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Researcher Spotlight: Dr Nichola Lax

28 Jul, 2014

With mitochondrial replacement therapy in the news at the moment, following a positive government response to the public consultation on the technique, we thought it would be good to talk to someone who works with faulty mitochondria. Dr Nichola Lax is a research associate working in the Wellcome Trust Centre for Mitochondrial Research at Newcastle University, and she shares her hopes about her research with us…

Dr Nichola Lax, Newcastle

What are you working on?

I’m working on a project that aims to understand how genetic defects (or mutations) in mitochondrial DNA cause mitochondrial dysfunction in neurons, leading to epilepsy.

Mitochondrial disease can have a variety of different symptoms because mitochondria are present in all our cells (apart from red blood cells). This means patients may have problems with their vision, muscle weakness, and neurological disorders. It is the neurological disorders that are most prominent in these patients and can also be most devastating, so I am interested in learning more about these so that we might be able to offer more effective treatments.

Epilepsy is very common in patients with mitochondrial disease and is a pathological condition where groups of neurons suddenly become intensely electrically active and fire information rapidly resulting in a seizure.

Our understanding about how the pathological processes begin and progress in patients with epilepsy is still limited and so the focus of my work is to address this problem. I use post mortem human brain tissues to investigate which neurons are most vulnerable to mitochondrial DNA mutations and try to understand how epilepsy develops in these patients.

What does your average day involve?

A typical day begins with my morning walk across the Town Moor to the Medical School, attempting to negotiate my way through the resident cows.

The first thing I do when I reach the lab is make a cup of coffee, check my emails and then power up my favourite microscope. For my work, I tend to use a variety of different microscopy techniques to look at neurons, but with this particular microscope I feel I have truly bonded. This one can only be described as the ultimate microscope, the Nikon A1R, it’s very fancy (expensive!) and it almost feels like I’m operating a spaceship when I’m using it!

It’s a confocal microscope, located in what affectionately call “the dungeon” downstairs, and this piece of equipment lets me photograph beautiful multi-coloured images of mitochondria inside a variety of different cell types in very thin sections of human brain.

This microscope has allowed me to look at proteins expressed inside the mitochondria to precisely establish how dysfunctional these mitochondria are within specific cell types, so for instance, in a typical experiment I label my mitochondria with a pink fluorescent tag, a protein called complex I with a red fluorescent tag and complex IV with a green tag and a marker for neurons with a blue tag. I can then photograph them and see whether all colours are located in the same spot and if any are missing, find out which ones – typically complexes I and IV are lost in neurons from patients. I want to understand the consequence of this.

Once I have my images, I go back upstairs to the lab – generally feeling a bit like a mole, and catch up with my colleagues and see if there any cake on offer in the tea room (our lab is full of incredible bakers).

I currently supervise three PhD students in our lab who have a shared interest in understanding the contribution of mitochondrial dysfunction in neurodegeneration in patients and so I would meet with them and find out how their research projects are progressing, talk about results and any issues they might be having. This is often hugely constructive as it allows us to discuss new ideas, focus our research questions and think about the broader picture of our research.

The Nikon A1R and a multicoloured neuron.

The Nikon A1R and a multicoloured neuron.

The remainder of the day, I perform image analysis (see how many pink, red and green spots are present within blue cells) and then take the numbers from this to try to interpret what is happening to these cells. If there is less red and green within the pink spots then this tells me that the machinery important for energy generation is missing and therefore these cells are what we call respiratory chain deficient. I want to understand how they become deficient and what it means for that particular cell. If it’s ‘Fridge Friday’, the day ends with pizza and beer with everyone from the group where we can have a chat about science or life in general.

Why is your work important?

So many patients with mitochondrial disease are affected by neurological impairments and this can have a huge effect on their quality of life and the degree to which they are disabled.

Epilepsy affects approximately one third of patients with mitochondrial disease, and currently treatment is limited, and prognosis may be poor for these individuals. It is enormously important that my work tries to understand why these patients get epilepsy and addresses the specific neural mechanisms that might help us devise new treatment strategies to prevent epilepsy.

This type of research also has important implications for other neurodegenerative disorders where mitochondrial dysfunction may play a role, such as in Parkinson’s disease.

What do you hope the impact of your work will be?

I really hope that my research will help increase our knowledge about mitochondrial function and dysfunction in the brain, and help us to devise better treatment strategies for patients so that we might be able to improve their quality of life.

How did you come to be working on this topic/in this field?

Brain cake (doesn't actually contain brains)

Brain shaped cake in our tea-room

I’ve been really interested in science from an early age, and I knew when I was studying for my A-levels that I wanted to pursue Science to a higher level.

I applied for the biomedical sciences degree at Newcastle University because it was at that point I knew I wanted to work in research, but I still wasn’t particularly sure which aspect. It became clear to me that neuroscience was an area that really appealed to me and was something I wanted to learn more about.

I did an undergraduate research project looking at dopamine receptor changes in the brain following nicotine addiction, and then went on to study an MRes in neuroscience where I investigated the molecular basis for visual hallucination in dementia with Lewy bodies. After my MRes, I had an interview for a PhD project investigating the neurodegenerative features in patients with mitochondrial disease and this is something that remains my major interest today.

How has Wellcome funding helped you/your research/your career?

Wellcome Trust funding has really allowed me to work on something that I feel very passionate about and allowed me to professionally develop from PhD student to post doc. This funding has enabled me to further my research studies at the bench to look at specific mechanisms of disease by giving me an opportunity to test new techniques and answer more ambitious scientific questions.

What’s the most frequently asked question about your work?

It depends on who is asking! People from the scientific community tend to ask me why certain parts of the brain are more vulnerable to mitochondrial dysfunction? Which is something I’m still trying to answer.

School children will ask me what the brain feels like? This is more straightforward and I can usually offer them an agarose jelly brain to feel.

Tell us something about you that might surprise us…

I have recently become a lot more active, bought a bike and starting running, in fact I am running the Great North Run half marathon for the Lily Foundation, a charity which supports families with mitochondrial disease, raises awareness of these disorders and also funds research.

What keeps you awake at night?

Usually I don’t have too many issues falling asleep at night, however that may have something to do with the wafer-thin curtains we bought when we moved into our house three months ago which means the sun wakes me up at 5am each day! If I have spent a lot of time of the Nikon A1R that day, I do have a tendency to dream about counting multicoloured neurons!

What’s the best piece of advice you’ve been given?

My supervisor always tells me that whenever I give a talk I should make sure it tells an interesting story!

The chain reaction question, posed by the previous spotlight participant, Dr Margaret Robinson, is this: What were your best and worst moments in science?

Best - As part of my work, I get travel to scientific conferences where many experts in my research field will meet to talk about the latest and greatest scientific research going on across the globe. This gives me an exciting opportunity to talk about my work, learn more about mitochondria, collaborate with people in different parts of the world and also see a bit more of the world!

Worst - When a seemingly straightforward experiment fails repeatedly (despite working well last week!) without any logical explanation. Fortunately, most of the time, these unlucky spells don’t last too long!

You can find out more about Nichola’s work and the Wellcome Trust Centre for Mitochondrial Research on their pages of the University of Newcastle website. Her most recent papers include Quantitative quadruple-label immunofluorescence of mitochondrial and cytoplasmic proteins in single neurons from human midbrain tissue and Early-onset cataracts, spastic paraparesis, and ataxia caused by a novel mitochondrial tRNAGlu (MT-TE) gene mutation causing severe complex I deficiency: a clinical, molecular, and neuropathologic study.

Image of the Week: Aspergillus fumigatus

25 Jul, 2014

Painting of Aspergillus fumigatus by Peter Thwaite

The image above is an artistic impression of a microscopic view of the fungus Aspergillus fumigatus, a common organism in the environment typically found in compost heaps and decaying vegetation. The green flower-like structure is the conidial head that produces thousands of spores (conidia), which can be released into the atmosphere.

It is estimated that all humans inhale at least several hundred conidia each day; typically these are quickly eliminated by the immune system in healthy individuals. However, in immunocompromised individuals, the fungus can cause severe and often fatal invasive infections, mainly arising in the lungs. Aspergillus fumigatus is also a ubiquitous aeroallergen affecting millions of susceptible adults and children. Severe asthma with fungal sensitization may affect between 3 and 13 million adults worldwide.

This image is from an original painting by the artist Peter Thwaites, a Land Agent/Chartered Surveyor by profession, based in Dorset. Peter has always used the medium of painting and drawing to record the natural world around him. He is self-taught, having been encouraged by one of the founding members of the Society of Wildlife Artists.

Peter has a love and understanding of macroscopic fungi and has produced many paintings of mushrooms and toadstools. However, much of the beauty of nature exists in microscopic form and so here, based on a series of light and electron microscopic images he was given, Peter has captured the elegance of the architecture of this fungus as a subject that is beyond the resolution of the human eye.

This painting, along with paintings of two other pathogenic fungi (Candida albicans and Cryptococcus neoformans), was commissioned by the Medical Mycology and Fungal Immunology Consortium to promote medical mycology research and increase public understanding of the clinical importance of fungal infections. The other aims of the Consortium, led by the Aberdeen Fungal Group at the University of Aberdeen and funded by a Wellcome Trust Strategic Award, are to promote cross disciplinary research across the UK, to build capacity in the medical mycology sector and to train a new generation of scientists from countries of low- and middle- income with high endemic burdens of fungal disease.

Image credit: Peter Thwaites

How the Wellcome Trust can play a part in sustaining global health

22 Jul, 2014

The Wellcome Trust is committed to funding research that will lead to improvements in global health. We are increasingly aware of the importance of the connections between environment, nutrition and health and the Trust’s new Sustaining Health initiative aims to build on these. Sarah Molton, from the Sustaining Health team at the Wellcome Trust explains our thinking…

“We have lived our lives by the assumption that what was good for us would be good for the world. We have been wrong.” – Wendell Berry, The Long Legged House (1969).

A colleague at the United States Environmental Protection Agency introduced me to Wendell Berry’s work. His words were relevant in 1969 and remain so today.

Global health is under serious threat. Humanity faces profound questions about how our planet can healthily sustain nine billion people by 2050. Demand for food is rising, fresh water is becoming scarce, climate change is impacting disease spread and those are just a few of the challenges we’re up against.

For the past year, my colleagues Saskia Heijnen and Ted Bianco and I, have been working on a new initiative for the Trust that we call Sustaining Health.

Sustaining HealthWe know that high-quality research in this area requires the development of new interdisciplinary and cross-sector partnerships. Problems like food and water shortage and the health implications of climate change are complicated. They will need people from diverse backgrounds and with diverse thinking to address them.

At the Wellcome Trust, we want to offer funding that will help to bring these people together – combining their intellectual power and experience to develop new ideas for global health.

Our first step has been the funding of five pilot projects to investigate the sustainability of the palm oil industry, health in urban areas, malnutrition in Sub-Saharan Africa, climate-change-resilient diets in India and interventions to improve cardiovascular health in rural China. There is currently a call open for further funding proposals.

In addition, we are already speaking to experts from across sectors and disciplines to see how the Trust might develop its impact in the field of Sustaining Health. Lord John Krebs has kindly agreed to help to shape our developing strategy as a member of a growing advisory panel and we have commissioned a group called Meteos with expertise in health, energy and climate change to run a structured dialogue on Sustaining Health for us.

These are global problems and we will obviously not be able to solve them alone, but happily we are not the only ones trying to tackle them. At a recent (and fascinating) meeting hosted by The Rockefeller Foundation with The Economist and The Lancet, there was much discussion around the idea of “Planetary Health”.

The meeting brought together a pioneering group of scientists, entrepreneurs, public health experts and representatives from business, government and NGOs to explore ways to create a healthier future for the planet and its inhabitants. It was truly a meeting of kindred spirits, a good start, but this movement needs to grow.

We need to take steps together – all of us – and just talking isn’t enough. We need to take action. Public engagement will be fundamental to the success of this mission, and if any of this strikes a chord with you then please get in touch. Engage with us. Tell us your ideas, we’re listening.

Returning to the words of Wendell Berry:

“We must change our lives so that it will be possible to live by the contrary assumption, what is good for the world will be good for us.  And that requires that we make the effort to know the world and learn what is good for it.”

Find out more about the Wellcome Trust’s work in the area of Sustaining Health and the other funding schemes that we run. 

Wellcome Trust Research Round-up: 21/07/14

21 Jul, 2014

Our fortnightly round-up of news from the Wellcome community.. 

Same genes drive maths and reading ability

AS0000141F22 Child, at primary schoolAround half of the genes that influence how well a child can read also play a role in their mathematics ability, say scientists from UCL, according to a collaborative study published Nature Communications as part of the Wellcome Trust Case-Control Consortium.

While mathematics and reading ability are known to run in families, the complex system of genes affecting these traits is largely unknown. The finding deepens scientists’ understanding of how nature and nurture interact, highlighting the important role that a child’s learning environment may have on the development of reading and mathematics skills, and the complex, shared genetic basis of these cognitive traits.

The study used data from the Twins Early Development Study (TEDS) to analyse the influence of genetics on the reading and mathematics performance of 12 year-old children from nearly 2,800 British families.

Twins and unrelated children were tested for reading comprehension and fluency, and answered mathematics questions based on the UK national curriculum. The information collected from these tests was combined with DNA data, showing a substantial overlap in the genetic variants that influence mathematics and reading.

First author Dr Oliver Davis, from UCL, said: “We looked at this question in two ways, by comparing the similarity of thousands of twins, and by measuring millions of tiny differences in their DNA. Both analyses show that similar collections of subtle DNA differences are important for reading and maths. However, it’s also clear just how important our life experience is in making us better at one or the other. It’s this complex interplay of nature and nurture as we grow up that shapes who we are.”

Brain activity in sex addiction mirrors that of drug addiction

Carved ivory statue, in the form of a copulating man and woman, Far Eastern (c) Science Museum, LondonPornography triggers brain activity in people with compulsive sexual behaviour – known commonly as sex addiction – similar to that triggered by drugs in the brains of drug addicts, according to a study published in the journal PLOS ONE. However the researchers caution that this does not necessarily mean that pornography itself is addictive.

Although precise estimates are unknown, previous studies have suggested that as many as 1 in 25 adults is affected by compulsive sexual behaviour – an obsession with sexual thoughts, feelings or behaviour – which they are unable to control. This can have an impact on a person’s personal life and work, leading to significant distress and feelings of shame. Excessive use of pornography is one of the main features identified in many people with compulsive sexual behaviour. Although there is currently no formally accepted definition used to diagnose the condition.

In this study, funded by the Wellcome Trust, researchers looked at brain activity in 19 male patients affected by compulsive sexual behaviour and compared them to the same number of healthy volunteers. The affected patients were those who had started watching pornography at earlier ages and in higher proportions relative to the healthy volunteers.

The study participants were shown a series of short videos featuring either sexually explicit content or sports whilst their brain activity was monitored using functional magnetic resonance imaging (fMRI), which uses a blood oxygen level dependent (BOLD) signal to measure brain activity.

“The patients in our trial were all people who had substantial difficulties controlling their sexual behaviour and this was having significant consequences for them, affecting their lives and relationships,” explains Dr Valerie Voon, a Wellcome Trust Intermediate Clinical Fellow at the University of Cambridge. “In many ways, they show similarities in their behaviour to patients with drug addictions. We wanted to see if these similarities were reflected in brain activity, too.”

Option of HIV care at home increases use of antiretroviral therapy

B0004953 Hand with AIDS ribbonAdults in Blantyre, Malawi, who are offered self-testing for HIV infection, and home care, are more likely to start antiretroviral therapy compared to those offered standard HIV care, according to a study funded by the Wellcome Trust.

The study was published in a special HIV/AIDs issue of the journal JAMA, released to coincide with the 20th International AIDS Conference.

Self-testing for HIV infection (defined as individuals performing and interpreting their own HIV test in private) is a novel approach that has seen high acceptance in Malawi and the United States. The process could overcome barriers to conventional facility-based and community-based HIV testing, which can lack privacy and convenience. Despite this, there have been no previous studies in high HIV prevalence settings have investigated the link to HIV care after HIV self-testing, say the study authors.

In 2012, an estimated 35 million individuals were infected with the HIV worldwide. Antiretroviral therapy (ART) substantially reduces the risk of HIV transmission as well as greatly reducing illness and death, raising hopes that high uptake of annual HIV testing and early initiation of ART could improve HIV prevention as well as care. Achieving high coverage of HIV testing in sub-Saharan African countries is a major challenge, due to low rates of HIV testing.

Dr Peter MacPherson, Wellcome Trust Clinical Research Fellow at the Liverpool School of Tropical Medicine, said“At a time when universal test and treat approaches to controlling the HIV epidemic are being considered, home initiation of HIV care shows high promise as a simple strategy to improve uptake of ART when HIV self-testing is carried out at home.”

In other news…

We’re refreshing our research framework – find out more in this post from Trust director Jeremy Farrar.

London School of Hygiene and Tropical Medicine Professors David Mabey and Polly Roy have both been honoured in this year’s Queen’s birthday honours list.

Congratulations to those behind the Wellcome Trust-supported film Ming of Harlem, which won Best International Film at the Marseille Documentary Film Festival.

Image credits: Anthea Sieveking , Wellcome Images; Stevie Taylor, Wellcome Images, and Science Museum, London

Image of the Week: Eye Contact

18 Jul, 2014

Eye Contact - window display at the Wellcome Trust

We’re used to looking in windows, but what if they were able to look back?

The image above captures a moment from the new window display on show at Wellcome Trust HQ – an art installation called “Eye Contact”. This artwork consists of over 650 coloured boxes lit by over 16,000 LEDs, which together form two giant pairs of eyes.

We encounter thousands of electronic images every day, via our phones, computers, projectors and televisions. But how does the digital screen mediate our reactions to what we see? Do we experience different emotional responses seeing faces via Skype or YouTube, than we would if we were truly face to face with them?

This installation by Peter Hudson, a recent graduate from Camberwell College of Arts, probes these questions of perception and recognition. It will be winking and blinking at passersby for the next year.

To create the work, Peter recruited 68 members of Trust staff to volunteer to have footage of their eyes recorded. He then transformed this into the heavily pixellated video display that is on show in the windows of our building on Euston Road.

The eyes will change and move throughout the day, displaying the idiosyncrasies of each individual’s gaze. At sunset, the eyes will ‘sleep’, remaining closed during the night, unless they are awoken by a passing pedestrian.

You can see the eyes for yourself in the window of the Gibbs building, at 215 Euston Road, or read more about the Wellcome Trust windows commission on the Wellcome Trust website. A full list of staff members who participated is available on Peter Hudson’s website.

Director’s Update: Thinking about our grant schemes

16 Jul, 2014

Dr Jeremy Farrar, Wellcome Trust

Since he joined us last year, Jeremy Farrar, Director of the Wellcome Trust, has been listening – to staff, to researchers, to members of the Wellcome community, and more. In this post he explains how your views have contributed to new ideas about the best ways we can offer our funding…

Nine months ago, I enjoyed the immense privilege of becoming Director of the Wellcome Trust. As a researcher who has long benefited from Trust funding for my own work, I already knew at first hand what a difference its support can make. What I had not fully appreciated was the breadth of outstanding research that the Wellcome Trust makes possible, in biomedical and clinical science, in humanities and social science, and in public engagement.

Over the past months, it has been fascinating to meet so many of the researchers we fund, and to learn how their work is helping to advance our mission. I am grateful to Sir Mark Walport and his leadership team for handing over such a remarkable research portfolio.

A change of leadership always offers an opportunity to take stock of an organisation’s direction, and I was keen to ensure that the Trust did this effectively. We have thus spent a great deal of time recently thinking over how best to deliver the Wellcome Trust’s vision and mission, as well as listening to the research community’s views about what we already do well and what we could improve.

To that end, I have visited more than 40 research institutions that receive Wellcome Trust funding in the UK and internationally, holding town hall meetings with researchers at every career stage, as well as talking to senior management. The Trust also commissioned a major survey of more than 4,000 current, former and potential future grant-holders, and I have encouraged and received a great deal of further direct feedback from the people we fund and those we do not. We are extremely grateful to all who have taken part – your candid and constructive feedback has been invaluable.

These discussions have helped us to make some broad decisions about how best to develop the Wellcome Trust’s funding framework. Our plans remain a work in progress, and I hope you will understand that we have not yet worked through the details of what they will mean for specific funding schemes. I thought though that the research community would find it helpful to know a little more now about our direction of travel.

I have been fortunate to inherit an excellent 10-year strategic plan for the Trust, launched in 2010, and there is no need for it to change in the immediate future. We remain committed to the vision and mission it set out, of advancing health by supporting bright minds and bright ideas in biomedical research and the medical humanities, and to the focus and challenge areas it identified for particular support. We also remain committed to our major grant schemes, including the Investigator Awards.

However, we do think that there are ways in which we should refresh our funding framework, and we have identified a few key areas in which we believe we can significantly improve our portfolio. We are especially keen to ensure that the Trust offers the best possible support to young people who will be the research leaders of the future, through an approach to funding that allows them to develop their ideas and head their own research teams.

This evolution in our support will therefore place particular emphasis on increasing the opportunities that we make available for early- and mid-career researchers. There will also be a major new scheme for collaborative research by teams, and a reformed approach to strategic awards for transformative work of importance to the mission of the Trust. We will have a new scheme for small, one-off seed grants to promote the development of innovative or high-risk research ideas, so that these can become competitive for larger awards. In addition, we are looking at our application processes, and at ensuring we do all we can to provide constructive feedback and support during and after the application and throughout the period of the award.

We will be developing the details of this refreshed approach over the coming months, and you can expect to hear more from us about the implications for specific funding schemes towards the end of the year. We expect the first awards under new and revised schemes to be made in the autumn of 2015.

I am sure you will appreciate that it is not yet possible for us to say precisely what will change and how, but you can be certain that we will communicate this fully as soon as we can, and in good time to plan ahead. We will continue to listen to your views as we develop these plans. Applications you are planning now will not be affected: many of our existing schemes will continue unaltered, and where schemes do change, it will be possible to move a pending application into the new framework.

These changes are taking place at a time when the Wellcome Trust’s spending on research grants is increasing. We want to make sure that as we enhance the overall level of our funding, the right opportunities are available for all the many kinds of researchers and research teams who can help us to make a difference.

Details of all our current grant schemes can be found at Although we plan to update some of the grant schemes we offer, this will not affect your current applications. Follow the Wellcome Trust on Twitter for the latest updates or check our website and blog for news on the new schemes later in the year.

The Great Brain Experiment: Mobile gaming provides robust scientific results

15 Jul, 2014

The Great Brain ExperimentA team of neuroscientists from the Wellcome Trust Centre of Neuroimaging at UCL used Wellcome Trust funding to create a smartphone app that allows people to play games and contribute to science. With over 60,000 players, The Great Brain Experiment has shown that mobile apps could be a useful source of data collection. Project scientist Dr Peter Zeidman explains their findings…

It’s a big week for us at the Wellcome Trust Centre for Neuroimaging.

A year and half ago, we sat around a table and designed a mobile app that would become The Great Brain Experiment. The idea was to take the psychology experiments we do every day in the lab and turn them into mobile games. By playing the games, people outside our field would be able to get a better idea of what we do, and in exchange we’d be able to receive data from a diverse group of mobile gamers.

A year after its launch our free app has been more popular than we could have imagined, with data sent back to us from more than 60,000 people. This week our initial findings are published in the scientific journal PLOS ONE.

Can mobile games be used to conduct psychology experiments?

The Great Brain ExperimentThis is the question we set out to address and we’re pleased to say the answer is “yes”. Psychology experiments generally involve small groups of volunteers coming to the lab and completing tasks in a carefully controlled setting. This approach works brilliantly for lots of research, however we knew it may not be practical for examining variability across large groups of people, for instance seeing how cognitive abilities change across age groups.

Mobile games offered us the possibility to conduct experiments with volunteers of different ages and backgrounds from around the world. We knew that if we could make the games fun, then contributing to scientific research wouldn’t be a chore. We also tried to keep the games snappy – we decided each should take less than five minutes, so they could be played on a train or bus journey without interruption. The ethical use of people’s data was also a vital consideration, and we made sure that our app explains exactly how players’ data is used, with the option to withdraw from the experiment at any time.

Scientifically, our biggest worry of using games for research was a lack of control. When volunteers take part, they could be travelling on a noisy train, standing at a bus stop or sitting quietly at home – we wouldn’t be able to control for these factors and they had the potential to interfere with the results. We hypothesised that with enough players sending us data, these differences would come out in the wash.

Today’s findings: it worked! 

It was all worth it. The results published today demonstrate that our games reproduced established laboratory findings of short-term memory, decision-making, inhibition and perception, despite not being conducted in the controlled environment of the laboratory.

We also showed that mobile games can reveal differences across age groups. For instance, one of our games tests players’ ability to remember certain items (the positions of coloured circles on the screen) while ignoring other distracting items. We found that older players had greater difficulty ignoring distractions than younger players, supporting the notion that older people find it harder to filter out distractions.

What next?

The Great Brain ExperimentAs scientists, we don’t just want to reproduce scientific results that have gone before, but we want to add new data to the knowledge base. Over coming months we hope to report back with new discoveries coming from the games in The Great Brain Experiment.

In the near future I think we’ll see many more scientific experiments using games to better understand ourselves. Indeed, in a recent project supported by the Wellcome Trust, a game called Axon was developed to investigate skill learning, and they recently published their first results. Another experiment, Hooked On Music, is just getting started at Manchester’s Museum of Science and Industry.

On behalf of The Great Brain Experiment team, I want to say a huge thank you to everyone who has played the games so far, you’re all part of something really exciting – please keeping playing!

We still need more people to download the app and play the games – especially the four new ones that we recently added. The app is available for free from our website or via the Apple/Google Play stores. We hope you continue to enjoy playing The Great Brain Experiment as much as we’ve enjoyed creating it.

The Great Brain Experiment is a collaboration between the Wellcome Trust Centre for Neuroimaging at University College London and The Wellcome Trust. It was developed by White Bat Games.


Researcher Spotlight: Professor Margaret Robinson

14 Jul, 2014

Professor Magaret RobinsonProfessor Margaret “Scottie” Robinson holds a Wellcome Trust Principal Research Fellowship and is a Professor of Molecular Cell Biology and the Cambridge Institute of Medical Research. Here she tells us about her research, eukaryotes, cakes and clarthrin…

What are you working on?

I’m interested in the organisation of cells like our own – that is, eukaryotic cells, which are filled with lots of different membrane compartments, as opposed to prokaryotic cells like bacteria, which have only surface membranes. What’s particularly fascinating is that eukaryotic cells are able to form all these different compartments, each of which is made out of a distinct set of molecules, and then they send molecules from one compartment to another, without everything getting mixed up.

We work on proteins called adaptors, which collect the right types of molecules from a particular compartment and package them into little carriers called coated vesicles, which then deliver the molecules to a different compartment.

It turns out that there are a lot more different types of coated vesicles and adaptors than we’d originally thought, so we’re trying to find them all and figure out what they do and how they work.

What does your average day involve?

I wish I could say doing experiments, but I don’t spend nearly as much time at the bench as I’d like to.

A cake made by the whole lab: a model of a cell with the different compartments baked inside.

A cake made by the whole lab: a model of a cell with the different compartments baked inside.

An average day would be divided between spending time in my office, mainly writing or reviewing (papers, grant applications, PhD theses, project reports…), and spending time in the lab talking with people about their results. There are normally 3-4 postdocs and 2-3 students in my lab, and every two weeks we have a group meeting in which we all show our data, exchange ideas, and enjoy homemade cakes.

But the best days are when I get to do some research with my own two hands.

Why is your work important?

Partly because it’s so fundamental – every form of eukaryotic life on earth – animals, plants, fungi, and unicellular eukaryotes – contains coated vesicles and adaptors, and it’s been speculated that this machinery played a key role in the evolution of eukaryotes from prokaryotes over two billion years ago. Our work also has medical implications, although these weren’t at all apparent when I first started working on coated vesicles nearly 40 years ago.

Some adaptors are mutated in certain genetic disorders, and adaptors are frequently exploited by pathogens. For instance, the HIV genome encodes a protein called Nef, which is essential for the development of full-blown AIDS, and which works by hijacking adaptors and using them to modify the surface of the infected cell.

What do you hope the impact of your work will be?

I hope our work will not only help to explain how coated vesicles sort cargo, but also provide tools that can be used by others to address their own favourite problems. For instance, we developed a new method that we call a ‘knocksideways’.

The idea was to get rid of proteins rapidly, instead of slowly as in a knockdown or a knockout, because cells are very good at compensating for the lack of something if you give them enough time to adjust.

The knocksideways technique has turned out to be very useful for another lab, who are interested in how particular proteins contribute to different stages of cell division, and I hope there will be many other applications as well.

How did you come to be working on this topic/in this field?

I became captivated by cell biology as an undergraduate, because of all the amazing structures that could be seen by electron microscopy. At that time, there were lots of descriptive studies, but almost nothing was known about what these structures were made of or how they worked.

Then as a PhD student I got interested in “the sorting problem” – why all the compartments in the cell don’t get mixed up – and it seemed as though coated vesicles might hold the key. The other reason I decided to work on coated vesicles is that they are absolutely gorgeous, particularly clathrin-coated vesicles, where the clathrin forms a lattice around the vesicle with the same sort of geometry as a football. That was in the mid 1970s, and I’ve been working on coated vesicles ever since.

How has Wellcome funding helped you/your research/your career?

I’m fortunate enough to have been funded almost exclusively by the Wellcome Trust for 25 years now, right from the time I first set up my own lab, and they’ve been exceptionally supportive.

What’s the most frequently asked question about your work?

What’s that thing that looks like a football?


Which question about your work do you most dread – and why?

Is your work going to lead to cures for diseases? It’s always tricky when doing basic science, because it sounds a bit frivolous to say that the main reason we work on coated vesicles is that we think they’re incredibly interesting, but I’m afraid it’s true. Having said that, one of the most rewarding things about our work is that we’ve stumbled upon a number of clinical connections, so maybe in the (very) long run our work might actually lead to cures.

Clathrin hatTell us something about you that might surprise us…

I’m a keen knitter, and one of my projects was to make a clathrin hat for a PhD student in the lab who was about to undergo chemotherapy for Hodgkin’s lymphoma and was expecting to lose most of her hair. As it happened, she hardly lost any hair at all. But the best news is that she made a full recovery and is now a Sir Henry Wellcome Fellow in Paris. (And she still has the clathrin hat.)

What keeps you awake at night?

When I have to give a talk the next day. But at least I’ve managed to get over throwing up every time I have to give a talk, which is what I used to do.

What’s the best piece of advice you’ve been given?

When I first moved to an independent position as a Wellcome Senior Fellow, back in 1989, all of the other independent investigators in my department were men, and nearly everyone assumed that I must have been working for somebody else – even when I told them otherwise. It was very frustrating, and I used to come home every evening and complain to my husband (who is also a scientist) that nobody seemed to believe I was my own boss. He would tell me not to let it get me down, but to carry on doing my best work, and eventually people would get the message. My response at the time was, “It’s all very well for you,” but of course he was right.

The “chain-reaction” question set by our previous spotlit researcher Prof Daniel Pick is this: What led you to agree to be spotlit?

I like to fly the flag for basic science – not just our own work, but curiosity-driven research in general, because you never know where it may lead.

You can find out more about Prof Robinson’s work on her lab page and you might also like to read her papers: Characterisation of TSET, an ancient and widespread membrane trafficking complex and A human genome-wide screen for regulators of clathrin-coated vesicle formation reveals an unexpected role for the V-ATPase. For more information about the types of funding that the Wellcome Trust offers, see the funding pages of our website.

Image of the Week: Mint

11 Jul, 2014

Mint leaf

This minty fresh image is an extreme close-up of the surface of a mint leaf, taken using a scanning electron microscope.

The blue circles are oil glands that are responsible for giving this plant its characteristic aroma, which is commonly used to flavour food, drinks and dental products. The spike in the lower left hand corner is actually a small hair (trichome) on the leaf.

Peppermint oil has been used for thousands of years to soothe stomach cramps, and is even mentioned in ancient Egyptian medical texts written on papyrus. There is a wide variety of ailments that people claim that mint can help, although the evidence for these claims is not robust. There is some evidence peppermint oil could help with heartburn, irritable bowel syndrome and tension headaches.

Have you ever tried holding your nose and eating a mint leaf? You’ll barely taste a thing until you let go of your nose. Give it a try next time you’re making a mint sauce or mixing a mojito!

Image credit: Annie Cavanagh, Wellcome Images

Wellcome Images is one of the world’s richest and most unusual collections, with themes ranging from medical and social history to contemporary healthcare and biomedical science. Over 100,000 high resolution images from our historical collections are now free to use under the Creative Commons-Attribution only (CC-BY) licence.

From Torture to Treatment: One Man’s Fight to Revolutionise Mental Health Treatment in Italy

10 Jul, 2014

Wellcome Trust funded researcher Professor John Foot spent two years exploring the history of revolutionary psychiatrist Franco Basaglia. Basaglia’s views on the treatment of psychiatric patients changed the political landscape of Italy and the field of psychiatry. Freelance science communicator Georgia Bladon found out more…

Up until the 1960s, psychiatric patients in Italy were stigmatised as ‘ill’ and asylums were little more than prisons. Franco Basaglia was among a group of psychiatrists who revolted against the cruelty inflicted on these individuals and advocated more humane treatments to take its place.

When the young Franco Basaglia took over a single asylum in northern Italy, he was horrified by what he found. Patients were locked up, neglected, abused and restrained, leaving them terrified and powerless with very little chance of recovery or rehabilitation into society. Basaglia, so affected by what he saw, took a radical and rare step and began a campaign to have all Italian residential asylums shut down.

This audio slideshow, recorded at the start of Foot’s project, gives an overview of Franco Basaglia’s work, and his movement to radically reform the treatment of psychiatric patients in Italy.

Basaglia refused to bind patients to their beds, abolished any isolation method and started a debate that, in 1978, resulted in the national reform bill ‘Law 180’, or ‘Basaglia Law’ which provided the closure of Italy’s mental hospitals.

This was the beginning of a new outlook on mental health in Italy that condemned institutionalism as catalysing the stereotypes of madness, and called instead for treatment without confinement, where doctor and patient could communicate as equals.

After the bill had been passed the asylums of Italy shut down and the focus of psychiatric care shifted from defense of society towards better meeting of patients’ wants through community care. The aim was for the mentally ill to be cured, not secluded; for psychiatric hospitals to cease to exist; and for the mentally ill to be granted civil rights and integrated into community life.

The asylums were replaced by unstaffed apartments, supervised hostels, group homes, day centres and cooperatives managed by patients. There is still much debate around the Basaglia Law in the psychiatric community and Italy remains the only country in the world where traditional psychiatric hospitals are outside the law.

The slideshow we made with Professor Foot was recorded at the outset of his research. Since then, he has become the first scholar to gain access to the Basaglia archive, and has discovered a movement for change far wider and deeper than he imagined when he began the project.

Foot has looked at the impact of the movement across a variety of Italian cities, including Gorizia, Perugia, Reggio Emilia, Trieste, Arrezzo, Parma, Venice and Ferrara. Each instance was different, with a unique set of local rivalries, debates and political disputes.

The project has changed and grown in many ways over the course of time but the importance of photography is one of the aspects that remained. Photography, film and journalism were powerful tools for shedding light on the cruelty that was being inflicted within the asylums and for spreading the word of the revolution against it. It seems apt then some of these materials – a small fraction of the wealth of the movement’s photographic record – are used to tell this story now.

John Foot’s book will be published in Italian by Felrinelli in December 2014 and in English by Verso in 2015.

Professor John Foot was given a Medical Humanities Research Leave Award from the Wellcome Trust to help fund his research. To find out about the wide range of grant schemes available from the Trust check out the funding pages of the Wellcome Trust website.

Wellcome Trust Research Round-up – 07/07/14

7 Jul, 2014

Our fortnightly update of stories from the Wellcome Trust research community…

Diagnosis of rare genetic disorders from family snaps

computer vision_figure

Computer analysis of photographs could help doctors diagnose which condition a child with a rare genetic disorder has.

Oxford University researchers funded by the Wellcome Trust, MRC and NIHR, have come up with a computer programme that recognises facial features in photographs; looks for similarities with facial structures for various conditions, such as Down’s syndrome, Angelman syndrome, or Progeria; and returns possible matches ranked by likelihood.

Using the latest in computer vision and machine learning, the algorithm increasingly learns which facial features to pay attention to and what to ignore from a growing bank of photographs of people diagnosed with different syndromes. The research is published in eLife.

While genetic disorders are each individually rare, collectively these conditions are thought to affect 1 person in 17. Of these, a third may have symptoms that greatly reduce quality of life.

“A doctor should in future, anywhere in the world, be able to take a smartphone picture of a patient and run the computer analysis to quickly find out which genetic disorder the person might have,” says Dr Christoffer Nellåker, an author of the study.

“This objective approach could help narrow the possible diagnoses, make comparisons easier and allow doctors to come to a conclusion with more certainty.”

Complex speech networks in the brain revealed

B0003254 Brain in the form of electronic circuitryScientists at Imperial College London have succeeded in untangling some of the complex neural pathways in our brain that enable us to speak.

The findings, published in the Journal of Neuroscience, improve scientists’ understanding of how speech is organised in the brain. The disruption to these pathways may help explain difficulties in patients with stroke who have impaired speech.

Each year, more than 150,000 people in the UK suffer a stroke. Around a third of stroke patients will be left with problems with speech and language, known as aphasia.

Using MRI scanning techniques, Dr Fatemeh Geranmayeh, a Wellcome Trust Clinical Research Fellow and her team, examined a cohort of 24 healthy volunteers to identify activity in different brain networks when a person is speaking and examine how these networks work together to enable speech.

The study isolated particular networks primarily responsible for speech, but also identified other, overlapping general brain networks that are activated or suppressed during the speech process. By examining how these networks are organised in the healthy brain, the researchers believe they can have a better understanding of how they are damaged in stroke patients who have difficulty in talking and ultimately hope to improve the function of these networks – through drugs or therapy – to improve patients’ speech.

Mice may hold the key to stopping Alzheimer’s-like diseases

C0018203 Black mouse

Tiny differences in mice that make them peculiarly resistant to a family of conditions that includes Alzheimer’s, Parkinson’s and Creutzfeldt Jakob Disease may provide clues for treatments in humans.

Amyloid diseases are often incurable because drug designers cannot identify the events that cause them to start. A new Wellcome Trust-funded study, published in the journal Molecular Cell, looked to mice for a way forward.

Professor Sheena Radford, Astbury Professor of Biophysics at the University of Leeds, said: “We already knew that mice were not prone to the build up of some of these plaques. This study, for the first time, observed the building happening and saw the differences between the mice proteins and their almost identical human equivalents.”

She added: “We mixed the mouse and human proteins and found that the mice protein actually stopped the formation of the plaque-forming fibrils by the human protein.”

The research was conducted completely in vitro using human and mice beta-2 microglobulin proteins produced in the laboratory. Plaques made up of beta-2 microglobulin are associated with Dialysis Related Amyloidosis (DRA). Instead of being a neurodegenerative condition like Alzheimer’s or Parkinson’s, DRA primarily affects the joints of people on kidney dialysis.

The team observed differences in the formation of the plaque-forming fibrils in samples containing only mouse protein, samples with only the human protein and samples containing mixtures of the two.

In other news…

  • A study in Nature found that drugs, called p110δ inhibitors, currently being used to treat leukaemia, have the unexpected side-effect of boosting immune responses against many different cancers. The study was led by scientists at UCL, the Babraham Institute, and Cambridge University and funded by CRUK, BBSRC and the Wellcome Trust.
  • Summit, a drug discovery and development company, has announced the beginning of a Phase 2 trial of the antibiotic SMT19969 for the treatment of C. difficile infection. Summit has received a Translational Award from the Wellcome Trust for the development of SMT19969.
  • B0004878 DNA double helix and sequencing outputA study published in Human Molecular Genetics updates the number of human genes that can generate proteins to 19,000 – 1,700 fewer than the genes in the most recent annotation, and well below the initial estimations of 100,000 genes.  The work was carried out at the Spanish National Cancer Research Centre, as with help from a collaboration that includes Wellcome Trust Sanger Institute and the University of California, Santa Cruz.

Image credits: Christoffer Nellaker/Oxford University, Brain circuitry – Heidi Cartwright, Wellcome Images , Mouse - Wellcome Library, London, DNA - Peter Artymiuk, Wellcome Images

Will Wolbachia help defeat dengue?

7 Jul, 2014

W0040192 Mosquito: Aedes aegypti adult

One of the Wellcome Trust’s areas of focus for research funding is combatting infectious disease.  We have recently agreed a strategic award of over £7.5 million to continue development of an effective and sustainable approach to reducing the transmission of dengue fever. The research is an international collaboration and project leader Professor Scott O’Neill, Monash University, Australia explains its importance…

Dengue fever is ranked by the World Health Organization (WHO) as the most important mosquito-borne viral disease in the world. With an estimated 390 million dengue infections annually, leading to tens of thousands of deaths, the hospitalisation of millions creates extremely high social and economic costs in developing countries.

IScreen Shot 2014-07-04 at 15.52.57t has to be stopped.

While others are working on vaccines and cures, we are working on what we hope will be a control method to support these initiatives and greatly reduce this rapidly spreading disease.

We – that is members of the Eliminate Dengue research program – are working with Wolbachia, an extremely common bacterium that is found in the majority of insect species, but not the dengue-transmitting mosquito Aedes aegypti. We have found that when the bacterium is introduced into the mosquito the dengue virus can’t grow as well – and if it can’t grow, it can’t be passed between people. We also found that the mosquitos with Wolbachia passed the bacterium to their offspring – and this set us buzzing.

While the target of our work is no bigger than a mosquito, moving from the microscope to over 100 dengue endemic countries is no easy ask of normally lab-restrained scientists. And, while we had great expectations of the science, how would we (and could we?) replace wild mosquito populations with Wolbachia mosquitoes and their dengue blocking progeny?

One thing we did know was that we certainly couldn’t do it on our own. We needed support not only from governments and regulators, but also householders in dengue prone communities.

If I came and knocked on your door to ask if you’d let me release mosquitoes with a bacteria that we’d introduced – in a lab – into your home, to feed on you and your family’s blood, would you welcome us in?


If you overcame your initial desire to shoo us away, you’d probably have a few questions you’d like to ask before you gave us your consent. These would probably be the same questions as residents in Cairns, far northern Australia, Yogyakarta, Indonesia and Tri Nguyen Island, Vietnam had. Thankfully we are able to answer them sufficiently well that we are currently releasing Wolbachia mosquitoes and conducting trials in all these communities.

While we are already seeing success in these trials with close to 100% of mosquitoes found in the 2011 Cairns field trial sites still carrying Wolbachia over three-years after our last controlled release, observing reduced dengue transmission is our ultimate goal.

In 2005 we were fortunate to be awarded funding by the Grand Challenges in Global Health initiative of the Bill & Melinda Gates Foundation which has enabled us to meet some amazing and, some unexpected, milestones in our research. With continued support from the Foundation, and now funding from the Wellcome Trust, we are about to enter the most important phase of our research – investigating the impact of the method in reducing the prevalence of dengue disease in endemic countries.

Following extensive government and community support, next year we hope to begin undertaking citywide trials in Yogyakarta and Nha Trang, Vietnam to compare dengue incidence in susceptible individuals who reside in areas with and without Wolbachia mosquitoes.

While we’re carrying out this engagement in south-east Asia, we are also preparing for a large trial in Townsville, northern Australia to begin later this year. This trial will allow us to develop our community engagement activities and refine the most cost-effective and efficient methods for the deployment of the Wolbachia control method across larger urban areas.

Entomological studies and community engagement activities from collaborating project members are also advancing in Rio de Janeiro, Brazil and Medellin, Colombia. With local government approval and community support it is also hoped to begin field trials in these cities in 2014/2015.

I invite you to join the Wolbachia buzz and follow our research through progress updates on our website –

Screen Shot 2014-07-04 at 15.59.10

You can put your questions to members of the Eliminate Dengue team via their website or subscribe to the programme newsletter – the current issue can be found here. We also have a short video about the research that we invite you to watch on the site.

Part of the Wellcome Trust’s vision is to combat infectious disease by finding new ways to prevent and treat bacterial, viral and parasitic diseases that kill millions of people worldwide. This funding to help continue development of sustainable dengue reduction measures is from a Wellcome Trust Strategic Award. You can find details of all our available grants an funding schemes on the funding pages of the Wellcome Trust website and keep up to date by following us on Twitter.

Image credits: Adult female Ae. aegypti mosquito - Liverpool School of Tropical Medicine courtesy of A Stich, Wellcome Images, all others courtesy of Eliminate Dengue.

Image of the Week: Ruby-tailed wasp

4 Jul, 2014

Ruby tailed wasp


There are over 100,000 different species of wasp on Earth and the majority of these are parasitic. Indeed for almost every pest insect, there is at least one wasp species that preys on it or acts as a parasite to it. This helps naturally control the numbers of pests.

Most of us will be familiar with the yellow and black stripes of the common wasp, but perhaps the most striking species is that of the ruby-tailed wasp, as pictured above. Its distinctive colours make it a truly remarkable sight with the head and thorax having a metallic blue-green, almost turquoise appearance whilst the rear half is a breathtakingly rich red. It is this colour that gives this wasp its name.

The image above was taken using a microscope while the wasp was in its distinguishing defensive position – their concave body shape allows them to roll up (much like hedgehogs do) when threatened. The photographer, Spike Walker, used two electronic flashes to highlight the vibrant colours of the wasp.

Ruby-tailed wasps are also known as “cuckoo wasps” because they lay their eggs in the nests of other wasps and bees. When hatched, their larvae then feast on the newborn larvae of their hosts.

Some species of ruby-tail are now very rare in Britain and are listed as ‘nationally scarce’.

Image credit: Spike Walker, Wellcome Images

Wellcome Images is one of the world’s richest and most unusual collections, with themes ranging from medical and social history to contemporary healthcare and biomedical science. Over 100,000 high resolution images from our historical collections are now free to use under the Creative Commons-Attribution only (CC-BY) licence.

Research Spotlight: Prof Daniel Pick

30 Jun, 2014

Professor Daniel PickProfessor Daniel Pick holds a senior investigator award from the Wellcome Trust and is professor of history at Birkbeck College, University of London. He is also a qualified psychoanalyst and Fellow of the British Psychoanalytical Society. Prof Pick combines these interests in his research of the history of psychoanalysis, psychology and psychiatry, currently taking a special interest in ‘brainwashing’. We asked him to tell us more about this emotive topic…

What are you working on?

I’m about to start a new project involving a number of other researchers that explores the history of ideas about brainwashing, mind control and hidden persuasion as these developed in Britain, the United States and various other states across the post-war period. I want to investigate how and why ‘brainwashing’ debates erupted into public consciousness during the Cold War and look at where such practices and cultural fears of ‘hidden persuasion’ led.

Fears about the unconscious power one person can exert over another are of course much older, but visions of brainwashing after 1950 gained extraordinary traction in popular culture, the human sciences and political thought.

I think the word ‘brainwash’ expresses a host of fears, old and new, about the susceptibility of mind to influence, but also the particular conditions of modern life, politics, commerce, and the role of the psychological sciences themselves.

Why is your work important?

One thing that concerns me in particular and that I think is important here is the contribution (real and imagined) that the clinical professions played in this history. I am interested to then investigate how the reputation and role of therapeutic disciplines was affected by fears of brainwashing.

It is clear that many branches of the human sciences were deployed in military and intelligence work during the Cold War. Some clinicians also produced influential warnings about the dangers of hidden persuasion in the treatment of POWs, not to mention in the world of advertising and political propaganda. Psychoanalysis and psychiatry seems to me to be at the eye of this storm in the post-war period.

At worst, the talking cure perhaps was perverted (along with other ‘psy’ professions) into a normative discipline, a mode of adaptation, or even, in extremis, an adjunct of social control or coercion. But all of this admittedly is far too broad brush as a characterisation. One needs to differentiate carefully between various approaches, to look at particular controversies, show what was done in the name of certain disciplines, in given times and places, often in ways far removed from the original, radical spirit of the discipline’s pioneers.

To hear about the role that some doctors and some psychologists have played in the so-called War on Terror, at Guantanamo and other camps, invites not only extreme concern and outrage (well portrayed in the recent documentary film, Doctors of the Dark Side), but also raises questions about these multiple earlier histories too.

V0011947 A psychiatrist with intense, bulging eyes. Colour process prWe might well ask: how did we get to here?  In the period in which the Allies fought against Nazi Germany, and across the Cold War, psychiatrists, amongst other clinicians, played a variety of significant roles in co-operation with government agencies of diverse kinds. For instance providing expertise on interrogation, propaganda, and ‘re-education’.

I am concerned to see what can be learned from this history – and the history of that history – to map how particular techniques could be used to shape and influence human desires, and shape minds, for good or ill, and also to look at the multiple cultural reverberations of this theme, for instance in Hollywood.

The work I will be leading has several strands, with different colleagues pooling their expertise; it ranges from exploring the experiences, and cultural representation of PoWs in the Korean War and Vietnam War (amongst others) to the idea of psywarfare in defeating ‘totalitarianism’. It draws upon memoirs of key participants, unearths forgotten archives, and analyses a host of different psychological and political fears.

We want to consider the rich history of debate on this topic, in order to ask what brainwashing fears may teach us about freedom and coercion in therapeutic encounters, education, judicial processes and prison systems.

This work bears upon contemporary policy discussion of mental health, the rights of PoWs, and the fate of prisoners of conscience, and considers new technologies of interrogation, and propaganda.

What do you hope the impact of your work will be?

I intend this collective work to lead not just to academic publications, but to several different kinds of writing, as well as a short film, an exhibition, website, some radio broadcasts, events, and more.

I hope that by pooling the research, making connections, bringing people into dialogue, and putting together topics that are often considered discretely (if at all) there will be real gains.

I have been struck already by the enormous potential there is to engage clinicians, historians, social scientists, journalists, and others in a large and shared public conversation about these themes. Whatever anyone might say critically or skeptically about the ambition of such a project, nobody I think would regard the underlying issues as trivial, or anything less than timely.

Daniel Pick - The Pursuit of the Nazi MindHow did you come to be working on this topic/in this field?

In an earlier project, for which I also received a Wellcome grant, I studied clinical archives of the 1930s and 40s, on both sides of the Atlantic, mapping contributions of psychoanalysis to the Allied struggle against Nazism. The effective terminus of that core, documentary research was the Nuremberg trials. This work brought to my attention a quite distinct and in fact much larger set of questions regarding abuses of psy science across and beyond the Cold War.

How has Wellcome funding helped you with your research and career?

I have previously had Wellcome Fellowships on two occasions. These have helped me greatly in my research, mainly by freeing up time to devote to the work. I also regularly use the Wellcome Library and archives, and have attended many events at Wellcome over the years. I have badgered many of the librarians, archivists and other staff there for advice.

Some years ago I had Wellcome support to explore the history of debates on fever and malaria in nineteenth-century Italy. This, in part, led to my book Rome or Death (2005). More recently, I was awarded Wellcome funding for my enquiry into the history of psychoanalytic investigations of fascism and Nazism, which formed the basis of my book The Pursuit of the Nazi Mind  (2012) as well as a website, conferences and other publications and activities.

Which question about your work do you most dread – and why?

I have so often been asked questions such as ‘Isn’t Freud defunct?’ that I rather dread hearing myself repeat my own responses as to why I disagree. Nor do I particularly relish it when people, on hearing I am an analyst, at a party, might say, ‘ah well can you analyse this dream I had last night?’ As Freud showed you need a dreamer not just a dream – associations, a whole process of analytic work – so reading off the ‘meaning’ of a dream from its casual iteration is really not what analysis can or should ever claim to do. Not that it stopped all of Freud’s followers from trying – in the early days they were often busy conducting such interpretations of one another’s unconscious motives on the hoof. It seems to me, however, that Freud’s own later advice that it is best to try and eschew ‘wild analysis’ was rather good advice.

Sometimes people misunderstand the nature of my interest and expertise, assuming that I am setting myself up as some kind of pundit who could explain the ultimate cause, via psychoanalysis, of social conflicts, wars and the rest.

L0015371 Portrait of S. Freud in 1891On occasion I have found this irksome, as well as, often enough, a bit absurd. Admittedly, some analysts, even Freud, great polymath that he was, were at times incautious about applying analysis, or claiming too much for it.

Nonetheless, I think psychoanalysis is an immense and indispensable resource, not only in various therapeutic contexts, but also as a body of knowledge about mind, groups, and social relationships. But it cannot replace history, economics, anthropology, and the rest. It needs to be part of a repertoire, not the privileged ‘key to all mythologies’.

Tell us something about you that might surprise us…

I am usually introduced as a psychoanalyst and historian, I admit this is always a surprise to me, even if it may not be to you, to have got here, to work in both those professions, not least perhaps a curious outcome because I don’t have a degree in History. Literature was where my university life started and I had no conscious intention of seeking to become an analyst or historian at that stage.

What keeps you awake at night?

Amongst other things, climate change and dogs barking.

What’s the best piece of advice you’ve been given?

I’m not sure about the best advice I’ve ever been given, but I do recall, during my analytic training, that one of my supervisors, Edna O’Shaughnessy, pointed out that to be any good at this work you have to be willing to be hated.

Now that you ask the question, I also recall a word of advice I was given when I became a lecturer. This was offered by a former academic mentor of mine, Tony Tanner, in Cambridge, not to be too in awe of the professors, to try not to overdo deference, without being rude… he said something about it being a mistake to imagine anyone however senior (he was probably borrowing from Lacan), ‘the subjects supposed to know’. He said of his professorial colleagues that the real frauds were the ones who felt fully entitled to occupy their positions.

I think he also once recommended to me that I should never, however, underestimate how thin-skinned, anxious for reassurance even the most senior colleague is likely to be deep down. I suppose the advice to try and tolerate the position of being hated as clinician has to be countered (this is the other side of the same coin) by the recognition that we want to be loved, and often more so than we consciously know.

The chain-reaction question, set by our previously spotlighted researcher, Dr Molly Crockett, is: What has been the most unexpected or surprising finding to come out of your research?

In the research that led to my first book, Faces of Degeneration, I was rather amazed to discover the sheer extent of concern, in the nineteenth century, with the flip side of evolution – the fear that we, or at least some people, could  ‘degenerate’, making them biologically prone to commit crime.

Some argued that criminals were simply born not made. Arguments for curbing the fertility of the so-called ‘residuum’, or the ‘unfit’ became prevalent. Given that Darwin was such a remarkably probing figure and to me, a Victorian intellectual hero, it came as a surprise to me to realise how far he and many of his associates were drawn towards the language and theory of degeneracy, one that we would tend now to consider so obviously dubious and sinister.

More recently I have been surprised, as my answers above already suggest, at the extent to which important figures within the psychoanalytical profession were drawn, for better or for worse, into applied work, caught up in major political struggles, policy questions, even sometimes work directly for agencies of the state.

Perhaps one point of origin of this kind of involvement was the contribution made by Freud and his associates to debates about ‘shellshock’ during the Great War. Analysis was never, for Freud, just a matter of seeing individual patients, but he might have been surprised too at some of the work undertaken in his name, in the context of anti-fascism, then of world war, and thereafter of Cold War.

Find out more about Daniel Pick and his publications here and listen to his radio documentaries  The psychiatrist and Rudolph Hess’, Witness, BBC World Service (from 9th May 2012) and  ‘The Roots of Extremism’, BBC Radio 4 (March 2014). He was the editor of ‘The Pursuit of the Nazi Mind’, archive, Birkbeck College  and presented on  ‘The Pursuit of the Nazi Mind’, How to Change the World? at the Nexus Conference in December 2012. 

Image credits: The psychoanalyst by Carl Josef and Portrait of Freud, both from Wellcome Library, London

Image of the Week: N is for Natural Curiosity

27 Jun, 2014

Illustration showing white magnolia blossom (Magnolia altifima) and its seed pod.


This week’s image is an illustration showing white magnolia blossom and its seed pod, taken from a book by Mark Catesby. The title of this beautiful book is proportionate to the length of time and labour involved in its making – consisting of no less than 79 words!

Here it is in full:

“The natural history of Carolina, Florida and the Bahama Islands: containing the figures of birds, beasts, fishes, serpents, insects and plants: particularly the forest-trees, shrubs, and other plants, not hitherto described, or very incorrectly figured by authors. Together with their descriptions in English and French. To which are added observations on the air, soil, and waters: with remarks upon agriculture, grain, pulse, roots, &c. To the whole, is prefixed a new and correct map of the countries treated of.”

Mark Catesby was an English naturalist with an insatiable curiosity about nature. This book documents the flora and fauna that he saw on a four-year trip to the south-eastern United States and the Caribbean. It took him seventeen years to prepare and its exquisite folio-sized colour plates were the first to be used in natural history books.

Visitors to Wellcome Collection can see the book in a newly opened exhibition entitled An Idiosyncratic A to Z of the Human Condition. The show offers an eclectic alphabet mediated through strange and wonderful objects drawn from Henry Wellcome’s collection and contemporary artworks, from A for Acts of Faith to Z for Zoonoses.

Whist offering intriguing medical artefacts, paintings, photographs and sculptures for consideration, the exhibition also calls for contributions from visitors. Each letter has both objects and an activity associated with it. Catesby’s book represents N for Natural Curiosity and it is accompanied by an invitation for visitors to discover their inner naturalist by sharing weird and delightful things they’ve seen in nature.

Tagging your contributions “#HumanNature” and sharing them via Instagram or Twitter will allow us to find them and display them in the gallery to foster natural curiosity in others.

The free exhibition, Idiosyncratic A to Z of the Human Condition, is now open to visitors at the Wellcome Collection. Find out about more objects for consideration and opportunities for contribution and see what others are sharing by following the hashtag “#HumanCondition” on social media.

Image Credit: Wellcome Library, London

Wellcome Images is one of the world’s richest and most unusual collections, with themes ranging from medical and social history to contemporary healthcare and biomedical science. Over 100,000 high resolution images from our historical collections are now free to use under the Creative Commons-Attribution only (CC-BY) licence.

Sharing lessons learnt about strengthening research capacity in LMICs

26 Jun, 2014

Seven principles for strengthening research capacity in low- and middle-income countries: simple ideas in a complex worldThe Wellcome Trust devotes a significant proportion of funds to health-related research conducted outside the UK, supporting over 3000 researchers in more than 50 countries. We, and many other funders, have a long history in strengthening research capacity in low- and middle-income countries (LMICs) and that experience has been shared in a new document published today. Claire Cunliffe from the international activities team at the Wellcome Trust introduces the “Seven principles for strengthening research capacity in low- and middle-income countries”…

Researchers based in LMICs are often best placed to identify and address health challenges in their own countries but they face many challenges related to their research environments, such as underinvestment in research institutions and universities, poor career prospects, and lack of access to cutting edge research findings.

It is now increasingly recognised that in order to harbour the largely untapped talent pool in LMICs and harness it for health research, there needs to be direct investment to improve the ability of individuals and institutions to undertake high-quality research and to engage with the wider community of stakeholders. That is, direct investment in improving research excellence (or capacity strengthening efforts). Members of the ESSENCE on Health Research collaboration, such as the Swedish International Development Agency (SIDA), the Fogarty International Centre, Canada’s International Development Research Center, and the WHO’s special programme for research training (TDR) and the Wellcome Trust have a long supported these efforts. Contributions have been extremely varied, have evolved over time, and often have been embedded in larger research programmes, which makes it difficult to evaluate their impact.

Screen Shot 2014-06-26 at 13.46.51Recognising the importance of sharing lessons learned, today, the ESSENCE on Health Research Initiative launches a new good practice document to provide broad guidance on how to strengthen research capacity in different contexts, including health based on their experience and a number of consultations.

Rather than being prescriptive, it is hoped that the “Seven principles for strengthening research capacity in low- and middle-income countries: simple ideas in a complex world”  will be used as a tool to generate discussion among anyone with a stake in improving research in LMICs, whether they are funders, researchers or policy makers. The document provides key guidance principles with illustrative examples and case studies to show how the principles have been used in practice, and identifies common barriers to their implementation, together with suggestions on how they can be addressed.

The seven principles identified in the publication were developed from the experiences of funders, researchers and research institutes engaged in research capacity strengthening. They are as follows:

  1. Network, collaborate, communicate and share experiences
  2. Understand the local context and accurately evaluate existing research capacity
  3. Ensure local ownership and secure active support
  4. Build in monitoring, evaluation and learning from the start
  5. Establish robust research governance and support structures, and promote effective leadership
  6. Embed strong support, supervision and mentorship structures
  7. Think long-term, be flexible and plan for continuity

Lessons from the Wellcome Trust’s own research capacity strengthening programmes have fed into the document. These include a case study focusing on our African Institutions Initiative, a £28 million programme linking 51 African institutions in 18 countries with 20 ‘northern partners’.

International activities adviser Marta Tufet, who led on the project at the Wellcome Trust, says “evaluating capacity strengthening efforts is challenging, but it is nonetheless essential that we try to gain an understanding of what has and hasn’t worked in the past, and what lessons we can take forward to better inform the design and implementation of new programmes.”

You can read “Seven principles for strengthening research capacity in low- and middle-income countries” in full and find out more about ESSENCE on their website. This good practice guide is the third in a series of documents developed by ESSENCE to share the lessons learnt by funders, researchers and institutes involved in capacity strengthening. The two other documents in the series are: “Planning, Monitoring and Evaluation Framework for Capacity Strengthening in Health Research” and “Five keys to improving research costing in low- and middle-income countries“.


Wellcome Research Round-Up 23/06/14

23 Jun, 2014

Our fortnightly round-up of stories from the Wellcome Trust research community…

Achilles’ heel in drug-resistant bacteria

E. coliA weakness in the outer membrane of bacteria has been identified by researchers at the University of East Anglia, suggesting a new method to disable bacteria and prevent antibiotic resistance.

In a study published in Nature, researchers show how gram negative bacteria cells transport ‘barrier building blocks’ called lipopolysaccharides, which make the bacteria particularly hard to penetrate, to their outer surface.

The team also discovered that if lipopolysaccharides are not able to get the bacteria’s outer membrane the bacteria become much more vulnerable and are easily killed.

Professor Changjiang Dong, Wellcome Trust Career Development Fellow, said: “We have identified the path and gate used by the bacteria to transport the barrier building blocks to the outer surface. Importantly, we have demonstrated that the bacteria would die if the gate is locked.”

“This is really important because drug-resistant bacteria are a global health problem. Many current antibiotics are becoming useless, causing hundreds of thousands of deaths each year. This research provides the platform for urgently-needed new generation drugs.”

The structure of the gram negative bacteria lipopolysaccharides was pinpointed using the intense light produced by the Diamond Light Source.

A tomato a day keeps the doctor at bay

TomatoesA daily supplement of an extract found in tomatoes may improve the function of blood vessels, according to new research from Wellcome Trust-funded researchers the University of Cambridge.

Recent dietary studies suggest that a Mediterranean diet reduces the incidence of events related to the disease, including heart attack and stroke, in patients at high cardiovascular risk, or those who have previously had the disease.

One component of the Mediterranean diet thought to play a role in reducing this risk is lycopene, a powerful antioxidant which is ten times more potent than vitamin E and found in tomatoes and other fruits. In a study published in the journal PLOS One, researchers demonstrate one mechanism by which they believe lycopene reduces the risk.

They found that 7mg of oral lycopene supplementation improved and normalised endothelial function in the patients, but not in healthy volunteers. Lycopene improved the widening of the blood vessels by over a half (53%) compared to baseline in those taking the pill after correction for those who took the placebo; constriction of the blood vessels is one of the key factors that can lead to heart attack and stroke. However, the supplement had no effect on blood pressure, arterial stiffness or levels of lipids.

Bird flu ‘danger zones’ mapped

Geographic distribution of predicted H7N9 infection riskScientists have mapped the “danger zones” in Asia which are vulnerable to the bird flu virus H7N9, which has infected 433 people (mainly in China) and killed 62.

In the study, published in Nature Communications, researchers from the Université Libre de Bruxelles (ULB), the International Livestock Research Institute (ILRI), Oxford University, and the Chinese Center of Disease Control and Prevention analyzed new data showing the distribution and density of live poultry markets in China and of poultry production overall in the country. Jeremy Farrar, Director of the Wellcome Trust was one of the study authors.

They found that the emergence and spread of the disease up until now is mainly linked to areas that have a high concentration of markets catering to a consumer preference for live birds and does not appear related to China’s growing number of intensive commercial poultry operations.

They have pinpointed areas elsewhere in Asia with similar conditions (places with a high density of live bird markets) that could allow H7N9 to significantly expand its range. Places at risk include urban areas in China where the disease has not yet occurred, along with large swaths of the Bengal regions of Bangladesh and India, the Mekong and Red River deltas in Vietnam, and isolated parts of Indonesia and the Philippines.

“We’re not saying these are areas where we expect to see infections emerge, but the concentration of bird markets makes them very suitable for infection should the virus be introduced there, and that knowledge could help guide efforts to limit transmission,” said Marius Gilbert, an expert in the epidemiology of livestock diseases at ULB and the paper’s lead author.

In other news…

Congratulations to Mat Fraser whose Cabinet of Curiosities (How Disability was Kept in a Box) won the Observer Ethical Award for Arts/Culture. Mat wrote this post for us about his project back in January.

Image credits: E.Coli David Gregory&Debbie Marshall, Wellcome Images, Tomatoes, Wellcome Library, London, Geographic distribution of predicted H7N9 infection risk from Predicting the risk of avian influenza A H7N9 infection in live-poultry markets across Asia

Image of the Week: GABA-A receptor

20 Jun, 2014

GABA receptor

This image is based on the first X-ray structure of a GABAA receptor, the human GABAA beta3, recently published in Nature by Dr Paul Miller and Dr Radu Aricescu from the Wellcome Trust Centre for Human Genetics, University of Oxford. The receptor is viewed from the outside of a neuronal cell. Its five subunits are coloured, and a patch of lipids from the surrounding neuronal membrane is modelled as grey spheres.

GABAA receptors play vital roles in neurological disorders such as epilepsy, insomnia and anxiety, and mediate the action of antidepressants, general anaesthetics and alcohol.

The neurotransmitter gamma-aminobutyric acid, known as GABA, dampens activity in neurons by binding to GABAA receptors in the nerve cell membrane. This means that GABAA receptors are the brakes of the brain: they spread calm and regulate excitement. When these regulators fail, brain activity increases, which can lead to a range of debilitating illnesses that affect tens of millions of people worldwide.

Researchers used their understanding from many years of research into various forms of human GABAA receptors to construct one that, unusually, they were able to crystallise successfully. They then used the powerful X-ray beam at the Diamond Light Source to obtain diffraction data from the crystal.

Their findings reveal a large structure consisting of five protein subunits that cross from one side of the cell membrane to the other and create a gated channel. Visualising the receptor at high resolution made it possible to identify the areas on the molecule where GABA and other inhibitory molecules bind. This helps to explain how that binding opens the channel so that chloride ions can enter the cell, making it less sensitive to excitatory inputs.

“Human GABAA receptor subunits are encoded by 19 different genes” says Dr Aricescu. “Although the structure we report can be considered ground-breaking, we have only scratched the surface of an enormously complex system. But we are extremely optimistic because most of the technologies we developed along the way should be transferable to other members of the same receptor family and facilitate rapid progress of the field.”

Image credit: X-ray crystal structure of the neurotransmitter receptor GABAA – Radu Aricescu, Paul Miller and Phillip Stansfeld

Reference: Miller P & Aricescu AR, Crystal structure of a human GABAA receptor, Nature (2014) doi:10.1038/nature13293


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