Wellcome Image of the Month: Sickle Cell Disease
Wednesday 19 June 2013 marks the 5th annual World Sickle Cell Day, created to raise global awareness of sickle cell disease and its serious impact on health.
Our image of the month shows two red blood cells taken from a patient with sickle cell disease. After taking blood from the patient, the cells were collected onto a polycarbonate filter (the pores in the filter are visible in the background of the image) and then further processed so that they could be imaged by scanning electron microscopy. The two red blood cells, one normal and one diseased, were then digitally coloured to highlight the striking differences in their physical structure. The orange cell in the foreground of the image has been affected by sickle cell anaemia which gives the cell its abnormal characteristic ‘sickle’ or ‘crescent’ shape. This change in shape makes the cell less flexible which can cause it to block blood vessels in the body. Sickle cells often die prematurely which means that the body can’t make enough red blood cells to support its needs (anaemia).
Sickle cell anaemia is a genetic disease in which an individual inherits two copies of a faulty haemoglobin gene. Haemoglobin is an iron-rich protein in red blood cells responsible for binding to and carrying oxygen around the body. When oxygen is released into respiring tissues, haemoglobin picks up waste carbon dioxide and delivers it to the lungs to be expelled. People who only inherit one faulty copy of the haemoglobin gene do not develop sickle cell disease but instead become carriers. This is called ‘sickle cell trait’ and provides a protective advantage against malaria infection. The World Health Organization estimates that approximately 5 per cent of the global population carry mutated genes for haemoglobin disorders, specifically sickle cell disease and thalassaemia.
This scanning electron micrograph was acquired by Jackie Lewen whilst at the EM Unit at the UCL Medical School, Royal Free Campus. It was a Wellcome Image Award winner in 2009.
Image credit: EM Unit, UCL Medical School, Royal Free Campus, Wellcome Images (Sickle cell anaemia)
Links
Would you donate a sample of butt fat for research? If asked, I would probably say no to letting someone take a chunk out of my ‘junk’. Fortunately for researchers at the Wellcome Trust Clinical Research Facility in Manchester, 22 people allowed them to do exactly that in order to investigate the effects of bariatric surgery (also known as weight-loss surgery).
There are a variety of surgical weight-loss options: the two most common are gastric banding and gastric bypass. A gastric band closes off part of the stomach, reducing the space available to receive food, while in a gastric bypass operation, the digestive system is rerouted to avoid most of stomach entirely. Within a couple of years, patients who keep to the accompanying diet and exercise plans can lose up to a third of their excess weight.
The Manchester team were interested in the shorter-term effects of these operations. They asked patients undergoing assessment for the surgery if they would be willing to donate a sample form their buttocks for research. After talking about it, patients were given reading material and contact numbers. Follow-up calls identified participants who then attended the research facility.
This is where the butt fat comes in, or rather, out. Read more…
Survey Quality: You gets what you pay for
Surveys are tricky– how do you know they are really representative of public opinion? Patrick Sturgis, Professor of Research Methodology at the University of Southampton, considers survey methodology and why the 2012 Wellcome Trust Monitor took pains to ensure “gold-standard random sampling”.
A few weeks ago the UK Education Secretary, Michael Gove, got himself into a spot of bother about the evidential basis of his claims that young people in Britain know next to nothing about key historical facts. According to Mr Gove, 20 per cent of young people believe Winston Churchill to be a fictional character, while a slightly higher proportion think Sherlock Holmes was a real person. It subsequently transpired (after some persistence) that these figures were taken from a ‘PR’ poll carried out by the well-known research power-house, UKTV Gold.
And, although no alternative figures have yet been produced to show that Mr Gove is wrong in his diagnosis of youthful historical ignorance, we were left in little doubt by the commentariat about what we should make of the robustness of his evidence. The public is generally unconcerned about dodgy survey methodology when polls are used to inform the marketing strategy of a cable TV channel. Citizens are rightly alarmed, though, if the same evidence is used to justify important changes in public policy.
The hoo-ha around this story begs the question of what we mean by a ‘dodgy’ poll and, by the same token, what constitutes a good one. With the publication of the 2012 Wellcome Trust Monitor survey report, my intention in this short post is to shed some light on how potential users of the Monitor might evaluate the quality and robustness of the survey as an evidence base for policy-making, both within the Trust and externally.
Survey methodologists have given a good deal of thought to the question of how to tell a good survey from a bad one (this is, after all, what we are paid to do) and have come up with a number of different dimensions of survey quality. Unfortunately, the most obvious criterion of whether a survey is any good – how accurate its estimates are – is almost always impossible to assess. This is because, for many population characteristics (such as the proportion of young people who think Churchill is a fictional character), there is no external criterion against which the survey can be validated. Surveys are all we have. And, in the relatively few cases where the ‘true’ value of a population characteristic is independently known, it is difficult to justify the expense of undertaking a survey to estimate it.
Beyond the holy grail of accuracy, then, an important quality criterion is transparency; if you can’t find any information about how the survey was conducted, this a pretty good indication in itself that you should be wary about its findings. It is notable in this context that the information that is available about Mr Gove’s historical facts survey does not appear to extend beyond the name of the organization that conducted it. However, what I suspect primarily underlies unease about the UKTV Gold numbers is that the sample interviewed may not have been representative of all young people in the UK. In particular, it may have over-represented the less well-informed.
How then do we collect a sample in a manner that makes it representative of a target population? The gold-standard approach is to draw the sample at random, so that everyone in the population has an equal (or at least known) probability of being interviewed. When done in this way, we can use long-established principles of statistical theory to draw accurate inferences about the characteristics of the entire population, based just on the sample of people we actually interviewed.
The term ‘gold-standard’ is apposite here because interviewer time is very expensive when scaled up over the thousands of households selected in a conventional survey sample. The reason interviewer time is so expensive in random surveys is that they have to keep calling back at sampled addresses until they get an interview with, or a refusal from, the particular individual selected. They can’t just switch to the more compliant next-door neighbour because this would violate the principle of random selection, only the selected respondent will do. As a result, it is not at all uncommon for interviewers on random surveys to make more than ten calls at a single address over a period of 6 to 8 weeks or more. So, random sampling is a labour-intensive and, therefore, expensive data collection strategy.
And, even with this high level of effort and expense, we usually obtain interviews with only around a half to three quarters of those selected to be in the sample. This ‘nonresponse’ leaves open the possibility that the estimates from our survey will be inaccurate, as a result of differences between the responders and the non-responders.
Given the high cost of probability sampling, then, research commissioners reasonably ask if a different (and less costly) approach could be used instead. The answer to this question is that, yes, surveys can be done more cheaply, primarily by using non-probability sampling methods. However, it should at the same time be acknowledged that any cost savings will be bought at the expense of an increase in the risk of inaccurate estimates.
The conventional approach to non-random sampling, whether done online, on the telephone or face-to-face, is to apply so-called ‘quota-controls’. For face-to-face quota samples, interviews are undertaken within a defined geographical area with anyone willing to be interviewed, subject to the constraint that the final sample must match the population on a set of known characteristics. These characteristics are usually gender, age group and employment status. By conducting interviews until the quotas are filled, we end up with a sample that is representative of the target population on the variables used to set the quotas. Quota sampling can yield very substantial cost-savings relative to probability methods, due to the reduction in expensive interviewer time that it produces.
So, why should survey funders like the Wellcome Trust resist the siren calls of those who argue that the same end product – survey estimates – can be achieved at substantially lower cost by ditching random sampling? Well, for one thing, if a sample is not drawn randomly then we cannot make use of the accepted statistical theory that enables inference from samples to populations. Instead, we must rely on a rather ill-defined set of assumptions about the relationship between the quota control characteristics and the variables measured in the survey. This lack of an underlying theory of inference is not very satisfactory.
Of more practical importance, however, is the greater potential for inaccurate estimates in a quota sample. For, if we are concerned about the accuracy of estimates from surveys with response rates in the range of 50 per cent to 60 per cent, we should be considerably more troubled by a sample for which a response rate is not even recorded (remember the point about transparency?). I am not aware of any published evidence on response rates for face-to-face quota samples and in many respects it does not make sense to try to calculate one. However, anecdotal evidence suggests that an approximation would likely place it at somewhere between 5 per cent and 10 per cent. Not very impressive.
The 2012 Wellcome Trust Monitor uses a gold-standard random sampling methodology which comes at considerably greater cost than commensurate endeavors, such as the RCUK Public Attitudes to Science (PAS) survey, which is non-random and based on quota controls. Does its random sample design guarantee that an estimate from the Monitor will be more accurate than the same variable measured in the PAS? Unfortunately, we will almost certainly never know. But, if asked to wager, I know where my money would be.
Patrick Sturgis
Patrick Sturgis is the Principal Investigator for the Wellcome Trust Monitor, Professor of Research Methodology at the University of Southampton and Director of the ESRC National Centre for Research Methods.
Image credit: Flickr/Marco De Cesaris
Vital statistics
The Wellcome Trust believes in bringing cutting edge science to the classroom. The latest edition of our Big Picture magazine for students and teachers focuses on making sense of numbers, teaching you how to spot bad statistics, and the importance of understanding risk.
Did you know that over 99 per cent of the population has a greater than average number of legs? It might seem counter-intuitive at first – the average person has two legs after all, so how could that be? The key is remembering how averages are calculated. Since some of the population have fewer than two legs, the average number of legs is lower than two, thus anyone with two legs technically has more than the average.
Mention statistics and you’re likely to either hear a cry of “boring!” or have someone tell you the “84.6 per cent of statistics are made up”, but statistics are an incredibly powerful tool to help us understand the world around us, and the risks inherent in life.
With the rise of “big data” it’s becoming increasingly important to be able to evaluate data sources, methodologies, sample sizes and understand the way that data is presented.
Although statistics might seem daunting, Big Picture: Number Crunching breaks the subject down into bite-size chunks, surrounded by brightly coloured graphics, and fun facts to make you think.
Additional resources online include lesson ideas for teaches and a detective-themed video approach to understanding how to test for correlation using fingerprint patterns in men and women. The video was created with the help of students from Carshalton Boys Sports College and is well worth a watch.
To explore these and more or subscribe to the print edition of Big Picture visit our website.
The Wellcome Trust funded development of the Primary Science Quality Mark award scheme to help improve and celebrate the quality of science teaching and learning in primary schools. A report on the mark and its use was recently published and we got Jane Turner, Director of the Primary Science Quality Mark, to explain why it is needed.
Although a core subject, primary science has often been rather neglected in comparison with English and maths. Recent research from SCORE shows that science is under-resourced and losing status.
Aware of the difficulties being experienced in schools and determined to raise its profile to inspire young people to be our future scientists, a partnership was formed in 2008 between the National Network of Science Learning Centres, the Association for Science Education and Barnet Local Authority with the aim to revive primary science in the UK/England.
This group devised the Primary Science Quality Mark (PSQM) - a nationwide scheme for raising the profile and celebrating the quality of science teaching and learning in primary schools. The idea behind the mark is that by focussing attention on the schools’ current science offering, and setting targets needed for attaining the mark, they will be incentivised to improve.
One participating school stated that as a driver for pursuing PSQM was that “We were acutely aware that the profile of science was in danger of being lowered to that of a foundation subject”.
In education, a number of quality marks already exist, but PSQM differs from other award schemes through being science-specific and in the methodology. The process begins by auditing a school’s science provision as soon as a school signs up to work towards the award. Subject leaders, supported by a local expert PSQM hub leader, then progress the scheme from this starting point to galvanise their colleagues, pupils, parents and governors to raise the profile and quality of science in their school.
Initiatives such as professional development sessions, advice, support, feedback and encouragement are examples of steps that can be taken towards PSQM status, which usually takes a year for a school to achieve. This culminates in a final submission stage, where subject leaders write reflections on the impact of their leadership over the last year against the initial audit and each of the PSQM criteria.
The Wellcome Trust funded a two-year PSQM pilot phase and, due to its success, also supported the model for a sustainable national roll out of the scheme in 2010.
This year a new partnership between the AstraZeneca Science Teaching Trust and the University of Hertfordshire was established to support the continuing development and growth of the PSQM programme. Since 2010, 600 primary schools across the UK have achieved PSQM and have been celebrating increased quality of their science teaching and learning. Another 410 schools are currently engaged in the programme, which means that at least 20,000 pupils have been enthused so far!
A new Wellcome Trust report about the mark gives readers insights into how PSQM schools have:
- approached the tiered quality mark,
- gained from achieving the award,
- faced the challenges in aiming to raise the quality of primary science,
- used initiatives created by primary science leaders to raise the quality of science in their schools, and
- received enlightening opinions from young people on how they feel about their science education.
Schools participating in the PSQM scheme have to collect and provide evidence relating to their primary science practice. Subject leaders report honestly the challenges they face and the strategies they use to address them. They describe the highs and lows of teaching science in primary schools today.
The lows are often related to external pressures or uncertainties; the highs are always to do with the very human satisfaction of a job well done. This data is rich and powerful for both the school – when evaluating and learning from its progress – and for others e.g. policy-makers, researchers, educationalists – when seeking evidence to help shape accountability measures or policy change that can affect school science.
Schools that have been awarded the PSQM can happily provide many positive stories about enthused and motivated children who enjoy learning science and do well. These stories are evidenced by their growing understanding and application of scientific ideas and processes. Once teacher commented: “If I had to use one word to describe our Science curriculum, it would be dynamic.”
At this time of significant change for curriculum, assessment and organisation in schools, this project has confirmed that PSQM submissions are indeed a valuable data source for all interested in ensuring that primary science inspires future generations.
Hundreds of schools are currently taking part in the PSQM award programme. If you would like to find out more or register your school for PSQM visit www.psqm.org.uk
Wellcome Funding for the PSQM was in the form of an Engaging Science grant. Find out more about out funding schemes on the Wellcome Trust website.
Zwelethu absorbs the sight of a massive shanty town
Over the course of four months, Barry Gibb visited our major overseas programmes in Africa and Asia to make a film about Wellcome Collection’s Art in Global Health project. In the last of his diary entries, Barry describes South Africa.
For a start, this was an incredibly compressed trip – around 36 hours from touchdown to take off and, on the day of the flight, I’d still not heard anything from the person who was my main interviewee, the artist Zwelethu Mthethwa. Reluctant to leave the house and travel more than 9500km without at least a hint of contact, I called Zwelethu, desperately hoping he would answer.
To my relief, the phone was picked up by a warm sounding man, full of good humour, and we discussed the next day’s plans. At the time, everything sounded so certain.
The 11 hour journey meant I arrived in Cape Town the next morning, with little sleep and just a couple of hours before the adventure with Zwelethu was due to begin. The trip from the airport to the hotel left no doubt I was in a new continent. Table Mountain loomed over us for the entire duration of the trip. Countryside gave way to shanty towns, urban spread and eventually to central Cape Town itself, a beautiful city with a distinct architectural feel.
Several bounced or missed calls later, Zwelethu and I eventually found each other in a frenetically cool café beside the hotel. Tucked away amidst the chic crowd, slurping espresso and sporting a Kangol cap plus long trench coat, Zwelethu felt like a mysterious, coiled spring of energy, intense and energetic. I was very much looking forward to asking him all sorts of questions about his work at the Africa Centre for Health and Population Studies in South Africa’s eastern region of Kwa-Zulu Natal.
Still standing, Zwelethu despatched his strong coffee with a practiced gulp before we exited the café like a stiff breeze, heading to his studio where I hoped we’d do the interview. The area of Cape Town we were in felt like a Parisian version of London’s Camden; hip, fashionable and full of people of every colour as they relaxed or shopped. It became clear this was Zwelethu’s domain, breaking off from our trip to briefly talk to friends, firm up arrangements, and so on. I was quickly building a picture of a man who is fully ‘on’.
In stark contrast to Katie Paterson’s pearl-esque studio in Berlin, Zwelethu briskly welcomed me into his frenetic studio; a living museum of his mind. Canvases were everywhere, piled up or mounted in various states of completion, the walls were covered in ‘notes’ and scribblings and more than anything there were pastels. Small pastels, big pastels, huge pastels like bricks; as if a rainbow had exploded in this room, shattering into these varied pieces of chalk and dust.
From a filmmaking perspective, this was a gift. As I set up the camera for our interview, Zwelethu took me by surprise, stating that he hadn’t been sure he was going to go through with the interview until he’d met me, to see if I was giving off the ‘right kind of energy’. Part of me was mystified – I’d travelled 9500km! However, even in those first few minutes together, I could see how tuned in this artist was to people – how easily he ‘got them’.
Relieved that I was, indeed, emanating the right vibe, we started the interview. Only now did I see how experienced Zwelethu was in front of a camera. There were no nerves, only long thoughtful pauses as he digested each question before unfalteringly providing a wonderfully articulate and insightful response. I should have known this would be the case in advance, after all, this man is one of the most prominent artists in South Africa.
Zwelethu allowed me to film various aspects of his studio. Naturally, a range of charcoal shots made it in but he also took great pleasure in showing me a very bizarre piece of furniture: a dresser filled with human hair. I was so struck by the oddness that I completely missed the intent of this particular piece of art, but there was something lyrical about this one specific component of a multitude of humans being hoarded into a drawer.
I’d explained to Zwelethu that during my other trips abroad it had been useful, if possible, to capture a sense of the place we were filming, largely to help create visually and culturally distinct locations for the film being made about the project. He thought for a long moment then smiled as he stormed away, ‘Let’s go, I have something special to show you.’
Even as we drove, Zwelethu wouldn’t tell me where we were going. His preferred weapon of choice is a beautiful, large format digital camera; at least when taking composed shots. But for general research whilst driving or walking around, he uses a cheap, plastic disposable camera. Riding along with Zwelethu amounts to lively conversation punctuated with the occasional ‘click and ratchet’ of his research tool as he captures another images to feed his imagination and wind on the film for the next shot.
At last I saw where he was taking me, the local township, or shanty town. As a London dweller, the sight of a full-scale township is so incompatible with my worldview, that it took a good while for it to sink in. A sea of thousands upon thousands of multi-coloured dwellings, none higher than one story tall, none larger than a decent sized shed. All of them made of a potpourri of basic materials, corrugated metal, wood, brick.
Just like Zwlelethu’s studio, the township was peppered with bright primary colours; attempts to add individuality, some vague uniqueness to the habitats in this monolayer of life so powerfully symbolic of the aftermath of years of oppression.
As we drove slowly through the streets, Zwelethu explained the history and meaning of the township (“click, ratchet”), that the people here are, by and large, content (“click, ratchet”), that he feels safe here and crime is low. He explained that, if someone from the township appears one day wearing designer trainers or underwear, they are not targeted for theft (“click, ratchet”). Instead, they are celebrated as a symbol of what is possible, that anyone can ‘make it’ in this new South Africa.
Spontaneously, Zwelethu decided he wanted to locate an illicit, unlicensed, bar he’d heard about from a friend, so off we drove. Past people, goats and dogs roaming the streets, savouring the smells of street markets and barbeques selling cooked meat. And everywhere, the ubiquitous sign for a brand of fizzy drink so popular I can’t bring myself to write it down.
When we did find the bar, it was not what I expected. Externally, it looked near identical to all the other loosely fabricated dwellings, if a little bigger. Inside however, the owner had taken pains to make this a decent, club-like environment. Sure, it was small, but there was a bar, soft seating, good lighting and a DJ. Expensive champagne, whiskey and a range of other spirits occupied the bar. Zwelethu, in a display of generosity bought an entire bottle of whisky for us and the owners to share. Clearly, he knew the team running this place and it was made abundantly clear to me that, even if I left my camera equipment sitting at the door of the bar, absolutely no one would take it – not whilst I was under the owner’s protection. Just one small insight into a layer of life I’d never have seen without Zwelethu’s guidance.
As I cautiously sipped away at my dram, we were brought some much needed nutrition on the house, a barbequed goat’s neck. Having eaten nothing all day, I attacked the neck with gusto, much to delight of my companions. In hindsight, my only faux pas was to avoid the fat – a lesson learnt a little too late as I watched them eat slabs of cooked adipose tissue with glee.
Turning a unique experience into a surreal one, a beautiful girl then glided into the bar who, it turned out, was a local music star. Carrying her album with her, she was going around the township, selling this album, symbolic of far more than musical creation. The owners insisted we have a photograph taken together, which is how I ended up with a photograph of myself looking baffled and confused, standing alongside this diminutive South African pop star.
As the night drew on and the bottle’s contents surrendered to good company, it was time for Zwelethu and myself to leave, waving goodbye to our new friends and one of the most special evenings of my life. Zwelethu wished to give me some of his actual photos for the film and insisted on driving me back to his apartment to burn them onto a DVD. Slightly confused, I asked him why he couldn’t just email them to me (they were digital, after all). His answer: “We started this journey together, we must finish this journey together”.
Barry J Gibb
Barry J Gibb is a Science Multimedia Producer at the Wellcome Trust.
Read Barry’s previous diary entries.
Find out more about Art in Global Health on the Wellcome Collection website.
June 2013 public engagement events
Credit: Daredevil Labs
The sun has finally arrived and just in time for festival season too. Make the most of the good weather and get out and about to some of the fantastic events supported by the Wellcome Trust’s public engagement awards.
Yesterday was the first day of the Cheltenham Science Festival. Once again, the team behind the festival have developed a varied programme to satisfy most appetites. For example, fresh from their expedition to Mount Everest, BBC presenter Greg Foot and mountaineer Nick Insley will be talking about their scientific escapades at the world’s highest lab. With a host of live demos and a whole-audience experiment, the Xtreme Everest Project is at midday on Saturday 8 June.
For the music fans among you, Professor Roger Kneebone’s World of Surgery series is taking place as part of the Cheltenham Music Festival, 3-14 July. Highlights include World of Surgery: The Ensemble Performance on 13 July: it’s a discussion with Professor Aaron Williamon on the secrets behind a successful ensemble, drawing a comparison between vascular surgeons and string quartet players.
Elsewhere in June, Elastic Theatre’s JULIUS, a multi-screen film exploring the nature of obsessional thoughts and the superstitious beliefs associated with them, will be showing 7-14 June at the Spitalfields Music Festival in east London. The screening on 12 June will be followed by a discussion, while on 21 June, the cast will present a live pop-up performance at the GV art gallery.
Beyond the festivals
Spanning 70 years and four interconnecting stories, Curious Directive’s multimedia play After the Rainfall is on 14 and 15 June, 7.30pm, at the Arts Depot in North Finchley, London. The play connects the arid Egyptian desert, the British Museum and a quiet village green, all the while likening the spread of human ideas to an ant colony.
Gendered Intelligence’s project GI’s Anatomy: Drawing Sex, Drawing Gender, Drawing Bodies will be showcased at the Central School of Speech & Drama in London on Thursday 27June, 5.30-9pm. An exhibition of life drawings from the project will be accompanied by a discussion exploring the science of sex and gender.
One for the kids, the BEANii children’s theatre show Harriet and Jake and the Victorian Adventure is at 6pm on Saturday 29 June at St Saviour’s Pimlico, St George’s Square. Created during a series of workshops exploring the health impacts of nutrition, exercise and mind-set, the show looks at the issues affecting children in the Victorian era compared with children today. A discussion event will follow the performance.
Still on
Jordan Baseman’s Deadness exhibition is at Matt’s Gallery in London until 21 July (open Wednesday to Sunday, 12-6pm). An exhibition in three parts, Deadness features multiple 35mm slide projections with sound, a film called ‘The Last Walk’ and a series of new photographic works. The exhibits explore the historical, cultural and sociological relationship between embalming and photographic portraiture.
If you are inspired to go along to any of the events above, please come back to leave a comment and let us know what you thought!
Thanks to our Engaging Science colleague Lois Browne for the info.
Carly Fleischmann with her father.
The following is an excerpt from Issue 12 of Guru Magazine, a Wellcome-Trust supported digital ‘science-lifestyle’ periodical available for free at gurumagazine.org and via Apple Newsstand and Google Play.
At the age of 10, Carly Fleischmann typed a simple message on her father’s laptop, “Help. Teeth hurt.” Such a message wouldn’t normally be impressive if written by a 10 year old, but for Carly it was different—she has autism. Until that day, Carly was thought to be severely mentally handicapped. Regularly throwing temper tantrums, she would thrash her arms and slam them on the table. So the sudden message startled her parents. Before those typed words, they had no idea that Carly could hear or understand anyone. But in that instant it became apparent that she may have silently understood everything said about her, and her handicap, in the preceding years. And it turned out that she had. While Carly’s sudden communication seems remarkable, she isn’t unique. In fact, a new theory of autism now predicts that all autists are much like Carly.
The present consensus among researchers is that genes are the most important factor in the cause of autism: up to 90 percent of the risk for developing autism is due to genetic factors. For a long time it was thought that the disorder may be the result of an ‘autism’ gene, but it is now believed that a combination of causes interact to produce autistic traits—that autism occurs when a developing baby with a genetic weakness for autism suffers some kind of ‘environmental insult’ before or after birth. Quite what this insult might be, no one knows—and neither do we know which genes lead to the genetic weakness.
Based on laboratory experiments with rats, neuroscientists Henry and Kamila Markram have proposed an entirely new theory, known as the ‘Intense World Theory’, which may radically shake up the way we look at autism. This theory holds that the brains of autistic individuals are ‘hyper-connected’ and ‘hyper-excitable’. Rather than suffering from a deficit in perceptual abilities, the theory suggests that autists experience the world so vividly that it becomes painfully intense—so painful that they take refuge by turning inward and avoiding interaction with the outside world.
The ‘Intense World Theory’ emerged out of studies investigating the link between autism and the anti-epilepsy medicine valproic acid. Valproic acid has been used to treat bipolar disorder, migraine headaches and schizophrenia, but taking it during pregnancy can lead to autism and birth defects in the child. Similar effects can be seen in other animals. Rats, for example, demonstrate decreased social interactions, increased repetitive behaviour, enhanced anxiety, hyperactivity, and altered pain sensation—the same symptoms that are found in autistic humans. Valproic acid given before birth also causes damage to particular areas of the brain (the brainstem and cerebellum)—and this pattern of damage is also similar in rats.
Given these similarities, Markram and Markram believe that rats offer a particularly good way of testing various theories about autism, so they performed a series of experiments using rats to explore the ‘Intense World Theory’. Studying their brains, Markram and Markram found that certain networks of brain cells in the valproic-acid treated rats were much more sensitive—they had much more brain activity—than normal. The researchers also found the brain cells in autistic rats to have notably more connections: their brains were ‘hyperconnected’. Consequently, the flow of information throughout the brain was enhanced, possibly explaining why the autistic rats were much better at discriminating between apertures of different sizes (similar to an autistic human’s ability to focus on fine detail). Finally, they discovered that the amygdala, a part of the brain responsible for fear processing, had a tendency to form new connections, which may explain the intense fear the autistic rats developed.
It might seem counterintuitive that brain areas experiencing a loss of neurons can have excess activity. One possible explanation involves the types of nerve cells that are affected: many brain cells have an inhibitory, or ‘braking’, effect on the rest of the brain. The cerebellum (a region at the back of the head needed for co-ordination) has a high concentration of these ‘inhibitory’ nerve cells. So it wouldn’t be surprising that a loss of this type of brain cell—an easing up of the brakes—would make for an increase in brain activity overall. The remaining, unharmed, brain cells of the autistic brain would therefore form more connections with one another—perhaps increasing the ability to focus and pay attention to details.
But this degree of intensity probably also leads to a ‘system overload’ and the anxiety that autists experience. “Autists see, hear, feel, think and remember too much, too deep and process information too completely,” said Henry Markram in a recent interview with Wrong Planet, an online autism community.
“You don’t know what it feels like to be me”
Autistic individuals develop strategies to actively avoid the intense pain of perceptual experience. If that doesn’t work, they resort to repetitive movements or radical behaviour. For example, children with autism often react to new sights, sounds and sensations with temper tantrums or extreme panic.
Carly, who suddenly communicated with her dad at the age of 10, expresses a disturbing discomfort from the world around her. “You don’t know what it feels like to be me, when you can’t sit still because your legs feel like they are on fire, or it feels like a hundred ants are crawling up your arms,” she writes. Carly says that people like her engage in repetitive behaviour and throw tantrums because it soothes the intense pain felt from sights and sounds. It’s a way of turning the mind inward, away from the painful outside.
How could the ‘Intense World Theory’ influence our treatment of and care for those with autism? For one thing, it would mean that autism isn’t thought of as being caused by a deficit. Rather than lacking in ability, autists simply have too much to interpret. The problem with the autistic brain is that certain regions may develop too quickly, going on to dominate other regions—which can make rehabilitation very difficult.
To counteract this problem, we might use medicines to suppress the brain activity arising from all of the extra connections. It seems nonsensical to treat a lack of communication in autism with a drug that limits the brain’s activity, but this counterintuitive approach works with other disorders: attention deficit hyperactivity disorder—a condition where children find it hard to concentrate and stay still—is treated with a stimulant, amphetamine. It is thought that amphetamine (the same drug as in ‘speed’, albeit at a very low dose) increases the activity of the control centers of the brain. The result: children with ADHD calm down and focus.
But reducing excess brain activity may not be the best way to deal with autism. One interesting prediction of the ‘Intense World Theory’ is that all autists have an ability to perform difficult intellectual tasks with incredible ease like savants—even if they can’t communicate it. Savantism is also believed to be the result of a hyperconnected brain. So autists who are not diagnosed with savant syndrome likely still share many of the exceptional abilities of savants. Assuming that people with autism learn to utilise their brains’ hyperreactivity, they may develop exceptional talents later in life. According to Markram, if the autist’s exposure to her surroundings is controlled after birth, “It’s possible to be a genius.”
References
- Markram, H., & Markram, K. (2013). Interview: Henry and Kamila Markram about The Intense World Theory for Autism. J. S. Holman (Interviewer), WrongPlanet.net.
- Markram, K., & Markram, H. (2010). The Intense World Theory – A Unifying Theory of the Neurobiology of Autism. Frontiers in Human Neuroscience, 4.
Berit Brogaard and Kristian Marlow
Berit Brogaard, DMSci, PhD is Professor of Philosophy with joint appointments in the Department of Philosophy and the Center for Neurodynamics at the University of Missouri in St. Louis as well as the Network for Sensory Research at the University of Toronto. She directs the Brogaard Lab for Multisensory Research, a laboratory focused on synesthesia, savant syndrome and autism.
Kristian Marlow is a graduate student, member of the Center for Neurodynamics and member of the Brogaard lab. Berit and Kristian began writing about the fascinating cases they’ve studied for their forthcoming book The Superhuman Mind: True Tales of Extraordinary Mental Ability.
Guru magazine is supported by the Wellcome Trust.
Brian Cox cool, science teachers cooler
For more Wellcome Trust Monitor infographics http://wellc.me/19ASRrU
Science, for so long the uncool subject as school, has had something of a renaissance of late and the decline in the number of pupils taking maths and science has turned around. And all this – if you believe the newspapers – is because one man, Professor Brian Cox, musician, chat-show regular and particle physicist, has made science sexy.
Science lessons are actually far more popular than most of us think. According to the Wellcome Trust Monitor over four out of five 14 to 18 year-olds find their science lessons interesting – in fact, most think they are more interesting than English, with its Shakespearean tragedies and feral children. This finding is consistent with the first survey in 2009 – back then, it came as such as surprise that our advisory panel thought we’d made a mistake (we checked and a follow-up study confirmed we were right).
This turnaround in interest in science is without doubt a good thing. We need a science-skilled workforce to help the UK’s long term economic competitiveness and we need a scientifically literate population to help make sense of the myriad health scares (as the recent measles outbreak in Swansea has shown). But is it really down to one man?
There will be many a science teacher who feels somewhat disgruntled to see Professor Cox getting all the credit for making science ‘cool’, as this oversimplification of the story ignores the tremendous work the education community has been doing. And the Monitor backs this up: when we asked young people what encouraged them to learn science, the most common answer was their teacher – nearly six in ten said a good teacher inspired them; worrying, though, that over four in ten said a bad teacher turned them off science.
There has been much work done to improve science education and to encourage science graduates to consider a career in teaching. Just over half of all physics teachers hold a physics degree (a good start, but we must do better) and four in five biology teachers have a relevant degree.
Just as important is ensuring that once in position, our teachers are able to grow and develop. One of the wonderful things about a career in science is that the subject is ever-changing. To make science teaching an attractive career, we must ensure that our teachers have the opportunity to embrace and use new knowledge, just as scientists do. Teachers must be able to learn and implement the latest development in pedagogy, but they must also be able to keep abreast of cutting-edge science and convey the excitement of it to their pupils. Newton’s law of inertia is important, but so too is the understanding that science itself never stands still.
The National Science Learning Centre at the University of York is leading the way for teachers’ continued professional development, and since its doors opened in 2005 has had well over 10,000 teachers and technicians on its courses, crucially offering bursaries to schools to help cover course costs, including travel and teaching cover. These bursaries, funded by the Government, industry and the Wellcome Trust, show the importance we all place upon excellent teachers and their ability to inspire their pupils to study science and go on to work in related careers. The Monitor, indeed, showed that teachers were the second main source of careers advice for pupils (behind their parents).
However, there is evidence that pupils form their opinions and make their decisions about science early, in fact often by the end of primary school. Unfortunately, there remains a woeful number of primary school teachers with science qualifications – less than one in thirty – and little focus amongst head teachers and senior leadership teams on the status and importance of science in primary schools. Too many schools focus on targets in English and maths, with science as a poor relation despite the fact that it is also a core subject. If on top of that, we have a primary workforce that has rarely studied science beyond GCSE, then who will champion science and convey not just confidence, but pleasure in it?
Wonderful as it is to have physicists, biologists and chemists like Brian Cox on TV to inspire our next generation of scientists, what we really need are physicists, biologists and chemists like Brian Cox to join our secondary and primary teaching workforce. Britain is excellent at science in all fields. Now let’s make sure it is excellent at science teaching at all levels.
Clare Matterson, Director of Medical Humanities and Engagement, Wellcome Trust
Wellcome Trust Monitor: www.wellcome.ac.uk/monitor
You might also find the resources available on the Science Learning Centres website useful.
The digital future of infectious disease maps
The spatial distribution of Plasmodium falciparum malaria endemicity in 2010.
You are stuck in bed with a snotty nose and flu. You grab your smart phone and use 140 characters to declare to your Twitter followers: “Feel awful. Fever burning up my bed #sickday”. Unbeknownst to you, your tweet could be part of a global effort to map infectious diseases.
Tweets have been shown to be extremely useful in predicting outbreaks of disease. In the US, studies have found that analysing trends on Twitter could indicate an outbreak of flu two or three weeks before the Centres for Disease Control and Prediction announce a problem. It does, however, come with a note of caution and a warning about common sense. In one study they found a massive spike monitoring the symptom word “fever”. Closer inspection revealed the tweets were a meme about pop star Justin Bieber (“Bieber Fever”).
Tweets are among the innovative information-gathering methods David Pigott and a team from Malaria Atlas Project (MAP) have recommended in a review of global mapping of infectious diseases.
Accurate maps make it possible to plan treatment strategies and infrastructure such as clinics. They also help researchers to know when a disease has spread to a new area and to predict how it may increase in places where they have no solid information.
However, the review found a massive deficit in accurate mapping. Of 355 diseases recorded by the Global Infectious Diseases and Epidemiology Network, 174 could do with accurate and up-to-date maps of where these diseases are occurring. But only seven had been mapped. Moreover, many of the disease maps were based on sketchy data, such as anecdotal evidence of where a disease is thought to occur.
The traditional way of getting information is to sift through reams of journals and grey literature. However, the worldwide web is offering new, innovative ways of measuring disease occurrence. The data gathered online is recent, and can be gained from outlying areas where academic research is less prolific. One example comes from a study published this month in Nature. In it, the MAP team and other researchers measured the global burden of dengue fever. Among their sources for new cases of infection was Health Map, an online tool that trawls through online news stories. Data gathered from Health Map accounted for between 20 to 30 per cent of the total data in the study.
The team is also borrowing tools from other fields of research. For example the genetic sequence database, GenBank, is widely used by microbiologists and the amount of data it holds is growing exponentially, doubling every 18months. MAP believe it might be an untapped resource for their own work where sequences are stored with geographic locations.
For the MAP team, malaria has been the key focus for several years, But they are actively moving beyond this and trying to tackle those 173 other map-needy diseases. “If there is going to a lot of money invested in specific areas of disease, you need a map to know where exactly this disease is,” says Pigott. The ultimate goal is to have a sophisticated online map that could automatically collect information from the web to predict where infectious diseases are going to strike next.
Reference
Hay S.I., Battle K.E., Pigott D.M., Smith D.L., Moyes C.L., Bhatt S., Brownstein J.S., Collier N., Myers M.F. & George D.B. & (2013). Global mapping of infectious disease., Philosophical transactions of the Royal Society of London. Series B, Biological sciences, PMID: 23382431
Theresa Taylor
Theresa is an intern at the Wellcome Trust.
The Malaria Atlas Project is supported by the Wellcome Trust.
Image credit: Malaria Atlas Project
Wellcome Film of the Month moves
For all fans of our Wellcome Film of the Month: a quick note to say it hasn’t disappeared but has moved to the Wellcome Library blog. The first in the new look column was posted today, on ‘Your children and you’. You’ll find the same fabulous film from our archives each month with commentary and analysis by Wellcome Film’s Angela Saward. And if you like that, why not have a scout around the Wellcome Library blog’s other excellent medical history posts?
We hope you’ll continue to enjoy Wellcome Film of the Month in its new home.
Around the World in 80 Days – Part 6: Germany
Over the course of four months, Barry Gibb visited our major overseas programmes in Africa and Asia to make a film about Wellcome Collection’s Art in Global Health project. In the latest of his diary entries, Barry makes a brief stop somewhere a little closer to home: Berlin.
As a researcher back in the early 90s, I spent several months living and working in Berlin, Germany, doing a spot of ad-hoc science at the Max-Planck-Institute for Molecular Genetics. I remember buses that ran like clockwork, the intense cold and Tacheles, a huge department store that had become a squat and home to some of the most amazing art and raves.
Back at Tegel Airport, memories began fighting their way through the treacle of time as I made my way to meet Katie Paterson, the artist-in-residence at the Wellcome Trust Sanger Institute in the UK (who, before you ask, lives in Germany – hence my being here and not back home!).
Arriving at Katie’s place, she and her partner immediately welcomed me into the space in which Katie thinks and creates; a cubic, entirely white room. Whilst often filled with materials and objects of inspiration (offering clues to Katie’s cerebral interests), today the contents of this room were minimal – perfect for our interview.
Despite the studio being right beside a main road, we were a few storeys up – far enough away from the traffic to stop noise being too much of an issue. And, thanks to large windows all across this street facing wall, I was able to place Katie looking directly into a flood of natural light, making the most of a sunny day and her unusually bright, blue eyes.
The interview itself was an opportunity to gather material for the film but also to gain a deeper insight into how Katie sees the world. As it turns out, she is interested in nothingness, the absence of things: space and time. Within the context of her apartment, beyond the studio, this manifests itself in meteorite fragments and rocks of varying texture, a physical map of the moon, books about space. At the Sanger Institute, her discussions with scientists led her down a path of inquiry into the genetic heritage of humanity; where did the first humans emerge, how did they spread across the planet?
In Katie’s own words, “I believe work being undertaken in genome sequencing at the Sanger Institute can allow us to penetrate questions of existence: contemplate who we are, where we have come from and how we relate to one another, and enable us to be part of a complex decision-making process about the possible direction of our species.”
After the interview, with a deeper respect for Katie and her work, there followed a filming challenge – how do you show the internal creative processes of a person who, when not busy creating their works, spends her increasingly rare moments of tranquility deep in thought, formulating ideas? Shots of Katie simply staring into space seemed a little hackneyed so, fortunately, Katie shared that she keeps written notes, notes she was prepared to add to. Bingo.
There are so many nuances of human behavior, even within the simplest of actions, that I now knew we’d have enough coverage of Katie ‘thinking’. Wide and mid shots, macro shots, the pencil moving across the page, the eyes as they pause and consider. Finally, Katie introduced me to their two new kittens, fragile lumps of fluff with legs. These had nothing to do with DNA and human heritage but everything to do with fun and the promise of moments of levity between those deeper thoughts.
The next morning came all too quickly. Leaving for the airport at 4am, time suddenly felt very present. I was about to travel across countries and time zones, flying beneath stars that still filled the dark sky, bathing the planet in light from millions of years in the past. This sudden, profound awareness of space and time, I have called, the Paterson Effect.
Barry J Gibb
Barry J Gibb is a Science Multimedia Producer at the Wellcome Trust.
Read Barry’s previous diary entries.
Find out more about Art in Global Health on the Wellcome Collection website.
Is it okay to use smart drugs?
In the past 5 years or so, there has been a huge increase in lifestyle use of prescription drugs that can enhance cognitive function in various ways. These so-called “smart drugs” include the stimulants methylphenidate (better known by its trade name, Ritalin), which is used to treat attention deficit hyperactivity disorder, and modafinil (also known as Provigil), used as a treatment for narcolepsy.
Off-label use of smart drugs is particularly prevalent among students, who face increasing pressure to improve their academic performance. They therefore take these drugs in an effort to focus their attention for longer periods of time and boost their overall productivity.
According to a 2008 survey conducted by the journal Nature, the use of smart drugs is increasing among academics, too. One in five of the approximately 1,600 researchers who responded to the survey said that they had used smart drugs – with Ritalin being the most popular – to focus their attention, memory or concentration.
Is it okay to boost brain function in this way? The question has divided the scientific community. Some researchers say ‘no’ for safety reasons: we still don’t know the consequences of taking smart drugs for long periods of time, and youngsters are particularly at risk because their brains continue to develop well into early adulthood. And the ease with which anyone can buy smart drugs online also raises concern.
Some object to cognitive enhancement on ethical grounds: it may increase the inequalities already present in society, because not everyone could afford to buy the drugs. And what about those who object because they think it would give an unfair advantage? Would they feel pressured into popping brain-boosting pills just to keep up with the others?
Others say that enhancement is not a dirty word, that more research should be done, and that the public should work together with scientists and policy makers to regulate the use of smart drugs. They emphasize the potential benefits that cognitive enhancement could bring to society. Recent research shows, for example, that smart drugs can improve the performance of sleep-deprived surgeons and nightshift workers. The U.S., British, French and Chinese military forces now use Modafinil routinely to combat fatigue in troops, and the drug has also been shown to improve some aspects of cognitive function in psychiatric patients.
Last year, the Wellcome Trust commissioned the second wave of its Monitor Survey, which was designed to assess the UK general public’s level of awareness and attitude toward this controversial issue. This is the most representative such survey to date, and included responses from nearly 1,400 adults and 400 young people aged 14-18.
The results show that opinion is similarly divided: About one-third of adults and young people said that long-term use of smart drugs to improve focus, memory or attention, or occasional use to improve exam performance or something similar, was acceptable, while about one-third said that it was unacceptable.
The results also suggest that the use of smart drugs is less widespread among the general public than within universities, with only 29 adults (or 2% of the total sample) and 9 young people (or 1%) saying that they had ever taken prescription medications for that purpose.
What’s your opinion? Join the debate using the Wellcome Trust’s Big Picture app.
Mo Costandi
Mo Costandi trained as a developmental neurobiologist and now works as a freelance science writer. He writes the Neurophilosophy blog, which is hosted by the Guardian, and his first book, 50 Human Brain Ideas You Really Need to Know, will be published in July. You can read more of his posts on our sister blog ThInk.
Wellcome Image of the Month: Mental Health
This week (13 – 19 May 2013) is mental health awareness week which aims to raise awareness of and challenge people’s views surrounding mental health issues. Mental health is unfortunately still often treated as a social stigma or taboo subject and this can leave people feeling even more isolated and vulnerable.
The Mental Health Foundation’s theme this year focuses on physical activity and exercise, which in addition to improving our physical wellbeing can also significantly affect mood, anxiety, stress levels and depression. Research also suggests that physical exercise may reduce the risk of developing dementia. In the UK, one quarter of the population will experience mental health issues of one form or another each year. In 2001, the World Health Organization estimated that 450 million people were affected worldwide.
Our image of the month is this hand drawn illustration from artist Bobby Baker. It depicts herself and journalist Jon Snow talking about mental health and human rights, on stage at The Barbican in London in September 2006. This drawing is one of over 600 personal diary sketchbook drawings that Bobby created over an 11 year period, through her own experience of mental health illness and navigation through the mental health system.
One of her performance pieces “How To Live” explored various therapies such as cognitive behaviour therapy and centred around a frozen pea diagnosed with a personality disorder. During the show’s September 2006 run, Bobby was asked to run a master class but instead opted for a post-show “in conversation” with Jon Snow. Having seen first-hand how people’s human rights can be breached, Bobby said “when this invitation came I thought that I needed personally to calmly express this knowledge publicly, in the context of my show How To Live. The most satisfying words I spoke are in the speech bubbles in the drawing.”
Bobby Baker is a performance artist and was the Drama Creative Fellow at Queen Mary University of London until 2008.
Image credit: Bobby Baker, Wellcome Images (Diary Drawings: Day 610)
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. All our images are available in digital form so please click the link above if you would like to use the picture that features in this post, or to quickly find related ones. Many are free to use non-commercially under the terms of a Creative Commons licence and full details of the specific licence for each image are provided.
How do you really feel about biomedical science?
One of the infographics from the Wellcome Trust Monitor. See more at
http://wellc.me/19ASRrU
The Wellcome Trust Monitor explores public attitudes about biomedical science. Now in its second incarnation, the survey shows surprising trends in public thinking around biomedical subjects. We asked the project’s manager, Hannah Baker, to tell us more.
What is the Wellcome Monitor?
It’s a tracking survey that measures adults’ and young people’s awareness, knowledge and attitudes on general scientific themes and related societal and ethical issues. There are other relevant, complementary studies out there, such as the Public Attitudes to Science and British Social Attitudes surveys, however the Wellcome Trust’s is a benchmark, one of few that represents population samples robustly and has a particular focus on biomedical topics.
Its findings and datasets can be used, for example, to shape science communication practice, identify research and policy priorities and it also provides a rich academic resource. The latest insights from Wave 2 provide a fresh and significant picture of the societal and educational context of biomedical research in the UK now.
Why do you want to know what people think?
As one of the world’s largest funders of biomedical research it is really important for the Wellcome Trust to listen to views and concerns around areas it funds, to monitor our progress and shape our work. We really want to know what the public thinks about science. After all, many of the applications from scientific research directly benefit or touch people’s everyday lives.
How many people did you survey?
When we first did the survey in 2009, we interviewed 1,179 adults and 374 young people. This second survey was conducted in 2012 by Ipsos MORI who interviewed 1,396 adults and 460 young people.
You did the survey in 2009 – why did you need to do it again?
What we wanted to do is not simply take a snapshot of what people think, but to monitor how attitudes change over time. The first ‘Wave 1’ survey in 2009 was really a baseline study, allowing us to gauge attitudes and answers to our questions for the first time. The really interesting part comes from now on, where we do the survey again and again – the results will build up to reveal how the public’s interests, experiences and needs change and give us a better understanding of opinions in these areas. This second survey, gives us our first longitudinal comparisons, with many of the questions asked in the 2009 survey repeated in 2012.
We hope academics will further explore the data, examining, for instance, the impact of gender or level of science education on attitudes and behaviours, or identifying how different groups acquire information about medical science. Policymakers can learn how citizens would like to be involved in science decision-making, or what people feel about personal versus public responsibility for decisions about vaccinations or weight and nutrition.
What have you learnt from the wave 2 results?
The good news, for us, is that it presents a predominantly positive context for the Trust’s work, with the majority of respondents being interested in science, enjoying science education, and feeling optimistic about the potential of biomedical research to improve our lives in the future. However, lest we get complacent, it also clearly highlights areas in which understanding, engagement or aspiration could be strengthened.
What was the thing that surprised you most?
It was really surprising that the public at large do not have a good understanding of some frequently used (at least around the Trust) terms like human genome and genetic modification. The Wellcome Trust was both a key strategic player and funder in the set-up of the Human Genome Project, and has since funded millions of pounds worth of related scientific research and public engagement work. Over 10 years on, with much media coverage of genetics (both good and bad press) and research activity, I suppose we thought that these terms might be commonplace. It serves as a reminder that you cannot assume that your audience, or even your co-workers, are familiar with the terminology or meaning of what you say. It’s a wake up call for us and anyone communicating any technical subject, and a good example about how the Wellcome Trust Monitor can inform the way we approach people, practice and policy.
Where can we find out more?
The full programme of work and all the data is freely available to download, use and share from:
#WTMonitor
Stress hormones released by a pregnant mother can cause the placenta to shrink and can directly affect the developing brain of the foetus. Now, researchers have identified the mechanism through which stress may damage an unborn child in the womb. An enzyme in the placenta of the mother and the brain of the foetus acts as a barrier to protect the unborn baby from chemicals released in times of stress. But during periods of prolonged stress – such as anxiety and depression or due to a traumatic event such as abuse – levels of the hormones can soar and are believed to overwhelm the protective barrier, resulting in a host of problems. The damage may make the child more likely to develop mood disorders such as depression, anxiety, and even schizophrenia.
Professor Megan Holmes of the University of Edinburgh has been looking into the mechanisms involved. She identified that an enzyme in the mother and baby, called 11-β HSD2, works by mopping up stress hormones called glucocorticoids (GCCs) and converting them to their inactive form. Using pregnant mice genetically engineered to lack the enzyme, her team showed that the increased exposure to GCCs (like cortisol) resulted in smaller pups, which went on to exhibit the signs of mood disorders. The mothers also had smaller placentas which meant a reduced flow of nutrients to pups in the womb – which could directly contribute to their mental condition.
When the team blocked the enzyme in the brains of the developing pups, but left the enzyme barrier in the placenta, the baby mice still showed some signs of damage. This indicates that both sites, the placenta and the foetal brain, play a role. The team are looking to see if one of the two sites has an overriding effect, although it’s thought to be a combination of the two.
This enzyme barrier is crucial during pregnancy as it maintains the difference between the relatively high levels of stress hormones in the mother and the low levels in the foetus. If too much GCC reaches the foetus it can affect the development of growing tissues. For instance, if the developing brain is exposed to cortisol it can cause the young cells to stop dividing and to start maturing instead. Although this is a key step in the normal developmental process, if it happens too early things can go wrong and it can result in faulty wiring of the brain. “The neurons may not be in right place yet and may be differentiating too soon” says Holmes.
But Holmes’ work suggests that stress exposure doesn’t just impact the brain in the womb, it can have an effect in adolescence too. Puberty is another key point in the timeline of the brain’s development, as it’s when existing connections and networks are strengthened or weakened. It’s a time when the brain is particularly sensitive to environmental factors, including stress.
In experiments, adolescent rats were conditioned to associate a flashing light with an electric shock and then had their brains scanned using functional MRI (fMRI). When they were shown the cue of a flashing light their emotional fear pathways were activated. In rats that had been stressed, the amygdala – the part of the brain which deals with fear and emotion – was overactive compared with rats that hadn’t been stressed. This indicated that the way in which the brain processed emotional stimuli had been changed.
The results suggest that the early teenage years are another critical period in the brain’s development in which stress could have an impact on the network of connections. The rewiring of emotional response pathways in the brain could result in long-term problems with mood disorders and emotional behaviour.
Presenting these findings at the British Neuroscience Association’s Festival of Neuroscience conference in London last month, Professor Holmes said that she hopes to use the animal models to uncover more about the pathways involved and to find more accessible targets for treatment. “We think this a really good translational model, so we can do the same tests or comparative tests to what are done in patient populations.”
It’s not all just mice and rats either, the damaging effect of stress hormones on the developing brain has demonstrated in human studies. Trials showed that the children of women who suffered from anxiety or depression during the pregnancy were more likely to develop the mood disorders themselves. In a telephone interview, Professor Vivette Glover, of Imperial College London, explained to me that in pregnant mothers with anxiety, production of the enzyme 11-β HSD2 decreases and this could expose the unborn baby to more cortisol. “The first thing is to look after pregnant women better,” said Glover. Although whether or not it’s a case for drug treatment isn‘t clear at this stage, “it’s an interesting idea”, she added.
Although genetic predisposition and environmental factors play a strong role in influencing the risk of developing mood disorders, this research hints at the potential for early therapeutic intervention. Currently, targeting 11-β HSD2 directly for drug treatment is difficult, so clinical trials may not be on the horizon just yet. “At the moment our intention is to use our models to see exactly which pathways are changing through development,” said Holmes, “and to try and find an alternative target that’s more easily targetable therapeutically.”
References:
- Holmes M (2013). Perinatal programming of stress-related behaviour by glucocorticoids. Abstract presented at BNA 2013, London.
- O’Donnell, K., Bugge Jensen, A., Freeman, L., Khalife, N., O’Connor, T., & Glover, V. (2012). Maternal prenatal anxiety and downregulation of placental 11β-HSD2 Psychoneuroendocrinology, 37 (6), 818-826 DOI: 10.1016/j.psyneuen.2011.09.014
- Giedd, J., Blumenthal, J., Jeffries, N., Castellanos, F., Liu, H., Zijdenbos, A., Paus, T., Evans, A., & Rapoport, J. (1999). Brain development during childhood and adolescence: a longitudinal MRI study Nature Neuroscience, 2 (10), 861-863 DOI: 10.1038/13158
Ryan O’Hare
Ryan is an intern at the Wellcome Trust.
Read more coverage of the BNA Festival of Neuroscience on our sister blog ThInk.
What can neuroscience teach education?
Do we really only use 10 per cent of our brain at any one time? And do we use one half of our brain more than the other? The answers are no and no, but that doesn’t seem to stop these claims circulating. The Wellcome Trust’s new education and neuroscience project seeks to banish these and other “neuromyths” and identify well-justified, evidence-based neuroscience interventions in educational settings, where and when appropriate. It’s a very exciting project and there are a number of ways that you can play a part in shaping the future of education.
The Trust spends around £50 million each year funding neuroscience research and many neuroscientists emphasise the potential of their work to affect education and use it to justify their work. However, translating findings into interventions that can be tested in educational settings is more challenging. Nevertheless, we believe that the interface between neuroscience and education has real potential to improve education. We need to work harder to understand where the greatest potential is and explore what approaches might be most beneficial and also acceptable and realistic. Although this area is at an early stage of development, we cannot sit idly by waiting for it to flourish – activities and technologies are already being developed in this space and we need to understand them better and maximise their potential for improving education.
We are generally interested in establishing a stronger evidence base for educational practice and the Trust’s Education team are developing this approach specifically in relation to neuroscience and education. We’re working in partnership with the Education Endowment Foundation, who are experienced in funding and evaluating evidence-based education projects and sharing evidence of what works using their Teaching and Learning Toolkit.
The vision of this project is to build research expertise at the interface between neuroscience and education, helping educators to make informed choices about different approaches. Ultimately this may enhance educational outcomes. Neuroscience is a strength in UK science and its fast-moving pace means that this project is important in establishing current practice and identifying how things can move forward. This work will explore how understanding about the brain can or does affect education. It fits within our Education team’s focus of Understanding Learning, a key part of the Trust’s 2010-2020 Education Strategy and also responds to one of the Trust’s Challenge areas: Understanding the Brain.
In the first phase of the project, we’re asking:
- What do teachers, parents and students already do to improve learning, based upon their understanding of neuroscience?
- What types of evidence convince teachers of the effectiveness of new educational interventions and encourage them to implement them in their own classroom?
- How strong is the evidence for interventions based on neuroscience that are already in use?
As part of this, we are collecting the views of teachers, students and parents about activities or techniques based upon findings from neuroscience that they use to enhance learning. We’re interested in hearing from teachers in the UK and internationally about examples of activities or techniques they use with an aim of enhancing learning. To this end we have launched a survey for teachers and are also encouraging teachers and parents to help us include the views of students and examples of activities they do to improve the way their brain learns. In collaboration with Mumsnet, we are hosting a discussion thread on their website, to ask parents for their thoughts on how findings from neuroscience might help improve the way children learn. Parents also have the opportunity to share their views through our survey for parents.
Surveys are open until the end of May.
Even if you’re not a teacher, student or parent, we are still interested in your views and we will be involving different groups in different parts of the work in the future. You can stay up to date with through our Education newsletter, follow the Education team on Twitter and keep an eye on our webpage.
Anna Simmonds, Education, Wellcome Trust
The end of a seven-year itch
Hookworm teeth
Credit: AJ Cann, flickr
It started about seven years ago. I thought it was just a fleeting fascination but the seeds had been sown for a lifelong affair – I was hooked. I would tell anyone who would listen. Always something of a chatterbox, I would wax lyrical about their variety, ingenuity and rapid ability to adapt. It was time to face the truth – I was in love with parasites.
My friends were very tolerant. At least, they were until I started to regale them with parasites’ lifecycles over breakfast. Dan stuck it out the longest but the hookworm was the final straw. I’m not sure if it was the burrowing through the bottom of the foot, the bursting out of the alveoli into the lungs or the sucking of blood from the intestinal wall that did it. I do know that the result was a slammed door and a half eaten bagel in the bin.
What is it about parasites that fascinate me so much? They are just so damn clever. By definition, parasites have an unequal relationship with their host, a bit like the ‘friend’ who always turns up just in time for dinner but never cooks in return. Parasites come up with equally cunning ways to scavenge resources such as nutrients or water, but to make the most of their host will also use their bodies as somewhere to live and breed. Over time, however, the hosts develop their own strategies to avoid or get rid of their sponging guests. Read more…
Around the world in 80 days – Part 5: Thailand
Over the course of four months, Barry Gibb visited our major overseas programmes in Africa and Asia to make a film about Wellcome Collection’s Art and Global Health project. In the latest of his diary entries, Barry finds himself in Thailand.
The distance between Vietnam and Thailand is more appropriately measured in time than kilometres. Arriving in Bangkok at night, it’s difficult to shake off images from Ridley Scott’s Blade Runner. The city appears to have come from the future, reminiscent of London but bigger, brighter, shinier. Gone were the bikes and mopeds of Vietnam; here, we have cars – luxurious cars (albeit with a lack of seatbelts). The scale of everything in Bangkok was so much bigger than what I’d experienced a few hours earlier in Vietnam, including the ‘hotel’. The place was like a small city; hundreds of rooms, several bars and restaurants.
The next day I had to hit the ground running. Not only would I be meeting several of B-Floor theatre company – the artists who were working closely with the Mahidol-Oxford Tropical Medicine Research Unit (MORU) at Mahidol University on the Art and Global Health Project – but we would immediately be leaving by plane for Ubon Ratchathani in the far east of Thailand, home to one of MORU’s research units. Experiencing something close to travel fatigue, I was desperate not to carry all my luggage yet again and crammed the minimum luggage necessary into the camera bag.
Nana Dakin, part of the core team of B-Floor, escorted me to the airport to meet the other members who were joining us on the trip, Teerawat Mulvilai, a.k.a. Kage (pronounced a bit like kang-ye) and Jarunun Phantachat, known as Jaa. This was a feisty trio. Curious, lively and dynamic, they wanted to know everything about what I was about and why I was here. In a reversal of roles, Kage filmed most of our conversations on his new pride and joy, a DSLR camera, while we chatted over tea.
On the flight to Ubon Ratchathani, Nana gave a potted history of Thailand in fluent English (one of her many languages), explaining the origins of the Yellow Shirts, the Red Shirts and all about the recent political crisis before seamlessly moving onto melioidosis, a disease widespread in Thailand and the current interest for herself and the B-Floor team. Melioidosis is a nasty disease. Largely infecting barefoot farmers through wounds in their feet, it is caused by a soil-based bacterium and can either manifest itself within days or lie dormant in its host for decades. When it presents, the disease hits every facet of the body, from bones to internal organs and external abscesses. Even with access to good medical care, the mortality rate is around 50 per cent.
At 4pm we checked-in to our small hotel in Ubon Ratchathani and the team suggested this may be the best opportunity to grab my main interview with them. I was hesitant. The sun was going to set in 2 hours and we had no idea where we could do the interview. But we all agreed outdoors, in natural light, would be best. The hotelier said there was a river nearby and that was enough encouragement for us to dive in a taxi to the location.
What the hotelier didn’t mention was the fact that this river, as beautiful as it was, was right next to a main road. And a slew of karaoke bars. Diminishing light not being enough to contend with, audio was also going to be an issue. Thank goodness I wasn’t also shooting into the sun. In order to get the right composition with Nana and Kage seated on the riverbank we needed seats, which the nearest karaoke bar was kind enough to provide. Next, having travelled light, I had no tripod, so a chair joined us too, affording me some serious stability over the course of the next hour. Things were looking up…
…until I took the camera out of my bag. The sudden change in temperature caused a flood of condensation on the lens – it was literally dripping with water. Doing my best to maintain professional composure, the moisture was removed, my interviewees mic’d up and then we were, at last, ready to go. It was less than an hour until sunset. Pausing only to silence an enthusiastically early karaoke bar’s music system, we managed to capture a great interview, ending just as the sun started to dip and no amount of boosting the camera’s signal would be useful.
At last, we were able to relax and start to get to know each other over beer and real, authentic Thai food. Before ordering, Nana asked how spicy I liked my food. In the UK, I told them, I love all manner of Thai, Mexican and Indian food. Addressing the others, she noted that they’d better get me mild food. She was not wrong; Thai food is remarkably hot to a western palette, a fusion of aromatics and spices that burn and excite, raging inside the mouth.
Over dinner, Kage revealed that he often appears in movies as an actor who, despite his wide smile and gentle character, is often favoured as the ‘bad guy’. I also discovered Jaa’s incredible curiosity about proteins, resulting in my explaining how DNA is converted into proteins with a range of hand movements and small drawings.
Early next day, with the temperature still in the low 20s (degrees C), we set off for the Ubon Ratchathani research centre. This was a key opportunity for B-Floor to meet and question, first-hand, doctors, scientists and possibly even a patient about the perils of living and working in an area with melioidosis. The purpose of the day was research and over the course of an entire day they grilled a procession of people about the many facets of the condition. Like Miriam Syowia Kyambi and James Muriuki in Kenya, an integral part of B-Floor’s process is extensive research, to really get to grips with a subject, to know it so well that an artistic idea can begin to emerge.
The best moment of the day was when B-Floor were brought into a laboratory. As someone who’s spent more than a decade working in various labs, it’s easy to forget how odd they can look to a non-scientist, how alien the equipment and procedures are. The team were mesmerised. A scientist prepared a specimen of melioidosis bacteria for the group to look at down a microscope, triggering a sense of awe and the idea of representing this sense of scale in a theatrical endeavour.
With most of my ‘art’ filming achieved, it was time to get into ‘science’ mode. Arriving at Mahidol University, I immediately met MORU Director, Nick Day, and a group of his core team. The afternoon passed quickly in the company of enthusiastic scientists with fascinating stories; melioidosis and its impact on those affected, malaria and its frustrating capacity to adapt and resist… In one lab, yellow boxes sat neatly stacked from wall to wall, floor to ceiling, all full of slides coated with blood containing malaria; an uncomfortable visual reminder of the scale of the problem.
Leaving MORU, it was time to finally see B-Floor in action as they rehearsed for an upcoming show. It was exhausting just watching them – they’re a very physical theatre group, pushing their own bodies as much as artistic boundaries. After an evening of laughing, contorting and generally being taken through an emotional joy ride, it was time to switch the camera off and go home. Again, I was saying goodbye to thoroughly lovely people just as I was getting to know them. But any sense of being maudlin was rapidly ejected by the memory that I’d be going home in less than 24 hours. I had the luxury of an entire week at home to look forward to before heading off to the Berlin studio of Katie Paterson, the artist-in-residence of the UK based Sanger Institute. Prior to leaving for the airport next morning, I decided a treat was in order and did what any self-respecting tourist should do in Thailand – I had the best massage of my life.
Barry J Gibb
Barry J Gibb is a Science Multimedia Producer at the Wellcome Trust.
Read Barry’s previous diary entries.
Find out more about Art in Global Health on the Wellcome Collection website.
Venki Ramakrishnan (right) at the Diamond Light Source in 2010.
The US, Germany and China are increasing research spending. We would be foolish to do the opposite, writes Venki Ramakrishnan.
Fourteen years ago, my wife and I took a decision to move from USA to Britain. I took a 40 per cent pay cut, and we left children and close family behind. We were willing to give up so much not because of any personal ties here, but because my scientific work had reached a crucial stage and this was the best possible place to pursue it. The stability of UK research funding, especially at the MRC Laboratory of Molecular Biology (LMB) in Cambridge, would allow me to work on an important but challenging problem. And I would be joining an outstanding intellectual environment, where a collegiate approach to sharing resources, including expensive facilities and equipment, is part of the culture.
It was a decision that paid off handsomely. I have done the best work of my life in Cambridge, and was honoured to share the 2009 Nobel Prize for Chemistry and to receive a knighthood.
My experience is not unique. Britain continues to punch well above its weight in science. The impact of British institutions like the LMB compares well with elite international rivals on any level, but when impact per pound is calculated, we are comfortably ahead. British science generates extraordinary returns on investment, whether measured in great advances such as DNA sequencing, monoclonal antibodies and MRI scanning that have won Nobel prizes, or in spinout companies and economic growth. The reason we succeed is a meritocratic scientific culture that encourages originality and initiative, and a funding system that provides stability while demanding efficient use of resources. British scientists know that sufficient funds will be spent on the best people over a sustained period of time, so they are free to focus on research.
I am grateful for what Britain’s support for science has allowed me to achieve. But I am also deeply concerned that the very factors that drew me here could now be threatened by cuts in next month’s spending round. It was reassuring when the Government ring-fenced the science budget in 2010, but no guarantee of similar protection has been offered this time. I have also heard worrying arguments that in light of that benign settlement, science must now take its turn to share the pain.
Were he to heed these arguments, the Chancellor would be making a grievous mistake. British scientists are already among the most efficient in the world. The normal ways of optimising efficiency, such as funding the most promising young scientists or senior ones with a proven track record, and avoiding waste by shared use of equipment, are already routine. If science funding is cut, there will be no alternative to eliminating productive jobs, closing important facilities, and reducing our research output.
The damage this would inflict would be irreversible. It takes over a decade to train a young scientist, who has often decided to forego a lucrative career in the corporate world. If such people are forced out of research, it is not possible simply to rehire them later – they will have new careers. A future government that wanted to invest more in science would have to invest in training a new workforce. It would be foolish to address a temporary fiscal crisis by impairing our long-term capacity for research. Also at risk is the excellent reputation of British science, which must compete internationally to thrive. An attack on the science budget would send a message that although our research is superb, our Government does not value it.
Rivals such as the USA, Germany, China and other Asian countries are increasing science spending even during austerity, because they recognize that a strong scientific culture is essential for economic growth and prosperity. We should do likewise. Doing the opposite would make it very difficult not only to recruit world-class researchers from overseas, but also to retain our best home-grown talent. It would also deliver insignificant savings: the science budget is about £5 billion, just 0.7 per cent of public spending. Any cut would barely dent the £120 billion deficit.
Since coming to Cambridge, I have discouraged many approaches to move back to the USA, where I would make a much higher salary. I have done this despite our continued separation from children and family because I enjoy working here, and because I feel a responsibility to help younger scientists to get as much out of Britain’s extraordinary research culture as I have. I am already established here, but if we’re to attract and keep the best young talent as well as researchers at their peak, we have to invest in support that will encourage them to make the same decision I made 14 years ago. The alternative is the inexorable decline of a great scientific culture — a culture without which we cannot hope to succeed in the increasingly competitive, knowledge-based global economy.
Professor Venki Ramakrishnan won the Nobel Prize for Chemistry in 2009, and is a Wellcome Trust Investigator at the MRC Laboratory of Molecular Biology in Cambridge.
A version of this article appeared in The Times on 7/5/2013.
