network
News from the
Medical Research Council
Spring 2015
Leading science for better health
Homing in on the big C
New developments in cancer research
Bench to boardroom
What's it like to launch a science spin-out company?
Network can also be downloaded as a PDF at:
www.mrc.ac.uk/network
CONTENTS
News
Ebola vaccine safe and ready for wider testing
NEWS
COMMENT FROM
4
Nobel Laureate appointed President Elect of the
Royal Society6
People
John
Savill
CHIEF EXECUTIVE
One of the MRC’s four strategic aims
is to support scientists, whether by
providing them with the best
research environments and
equipment, or by training and
developing the next generation of
research leaders.
Remembering Mary Lyon and her impact
on mouse genetics14
Latest discoveries
Protective drug slashes HIV infection risk 12
Why weekend lie-ins could make you fatter 13
Funding
New multimillion pound India-UK research centres
16
Nurturing early collaboration with industry
17
Features
Homing in on the big C
10
Working life: Professor Stefan Neubauer,
on setting up a spin-out company
18
In clinical research, scientists have used careers maps for
years to inform decisions about the direction in which to take
their careers. But career paths in basic medical research are
less clear cut, and no such maps have existed for these
careers. To address this, the MRC has produced the
Interactive Career Framework, an interactive online resource
to help clarify the options available to people at any stage of
a biomedical research career. To our knowledge, the
framework is the first of its kind.
The framework sets out career stages and signposts available
options, including both traditional and alternative choices. As
well as early-career researchers, the framework will be of use
to mentors, supervisors, careers advisors and line managers.
Green light for mitochondrial donation
New regulations to approve mitochondrial donation were passed by MPs in the House of Commons
and by members of the House of Lords in February, allowing the UK to become the first country in the
world to carry out clinical trials of the technology.
Mitochondrial donation – a technique pioneered by scientists at
Newcastle University with funding from the MRC – has the potential to
eradicate inherited mitochondrial diseases, many of which are fatal. Each
use of the technique in people will need approval from the Human
Fertilisation and Embryology Authority.
It involves transferring the nucleus from a fertilised egg with faulty
mitochondrial DNA into an egg from a healthy donor with the nucleus
removed. The resulting baby, and his or her descendants, will therefore
be free of mitochondrial disease. Mitochondrial DNA accounts for just 37
of our 23,000 genes and is entirely separate from the DNA within the
nucleus – the part which codes for all of our physical characteristics –
so the technique has been likened to replacing the batteries in a
laptop computer.
Learn more about mitochondrial donation research on our blog at
http://mrc.io/1C6EUTI and watch our 2012 interview with Professor Doug
Turnbull, one of the scientists who developed the technique, at
http://mrc.io/1K7OImP
Pronuclei taken from a fertilised egg with faulty mitochondria are transferred
into a donor egg with healthy mitochondria © University of Newcastle
New career resource for medical researchers
It is part of a wider piece of work done here at the MRC.
We have been carrying out a review to better understand
community concerns in pursuing a career in medical research
and have reviewed our existing support mechanisms to make
sure we are providing the right support at the right time.
The MRC has launched an online resource which, for the first time, highlights
the options available to people at all stages of a biomedical research career.
Find out more about the Interactive Career Framework
and review on page 3.
The Interactive Career Framework includes case
studies, routes to funding, required skills and
experience, and information on the day-to-day
work involved in different job roles.
John Savill
MRC Chief Executive
The framework is intended to be of use not only
to those in, or thinking about, a career in
research but also to mentors, supervisors,
careers advisors and line managers.
MRC Programme Manager Simone Bryan
explains: “Pursuing a research career can be
challenging and the range of options are
increasing. There is no formulaic career path.
The MRC’s framework is a first for early career
scientists in basic research, signposting the
choices available to help researchers make
informed decisions about their careers.”
The MRC has a leading national role in
developing future research leaders.
Find out more about the careers review at
www.mrc.ac.uk/careerframework and visit
the framework at
www.mrc.ac.uk/interactiveframework
MRCNetwork | 3
NEWS
EBOLA VACCINE SAFE AND
READY FOR WIDER TESTING
Results from an MRC-funded UK trial of an Ebola vaccine candidate suggest
that it is safe and able to generate an immune response. A larger trial in
West Africa is now underway to test how effective it is in protecting
people against the virus.
Varying doses of the vaccine were tested in 60 healthy volunteers
between September and November 2014 at Oxford University’s
Jenner Institute.
“The results are very encouraging in terms of the safety profile of the
vaccine,” said Oxford University’s Professor Adrian Hill, Principal
investigator on the trial. “We have seen an immune response in the great
majority of people receiving the vaccine. It is possible to be optimistic
about the immune responses we've seen; it's also hard to be really
confident the levels would be protective. Larger trials in West Africa will
be able to tell us more. We are also currently assessing another option,
involving a booster dose, for improving immune response levels.”
The candidate vaccine is being co-developed by the US National
£14m to find more
targeted treatments
The MRC has made a further £13.7m investment in stratified
medicine research collaborations covering a spectrum of
diseases from rare condition Systemic Lupus Erythematosus
to common conditions affecting millions of patients,
including cancer and heart disease.
The four new awards, announced by Minister for Life Sciences George Freeman at the Healthcare Investor Forum in
January, bring the total MRC funding to £52m, invested in 13 stratified medicine consortia.
Institutes of Health and GlaxoSmithKline against the Zaire strain of Ebola,
the one currently circulating in West Africa. The first doses for use in
large-scale trials in West Africa have been delivered to Liberia by GSK.
Stratified medicine research uses diagnostic tests or techniques to group patients within a disease area by their genes or
symptoms, to find more targeted treatments based on their disease risk or expected response to treatment. This
approach also has benefits for industry with the potential for more efficient therapeutic development.
The UK trial was also funded by the Wellcome Trust and the Department
for International Development (DFID). Of the original volunteers, 30 have
been invited back and received a second candidate ‘booster’ Ebola
vaccine, made by Danish company Bavarian Nordic, to find out whether
it could further increase the immune responses.
The 13 collaborations have attracted UK and international industry partners, 32 academic partners, and a number of
charities including Cancer Research UK, the British Heart Foundation and Arthritis Research UK.
Speaking in January, Professor Hill added: “The speed at which all this is
happening is remarkable. We'd especially like to thank all the volunteers.
It's also thanks to the hard work of many scientists, funders, pharma
firms, regulators and agencies, all coming together, that we can make
such rapid progress.”
George Freeman said: “As part of our strategy for the life sciences we are bringing together industry
with the assets and capabilities of researchers in universities and the NHS to revolutionise the way
we look at getting better treatments into the health service and make sure that the UK remains
one of the best places in the world for 21st Century medical innovation.”
Case study: targeting severe asthma
Led by Professor Liam Heaney of Queen’s University, Belfast, the RASP-UK (Refractory Asthma
Stratification Programme) consortium has been awarded £4.8m to study severe asthma.
Joining the fight against Ebola
• When the World Health Organization declared the West Africa Ebola
outbreak an emergency in August 2014 the MRC joined forces with the
Wellcome Trust and DFID to provide £2.8m funding for the first UK
safety trial of an ebola vaccine candidate. This trial paved the way for
larger scale efficacy trials in affected countries.
• The MRC Centre for Outbreak Analysis and Modelling published a paper
alerting the world to the scale of the epidemic in October 2014: http://
mrc.io/1wVZVkJ
4 | MRCNetwork
• Extra strategic funding to the MRC Human Immunology Unit in Oxford
is supporting ongoing development of new immune-therapeutics
against emerging infections, including Ebola.
• In December 2014, the European and Developing Countries Clinical
Trials Partnership – of which the MRC is a UK partner - expanded its
scope to encompass Ebola and other emerging infections in Africa.
Despite wide variation in the severity of symptoms, international treatment guidelines
recommend a ‘one-size fits all’ approach; all patients are given inhaled and oral steroids
in escalating doses. The consortia will investigate two groups of asthma patients based
on different types of inflammation present in their lungs. They will test a new drug
on one group, and study the other group to understand more about their disease
with the potential to identify new treatments effective for this specific subset
of patients.
Find out more at www.rasp.org.uk
• The MRC-supported UK Collaborative on Development Sciences has
created a database of Ebola related activities as a public resource
http://mrc.io/1BmIARN
MRCNetwork | 5
NEWS
Nobel Laureate appointed
President Elect of the
Royal Society
Venki Ramakrishnan, Deputy Director of the MRC Laboratory of Molecular Biology
(LMB), Joint Head of the LMB’s Structural Studies Division and Nobel Laureate, has been
confirmed as President Elect of the Royal Society.
Venki will take up the post of President on 1 December 2015. His research focuses on
the structure and function of the ribosome, the molecular machine that synthesises
proteins by translating genetic information held in mRNA, and on the action of
antibiotics on this process. For this work Venki shared the Nobel Prize for Chemistry in
2009 with Tom Steitz and Ada Yonath and was awarded a knighthood in 2012.
Venki follows in the footsteps of the previous LMB Director and Nobel Laureate, Aaron
Klug, who was President of the Royal Society from 1995 to 2000.
EUROPEAN BOOST TO
DEMENTIA RESEARCH
A £50m pan-European study to
improve drugs that could prevent
dementia is set to begin.
The European Prevention of Alzheimer’s Dementia (EPAD) initiative
involves 35 partners from academia and industry. It will establish a
Europe-wide register of 24,000 people deemed at high risk of developing
dementia, drawing upon the MRC’s Dementia Platform UK (DPUK) - a £53
million academic and industry research collaboration launched in 2014.
Tackling dementia is one of the Prime Minister’s priorities.
The research team hopes to break new ground in the understanding and
management of Alzheimer’s disease in people with very early symptoms,
or none. By identifying molecules in tissue or blood that indicate disease,
they hope to detect people with early stage dementia even if they have
no noticeable symptoms. Those patients at highest risk will be invited to
join trials of new preventative medicines.
Edinburgh University’s Professor Craig Ritchie, a member of the DPUK
leadership team, described the project as “a genuine game-changer in
the fight against dementia.”
“By joining forces, scientists and pharmaceutical companies across
Europe can deliver a real benefit to people at risk of this disease.
Together, we can identify people at risk in their middle age, accelerate
their treatment and offer a range of medical options rapidly within the
same trial,” he added.
EPAD is led by the University of Edinburgh and includes partners from the
Universities of Cambridge, Leicester, Oxford and Cardiff.
6 | MRCNetwork
MRCNetwork | 7
NEWS
Brightest young minds in dementia research
gather in London
Farewell to NIMR, hello to The Crick
Some of Europe's brightest young leaders in
dementia research met in London in March to
discuss innovative ideas to address the disease.
Dementia now affects 44 million people across the
globe and the UK government has made treating the
disease a priority.
After a century of producing world class science – from the discovery of
the flu virus to development of the alcohol breathalyser – the MRC
National Institute for Medical Research (NIMR) was dissolved on 31
March to become part of a cutting edge new institute.
From 1 April, all NIMR staff will officially begin working for the The
Frances Crick Institute, which will exist as a multi-site institute until the
new building in central London opens towards the end of 2015.
The NIMR was the UK’s first government-funded institute with staff
dedicated full-time to biomedical research. You can learn more about the
NIMR’s history at www.nimr.mrc.ac.uk/about/history and find out the
latest on the Crick Institute at www.crick.ac.uk
You can read a storify account of the event,
organised by the UK Science and Innovation
Network in partnership with the Joint Programme on
Neurodegeneration and Dementia (JPND) and
Alzheimers Europe, at https://storify.com/UKinFrance/european-dementia-event
Cravings: Can your
food control you?
From the flavours to which we were
exposed in the womb to the very next
bite we take, our appetites have been
shaped by food. Through personal stories,
fascinating objects and cutting-edge
science and technology, a new MRCsupported exhibition at the Science
Museum – ‘Cravings’ - explores how food
affects our bodies, brains and eating
habits. The exhibition runs until 1 January
2016. http://mrc.io/1zLH5vJ
A special mattress developed at NIMR in the late 1960s to detect sleep apnoea in
babies on busy hospital wards. It worked by electronically detecting the change in air
flow inside the inflatable mattress that occurred if a baby stopped breathing, raising
the alarm to clinical staff.
Prions in the art gallery
Objects and documents from the MRC Prion Unit have found a temporary new home at the Hayward Gallery in London as part of the
History is Now exhibition. Running until 26 April, the exhibition is the work of seven artists, each looking at an idea or topic that has shaped
the nation from the post-war period to the present day, including the Cold War and feminism.
Patients welcome genome sequencing
London-based artist Roger Hiorns – supported by the Wellcome Trust – explores the BSE (bovine spongiform encephalopathy) crisis of the 1980s
and 1990s. Included in his strand of the exhibition are the original Western blot test from 1996 showing that variant Creutzfeldt-Jakob disease
(vCJD) was caused by BSE and a mock-up of the world’s first blood test for vCJD.
Unit Director Professor John Collinge will take part in a panel discussion at the gallery on 25 April. http://mrc.io/1M9n6MB
Patients are broadly positive about genome sequencing, according to a new
patient charter published by Genetic Alliance UK in February.
With support from the MRC and other funders, Genetic Alliance UK sought
the views of patients through four online engagement sessions to shape
recommendations that need to be considered before genome sequencing
becomes incorporated into NHS services.
Those who responded said they wanted to receive as much information as
possible about their health from genome sequencing; valued genetic counselling;
welcomed the sharing of their genomic data for research; and thought that the
NHS needed to make more progress towards preparing for the integration of
genome sequencing into clinical practice.
http://mrc.io/1FEvXkN
Roger Hiorns' curated section of the
History Is Now exhibition, which
includes Damian Hirst's 'Out of sight.
Out of mind.' (left).
8 | MRCNetwork
MRCNetwork | 9
FEATURE
Homing
in on the
BIG C
One in two of us will get cancer at some point in our lives, according to
new figures from Cancer Research UK. Sarah Harrop looks at two recent
MRC-funded developments in cancer research, one that’s already helping
patients to live longer and another which holds promise for the future.
“It is meddlesome and unkind to give radiotherapy to patients whose
prostate cancer has spread locally,” said one cancer specialist in the early
1990s. These are words which Cardiff University’s Professor Malcolm
Mason will always remember. The findings of a clinical trial he led,
spanning 10 years and involving over a thousand British and Canadian
patients, have firmly disproved this once widely held view.
That’s something that’s already come to pass. Since interim results from
the PR07 trial were published five years ago, UK, Europe-wide and US
guidelines for the treatment of prostate cancer patients with locally
advanced disease have been changed to include radiotherapy, meaning
that thousands more lives will be saved. And there are wider
benefits, too.
“We showed that adding radiotherapy to the standard care in these
patients more than halved the number of deaths from prostate cancer.
So it’s an absolutely essential part of these patients’ therapy,”
says Malcolm.
“Treating advanced cancer is very expensive, as well causing a traumatic
and terrible time for patients and their families. So if we can prevent that
situation from arising in the first place, there would be substantial cost
savings to the NHS. And of course, not all prostate cancer patients are
elderly – so if we can cure prostate cancer in younger patients they will
go on to have many more years of active and productive life,”
comments Malcolm.
Around 40,000 men are diagnosed with prostate cancer each year in the
UK. The patients in this study were those whose cancer had spread
outside the surface of the prostate gland, but not to other parts of the
body. Half of the men were given the usual treatment of androgen
deprivation: drugs to stop the production of male hormones which fuel
the growth of the cancer. The other half received these drugs
alongside radiotherapy.
After eight years there was a 30 per cent improvement in survival in men
who had radiotherapy alongside androgen deprivation, compared with
those who had received the drugs only. Deaths from prostate cancer
during that time were reduced by an impressive 54 per cent.
“We were elated when we saw these results because we had evidence of
something that was really going to benefit patients and could be
reflected in guidelines that were being given to cancer physicians
worldwide,” says Malcolm.
10 | MRCNetwork
Huge international clinical trials like PR07 are enormously expensive and
time-consuming to plan and carry out. So are they really worth it?
“They are absolutely essential,” says Malcolm. “It would have been
impossible to get an answer to this question in any other way than
carrying out a randomised trial. Without PR07 we would have been no
further on from the situation where we were just treating people on the
basis of a hunch, which for these patients would have been that
radiotherapy is – well – ‘meddlesome and unkind’. Clinical trials benefit
everybody – the patients of today because they get the best quality of
care if they take part in a trial, and by learning something about how we
might improve treatments that benefits the patients of tomorrow. We’ve
absolutely got to continue doing them.”
Dr Sam Janes.
Targeting tumours
Radiotherapy looks set to remain a mainstay of cancer therapy. But
cancer medicine is increasingly moving towards targeted treatments to
avoid the unpleasant side effects of cruder therapies which kill healthy
cells as well as cancer cells.
In laboratories deep in the bowels of the Royal Free Hospital in London,
exciting things are afoot inside the bioreactors. Under the direction of Dr
Mark Lowdell, and with £2m funding from the MRC, 100 billion human
cells are to be grown for a pioneering trial of a combined cell and gene
therapy for lung cancer – the biggest ever study of its kind.
The treatment uses stem cells like Trojan horses to deliver a potent
anti-cancer protein to cancer cells. Once it reaches a tumour the gene
prompts cancer cells to self-destruct, while leaving healthy
cells unharmed.
The trial is being led by University College London’s Dr Sam Janes,
a respiratory consultant and researcher.
He explains: “We focused on stem cells from the bone marrow which
normally form fat and cartilage in the body, but which, for some reason
– we’re still not sure why – are attracted to tumours. We wondered if we
could use these cells to deliver a therapy directly to the tumour. So we
put a gene which makes a protein called TRAIL* into the stem cells.
What’s really magical about this little protein is that it kills cancer cells,
but not healthy cells.”
Sam and his team discovered that the TRAIL-carrying cells were able to
shrink tumours and even cure cancers altogether in mice with a range
of tumours which had spread around their bodies.
cause of death from cancer. The outlook for patients is bleak, with just
over 30 per cent surviving a year after diagnosis and only around six per
cent surviving for five years.
“Most patients aren’t diagnosed until the disease has spread, which
means it’s too late to give them curative treatments like radiotherapy and
surgery. That leaves chemotherapy, but only 40 per cent have any
response at all to that and even then they only live an extra three to six
months. So it’s not wonderfully effective. So our hope is that with our
gene/cell therapy combined with chemotherapy we can help people with
lung cancer survive much longer,” says Sam.
It will take 18 months to grow the billions of cells needed for the trial.
The job involves taking stem cells from the bone marrow of three donors.
These cells are then infected with a virus which will insert the TRAIL gene
into the cells’ DNA. Finally the numbers of TRAIL-producing cells will be
expanded at the Royal Free’s high-tech facility.
The trial will start in 2016 at University College London Hospital and
then the team will carry out a second trial - a phase II study in 56 patients
to compare the gene/cell therapy plus chemotherapy with standard care.
The research has already caught the attention of a pharmaceutical
company so Sam hopes he and his colleagues will be in a good position
to license the therapy to industry if it shows promise in phase II trials.
From clinical trials testing the best possible treatment combinations to
targeted therapies and personalised medicines – another important area
– medical research is making progress on all fronts against the Big C.
*TNF Related Apoptosis-Inducing Ligand (TRAIL)
Curing cancer in mice is one thing, but treating people is quite another.
So the next step is to test whether it works in lung cancer patients whose
cancer has spread throughout the body. Lung cancer is the commonest
MRCNetwork | 11
LATEST DISCOVERIES
Baby eye movements may
predict autism
Protective drug slashes HIV
infection risk
Brain cooling offers Alzheimer’s
prevention clue
Why weekend lie-ins could
make you fatter
Six-month-old babies who move their eyes
frequently are more likely to meet criteria for Autism
Spectrum Disorder (ASD) as children, according to
a study hosted at Birkbeck, University of London.
Sexually active gay men who take anti-retroviral
therapy before exposure to HIV can cut their risk
of infection by 86 per cent - suggesting an
effective way to stem the tide of new infections in
this population.
A protective process has been discovered in brain
cells that is activated when body temperature is
lowered, pointing the way to new drugs to protect
against neurodegenerative diseases.
Weekend lie-ins are linked with obesity and
related diseases such as diabetes, MRC-funded
research suggests.
Using eye tracking technology, the MRC-funded researchers
measured how often 104 babies (aged 6-8 months), at high or low
family risk for ASD, moved their eyes when scanning a static image. Babies who were later diagnosed with ASD tended to move their
eyes more frequently – three times a second – than other babies,
suggesting that they were scanning the image more rapidly.
Lead author, Dr Sam Wass of the MRC Cognition and Brain Sciences
Unit, said: "Adults with ASD can sometimes process visual
information more rapidly than other people, and perhaps that was
happening for infants in our study. Alternatively, it could be that
these babies need a higher level of stimulation, so they move their
eyes more frequently to get more stimulation. Or it could be that
when they look at something they are not engaging with it in the
same way as other children tend to."
The researchers hope in future these findings may help contribute
to better ways of identifying babies with early signs of possible
behavioural difficulties in future.
The study, in 545 men across 13 NHS Trusts, looked at whether
offering daily treatment with an anti-HIV drug called Truvada was a
reliable way to prevent men at high risk from becoming infected in a
‘real world’ situation. Those taking part in the trial took Truvada
alongside other risk-reducing measures including condom use. Of the participants, 276 received Truvada immediately and 269
deferred for 12 months before receiving it. During the first year of
the study, 22 people became infected with HIV; 3 in the immediate
group and 19 in the deferred group.
Dr Des Walsh, the MRC’s Head of Infections and Immunity, said:
“HIV remains a serious public health concern - in 2013 alone, around 2,800 gay, bisexual and other men who have sex with men became
infected. Clearly, additional approaches are needed to tackle the
HIV epidemic, particularly for populations at higher risk. This study
shows that a relatively straightforward intervention based on
existing therapy – pre-exposure prophylaxis – could have a major
impact in preventing HIV infection.”
The PROUD study was co-led by Professor Sheena McCormack at
the MRC Clinical Trials Unit and Professor Noel Gill at Public Health
England.
It’s well known that during hibernation, the synapses (connections)
between a mammal’s brain cells break down while it enters a state
of low brain activity, allowing it to survive without food. As the
animal warms up in spring, the connections are reformed. The researchers studied this process in healthy mice by reducing
their body temperature to 16-18ºC for 45 minutes. They found that
the synapses of these mice, which do not naturally hibernate, also
dismantled on cooling and regenerated on re-warming.
By repeating this cooling in mice with features of neurodegenerative
diseases they found that the capacity for synapse regeneration
disappeared as the disease progressed, accompanied by a drop in
levels of a ‘cold shock’ protein produced by the brain called RBM3.
When the scientists artificially boosted levels of RBM3 they found
that this alone was sufficient to prevent synapse and brain cell
depletion in the diseased mice, reducing memory loss and
extending lifespan.
Lead author Professor Giovanna Mallucci, at the MRC Toxicology
Unit, said: “By identifying how cooling activates a process that
prevents the loss of brain cells, we can now work towards finding a
means to develop drugs that might mimic the protective effects of
cold on the brain.”
The researchers assessed the height, weight and waist
circumference of 800 people from the Dunedin Longitudinal study,
and also their levels of C-reactive protein and glycated haemoglobin
in blood - biomarkers for inflammation and diabetes. They then
compared these findings with results from a questionnaire which
assessed participants' sleep duration and preference in sleep timings.
They discovered that just a two-hour difference in sleep patterns
at the weekend was associated with a higher body mass index
and biomarkers for inflammation and diabetes than those with little
or no difference in sleep patterns between week days and
the weekend.
This so-called 'social jetlag' often happens for the majority of
an adult’s working life so it can cause chronic consequences
for metabolism.
Dr Terrie Moffitt from King’s College London, co-author of the paper,
explains: “These findings help us start to actually understand the
physiology of social jetlag and how it impacts upon obesity and
obesity-related disease.
“Further research that determines this association could help
inform obesity prevention by influencing policies and practices
that contribute to social jetlag, such as work schedules and
daylight savings.”
Published online at www.nature.com/srep, February 2015
12 | MRCNetwork
Results (not yet peer-reviewed, but submitted to a peer-reviewed
journal) were presented at the CROI conference in Seattle
in February.
Nature, 518, p236-239 (12 February 2015)
Published online at www.nature.com/ijo, December 2014
MRCNetwork | 13
PEOPLE
Remembering Mary Lyon and her
impact on mouse genetics
Dr Mary Lyon, an important figure in the field of mouse
genetics, died in December. Katherine Nightingale looks back
on her career.
It’s not often that the MRC names a building after a scientist, even
with our roll-call of scientific greats. But the Mary Lyon Centre at MRC
Harwell in Oxfordshire is one exception. Opened in 2004, the centre is
a national facility for mouse genetics where genetically modified mice
are produced, cared for and studied.
Mary Lyon, who died on Christmas day 2014 aged 89, worked with
mice throughout her scientific career, becoming one of the foremost
geneticists of the 20th century through her research on mice with
mutated genes. She made her most famous discovery, named
‘lyonisation’ in her honour, during her time at MRC Harwell. Mary discovered lyonisation, or X-chromosome inactivation, in 1961
by studying the mottled patterns on the coats of a particular strain of
mouse. Females have two X chromosomes and males an X and a Y.
Using a series of mouse breeding experiments and observations, Mary
suggested that early in the development of female mammals, each
cell inactivates one of its X chromosomes. This is a random process,
meaning that in some cells one X chromosome is active and in others
it is silenced, and the other is active.
This has important medical implications. Some diseases, such as
Duchenne muscular dystrophy and haemophilia, are caused by
mutations on the X chromosome. Because women have two X
chromosomes they are often protected from X-linked disease, while
men are affected. However, because of X-inactivation women who are
carriers of these diseases can display symptoms.
A deep thinker
Mary was born in Norwich in 1925 to schoolteacher Louise (nee Kirby)
and civil servant Clifford Lyon. It was at grammar school in Birmingham
that she developed her interest in science after winning a set of books
on nature in an essay prize.
She went on to be one of just 500 women allowed to study at
Cambridge University alongside 5,000 men in her year — though
women weren’t technically members of the university. Despite
attending the same lectures and practical courses as the men, she
received a ‘titular’ rather than official degree in zoology, physiology
and biochemistry.
mannered. However she was a tenacious fighter on scientific matters on
which she felt strongly and she didn’t suffer fools gladly. She could also
be very kind and helpful,” says Professor Jo Peters of the MRC Mammalian
Genetics Unit.
Her list of prizes and honours is long. She became a Fellow of the Royal
Society in 1973 and received the society’s Royal Medal. In 2014 the UK
Genetics Society established the Mary Lyon Medal in her honour.
She began a PhD at Cambridge in 1946 but later moved to Edinburgh
to access better facilities for mouse genetics such as mouse breeding
and histology. Post-war worries about atomic radiation meant that
after her PhD she spent five years in Edinburgh doing MRC-funded
work researching the effects of radiation on mice. This included
studying mutant mice with names like twirler (a mouse with no sense
of balance due to inner ear problems).
Why she never received the Nobel Prize or was made a Dame is a
mystery to many. But Dame or not, she was one of the greats of
British science.
The move to Harwell
At Harwell, the MRC was funding work looking at radiation and cancer,
and in 1954 Mary moved to the MRC Radiobiological Research Unit.
As well as assessing the types of genetic damage caused by radiation,
Mary pursued the study of the mouse mutants themselves, often in
her spare time.
She also had the foresight to recognise the importance of cataloguing
and archiving mouse strains by freezing them. Harwell’s extensive
collection of frozen mouse embryos would not be the important
international resource it is today without her work.
She was the unit’s Head of Genetics from 1962 to 1986, and, although
she had to retire in 1990 due to age restrictions in place at the time,
she continued to work at Harwell a few days a week until just a couple
of years ago.
“Mary was a very clear thinker and careful experimentalist who made
a massive contribution to genetics. She was quiet, serious and mild
Mary Lyon in her youth and several decades on.
She continued to work at Harwell well into her 80s.
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FUNDING
For the latest information on MRC funding
opportunities, visit www.mrc.ac.uk/funding
Nurturing early collaboration
with industry
£3 million has been invested by the MRC in a new
scheme to help academics and industry work
together in new and innovative ways.
New multimillion pound India-UK
research centres
The MRC and the Indian Government’s Department for
Biotechnology (DBT) have joined forces to fund three
major UK and India-based research centres. Two centres will focus on antimicrobial resistance; one on tackling the
sharp rise in cases of multidrug resistant tuberculosis and the other on
finding solutions to the excessive and inappropriate use of antibiotics.
The third centre will focus on cancer biology and therapeutics.
Dr Mark Palmer, MRC Director of International Strategy, said: “We know
diseases don’t recognise international borders and that addressing
health problems around the world demands a global response. These
exciting partnerships between excellent scientists in India and the UK
are a key part of our international effort to pool expertise and resources
and deliver research that will make a real difference to global health.”
The Proximity to Discovery: Industry Engagement Fund has supported
16 universities to develop new ways to form collaborations and
knowledge exchanges with industry, for example people exchanges,
creation of technology demonstrators, showcase events,
commercialisation workshops and ‘entrepreneurs in residence’ schemes.
The funding will help universities to form alliances at the very earliest
stage and gives them greater flexibility to respond rapidly to
opportunities when they arise. It can be used to support activities that
promote the value of academic-industry partnership and which facilitate
and enhance understanding.
Catriona Crombie, MRC Programme Manager for Industry Liaison,
explains: “People exchanges are a key component of the scheme and
include people at all career stages in medical science and in technology
transfer. Establishing positive relationships early on will help
shape individuals and deliver the required skill sets for future exciting
developments in medical research.”
Nearly £3.5m will be invested in the centres by the UK, through the MRC
and the Newton Fund, with matched funding provided by DBT.
Find out more at www.mrc.ac.uk/india-uk
What is the Newton fund?
The Newton Fund is an initiative which will harness the UK’s strength in
research and innovation to promote the economic development and
social welfare of 15 partner countries.The fund will help countries that
are rapidly improving their own scientific capability and will help to
unlock further opportunities for science and innovation collaboration.
The fund was launched by the Chancellor in April 2014, and will provide
£375m funding over the course of five years, including several calls and
initiatives run by the MRC. Find out more at www.mrc.ac.uk/newtonfund
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WORKING LIFE
Cardiologist Professor Stefan Neubauer has set up a spin-out company
based on a new test for chronic liver disease that could cut diagnosis time
from months to a single day.
I’m a professor of cardiovascular medicine and, in a nutshell, my job is to
develop new ways to characterise the inner workings of the heart, based
on magnetic resonance (MR) imaging and spectroscopy. I’m Director of
the Oxford Centre for Clinical Magnetic Resonance Research, and setting
up this clinical research unit from scratch – which is now recognised
worldwide – has been the highlight of my academic career. But in 2012, I
also took a leap into the world of industry. Together with three
colleagues I founded a spin-out company based on an important
discovery we made.
I remember the moment we first realised that we’d found something
with commercial potential. A PhD student of mine at that time, Dr
Rajarshi Bannerjee, was doing a project looking at the cardiac changes in
obese people. We saw these interesting bits of the liver at the edge of
our images and realised that the MR imaging technique we were applying
to the heart might also tell us important things about the liver.
So we studied patients who’d been referred to the hospital for liver
biopsy – currently the ‘gold standard’ for diagnosing fatty liver disease –
and compared the MR imaging with the biopsy results. We were
astonished to discover that our test accurately predicted the main
parameters that pathologists would look at in a liver biopsy sample: fat
content, iron content and inflammation/fibrosis.
The test clearly had enormous clinical and commercial potential, but
we weren’t sure how to take it forward. So we talked to our colleague,
Professor Sir Mike Brady, a serial entrepreneur who has successfully set
up several medical imaging companies. He immediately saw the test’s
promise, and together with our chief MR physicist Professor Matthew
Robson, we founded Perspectum Diagnostics in 2012. Working with the
university’s intellectual property branch we also filed five patents to
protect our invention.
Fatty liver disease is a looming epidemic worldwide, mainly due to rising
obesity rates. It already affects 10 per cent of the UK population, and
projections for future figures are frightening. It’s known as a ‘silent killer’
because generally it doesn’t cause symptoms until tissue damage is
severe and irreversible. It’s usually diagnosed with a needle biopsy, which
is costly, painful and carries a risk of bleeding. Biopsy can also be
inaccurate because if you happen to take a sample from a less diseased
area of the liver you won’t get a full picture of the organ’s overall health.
In contrast, our LiverMultiScan test gives detailed information on tissue
characteristics of the whole liver from a 10-minute, painless scan. It’s also
quantitative, repeatable and easy to read - we use traffic light colours on
the image which change with increasing severity of fibrosis.
Presently it can take several months for patients to get a diagnosis.
They’d usually have to have an ultrasound, liver clinic appointment, a
biopsy and a further appointment to discuss the results. Soon we may be
able to replace all of this with a single LiverMultiScan test and get a
same-day diagnosis.
Starting up a spin-out company gives an academic scientist insight into
a completely different world with opportunities that are difficult to
achieve in the traditional academic environment. One can raise funding
and realise ideas relatively quickly, and bring new concepts into clinical
practice in a short space of time.
the ‘real world’. We also achieved CE marking last September so that we
can sell the test in Europe, and we’ve applied for FDA approval in the US.
I’m still first and foremost a clinical academic, and I am fortunate in that
I really love what I am doing - my work is my hobby. As a clinician I’m
always glad if I can help diagnose a difficult case or guide challenging
treatment decisions so that a patient receives the best care. As a scientist
I love to push the boundaries or our knowledge and develop new
techniques. I hope that LiverMultiScan will be a great success but if, by
the end of my career, I can say I’ve made a lasting contribution to
improving patient care in cardiovascular and liver diseases and to training
the next generation of scientists, I’ll be happy.
Career in brief
• Trained in medicine at the University of Wuerzberg, Germany
• Postdoctoral Research Fellowship, Harvard University
• Specialised in cardiology and worked on the early applications of
cardiac magnetic resonance (MR) scanning
• Founder and Director of the University of Oxford Centre for Clinical
Magnetic Resonance Research, John Radcliffe Hospital, Oxford
• Chief Medical Officer, Perspectum Diagnostics plc
If, as academics, we feel we work in a high pressure environment, it’s no
different in industry - the investment you’ve got sets the runway, and
there’s a limited and strictly defined time to either succeed or fail. As in
academia, there are no guarantees of success, and it’s extremely
hard work.
The best advice I’d give to a scientist looking to set up a spin-out
company would be to ask the experts for help early, and choose the
right people for your core team. Their vision and enthusiasm is as least as
important as the actual idea and the intellectual property. With the right
team in place, a clinical academic can realistically set up a company
without it eating too much into the time dedicated to academic work.
When you make a discovery with commercial potential, it can be hard to
suppress the academic’s instinct to rush to submit an abstract or sneak it
into slides for your next plenary talk. But you have to keep it under your
hat and think about protecting it first, because if you show your data in a
public forum that negates any intellectual property you might want
to file.
These are exciting times because we expect the company to grow
rapidly over the next year or two and to begin marketing this test
worldwide. We now have 12 staff, and last year we got further funding
from Innovate UK to develop the scan further and show that it works in
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YOUR
FEEDBACK
Network is for anyone who has an interest in the work of the
MRC, including scientists, doctors and health professionals
involved in medical research, government departments and
parliamentarians, and university staff and students. The aim is
to provide a quick, easy-to-read summary of activities across
the MRC, from research news through to funding, grant
schemes and policy issues, with pointers to more in-depth
information on websites and in other publications.
We are keen to receive feedback on Network and suggestions
for new features from our readers. So if you have any
comments, please email: [email protected]
Deadline for contributions to summer issue: 22 May
Deadline for autumn issue: 8 July
Network is produced by the MRC Corporate Affairs Group.
Editor: Sarah Harrop
Designer: Vin Kumar
A limited number of copies are available in print.
Network can also be downloaded as a pdf at:
www.mrc.ac.uk/network
IMAGES
Front and back cover: © Science Photo Library
Page 3: © University of Newcastle,
Page 4: NATIONAL INSTITUTES OF HEALTH/SCIENCE PHOTO LIBRARY
Page 6: © Max Alexander
Page 9: © UK Foreign Office, © Linda Nylind
Page 10/11: STEVE GSCHMEISSNER/SCIENCE PHOTO LIBRARY
Page 11: © University College London
Page 12: © Emily Jones, Centre for Brain and Cognitive Development, Birkbeck,
University of London
Page 13: DON FAWCETT/SCIENCE PHOTO LIBRARY
Page 16: EYE OF SCIENCE/SCIENCE PHOTO LIBRARY
Page 17: © Novo Nordisk A/S
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