 15 without. To avoid any external
distractions or stressors, the researchers used
their Wellcome Trust-funded mobile lab – a
well-equipped soundproof van.
Developing-country dementia
Levels of dementia in developing countries
could be much closer to those in developed
countries than previously thought.
New research, conducted by the 10/66
Dementia Research Group, an international
collaboration part-funded by us, suggests that
policy makers in low-income and middle-
income countries may need to re-examine the
burden of dementia on their health services.
The researchers assessed almost 15 000
people over the age of 65 in 11 countries,
including India, China, Cuba and Peru. The
assessment consisted of interviews with the
affected individual and, typically, a family
member, as well as a physical examination
and a blood test. According to the study, the
prevalence of dementia in urban settings
in Latin America is comparable to rates in
Europe and the USA, though the prevalence
in China and India is lower.
10 | WellcomeNews | Issue 56
The researchers found that children with
autism were able to respond to a speech
sound (such as ‘ah’) when it was presented in
a sequence of nonverbal sounds (beeps).
However, when a beep was presented in a
series of speech sounds, the brains of the
children with autism did not respond as
expected – they had ‘switched off’.
“Although in its early stages, this kind of
research could change educational practices,”
says Dr Whitehouse. “If children with autism
switch off to speech sounds then you might
want to teach them in a different way, so
you’re not always talking or so you’re using
more pictures.”
Whitehouse AJ, Bishop DV. Do children with autism ‘switch
off’ to speech sounds? An investigation using event-related
potentials. Dev Sci 2008;11(4):516–24.
The team found evidence that people
in developing countries were less likely to
perceive or report that their elderly relatives
were experiencing difficulties, even with
clear evidence of disability and memory
impairment.
“Our data suggest that, even if it is not
recognised as dementia, the illness places
a heavy burden on both the elderly patient
and their relatives,” says Professor Martin
Prince from the Institute of Psychiatry,
King’s College London, who leads the group.
“Being able to estimate accurately the true
population of people living with this burden
is the first important step towards putting
into place appropriate health and social
care systems.”
Llibre Rodriguez J et al. Prevalence of dementia in Latin
America, India, and China: a population-based cross-
sectional survey. Lancet 2008;372(9637):464–74.
Stutter risk
Bilingual children have a greater risk of
stuttering than monolingual children,
particularly if they do not wait until they
start school to learn their second language,
Professor Peter Howell from University
College London and colleagues have found.
Their study provides evidence for the link
between bilingualism and stuttering – long
hypothesised but poorly supported by data –
and also shows that bilingual stutterers tend
to stutter in both languages they speak.
The researchers studied 317 children aged
eight to 12 years who stuttered, looking at
their stuttering history, school test results
and stuttering recovery/persistence. Of the
38 children who used a language other than
English at home, 23 spoke both English and
the non-English (minority) language from
birth. The remaining 15 learned English only
once they started school.
The results suggest that the risk of
stuttering can be reduced if children who
speak a minority language at home wait
until they are five to start learning English.
Deferring the time bilingual children
learn English also improves the chance of
recovering from a stutter later in childhood.
School performance was not affected by
whether a child had a stutter or not, nor
did it depend on whether a bilingual child
learned English alongside or after a minority
language.
Howell P et al. The effects of bilingualism on stuttering during
late childhood. Arch Dis Child 2008 [Epub ahead of print].
Prof. Peter Howell carries out a motor assessment
on a participant.
Building brains
Size isn’t everything when it comes to brain
power, scientists working at the Wellcome
Trust Sanger Institute, the University of
Edinburgh and Keele University have found.
They suggest that increasing sophistication
in the molecular processing of nerve impulses
during evolution allowed complex brains –
including those of humans – to evolve.
Emes RD et al. Evolutionary expansion and anatomical
specialization of synapse proteome complexity. Nat
Neurosci 2008;11(7):799–806.

On your nerves
Trouble concentrating? Research by Professor
Alex Thiele from Newcastle University and
colleagues has revealed that the nervous
system chemical acetylcholine is vital for
preparing our brain cells to pay attention to a
demanding task.
Another neurotransmitter, serotonin, has
been shown by Professor Trevor Robbins at
the University of Cambridge and colleagues
to play a critical role in regulating emotions,
such as aggression, during social decision
making.
Herrero JL et al. Acetylcholine contributes through
muscarinic receptors to attentional modulation in V1.
Nature 2008;454(7208):1110–4.
Crockett MJ et al. Serotonin modulates behavioral
reactions to unfairness. Science 2008;320(5884):1739.
Aggression is regulated by serotonin.
Craig Wactor/iStockphoto
Sharing memories
Our visual memory can be used more flexibly
than previously thought, according to Trust-
funded research carried out at University
College London. For almost 50 years,
scientists have believed that when we look
at a visually ‘busy’ scene, we are only able to
store a very limited number of objects in our
visual short-term or working memory, the
memory that we hold for a few seconds after
looking at a scene.
Now researchers have shown that this is
not the case: our visual working memory can
be shared out across the whole image, with
more memory being allocated to objects of
interest and less to background detail.
Bays P, Husain M. Dynamic shifts of limited working memory
resources in human vision. Science 2008;321(5890):851–4.
Regional variation
A trio of publications has boosted our
knowledge of the function and activity of
different parts of the brain.
Research at the University of Cambridge
– led by Wellcome Trust Senior Research
Fellow Professor Paul Fletcher – has shown
how patterns of brain activity in healthy
participants may help to predict symptoms
of psychosis in people with schizophrenia.
Also at the University of Cambridge,
Dr Sam Chamberlain and colleagues have
found that the brain regions responsible for
stopping habitual behaviour are underactive
in people with obsessive–compulsive disorder
and their unaffected close relatives.
Dr Bianca Wittmann from the Wellcome
Trust Centre for Neuroimaging at University
College London and colleagues have identified
a key region located in a primitive area of the
brain that encourages us to be adventurous.
Honey GD et al. Individual differences in psychotic effects
of ketamine are predicted by brain function measured under
placebo. J Neurosci. 2008;28(25):6295–303.
Chamberlain SR et al. Orbitofrontal dysfunction in patients
with obsessive-compulsive disorder and their unaffected
relatives. Science 2008;321(5887):421–2.
Wittmann BC et al. Striatal activity underlies novelty-based
choice in humans. Neuron 2008;58(6):967–73.
Controlling sleepiness
A set of nerve cells in the eye controls our
levels of sleepiness according to the brightness
of our surroundings, University of Oxford
researchers have discovered. In the study,
supported by Wellcome Trust and European
Commission funding, the researchers showed
that retinal ganglion cells directly regulate
the activity of sleep centres in the brain,
providing a new target for the development
of drugs to control sleep and alertness.
“We have discovered a new pathway that
modulates sleep and arousal,” says Professor
Russell G Foster of the Nuffield Laboratory of
Ophthalmology. “If we can mimic the effect
of light pharmacologically, we could turn
sleep on and off.”
Certain retinal cells make us sleepy depending on how bright it is. Dianne Harris
research
Baby face
Babies as young as four months old can
recognise nonverbal communication signals,
suggesting that infants’ brains may have an
innate capacity for social communication.
Using two imaging techniques, researchers
at Birkbeck College and University College
London studied the brain activity of infants
in response to dynamic faces on a screen.
The faces either established eye contact or
averted their gaze, then raised their eyebrows
and smiled.
Two brain areas – the prefrontal cortex and
the temporal cortex – responded to the face
that established eye contact. These areas, part
of the cortical network, are the same as those
implicated in nonverbal communication in
adults.
This suggests that the cortical network
specialises early or may even be hard-wired
to perceive facial communication cues –
essential for an infant’s ability to interact
with, and learn from, others.
Grossman T et al. Early cortical specialization for face-to-
face communication in human infants. Proc Biol Sci 2008
[Epub ahead of print].
Professor Foster and colleagues have
previously shown that the eye contains a
group of retinal nerve cells that are sensitive
to light. Working on mouse models in which
these retinal ganglion cells have been turned
off genetically, the research team found that
the effects of light on sleep and alertness were
completely abolished.
The researchers were able to track this
sleep pathway to the brain, where two sleep-
inducing centres are directly activated by the
cells, turning sleep on or off.
Lupi D et al. The acute light-induction of sleep is mediated
by OPN4-based photoreception. Nat Neurosci 2008 [Epub
ahead of print].
WellcomeNews | Issue 56 | 11
research

Counting Crohn’s
New research has trebled the number of
Q&A
genetic regions known to be implicated in
For the immune system, preventing showed fewer symptoms and a huge
Crohn’s disease, a form of inflammatory
an inappropriate response to a reduction in lung inflammation. We
bowel disease, to over 30.
harmless antigen is just as important concluded that CD200 is important in
The study also identified a number of
as responding to one that poses a controlling if an immune response is
potential targets for drug development,
genuine threat. We asked Sir Henry initiated, as well as the amplitude and
and revealed surprising new links between
Wellcome Fellow Dr Robert Snelgrove duration of any such response.
Crohn’s and other common diseases,
about his recent Nature Immunology
including asthma.
paper, which showed the importance What’s next?
The first two Crohn’s susceptibility genes
of a protein called CD200 receptor We’re now looking at other ways we can
were discovered in 2001, followed by a third
(CD200R) in controlling the immune alleviate the inflammation caused by flu by
in 2006. The Wellcome Trust Case Control
response in flu. targeting the excessive immune response.
Consortium and parallel studies took that
This is very early-stage research, but we
number above ten the following year. Now
Why study CD200R? hope that this kind of treatment could be
researchers have linked 32 genetic regions
In the airway, the primary type of immune progressed into humans, where it could
to susceptibility to Crohn’s.
cell is the alveolar macrophage, which is have broad ramifications for the many
The team of scientists and clinicians
important in judging the environment and diseases in which an excessive immune
involved used DNA samples from almost
whether an immune response should be response is the problem.
12 000 people. Many were from UK patient
made or not to a particular antigen. These
collections and analysed originally in the
cells have high levels of CD200R on their What difference has your
Case Control Consortium. Others came from
surface, and when this binds to CD200 fellowship made?
European and North American collections.
on the surface of other cells in a healthy It was a fantastic opportunity because of
“We now know of more than 30 genetic
lung the macrophage is switched off. This the amount of flexibility it gave. I could
regions that affect susceptibility to Crohn’s
switching off can be overridden when a real choose the area I was passionate about and
disease,” says Dr Jeffrey Barrett from the
threat is detected. then do cutting-edge research in any lab
Wellcome Trust Centre for Human Genetics
I liked around the world – I’m currently
at the University of Oxford, lead author of
What goes wrong in flu? in Alabama. Already, at an early stage in
the study. “These explain only about a fifth
A lot of the symptoms of flu – like my career, it’s given me a taste of being an
of the genetic risk, which implies that there
breathlessness, fever and weight loss – independent researcher.
may be hundreds of genes implicated in the
are worsened by an excessive immune
disease, each increasing susceptibility by a
response. One of the reasons this might What do you do outside of the lab?
small amount.
happen is because the immune cells that I’m a massive Tottenham Hotspur fan but
“While this study shows the power of
invade the airways to fight the infection trying to keep in contact with football from
genome-wide association studies to reveal
reduce the number of CD200 proteins Alabama is a bit of a challenge. Everyone’s
the genetics behind common diseases,
on their surface. This means that they so friendly here though – we managed to
it also highlights the complexity of
can’t deliver an inhibitory signal through find a pub that would open especially for
diseases such as Crohn’s.”
CD200R, so you have a problem switching us at lunchtime so we could watch the
Barrett JC et al. Genome-wide association defines more
than 30 distinct susceptibility loci for Crohn’s disease.
off inflammation. European Championship before we went
Nat Genet 2008;40(8):955–62. back to work.
What did your study show? Snelgrove RJ et al. A critical function for CD200 in lung
When we gave mice a mimic of CD200 immune homeostasis and the severity of influenza
infection. Nat Imm 2008;9(9):1074–83.
A granuloma of the kind often seen in cases of to replace that which is lost in flu, they
Crohn’s disease.

12 | WellcomeNews | Issue 56

Class findings
Kenyan children receiving intermittent preventative treatment for malaria. Sian Clarke
Intermittent treatment with antimalarial
drugs can reduce anaemia and improve
classroom attention in Kenyan
schoolchildren, says research by a
multidisciplinary team of Kenyan and
British researchers.
While many African children have
developed partial immunity to malaria by
school age, the disease still accounts for a
fifth of all deaths among school-aged
children. Asymptomatic infection also causes
problems, including anaemia and
absenteeism.
A new method of tackling malaria,
intermittent preventative treatment (IPT),
involves mass administration of a full
therapeutic course of antimalarial drugs at
specific intervals. In this study, the
researchers examined the effects of IPT at 30
primary schools in a rural area of high
malaria transmission in western Kenya.
Nearly 5000 children were given either
IPT (sulfadoxine-pyrimethamine with
amodiaquine) or a placebo once a term for a
year. The children were surveyed six weeks
Professor Bob Snow. Caroline Penn
after the last treatment and the researchers
found that the IPT had reduced the
occurrence of anaemia and asymptomatic
malaria infection, and increased the
children’s attention in class. IPT had
no effect on educational achievement.
The authors conclude: “The pronounced
effects of the IPT intervention…highlight
the issue of the continued, and often
unrecognised, malaria burden among
school-aged children in Africa and the
potential of school-based programmes for
tackling the problem.”
We are funding future work to explore the
effectiveness of the approach through Career
Development Fellowships to study authors
Dr Simon Brooker, currently based in the
Kenya Medical Research Institute in Nairobi,
Kenya, and Dr Siân Clarke, who will work
in Senegal.
Clarke SE et al. Effect of intermittent preventive treatment
of malaria on health and education in schoolchildren: a
cluster-randomised, double-blind, placebo-controlled trial.
2008;372(9633):127–38.
• This research was funded in part by the Wellcome Trust.
Fairer funding
The Millennium Development Goal to
halt and begin to reverse the incidence of
malaria globally is unlikely to be met, warns
Wellcome Trust Principal Research Fellow
Professor Bob Snow. In a report in
the journal PLoS Medicine, Professor Snow and
colleagues call for more money to be invested
in tackling malaria, and for this support to be
distributed more equitably.
Snow RW et al. International funding for malaria control
in relation to populations at risk of stable Plasmodium
falciparum transmission. PLoS Med 2008;5(7):e142.
research
A sticky end for malaria?
Scientists have found a key mechanism that
enables malaria-infected red blood cells to
stick to the walls of blood vessels and avoid
being destroyed by the body’s immune
system.
The research, funded through our
Functional Genomics Development
Initiative, highlights an important potential
new target for antimalarial drugs.
When the malaria parasite infects healthy
red blood cells, it secretes a ‘glue’, known
as PfEMP1, that travels to the surface of the
cells, leading to the formation of knobs
there. The cells stick to the walls of the blood
vessels, which prevents the cells being flushed
through the spleen (where the parasites
would be destroyed by the body’s immune
system) and also restricts blood supply to
vital organs.
Now, an international collaboration
of scientists has identified eight proteins
that transport the Plasmodium falciparum
parasite’s ‘glue’ to the surface of the infected
red blood cells. Removing just one of these
proteins prevents the infected red blood cells
from sticking to the walls of the blood vessels.
“Malaria parasites are evolving, making
our current treatments increasingly less
effective,” says Professor Alister Craig from
the Liverpool School of Tropical Medicine,
who collaborated on the project. “A drug
which prevents disease rather than killing the
parasite might be important because it could
retain natural inoculation in the patient,
limiting damage caused by the parasite and
providing protection from further infection.”
Maier AG et al. Exported proteins required for virulence
and rigidity of Plasmodium falciparum-infected human
erythrocytes. Cell 2008;134(1):48–61.
Red blood cells, vulnerable to malaria infection.
Annie Cavanagh
Sex change
Malaria parasites produce more sons than
daughters when conditions are difficult,
according to research led by Wellcome Trust
Research Career Development Fellow Dr
Sarah Reece at the University of Edinburgh.
The change in sex ratio increases the overall
chance of parasite genes being passed on and,
hence, the successful spread of malaria.
WellcomeNews | Issue 56 | 13
research

Inside the interactome
Forget gene number: it’s the number of
protein interactions in an organism that
appears to reflect biological complexity.
What’s more, it’s hoped that in the future,
comparison of protein interaction networks
could help researchers to understand the
different effects of similar organisms – for
example, why some fungal species can be
used to make bread and beer while others can
cause fatal fungal infections.
In the study, researchers from Imperial
College London worked with colleagues
from the Max Planck Institute for Molecular
Genetics in Berlin and the University of
Aarhus in Denmark to devise a mathematical
tool that allowed them to predict the size of
an organism’s protein interaction network, or
interactome.
While humans have fewer than twice
as many genes as fruit flies, the human
interactome is around ten times bigger than
that of fruit flies, and around three times
bigger than that in the nematode worm
Caenorhabditis elegans.
“Understanding the human genome
definitely does not go far enough to explain
what makes us different from more simple
creatures,” says Professor Michael Stumpf
at Imperial. “Our study indicates that
protein interactions could hold one of the
keys to unravelling how one organism is
differentiated from another.”
Stumpf MP et al. Estimating the size of the human
interactome. Proc Natl Acad Sci USA 2008;105(19):6959–64.
You are what your mum ate
Junk food eaten by pregnant or breastfeeding
mothers can affect the child’s health. iStockphoto
Mothers who eat an unhealthy diet during
pregnancy may be putting their children
at risk of developing long-term, irreversible
health issues, including obesity and raised
cholesterol levels.
The Wellcome Trust-funded research,
carried out in rats, suggests that the effect is
most pronounced in female offspring.
Dr Stephanie Bayol and Professor Neil
Stickland from the Royal Veterinary College,
London compared the offspring of rats fed a
diet of processed junk food during pregnancy
and lactation with the offspring of those fed a
healthy diet of regular feed.
The offspring of the mothers fed junk
food had raised levels of cholesterol as well
as higher levels of triglycerides, a type of fat
found in the bloodstream. Both are known to
increase the risk of developing heart disease.
They also had higher levels of glucose and
insulin, which both increase the likelihood of
developing type 2 diabetes.
“It seems that a mother’s diet while
pregnant and breastfeeding is very important
Proofreading protein
Scientists from the Structural Genomics
Consortium have determined the three-
dimensional structure of a key protein
component involved in enabling ‘epigenetic
code’ to be copied accurately from cell to cell.
Epigenetic code is a series of chemical
switches added on to DNA to ensure that
body cells can form different types of
tissue, despite having identical DNA code.
It is essential that the epigenetic code is
copied accurately when DNA is copied from
cell to cell, as a breakdown in this system
might mean that a gene for cell growth
is accidentally switched on, for example,
leading to unregulated cell growth and the
development of tumours.
Research published in 2007 showed the
importance of the nuclear protein UHRF1
in ensuring that the epigenetic code is
accurately copied. The key element of UHRF1
involved in this ‘proofreading’ process is
known as the Set and Ring Associated (SRA)
domain. Now, three papers published in
Nature have revealed the mechanisms by
which this domain accomplishes this task.
A co-author of one of the papers, Professor
Sirano Dhe-Paganon from the Structural
Genomics Consortium laboratories at the
University of Toronto, Canada, says: “Given
the increasing focus on epigenetics as a
mechanism behind cancer, elucidating the
structure of UHRF1 may provide crucial
insights into what goes wrong.”
Avvakumov GV et al. Structural basis for recognition of
hemi-methylated DNA by the SRA domain of human UHRF1.
Nature 2008 [Epub ahead of print].

for the long-term health of her child,” says

C. elegans, which has a much smaller interactome than
humans. Dr David Becker
Dr Bayol. “We always say ‘you are what you
eat’. In fact, it may also be true that ‘you are
what your mother ate’. This does not mean
that obesity and poor health is inevitable…
but it does mean that mothers must eat
responsibly while pregnant.”
Bayol S et al. Offspring from
mothers fed a ‘junk food’ diet

In sequence in pregnancy and lactation

exhibit exacerbated adiposity
that is more pronounced
in females. J Physiol
Genomic sequencing studies can uncover 2008;586(13):3219–30.
unexpected findings. Research by a team at
the University of Bath has shown that the
bacterium responsible for Lyme disease,
Borrelia burgdorferi, did not originate in
America as thought, but in Europe, before
the Ice Age.
Meanwhile, the sequence of a newly
emerging superbug, ‘Steno’ (Stenotrophomonas
maltophilia), completed by scientists at
the Wellcome Trust Sanger Institute and
the University of Bristol, has revealed that
the bacterium has a high capacity for drug
The nuclear protein UHRF1.
resistance. Structural Genomics Consortium

14 | WellcomeNews | Issue 56
When Pat Martino awoke
from surgery to remove
a brain tumour, he had
forgotten that he was
a world-renowned jazz
guitarist. He made a
remarkable recovery from
the amnesia and returned
to playing seven years later.
Martino Unstrung, a
documentary film funded
by a Wellcome Trust Sciart
award and produced by
director Ian Knox and
neuropsychologist Paul
Broks, explores his musical
rediscovery. By Barry Gibb.
Finding Pat Martino
Pat Martino may not be a household name,
but in the world of jazz his guitar playing is
legendary. Indeed, the opening sequence of
Martino Unstrung is in a New York guitar store,
with a jazz fan in a near gibbering state of
excitement, exclaiming to camera that his
whole world has flipped from one of tears of
hopelessness to bliss because he has just seen
Martino: “it’s like finding da Vinci!”
Born in 1944 and playing at a professional
level since his early teens, Martino saw his
career take off in the 1960s as a sideman
and then leader. He created a prolific back
catalogue of vinyl and gained an enviable
following of fans and friends (including Les
Paul, inventor of the electric guitar, and film
star Joe Pesci, who appear in the film). To
counterpoint this success, however, Martino’s
mental state was declining, to the extent
that electroshock therapy was sought as a
treatment for his darker episodes.
Neurosurgeon Fred Simeone removed the
real cause of Martino’s mental problems in
1980: a bleeding ‘bundle of worms’ the size
of an apple in the left hemisphere of his
brain – a tumorous growth, or arteriovenous
malformation. But the surgery also took a
slab of Martino’s identity – including the
knowledge that he was a world-class guitarist.
Martino Unstrung explores this profound loss
of identity and Martino’s long journey of
personal – and musical – rediscovery.
Pat Martino, who used videos of his former self to relearn guitar playing. Ian Knox
Usually a director of fiction, Ian Knox
didn’t set out to make a documentary about
Martino, but was inspired to do so when, in
2004, he went to hear the guitarist who had
‘forgotten more music than most musicians
learn in a lifetime’. Knox says: “I went along,
the gig was amazing, absolutely fantastic.
And in between sets, when I was downstairs
in Ronnie Scott’s, I spotted him sitting in the
Green Room bar and I just stuck my head
in…” A couple of beers later and the idea
was born.
Neuropsychologist and author Paul Broks
joined Knox on the project: “The very
fact that he [Martino] had this abnormal
collection of blood vessels in a particular
part of his brain would have affected brain
function, it might well have shaped his
personality, his musical ability even, in ways
that we can only speculate wildly about.”
Indeed, scanning technology reveals Martino
had lost a large portion of his left temporal
lobe during surgery, removing regions
associated with memory and emotions – and
only narrowly missing areas associated with
musical interpretation.
Martino rediscovered music on a primitive
computer while confined to a locked ward
at New York’s Mount Sinai hospital. The
computer’s 127k memory contained a
music program, which he began to play.
It was an epiphany. After 17 years of silence,
he took up the guitar again, studying
technique, via tuition videos, from a great
teacher – his former self.
“What he had probably lost was memory
that he was a player, motivation to play, and
semantic [fact-based] memory for music;
when he did pick up the guitar again to play,
it wasn’t with any great confidence…maybe
by discovering the music, he rediscovered
himself,” reflects Broks.
Filmed in the USA in 2006 and 2007, the
film departs from contemporary, graphically
intensive approaches to science, opting
instead for a lighter, more poetic visual
touch. The city itself becomes a metaphor
for the physical and emotional landscape
of Martino’s brain, an approach more artful
and abstract. Broks comments: “The idea
was to use images of the city and images of
machinery impressionistically…Ian would
say, ‘go out and find me some brain imagery’,
so I would wander round the streets, round
the park and look at things that might have
some connotation of brain damage or brain
function.”
Screenings of Martino Unstrung will be
announced later in 2008. Our Sciart and Pulse
funding schemes were amalgamated and
relaunched in 2007 as the Arts Awards. For
more details see www.wellcome.ac.uk/arts.
WellcomeNews | Issue 56 | 15
The curious case
of the Glasgow Spy
Press coverage of the Glasgow Spy trial, 1918.
Chris Beckett tells a tale of espionage, forgery and astute
bureaucracy from the Wellcome Foundation Archive.
Armgaard Karl Graves, referred to in press
reports as ‘the Glasgow Spy’, was the first
person to be convicted in Scotland under the
Official Secrets Act (1911). On 23 July 1912,
at the High Court of Judiciary, Edinburgh,
Graves was found guilty of making or
obtaining a telegraphic code for the purpose
of communicating information relating to
the British Navy and land fortifications. The
code had been concealed within the pages of
a Burroughs Wellcome & Co. diary, and the
firm’s headed paper had been used to cloak
communication with an accomplice
in Brussels.
Graves went to considerable lengths to
establish his identity as a doctor who had
practised in Australia, and was now visiting
England to undertake further training
in Edinburgh and to conduct clinical
experiments. His first port of call was not
the Firth of Forth but the Wellcome Medical
Museum in Wigmore Street, London. This
was not the casual visit of a medical man with
wide interests and time on his hands but a
calculated move in establishing a consistent
identity.
The Wellcome Foundation archive
contains a revealing record of this visit on
14 February 1912. After showing an interest
in various Burroughs Wellcome & Co.
16 | WellcomeNews | Issue 56
products (“he would like literature re all
our newest products sent to his Edinburgh
address,” it was noted), Graves reinforced
his credibility by association: the Medical
Officer of Southern Australia was presently
staying in London, he explained, and should
be contacted as a valuable source of business.
Graves’s final comment was to remark that
he had not received a Burroughs Wellcome
& Co. diary since 1909 and would greatly
appreciate one (thereby pushing further
back into time his fictive identity).
In fact, the company had been carefully
selected as a suitable source of cover for
communication. Counterfeit Burroughs
Wellcome & Co. envelopes and headed paper
had been fabricated in advance of the mission
and were used on occasion to convey coded
information about Britain’s expanding naval
capacity (construction of the Royal Naval
Dockyard at Rosyth began in 1909), and to
send payment to Graves in return. The note
of his attendance at the Wellcome Museum
included an observation that could not pass
unrecorded, in the midst of a national mood
of contagious spy fever: Graves was German.
In Edinburgh and Glasgow, Graves fleshed
out his identity still further. He applied
for a position as a locum, and his medical
knowledge was sufficiently convincing to a
Dr Leith, who interviewed him. But, as Leith
was to tell the court, he did not like the
German accent. “It is does not do in Leith?”
quipped the Solicitor-General, to the local
court’s amusement.
The strict application of Post Office
procedure contributed to Graves’s undoing:
he was refused collection of a letter addressed
to James Stafford Esq. (one of Graves’s many
aliases). The letter, which bore the name of
Burroughs Wellcome & Co. imprinted on
the envelope, was returned to its ostensible
sender. At the company’s office in Snow
Hill, London, the envelope was immediately
recognised as counterfeit. When Inspector
Edward Parker of the Yard, who was already
on the case, called at Snow Hill on Saturday
13 April he was told, somewhat proprietarily,
that the matter had been placed in the
hands of the company solicitor, who was not
available until Monday. Parker left his card,
and when he returned on Monday, he left a
detailed receipt – an inventory –
of everything: two letters in German and
an inner envelope containing one five-
pound note and one ten-pound note. In the
intervening period before Parker took away
the items, Burroughs Wellcome & Co. had
photographed all: the set of photographs sits
today in the archive, along with Inspector
Parker’s calling card, and several statements,
letter translations and newspaper cuttings
from the trial.
Graves was sentenced to 18 months’
imprisonment. If his memoir is to be
believed, the unsuccessful Glasgow Spy
undertook subsequent work for the British
Secret Service. His life remained colourful:
in 1916, he was arrested in Washington on
a charge of blackmail (the charges were
eventually dropped), and in 1929 he was
arrested in Los Angeles for grand theft.
Chris Beckett is an Assistant Archivist of the Wellcome
Foundation Archive, Wellcome Library, London. A longer
version of this article appered in Wellcome History 38.
See www.wellcome.ac.uk/wellcomehistory
Wellcome Foundation
The Wellcome Foundation Archive
dates from 1860 to 1995, and covers
the period from Henry Wellcome’s
business partnership with Silas
Burroughs (Burroughs Wellcome & Co.)
to the emergence and consolidation of
a highly recognised international
pharmaceutical company. Wellcome
established the Wellcome Foundation
Limited in 1924, bringing together his
non-commercial and commercial
interests under a single corporate
umbrella.
 noticeboard
EMONY CHOLINESTERASE MOSAIC EMBLEMATIC OIL ASYMPTOTE ASKLEPIOS LEARNING ELECTRON MICROSCOPE BASES PULMONARY NE
E SUBLIMINAL INVITING SUPER FASCINATING NEURON HIEROGLYPHICS ANEURYSM CHARIOT RETICENT PHOTOGRAPHY PRESERVATION LA
ONISATION PERSPICACITY SOLUTIONS MILLION MATERIA MEDICA NURSE FROND NINETEEN MOLECULAR TORTURE REVOLUTIONARY INSPIR

ART AND MUSIC

BRYO PHLEBOTOMY ANKLET LYMPH NODE OPERATION GLUCOSE GLORIFICATION ENGLISH PANELLING CONTINUOUS PROCESS OF REINCAR
WER MICROSCOPE QUERIST ICONOGRAPHIC NEUROFIBROMATOSIS CURIOUS NUDE GENETICS CENTURY ANTHROPOLOGY COSMOPOLITAN
FORAYS COIFFURE SCAMPER EUGENICS LONG RECEIPT UNUSUAL BULLET INFORMING DECORATED SORANUS JOINTS MONUMENTAL MUS

THIS AUTUMN
LETAL IMPROVING ROSES ANIMAL SUBSTITUTE KING ENLIGHTEN ENGAGEMENT POSSET RESTORATION PLETHORA NOMENCLATURE ORIEN
CRATES SYLLOGISM MICROBIOLOGIST IMPROVEMENT ARCHIVES TRANSCRIPTION KNOCKOUT INTERIOR SOURCE SNAPSHOT APOCALYPTIC
NON THE DANGEROUS ART OF SURGERY FLOATING OPTOMETRY PROTEINS STEROID FIDUCIARY SOMMONTE SWIM CANOPIC ACADEMY CHA
OCARDIUM ALLEGORICAL ILLUMINATIVE CONSERVATION BLING COUNTERPOINT PROPERTY FIFTEENTH BIRD DEPICTING SILVER COMPARTME
E CADUCEUS ALLOPATHIC JEWEL TIMELESS SCROLLS CHILD MONOCHROME BIOHAZARD NEOCLASSICAL EARCAP IMPRESSED ANTRUM NO
TUNE IN:
LABILITY CONFOCAL MUSIC CHASTITY
COMPASS MATERIALS
BIOARCHAEOLOGY MASK FIGURE STILL ZOONOSES FETUS PEOPLE ODDITY SANDAL BRUSH SCI
WITH
AL AND VISUAL THE BRAIN
LANDSCAPE LIBRARY
MENDELIAN ENIGMA BRAHMAN REVEAL FRAGMENT AMAZON COLOSSUS SCAR RENOVATION SHRUNKEN BIBL
IN MIND PRESENTS ‘HAIR’
8 NOVEMBER 14 NOVEMBER

Listen to live Touch, examine,

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