The Wellcome Trust has launched Science Learning+ to support collaborations between researchers and practitioners of informal learning. This new scheme will provide £9 million of funding to help us better understand the value and impact of science learning outside the classroom. Holly Story from the Wellcome Trust Education and Learning Team gives an insight into the aims of this ambitious scheme.
Around 80% of a child’s waking hours are spent outside of school. That’s a big chunk of time, especially when you’re eight years old and the summer holidays are stretching out in front of you, and children don’t stop learning when they leave the school gates. This time is a fantastic opportunity for children to learn in different contexts and through more informal channels: through activities or events, festivals or games.
The science engagement community in the UK provides many exciting and innovative opportunities of this kind for people of all ages. However we know relatively little about how these informal encounters impact upon young people’s engagement with science.
Our Review of Informal Science Learning, published in 2012, found that, “the evidence base for the long-term impact of informal science learning activities in the UK is highly limited”. It also identified a gap between research and practice; those delivering informal learning activities do not often engage with the academic literature.
Science Learning+ aims to bridge these gaps by encouraging communication and collaboration between practitioners and researchers and stimulating research. The first phase of funding will focus on the former, providing grants to enable interested groups to meet and develop ideas.
While the UK has only a small research base supporting investigations into the methods and outcomes of informal learning, in the US it is more established; a literature review showed that over half of the most widely-cited papers on the subject were published in America and the National Science Foundation (NSF) run a program of grants aimed at improving informal STEM learning. At the same time, the UK has a highly active community of informal learning practitioners. Science Learning+ will seek to bring together expertise from both countries, supporting partnerships between practitioners and researchers.
It’s only right that the scheme has support from both sides of the Atlantic: it was established by the Wellcome Trust, the US National Science Foundation (NSF) and the UK Economic and Social Research Council (ESRC), in collaboration with the MacArthur Foundation, the Gordon and Betty Moore Foundation, and the Noyce Foundation. In coming together to support research in this way, the funding organisations are setting an example for collaboration that they hope applicants will follow.
Sir John Holman, Senior Adviser in Education for the Wellcome Trust, is clear that fostering partnerships should be a priority for those planning to apply:
“Applicants should begin by thinking about partnerships, partnerships between the US and the UK, partnerships between practitioners and researchers. We want to know more about the impact of informal science learning, and about how the outcomes, emotional and cognitive, can be optimised. This is a big opportunity to develop capacity for research.”
Phase 2 of the funding scheme will support research programmes in the longer-term. This could be up to five years, enough time to embark on an ambitious and extensive piece of research, and the partners have high hopes for what these projects might achieve.
For example, research programmes may, as Clare Matterson, Director of Medical Humanities and Engagement at the Wellcome Trust, suggests, “help us to understand how [informal learning] can work for different types of young people”, including those who have a lower uptake of science in the formal education system.
Adrian Alsop, Director of Research, Partnership, and International at ESRC, agrees that this scheme could help us to connect a wider group of young people with science by suggesting how we might improve practice to combat damaging trends.
“A challenge for us here in the UK is that a number of bright young women drop out from the study of science, not because they don’t find it interesting, but because they don’t think it’s ‘for them’.
It is also all too often assumed that science is only for the ‘brainy’, when in reality there are many opportunities for STEM careers, and many benefits of studying science in terms of employability and citizenship, for people of all abilities.
If we can find a way to ensure that all young people understand the opportunities which science provides that would be a major return from this investment.”
These are big asks but with a budget of £9 million, and a scope that crosses continents, the scheme is a bold commitment on the part of the funding organisations. We are looking for applicants who will embrace the scale of the scheme and propose exciting, ambitious trans-Atlantic projects.
Science Learning+ is an international initiative established by the Wellcome Trust, the US National Science Foundation (NSF) and the UK Economic and Social Research Council (ESRC), and in collaboration with the MacArthur Foundation, the Gordon and Betty Moore Foundation, and the Noyce Foundation. It will provide £9 million of funding to further our understanding of the power of informal learning experiences inside and outside of school.
We scoured the Wellcome Image collection to bring you a special Easter treat this week. No chocolate eggs, but golden ones instead with the game of the golden goose to keep you and your family entertained.
Published in 1848, the object of this board game is to get your counter to land exactly on number 63. But beware! There are plenty of traps along the way. Dodge prison and death and avoid paying a stake at the ale-house if you want be crowned champion.
You can download the full size version of this image and give the game a go. It is just one of many thousands of images from Wellcome Images that we’ve released in high-resolution with a CC-BY licence.
Have fun deciding what the stakes will be – my vote is for chocolate!
The rules, as they appear on the board, are as follows:
RULES TO BE OBSERVED IN THIS GAME
1st This Game is play’d with a pair of Dice, and any Number of Persons may play at it.
2nd Whatever Number it is that any one throws that person much place his Counter in the white Space* under the same Number. For Example,… Should the Case be 6 and 3, he must place the Counter at 9; if the Case be 6 and 5, he must place it at 11; and, when he throws again, he must add the Number to that where his Counter lies, and so remove accordingly.
3rd he that throws 6 must pay a Stake for his paƒsage over the Bridge, and go to Number 12.
4th He that throws a Goose, must double his Cast forward from his last place.
5th He that throws 19, where the Ale-house is must pay a Stake & Drink till his turn comes to throw again.
6th He that throws 31, where the Well is must stay there till everyone one has thrown twice, unleƒs somebody else throws the same and the he must return to that person’s place.
7th He that throws 42, where the Maze is must pay a stake and return back to the Number 29.
8th He that goeth to 52, where the Prison is, must pay one, and and stay there a Prisoner till somebody relieves him by throwing the same Number.
9th He that goeth to 58, where Death is, must pay one and begin again.
10th He that is overtaken by another much return to his place that overtook him, and both must pay a Stake.
11th he that overthroweth the Number 63 must return back and begin as at first.
12th He that throweth the just Number 63 winneth the GAME.
* Note that the white spaces have been coloured in on this copy of the game.
Is it time for greater clarity and recognition of who did what in the publication of research? Jo Scott and Liz Allen in the Wellcome Trust Evaluation Team discuss the potential of a new contributor “taxonomy”…
Original research papers with one author – particularly in the life sciences – are increasingly rare. We know that there are many contributors to research and associated published outputs, but it’s not easy to tell who did what, and author position is an imperfect representation of contribution. Inflation of author numbers on papers, partly driven by a combination of national research assessment exercises and the emergence of big, collaborative and ‘team’ science, has also contributed to this ambiguity. Greater clarity around the different and varied contributions to research outputs could have benefits for all the stakeholders in research.
The recent San Francisco Declaration on Research Assessment emphasised a commitment to move away from Journal Impact Factor as a measure of research quality. Initiatives that would bring greater clarity to authorship would provide a new basis upon which to recognise researcher contribution and research use and re-use.
What are the benefits of greater clarity?
For researchers, having the ability to better describe what they contributed to a piece of research would remove the opacity caused by expanding author lists. Roles that have not traditionally qualified as “authorship” could be recognised and researchers could draw attention to their specific contributions to published work to demonstrate their skills and potential. We feel this would be of particular benefit to people who are starting out in a research career, where the opportunities to be a ‘key’ author on a paper can prove elusive.
For funding agencies, better information around the previous contributions of individual grant applicants would aid the funding decision-making process. Greater visibility of research contributions would also help those looking for the most apt peer reviewers. For institutions, understanding a researcher’s unique contribution is fundamental to the academic appointment and promotion process. And for publishers, greater transparency in contributor assignment would help to reduce the volume of authorship disputes being managed by journal editors.
A new approach
Following a workshop in 2012, a small group of journal editors joined forces with Harvard University (led by Amy Brand, who is now at Digital Science) and the Wellcome Trust Evaluation Team to develop a simple contributor-role taxonomy to test with researchers. We wanted to develop something that could be used when researchers are thinking about submitting a paper for publication that would yield meta-data on the contributions, to complement – or perhaps even replace – an author list.
A 14-role taxonomy was developed and feedback was sought from a sample of corresponding authors of recent work published in PLOS, Nature Publishing Group and Elsevier journals, Science and eLife. Overall feedback on the concept of enabling better definition of contributor roles and the test taxonomy was positive. We are mindful that any new approach must not add to researchers’ burdens in submitting and publishing work nor bring about unintended, negative consequences.
We will be engaging with a broader cross-section of the research community to evolve the taxonomy in response to the feedback received to date. Over the next year we will try to ascertain the value of greater specificity in contributor roles to the research ecosystem and consider models of implementation.
You can find the full article ‘Credit where credit’s due‘ in Nature.
Image credit: “Question mark sign” by Colin Kinner CC-BY, on Flickr.
1. Figure out why you want to blog
Maybe you’re a PhD student wanting to share your research with the world, or take a break from it to explore some other interesting science. Or perhaps you’re a budding science writer keen to build a profile and get your name out there. Think about who you want to reach with your writing – be it potential collaborators, potential employers, or people on the street. Sum up your goals in a sentence or two and write that down before you do anything else.
2. Set it up
The best platform for you will mostly depend on the type of posts you’re going to write. If you’re planning longer writing, a traditional blogging platform like WordPress might suit you best. For shorter, snappier posts or posts that are more image-led, Tumblr could work for you.
This is also when you’ll get to play about with themes and make your blog look exactly as you like. That’s great fun, but don’t let it distract you from the business of actually writing.
3. Think about joining a network
You’ve probably noticed that a lot of established science bloggers write on blog networks rather than their own sites. If it’s an option for you, joining a blog network can be a great thing. You’ll get colleagues to help you out, a boost in traffic and a whole new potential audience.
Usually an invitation to join a network comes after you establish yourself, and starting off on your own will provide the breathing space you need to work out exactly how to drive this thing.
There can be advantages to going it alone too: no schedule to stick to, a chance to experiment, and more control over things like comment moderation.
4. Get writing
Most successful blogs find a niche and more-or-less stick to it. That could mean blogging about your own research, following one particular field of science in a lot of detail, or finding a unique way to write about stories other people will be covering too.
If you make yourself the go-to person for a particular kind of science writing, you’re more likely to build an audience.
5. Use the internet properly
The internet is an amazing place and you should make the most of being a part of it. This means adding links to sources, news articles and other people’s blog posts in your own. It also means using images or video when they are a better way to communicate than words.
And, thanks to the unlimited space online, you don’t have a word count. But as well as giving you the space to go in-depth when you want to, it means you can write short if the subject doesn’t need a dissertation-length exploration. Don’t write an essay just because you can.
6. Write good headlines
If you want people to read what you’ve written, you’ll have to make them want to. Don’t fall into the trap of typing up any old headline and hitting publish after spending ages polishing the blog post itself. Always ask yourself if you’d click on a link based solely on the headline (and be honest). If you wouldn’t, change it.
Descriptive headlines that tell a reader exactly what to expect often work well. You should think about getting key words in there, but don’t fret too much about search engine optimisation. It’s more important to make actual humans want to read your work than it is to try to pander to Google.
7. Shout about your work
So you’ve written your first post, thought carefully about your headline, and pressed publish. Don’t relax just yet – if you don’t do any promotion, nobody bar your immediate family is going to read it. Ideally you’ll have established social media accounts already so you can share your work with people you know on Facebook and your professional community on Twitter.
Don’t be afraid to send the post directly to certain people who you think will be interested in it. (But, equally, don’t be offended if you don’t get a reply.)
It’s also worth getting set up on science blog aggregator scienceseeker.org and any subject specific ones. They might not be huge traffic drivers but they’ll help get you noticed in the science blogging community.
8. Don’t steal images
Being “just” a blogger doesn’t mean you don’t have to source images properly. Luckily, there are plenty of ways you can find images to use without either paying or breaking the law. Searching on Flickr or Google for Creative Commons (CC) licensed images is one option. Wikipedia and the British Library have a lot of public domain images available for reuse and Wellcome Images has released thousands of their historical images too. If you find something that’s not available under CC, you can always just ask the copyright holder – chances are if it’s for a personal blog, they’ll be happy for you to share their work. Make sure you follow the terms of the specific CC licence for the image. This usually involves crediting the image creator, noting the licence type and may mean you can’t change the image.
9. Decide on your comments policy
While a lot of discussion around blog posts has moved to social media these days, you’ll still need to think about how to handle comments. Will you moderate up front, or after they’re posted?
Take a look at the commenting policies of blogs you read and borrow your favourite bits. Don’t let anyone bully you into thinking they have a right to spout rubbish underneath your beautifully crafted writing. Your blog is your home online and if you want people to play by certain rules you’re entitled to make them do that or get out.
10. Stave off boredom
Sometimes you might not feel like blogging and occasionally, that’s fine. But if you’re stuck in a rut, try posting something small: a cool picture or video, with a few words of explanation. Or set yourself a challenge to write x words in a certain amount of time (find other people doing the same thing at #madwriting on Twitter).
In a nutshell
- Find a niche.
- Use images and videos when they add to your post.
- Think of a blog post as part of the conversation, not the final word.
- Steal other people’s photographs.
- Be afraid to shout about you blog.
The Wellcome Trust Science Writing Prize 2014, in association with the Guardian and the Observer is open for entries now. Get writing and submit your piece before the deadline on 11th May 2014 for your chance to win £1000 and a chance to get your work published. We are running a series of “How to” posts giving you tips on how to write a good science story from a research paper, how to interview someone, how to write a science feature and more in the run-up to the competition deadline.
Full details and terms and conditions can be found on the Science Writing Prize pages of the Wellcome Trust website. Good luck!
The Wellcome Trust research round-up brings you news from our research community every fortnight.
Young male smokers could have fatter sons
The sons of men who started smoking before the age of 11 were found to have 5-10 kg more body fat than other boys whose fathers started smoking later in life or not at all. The study suggests that a father’s experiences before puberty could influence the development of his future sons.
The team suggest this could be due to the switching on of certain genes by environmental factors, a process known as epigenetics. The weight of daughters was not affected.
The study is the 1000th paper published by the Children of the 90s study, an ambitious project at Bristol University funded by the Wellcome Trust and the MRC, that has been collecting detailed information more than 14,000 families since 1990 to track how genetic and environmental factors affect human development.
“This discovery of trans-generational effects has big implications for research into the current rise in obesity and the evaluation of preventative measures,” said Professor Marcus Pembrey, who led the study.
Scientists unconnected to the research have warned that more work would need to be done before establishing a firm link, since only 166 fathers reported smoking before the age of 11.
Pneumonia and Malaria biomarkers found
A blood test could help doctors distinguish between pneumonia and malaria, according to new research published in the journal Clinical Infectious Diseases.
Pneumonia is the leading cause of death in children globally. The disease has many causes and is characterised by inflammation of the lungs but can be difficult to distinguish from other respiratory problems and also malaria.
Now researchers at the Wellcome Trust Centre for Human Genetics at the University of Oxford have identified the protein Lcp-2 which can help diagnose the disease, as well as give doctors an indication of how severe the infection is. Concentration of the protein in blood plasma identified severe pneumonia in patients with 95 per cent accuracy. Another biomarker, the protein haptoglobin, was used to distinguish between bacterial and malarial causes of pneumonia with 99 per cent accuracy.
“To reduce the number of deaths caused by pneumonia it is critical to diagnose severe cases and those due to bacterial infection early so that appropriate treatment can be administered promptly,” reported researchers in the paper.
Computer program predicts stroke treatment risk
Researchers at Imperial College London have trained a computer program to identify patients that might suffer dangerous side effects from a common treatment for stroke.
Intravenous thrombolysis, an injection that can break up stroke-causing blood clots in the brain, can lead to dangerous bleeding in about six per cent of patients. The new computer program uses machine learning to spot patterns in brain scans to predict who might be at risk of bleeding and predicted dangerous bleeding with 74 per cent accuracy, an improvement on the 63 per cent accuracy achieved by doctors looking at the scans.
“Intravenous thrombolysis carries the risk of very severe side effects for a small proportion of patients, so having the best possible information on which to base our decisions is vital,” said Dr Paul Bentley from the Department of Medicine, who led the study.
The research is published in the journal Neuroimage Clinical.
Targeting mosquito sperm to fight malaria
Reducing the fertility of malaria-carrying mosquitos could provide a new weapon against the disease, according to research published in the Proceedings of the National Academy of Sciences.
Female mosquitos only mate once in their lives, during which they store the sperm in an organ called the spermatheca and use it to fertilise the eggs that they subsequently lay.
Wellcome Trust-funded researchers at Imperial College London have discovered an enzyme that keeps the sperm healthy inside the spermatheca, and by interfering with it, they were able to reduce the number of offspring that each female mosquito could produce.
Dr Robert Shaw, one of the lead authors of the research said, “There is no single magic bullet for tackling malaria, but making mosquitoes less fertile could provide us with a valuable weapon against the disease.”
In other news
- The Wellcome Trust Sanger Institute has received an Athena SWAN Bronze Award for taking the first steps to advance women’s careers and improve equality in the workplace.
- Open access books published by The Wellcome Trust will now be featured on OAPEN, a depository for open access academic books in the humanities and social sciences.
- Researchers at Imperial College London have identified the protein Lin28a, involved in brain development, which re-establishes in cancer cells and could be a new target for cancer treatment.
- A coalition of 31 leading research funders, research organisations, learned societies and patient groups – including the Wellcome Trust – has issued a joint statement supporting funding for stem cell and reproductive health research in Europe. The statement calls on the European Parliament and European Commission to oppose the ‘One of Us’ Citizens’ initiative that is seeking a ban on all financing of activities that presuppose the destruction of human embryos, including stem cell research.
This week’s image is of the little mite that might cause the end of food production as we know it. The varroa parasitic mite attacks the honey bee populations needed to pollinate a range of valuable crops including sunflowers, almonds and tomatoes. After attaching itself to the underside of the bee, the mite sucks the hemolymph, a substance that surrounds all the bees’s cells.
It is only possible to see this varroa mite so clearly because the image was created using a scanning electron microscope. Verroa mites are actually only 1.5mm by 1mm making them almost impossible to see on a live adult bee. In reality this mite would also be a red brown colour providing camouflage against the surface of its victim. All images created with a scanning electron microscope are originally colourless, and in this image the purple and green colouring was added later to help us see the mite more clearly.
Unfortunately, there doesn’t appear to be a simple way to save our humble honey bee. The mysterious and alarming increase in bee deaths over the past decade is caused by several factors. Pesticides and a lack of nutrition due to farming practices and the spread of verroa mites have all contributed to the decline of the honey bee population.
Since bees are vital to ensuring plants are pollinated, a decline in their numbers could have devastating effects. In China, some farmers have resorted to hand pollinating their fruit trees, painstakingly collecting, drying and then reapplying pollen to individual flowers. Unsurprisingly this method is no match for the bees, as a single bee can visit more than a hundred flowers in a single flight!
This week’s image reminds us of how very small things can have a big effect and shows how much we depend on the complex biological systems that surround us.
Image credit: Kevin Mackenzie, University of Aberdeen and Wellcome Images, 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. All our images are available in digital form and many are free to use non-commercially under the terms of a Creative Commons licence.
The Wellcome Trust Science Writing Prize 2014 is open for entries – offering you a chance to win £1000 and see your article in The Guardian or Observer. We know that staring at a blank page can be daunting, so we asked Nicola Davis, commissioning editor for Observer Tech Monthly to share her advice on how to write a feature.
1. Choose your topic and length carefully
Be realistic about the issue you are covering – does it have enough dimensions to hold a reader’s interest for a long feature? If the story can be summarised in 180 words, you don’t need to write a 1,800-word feature. And anything beyond 4,000 words is a very long read.
2. Have a plan
Make a list of all the points you want to cover in the article then put them into an order that allows you to move with the most ease from one point to the next. Remember to pepper fascinating points throughout the article – if you put all the juicy stuff in the first 500 words, why would a reader continue to the end?
3. Come back to the intro again, and again, and again…
Writing introductions is always a tricky business. The best introductions conjure up a clear, compelling scene, an unusual conundrum or a stark situation. Avoid rambling opening paragraphs and remember that if a sentence doesn’t sound quite right, it isn’t right. Move on to the body of the piece and come back to it. The introductions that seem the most effortless have probably taken the most work.
4. Get on the phone, or better still on the road
A good feature is not an extended essay, a regurgitation of undergraduate topics, or a stream of consciousness. Don’t indulge in covering too many historical aspects of the issue – use them only where strictly relevant. The same goes for technical details. Remember, your audience may not have the burning interest in genetics you do, or be familiar with what an allele is.
A feature should be rich with voices from those involved with the issue you are focusing on. Speak to researchers, speak to those affected by the issue and speak to people with different viewpoints. Record your interviews – when you listen back you may be surprised at the gems you find.
5. Get building
Once you have your transcripts from all your interviews, make one document with the quotes you want to use and the points you want to make. Then shuffle these around to create the skeleton of your feature. Then you can add detail and refine paragraphs as you go along.
6. Choose your structure carefully
A feature could take many forms, for example a long “write-through” or continuous narrative, a Q&A format, or a series of distinct sections. Would a detailed explanation of how mitochondria work be better in a separate, pull-out section, suitable for a tinted box on the printed page? Would a graphic save you 300 words? Use such furniture wisely and it will improve your feature.
7. Know what you are trying to say – don’t waffle
No feature can cover every aspect of an issue. There will always be other points or angles. Make sure you have a clear idea of what is relevant to the overall thrust your piece and don’t try to shoehorn in tangential information.
8. Get your facts straight
Double-check everything. If someone gives you a figure for the cost of a medical procedure, check it in the literature and ask the experts. Make sure your sources are up to date and accurate and remember to differentiate between facts and opinion. If your piece will be published online include links so that readers can easily access your sources, if it’s in print give enough information for them to track it down for themselves.
9. Change the pace
A monotone approach makes for a tedious read. Change the pace throughout the article – emotional experiences, sobering facts, funny quotes and informative sections keep your reader engaged to the end. Like a good play, sections of a feature can also move back and forwards in time and be set in different scenes.
10. Kill your darlings
Your hilarious sentences and painfully crafted metaphors may seem like works of genius, but they are probably too esoteric to appeal to anyone else. Write them, love them, cut them.
In a nutshell:
- Interview a variety of people
- Have a clear angle
- Get your facts straight
- Waffle on
- Put all the interesting stuff in the first 500 words
- Write in a monotone
Image credits: (top) Matthew Herring, CC-BY-NC-ND,Wellcome Images, “Alex + Banana Phone” by tomcensani CC-BY-ND on Flickr, “59/366: Blah blah blah” by theunquietlibrarian CC-BY-NC on Flickr, “128 Angle Protractors” by macattck, CC-BY-NC-SA on Flickr.
The Wellcome Trust Science Writing Prize 2014, in association with the Guardian and the Observer is open for entries now. Get writing and submit your piece before the deadline on 11th May 2014 for your chance to win £1000 and a chance to get your work published. We are running a series of “How to” posts giving you tips on how to write a good science story from a research paper, how to interview someone and how to pitch to an editor in the run-up to the competition deadline.
Full details and terms and conditions can be found on the Science Writing Prize pages of the Wellcome Trust website. Good luck!
Wellcome Trust Senior Investigator Mary Dixon-Woods is Professor of Medical Sociology at the University of Leicester. She was recently involved in a large international team that published the TIDieR checklist in the BMJ, aimed at improving the way interventions are described in research papers. Better descriptions of interventions can help ensure better care for patients and cut research waste. Here she and her co-authors Tammy Hoffmann and Paul Glasziou, from Bond University in Australia, explain how researchers can go beyond the traditional peer-reviewed article to enable patients and clinicians to adopt useful interventions and support researchers in replicating studies.
Back in the early 20th century, branded drugs could not be evaluated independently because they contained secret ingredients. Fortunately that’s no longer true, thanks to persistent campaigning. Yet poorly described health interventions – whether they are drugs or health promotion campaigns, or anything else – remain remarkably common.
Now, incomplete intervention descriptions arise not because manufacturers are jealously guarding trade secrets, but instead because of problems in communication, awareness and attention among authors, editors and reviewers – as well as restrictions on word limits in journals.
The traditional medical journal article may well be too stifling a format for communicating the content and mechanisms of interventions in full. Researchers are now embracing more creative multimedia solutions to ensure full and explicit accounts of interventions are available. Below aresome examples. We hope that use of the TIDieR checklist that we have developed, alongside more innovative methods of sharing information, will help to solve the issues related with poor communication of, and lack of space for, information about the interventions.
A trial or study website can be used to host multiple resources, including published peer-reviewed papers, intervention manuals, data collection templates, patient information leaflets, participant newsletters, online appendices, protocols, a PaT plot (a graphical method of depicting the components of complex interventions)and links to participating organisations – all in one place.
An example is www.pacetrial.org, the website of a large-scale trial that was the first to test and compare the effectiveness of four of the main treatments for people suffering from chronic fatigue syndrome (CFS).
Online handbooks can provide highly structured and accessible ‘how to’ guides for the consumers or deliverers of interventions. The free-to-access HANDI site (Handbook of Non-Drug Interventions) was developed in partnership with the Royal Australian College of GPs.
Aimed at clinicians, the entries range from the ‘mother’s kiss’ technique for removing foreign bodies from the nose to pulmonary rehabilitation for COPD. Readers are invited to give feedback and submit suggestions of interventions for inclusion into this database. The format of the HANDI entries, together with its interactive features, may offer a useful model for authors seeking to provide a comprehensive range of materials related to their interventions.
Apps are a great way of connecting with the potential users of interventions, though they do require the right expertise and a budget for app development, and they are likely to be suitable only for some kinds of intervention.
Interventions that involve patients in ‘doing something’ (e.g. home-based exercise programmes, dietary interventions) may especially lend themselves to this interactive, ‘carry everywhere’ format. An example is the Dutch ‘Versterk je Enkel’ (Strengthen your Ankle) interactive app available on iOS and Android. As well as general advice on bracing and taping, the app delivers an evidence-based, cost-effective neuromuscular training programme to prevent ankle sprains.
Videos, made available online (e.g. with YouTube/Vimeo), or by DVD are likely to be especially helpful for interventions with difficult-to-describe procedures (such as physiotherapy manipulation techniques and surgical procedures). Depending on the amount of voice-over required, they may also provide a way around language translation issues.
Well worth a look is the ‘first scientific video journal’ JoVE, the Journal of Visualised Experiments. It is a peer-reviewed, PubMed-indexed journal devoted to the publication of biological, medical, chemical and physical research in a video format.
The advantages and disadvantages of using multimedia in communicating intervention details are worth bearing in mind.
On the plus side many new formats are flexible and user-friendly. Without limitation of word limits or particular styles of writing, they can enable fuller, more explicit descriptions and create interactive learning opportunities. But they also require careful design to avoid the pitfalls of unwieldy navigation and they may be time-consuming and expensive to develop. At the moment they may not attract the academic kudos of other outputs.
Perhaps more mundane but nonetheless important are practical issues such as obtaining copyright permissions, ensuring compliance with legal requirements, and ensuring all URLs are live and remain unbroken. And finally, access to descriptions of interventions should be free where possible, so funding models to enable this will need to be found.
We hope our efforts to improve descriptions – the TIDieR checklist – will be the first step in an intervention description revolution and we look forward to seeing how people implement it.
Last week the Progress Educational Trust held an event called Relative Risk: Breast Cancer and Genetics, supported by the Wellcome Trust. This was the first event in a series looking at issues surrounding breast cancer, and focused on the genetics and relative risks associated with carrying predictive genes. James Heather attended, and shares a taste of the evening…
In most situations, knowing you have a mutated copy of a gene that is often associated with cancer is a bad thing. Or so I thought, until I attended the Wellcome Trust supported event Relative Risk: Breast Cancer and Genetics where it seemed to many to be a source of camaraderie. ‘Oh you’re BRCA1?’ I overheard one woman excitedly exclaiming to another, ‘I’m BRCA2!’.
For those in the know, this snippet is probably enough information to guess the general theme of the evening: the genetic risk of developing breast cancer. Mutations in the best-studied genes, BRCA1 and BRCA2 (often pronounced ‘bracka’), are associated with a higher risk of developing breast (and ovarian) cancer.
A panel of experts from a range of backgrounds – from policy and fundraising, through practice and research, to personal patient experience of the disease – introduced the discussion.
The first speaker was Baroness Delyth Morgan, Chief Executive of the charity Breast Cancer Campaign, who opened the evening by reminding us all of the need to prioritise funding so as to fill gaps in our understanding of cancer biology.
The next three speakers shared their clinical and research knowledge.
Gareth Evans and Diana Eccles, professors of cancer genetics at the Universities of Manchester and Southampton respectively, spoke about how people tend to discuss and interpret risk. Doctors, we were told, have some work to do in understanding how best to convey risk statistics in terms that people can understand, while bearing in mind that most people’s perception of disease risk will be based heavily on personal experience of the relevant disease.
Wrapping up the medical component was Professor Gordon Wishart, a consultant breast and endocrine surgeon who performs risk reduction surgery for patients at risk of breast and other cancers, such as the surgery opted for by actress Angelina Jolie last year. He explained that while such surgeries tend only to be performed on a relatively small number of women with an extensive family history of breast or ovarian cancer, increased genetic testing for risk-associated genes such as the BRCAs is likely to increase demand. Given how cost- and labour-intensive these surgeries can be, extra resources would have to be found.
The final speaker of the evening went beyond the statistics and the abbreviations to shed light on the personal impact of cancer and risk. Kerry Andrew‘s mother died of breast cancer at 35, while her grandmother survived breast cancer at 32 only to succumb to ovarian cancer two decades later. This family history informed Ms Andrew’s decision to undergo a double mastectomy aged 24. As she is the carrier of a BRCA1 mutation, this operation is thought to have dropped her risk of breast cancer from 80% to below 10%.
The introductions, while illuminating, were kept concise to leave time for what felt like the main event – questions from the floor. The response was incredible. The speakers fielded questions from other researchers and clinicians, from the press, and from support groups. But by far the greatest number of questions came from breast cancer patients and their family members – many of the latter, of course, being at increased risk of cancer themselves.
This was probably the most engaged and eager questioning of scientists by the public I’ve ever seen, an inspiring demonstration of affected individuals seeking out knowledge to understand the risks they face. The thirst for knowledge was palpable: questions were asked about everything from insurance to epigenetics, from screening to support.
‘I don’t regret the fact I have this gene’, Ms Andrew told us in her closing remarks, which seemed to resonate strongly with the audience. ‘While this gene is a big part of my life, it’s only a part of my life.’
BRCA mutations were certainly a big part of the lives of many who were present in the room that night, and will remain so. Others will also find that genetics is of personal importance, as our knowledge of risk-associated genes increases and as genetic screening becomes more widely available. All of which makes me glad there are events like this to attend.
The next free-to-attend event in the Wellcome Trust supported ‘Breast Cancer: Chances, Choices and Genetics’ series is Risk Assessment: Breast Cancer, Prediction and Screening, taking place at University College London on Thursday 8th May at 6.30pm.
Top Image credit: Peter Artymiuk, Wellcome Images
On the Wellcome Trust blog we like to celebrate the people and the work that define who we are. In our new Researcher Spotlights series we will introduce you to some of the great people that we fund, and give you a peek into the work they are doing.
Dr Colm Cunningham is a Wellcome Trust Senior Research Fellow and Research Lecturer at Trinity College Dublin. We asked him to tell us what he’s working on, and if anything keeps him awake at night…
What are you researching?
The interaction between systemic inflammation and existing neurodegenerative processes – in essence, why is it that relatively mild inflammatory insults, which produce only mild feelings of sickness in the normal healthy person, can produce profound confusion, and attentional and cognitive disruption, in those with prior neurodegenerative changes in their brains?
Delirium is the extreme end of this spectrum and these disturbing episodes also contribute to the worsening of the underlying condition, accelerating the cognitive and functional decline of these people, but we understand very little about how this occurs.
What does your average day involve?
We design and perform animal experiments that attempt to mimic the sorts of situations that lead to delirium in the clinic. What is ‘average’ tends to change with the flow of our experiments. We examine changes in animals’ behaviour, measure inflammation in the blood and in the brain, and study early activation and later pathological signs in the brain.
I lead a team of four researchers and collectively we may undertake surgery, behaviour, molecular analyses or microscopy techniques. As results emerge, I start to think about how our papers should present these data, but also how they can best be articulated for the clinical audience that we are trying to reach. Writing our basic research papers and presenting them to our clinical colleagues are totally different endeavours!
Why is your work important?
Delirium is extremely common in the older hospitalised population and in intensive care units. The negative outcomes are many: longer hospital stays, shortened time to dementia, permanent institutionalisation and death. But the fundamental scientific knowledge on the subject is very limited. With little basic research in the field, it has been difficult to generate and test hypotheses in clinical cohorts. It’s still ‘tip of the iceberg’ stuff, but we are generating testable hypotheses in mice and beginning to test them in patients.
What do you hope the impact of your work will be?
The field of delirium has suffered from a near total lack of basic research activity. We approached this field a few years ago with grand notions of bridging the gap between basic neuroscience research and clinical practice.
I wanted to directly influence the way in which clinical researchers thought about the delirium episode and to develop better ways to prevent and treat this extremely common but largely neglected phenomenon. It is a facile statement that there is a gulf between basic research and clinical practice, but there is no doubt that it is true.
I think we have had some success in influencing how geriatricians think about this problem, but I have also seen an evolution in my own views of how this grand brain failure works. We need these new ideas to keep pushing the basic research forward, but without concerted effort, these ideas do not permeate clinical thinking, so there is a public relations job to be done too! Your average geriatric psychiatrist is not going to take time out of their day to read about mice making bad decisions in mazes, so I have been working hard to articulate the same information in different ways for different audiences.
How has Wellcome funding helped?
I think the Wellcome Trust has invested in a field that is woefully understudied and they have invested in me to help make inroads into this unexplored area. It would be easy to succumb to the criticism that delirium is complex and that these mouse models are too simple to capture it, but the Trust has taken a leap of faith in the questions we are asking and I certainly believe that the models we are using will provide valuable information on how systemic inflammation interacts with the vulnerable brain.
I have already tasted just enough rejection elsewhere to know that most funders are more risk averse. The funding has allowed me to establish myself, and our group, as credible contributors to this field and has provided an amazing source of support for the work.
What’s the most frequently asked question about your work?
How can you tell if a mouse is delirious?
Which question about your work do you most dread – and why?
How can you tell if a mouse is delirious? (!!)
I don’t honestly dread it, but there is often the perception that an animal model must display every feature of the clinical condition it purports to mimic. Sometimes people are reluctant to believe that models are just that: model systems that allow you to manipulate the system and see if it behaves in the way you predict.
If one’s prediction is correct, you can move on to the next, more advanced, question in that system and if the prediction is wrong you can revise your thinking and refine the hypothesis. Our work uses systems relevant to delirium during dementia in a general sense and is proving consistent with existing clinical observations.
Tell us something about you that might surprise us…
I left science after my PhD to indulge my fantasies about being a musician, and also took a year out to travel the world after my first post-doc – only to discover in my conversations with fellow travellers that this is what I want do. We are not encouraged to take time out, and indeed are actively discouraged by many funders and employers, but I have certainly benefitted from taking time to reflect on my direction.
What keeps you awake at night?
Referee three! Is the hypothesis correct? Will we still be funded in five years?
I think I have become a little more philosophical and therefore a little less stressed about all of those things but I definitely want to feel that I have spent my time wisely and moments of doubt keep me awake.
Dr Colm Cunningham works in the Institute of Neuroscience, Trinity College Dublin. You can read more about his work in the following papers (available on PubMed):
Q: What connects Shakespeare, Sammy Davies Junior and Nick Griffin?
A: Artificial eyes, as featured in this Image of the Week. Shakespeare wrote of them in King Lear – “get thee glass eyes; and, like a scurvy politician, seem to see the things thou dost not” – whilst the other two either wore or wear one. And as this photograph shows, artificial eyes come in all different shapes, sizes, and colours.
Artificial eyes have a fascinating history – and one which reflects changes in their purpose and design.
To select just three points on this journey:
Egyptian mummies were frequently given artificial eyes, often made from plaster-filled bronze, and the purpose of them was to allow the dead to see once in their next life.
Glass eyes. We don’t know a precise date when these emerged. However, given Shakespeare’s reference to them it seems likely they were about from at least the early 17th century. They became increasingly common in the 19th century, and ocularists would stock different models in their stores for customers to try on and find a right fit.
Stepping forward to the modern day, recent innovations have seen artificial eyes that are able to replicate the movement of the pupil, and interact with living tissue.
Researchers are currently looking at ways of enabling artificial eyes to function near-fully like a standard eye, by using retinal implants to treat blindness. We’ll keep an eye out for news.
Image credit: Science Museum, London, 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.
Using original quotes when you write can really bring your piece alive, but how do you persuade people to take the time to talk to you? As part of “How to” series of posts to help you with your entires to the Wellcome Trust Science Writing Prize, Chrissie Giles, Senior Editor at the Wellcome Trust, shares some thoughts on how to get the best out of interviews.
It’s nice to be nice
When you’re asking someone for their time, be clear about what exactly you would like from them. Your potential interviewee might get hundreds of emails a day, so make yours concise, simple and direct.
In the subject line make your purpose clear (Interview request for Lovely Cat magazine). In the body, be friendly but not verbose. State how urgent your deadline is and perhaps suggest times you’re free. I’d like no more than 30 minutes of your time. I can come and meet you or we can talk by phone or Skype. Do you have any time Tuesday 10th, perhaps between 1 and 5pm? Remember, being polite costs nothing.
Where will you meet and when? It sounds simple but these things can go wrong very easily. Pick a convenient place with the privacy and quiet you need. Check timezones and dates carefully, to avoid being stood up – or worse, standing your interviewee up!
Keep a record
Some writers take notes as they interview, others use an electronic recorder or phone. If you want to record, make sure that you ask permission from the person you’re interviewing. It’s up to you how you record your conversation, but make sure that your chosen method is reliable. Are the batteries charged? Is the volume high enough? Do you know how to turn it on? It also needs to be as stress-free as possible. You don’t want to miss all those juicy quotes because you’re scribbling down the answer to the previous question or worrying about the recorder.
You might have to ask probing or personal questions of an interviewee you barely know. This can be awkward for both parties. Make small talk when you first start chatting to try and break the ice – how was their journey? Have they been doing a lot of interviews?
It’s not about you
Drafting questions beforehand can help you think about what you want to ask and in which order – but be flexible.
While it’s great to have a conversation rather than a terse back-and-forth, the main point of an interview is to get the best, most interesting and honest responses from your interviewee, not to show off what you know on a topic, or to share your personal experiences.
If you’re one of nature’s nervous babblers, then try and stick to your drafted questions to avoid rambling for minutes without actually asking anything.
Go with the flow
Interviewees often go off on tangents. This can be great for finding out new, unexpected things. Keep half an eye on your question list, but make sure you’re engaging with this unanticipated information. After all, it could be the making of your piece.
If, however, your interviewee is talking at length about something you know isn’t relevant, you need to steer them back. Breaking eye contact, putting down your pen and minimising your active listening mm-hmms can all help get the message across in a more subtle way than interrupting them (although you might need to do this too).
You might need to ask challenging questions. Rather than directly criticising your interviewee, you could frame a difficult question another way: “What have critics of your work said about this paper?”, “Our readers might think…”.
The thing about silence is that people feel compelled to fill it. Keeping quiet after a person answers you can be as effective as asking another question: they carry on talking, so you get more detail than they might otherwise have offered. If you’re trying to find out specific information – how much the failed project cost, say – you could suggest a figure and wait for their response (“OK, but was it under £20 million?”). If you keep it buttoned, they may feel compelled to speak.
In a nutshell:
- Use open questions. Closed questions (that can be answered with a yes or no) have their place in an interview, but open questions can invite more thoughtful answers.
- Be mindful of your body language. Keeping your arms uncrossed, smiling and good (but not continuous) eye contact can help put your interviewee at ease.
- Break out of the norm. You don’t have to stay sat in a person’s office. You might get your best material whilst queuing up with them to pick up their dry cleaning.
- Wrap up well. Ask at the end of the interview if there’s anything else they want to add.
- Be shy to ask for more. If you need more detail from an answer, just ask. “Can you tell me more about that?”, “When you say ‘It was unexpected’, in which ways do you mean?”.
- Stop listening too soon. It’s often said that you can get the best material at the end of an interview, as your interviewee relaxes. Keep listening, and even perhaps recording, so you don’t miss out on any unexpected gems.
- Skimp on the research. You don’t need to show off all you know, but you do need to have sufficient background on your interviewee to be able to ask the right questions.
- Panic! Unless things go disastrously wrong, most interviewees will be happy to follow up any queries with you by phone or email after an initial interview.
Chrissie Giles is a Senior Editor at the Wellcome Trust and Commissioning Editor for Mosaic, the new digital publication that explores the science of life.
Image credit: “Plan. Write. Remember” by Jorge Quinteros on Flickr. CC-BY-NC-ND
The Wellcome Trust Science Writing Prize 2014, in association with the Guardian and the Observer is open for entries now. Get writing and submit your piece before the deadline on 11th May 2014 for your chance to win £1000 and a chance to get your work published. We are running a series of “How to” posts giving you tips on how to write a good science story from a research paper, how to set up a science blog and how to pitch to an editor in the run-up to the competition deadline.
Full details and terms and conditions can be found on the Science Writing Prize pages of the Wellcome Trust website. Good luck!
Do we have any leverage against drug-resistant organisms? Dr Maciej Boni explains the biological fitness cost of drug resistance and the worrisome scenarios that could develop if we lose this small advantage in our fight against drug-resistant pathogens. Dr Boni is a Wellcome Trust–Royal Society Sir Henry Dale Fellow leading a research programme on the epidemiology and evolution of influenza in the tropics. Parts of his doctoral and postdoctoral work focused on developing public health strategies aimed at rolling back drug resistance.
Can we eliminate drug resistance?
In some areas of global health we have made great strides over the past decade. Although much remains to be done, great progress has been made in the fields of malaria, HIV, the neglected tropical diseases, tuberculosis and many other infections. Maternal and child health have been improving, and funding for global health programmes has increased significantly. But the rise of drug resistance puts many of these advances at grave risk.
Drug resistance became a major public health problem in the later decades of the 20th century, as the world’s most serious pathogens began to repeatedly demonstrate the ability to elude our best treatments. In the 21st century this international threat to public health cannot be ignored.
Under extreme pressure from antibiotics, antivirals or other drugs, the majority of the world’s pathogens have – sometimes quickly, sometimes slowly – evolved resistance to the drugs we use to combat them. For the pathogens, this benefit of drug resistance has typically come at a cost; although resistant pathogens have a biological advantage in the presence of an antibiotic, they are less fit than sensitive pathogens when the antibiotic pressure is removed and tend to die out. Thus, it appeared that natural selection had given us a foothold on this problem by making drug-resistant organisms more flawed than their drug-sensitive counterparts. However, recent results from a team of Wellcome Trust investigators and a team of NIH-funded investigators have shown that some pathogens are now able to develop drug resistance without that biological cost.
“This would be a nightmare scenario”
“This would be a nightmare scenario,” says Dr Jeremy Farrar, Director of the Wellcome Trust, “that resistant pathogens might be selected when exposed to antibiotics, but would expand in numbers even if the antibiotic pressure is removed”.
“Much of the wonderful progress in global health over the last 20 years would be at risk, and this is not just an issue for the resource-limited world – it would change the way we practice medicine in this country” he says.
From past experience we know that bacteria have invented pumps to remove antibiotics from the confines of the cell wall, but operating these pumps requires energy that could otherwise be used for reproduction. Influenza viruses have changed the shape of one of their surface proteins that is bound by the drug oseltamivir (Tamiflu), but this altered protein shape means that new virus particles experience difficulty exiting the cells they are born in. This slows down the cell-to-cell spread of the virus.
In each of these examples these pathogens have been forced to trade some of their usual Darwinian fitness to become more drug-resistant.
Survival of the fittest
Fitness, the centrepiece of Darwin’s theory of natural selection, determines both how likely an organism is to survive to reproductive age and how many offspring it will have once it gets there. As the generations pass, fitter organisms that produce more offspring crowd out organisms that produce fewer offspring, and this increases the chances of extinction for the less fit organisms.
If drug-resistant organisms are forced to compete with non-resistant strains, they will be outcompeted if the drug they are resistant to is not present. This is due to the fitness cost associated with drug resistance mutations, and it means that we may have a chance at eliminating certain types of drug resistance. A real-life example of this was seen in Malawi in the 1990s with the elimination of chloroquine-resistant malaria; this was possible because the resistant strains were noticeably less fit than the chloroquine-sensitive strains.
It’s not quite as simple as it sounds though. The big catch is that drug-resistant organisms can only be forced into this losing scenario in the absence of drug treatment. In Malawi, chloroquine was completely withdrawn from use in 1993, but this was only possible due to the availability of other antimalarials. Switching to using different antimalarials removed the benefit of chloroquine resistance, allowing chloroquine-sensitive strains to outcompete the chloroquine-resistant strains. The chloroquine-resistant strains disappeared after eight years.
The good news is that with the availability of multiple types of antimalarials and multiple types of antibiotics, we may have an opportunity to selectively withdraw certain drugs – or at least to reduce their use by managing the simultaneous use of multiple types of drugs. The more types of drugs that are available, the more easily this can be done. In both academic and pharmaceutical-industry research planning this simple fact should serve to underscore the critical need for continual development and discovery of new drug classes.
‘Resistance management’ strategies have been gaining popularity over the years, and if executed correctly they might help turn the tables in our battle against drug resistance. But all of these strategies rely on the simple biological assumption that if a certain drug is prescribed infrequently, drug-resistant strains will be outcompeted, and resistance to that drug should fade.
The bad news is that recent research has shown this assumption may not always hold true.
Late last year, Wellcome Trust-funded and NIH-funded scientists published results showing that recently emerged drug-resistant strains of Salmonella enterica and influenza virus have not been associated with any fitness costs. With no obvious fitness cost to the organisms, even if we were to completely change our treatment guidelines for these pathogens, these drug-resistant strains would be predicted to spread worldwide.
“…entire classes of drugs would be rendered useless, and the situation would be irreversible”
If the laboratory results from these studies hold up in a natural setting, entire classes of drugs would be rendered useless, and the situation would be irreversible.
In the lab
Dr Stephen Baker, a Wellcome Trust–Royal Society Sir Henry Dale Fellow, and Head of Enteric Infection Research at the Oxford University Clinical Research Unit in Vietnam, was interested in showing how costly fluoroquinolone resistance would be to Salmonella bacteria – the causative agents of typhoid fever. Fluoroquinolones are the globally recommended first-line treatments against typhoid fever, and determining the fitness cost of fluoroquinolone resistance would help in planning public health strategies to reduce resistance levels. “We were shocked to find in our lab experiments that the fluoroquinolone-resistant strains were better at replicating than the sensitive strains, in the absence of any antimicrobial pressure,” says Dr Baker. “If these characteristics translate to a clinical setting, it means that we are left with no options for reducing fluoroquinolone resistance. These resistant genotypes are here to stay.”
“If these characteristics translate to a clinical setting, it means that we are left with no options for reducing fluoroquinolone resistance. These resistant genotypes are here to stay.”
On the other side of the world in New York City, Dr Nicole Bouvier’s group at the Icahn School of Medicine at Mount Sinai has been performing similar experiments on the H7N9 influenza subtype that emerged in coastal China in early 2013. The most effective class of drugs against influenza virus infections is the neuraminidase inhibitors – drugs that bind and disable the influenza protein neuraminidase, which is critical for viral spread in lung tissue. “We set out to determine the fitness differences between drug-sensitive and drug-resistant influenza strains, as the drug oseltamivir is likely to be used in a wide range of clinical settings for treating H7N9 infections,” says Dr Bouvier. “Unfortunately, we found that the sensitive and resistant viruses showed no detectable differences in the rate of replication in human lung tissue, in virulence effects in mice, or in their ability to transmit among guinea pigs. Transmission was inefficient for both of the H7N9 viruses that we tested in our experiments, but, surprisingly, transmission of the drug-resistant virus was no less efficient than that of the drug-sensitive version.”
If oseltamivir resistance becomes entrenched in H7N9 influenza viruses, it may be impossible to eliminate, neutralising the most important drug we have to treat influenza infections.
Both typhoid fever and avian influenza carry a high risk of death if left untreated. Case fatality rates for untreated typhoid are between 10 per cent and 20 per cent, while the various avian influenza outbreaks the world has experienced since 1997 have come with reported mortality rates of between 30 per cent and 60 per cent. If drug resistance erases our ability to treat these infections, patient outcomes in clinical settings are likely to worsen.
For typhoid this could translate into a major public health concern, as there are an estimated 22 million cases of typhoid reported globally per year. The availability of second-line drugs, such as third-generation cephalosporins, ameliorates the problem to some extent, but these drugs have poor penetration against intracellular infections like typhoid and are less effective.
For avian influenza we are not so lucky, as there are few alternate drug classes available to treat this viral infection. Our only hope is that new therapies are developed and that such infections remain rare.
It is impossible to say if other types of drug resistance will present us with the same challenges, but we know that new types of drug resistance emerge every year. Perhaps the next research challenge in this field will be classifying these resistance mechanisms by whether they do or do not carry a fitness cost. Drug-resistant pathogens that do not carry fitness costs present a significant challenge as we currently have few available tools to fight these newly adapted pathogens.
“We are at a tipping point when the rise of drug-resistant untreatable infections is a very real possibility”
Wellcome Trust Director Jeremy Farrar comments: “I believe the most important emerging infection challenge of the 21st century will be the development of drug resistance in existing infections. We are at a tipping point when the rise of drug-resistant untreatable infections is a very real possibility. This work, which challenges the dogma, highlights how important this issue is.
“I qualified in medicine just at the start of the HIV epidemic when the infection was untreatable. It was a horrific time when people died for the lack of any effective treatment. The emergence of drug resistance across many infections risks us returning to the pre-antimicrobial era when simple infections were similarly untreatable.”
The research papers referred to in this feature are:
Hai R, Schmolke M, Leyva-Grado VH, Thangavel RR, Margine I, Jaffe EL, Krammer F, Solorzano A, Garcia-Sastre A, Palese P, Bouvier NM (2013). Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility. Nature Communications 4:2854.
Baker S, Duy PT, Nga TVT, Dung TTN, Phat VV, Chau TT, Turner AK, Farrar J, Boni MF (2013). Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure. eLife 2:e01229.
Spring into British Summer Time and check out the engaging science events that we have on offer. We’ve got puppets and a prize, food and phytology and much more besides. What will you choose?
Killing Roger – The Hat Factory, Luton – UK tour begins 23rd April
Using stunning life-sized puppetry and original live music, this play raises one of the most important questions of our generation in a moving and humorous tale of an old man and a boy at opposite end of their lives. As the memories of Roger’s life unfold before us, Billy’s troubled mind faces an unexpected question. Can the boy become a man and make a decision that will change both of their lives forever? Find out about tour dates and locations on the Sparkle and Dark website.
The Nine O’Clock Slot – Red Gallery, Shoreditch – now until 19th April
Nine o’clock: the time of day that Councils bury the poor, the isolated, and the forgotten – the funerals that no one attends. This site-specific theatre production about the rise in paupers’ funerals in modern Britain is based on true-life accounts where heart-breaking stories find comic touches and uplifting conclusions.
Phytology, the urban physic garden – Bethnal Green Nature Reserve – until March 2015
Phytology is an action-research project bringing together artists and botanists to explore the ecology and medicinal properties of wild plants and weeds common to derelict and undeveloped urban sites. The partnership of artists and botanists will seek to create a fresh language in which to challenge perceptions of the value of un-manicured growth, revealing practical biomedical usefulness, and suggesting a wider eco-connectivity.
Teaching your eyes to feel – Royal Institution, London – 7pm 2nd April
Keyhole surgery requires surgeons to operate ‘at a distance’, but how can they feel without touching? Professor Roger Kneebone, a Wellcome Trust Engagement Fellow, and Dr Fernando Bello from Imperial will explore the fascinating world of minimally invasive surgery at this event at the Royal Institution. See how the latest technology is helping to train the new generation of specialists, and even try your hand at cutting-edge surgical simulations! Tickets available via the Royal Institution.
Breast Cancer: Chances, Choices and Genetics – University College London
The Progress Educational Trust (PET)’s new project supported by the Wellcome Trust will explore and clarify breast cancer and risk for the general public, current and prospective patients, and professionals. There are four events as part of the project, all taking place at UCL on Thursday evenings. Events are free to attend but booking is essential.
‘Relative Risk: Breast Cancer and Genetics’ – 3rd Aprilexplores actress Angelina Jolie’s decision to undergo a double mastectomy and to what extent her situation was representative and her response proportionate.
‘Risk Assessment: Breast Cancer, Prediction and Screening’ – 8th Maylooks at the different types of risk around breast cancer and the effects they have on decisions.
‘Risk Management: Breast Cancer, Business and Patents’ – 5th June discusses the cost of testing for breast cancer and how detection of tumours can affect insurance for patients.
Concluding event – 3rd Julythat will be decided based on suggestions from the audience at the first three events.
GastroFest – Edinburgh International Science Festival – 5th-20th April
This mini festival of the science of food and drink showcases the importance of science in our lives in the most delicious way possible; through a series of innovative events exploring the centrality of science to our culinary experience. Bringing together producers, artisans, scientists and chefs, our events will lead you on an alimentary odyssey, taking in everything from the neuroscience and psychology of taste perception to slow food and cutting-edge molecular cocktails. Events include:
Mad Hatter’s Tea Party – 5th April: Confound your senses with a trip down the rabbit hole to explore the science of human intoxication. Join ethnobotanist Dr Ian Edwards of the Royal Botanic Garden Edinburgh for a voyage of drug discovery from opium dens to the Olympics, taking in zombie caterpillars, afternoon tea, and the surprising patent medications of fashionable Victorians.
Brainwaves: Sensory Dining – 7th April:The BBC Radio Scotland series, Brainwaves, explores the science behind our everyday experiences, and nowhere is this centrality of science to our lives more evident (and delicious!) than in the area of food and drink.
Taking North London’s Pulse – Camden Local Studies and Archives Centre – Tuesday, 15th April – 6pm-8pm
This Insight talk uncovers the rich content of London’s Pulse, a major digital resource for the history of London. This event will be themed around North London and will illustrate the health of the area over the last 150 years, drawing upon the fascinating content of London’s Pulse and the collections of Camden Local Studies and Archives Centre.
Wellcome Book Prize
The Wellcome Book Prize celebrates the topics of health and medicine in literature and aims to stimulate interest and debate about medical science through books and reading. This year’s judging panel consists of Sir Andrew Motion, Hadley Freeman, Michael Mosley, Lisa Appignanesi and James Runcie. The full shortlist, which includes one novel and five works of non-fiction can be found at WellcomeBookPrize.org
Books for the Incurably Curious – Cambridge Literary Festival – Sunday 6th April – 7.00pm
Wellcome Book Prize Judge Michael Mosley and shortlisted authors Sarah Wise and Emily Mayhew discuss how science and medicine shape our daily lives, the state of contemporary fiction and nonfiction writing in the field, and how curiosity drives us.
The Art of Curiosity – Southbank Centre, London – Wednesday 23rd April – 6:30pm
Sir Andrew Motion, Lisa Appignanesi, Hadley Freeman, Michael Mosley and James Runchie (the five Wellcome Book Prize judges) discuss the state of contemporary fiction and nonfiction writing about science and medicine, and the six shortlisted books that challenge our curiosity, fire our imagination, inspire debate, and help us to think differently about the world around us.
Authors in Conversation – Wellcome Collection – Saturday 26 April 2014, 3.00pm
Join Anne Karpf in conversation with shortlisted authors for the Wellcome Book Prize. These critically acclaimed authors will reflect on the creative process of writing while exploring the broader context of medicine and literature. Confirmed speakers: Emily Mayhew, Elizabeth Gilbert
Talks for the Incurably Curious - Wilton’s Music Hall – Sunday 27th April – 4.00
Storytelling experts 5×15 bring you an afternoon of extraordinary and unexpected talks featuring three of the Prize’s shortlisted authors: Elizabeth Gilbert, Emily Mayhew and Sarah Wise. Hosted in Wilton’s, this is a unique opportunity to hear inspiring speakers in an atmospheric historic space.
False Memory Archive:the collection of contemporary artworks and personal accounts is at the Talbot Rice Gallery in Edinburgh until 19th April.
The Anatomy of Melancholy: the stage adaption of this 400 year-old book is still on tour.
For a trial period of two months we’ll be bringing you a fortnightly update of news from our researchers. Here’s the second edition, we hope that you find it useful.
New research funded by the Wellcome Trust indicates that obesity in the general population may be genetically linked to how our bodies digest carbohydrates.
Published in Nature Genetics, the study investigated the relationship between body weight and a gene called AMY1, which is responsible for an enzyme present in our saliva known as salivary amylase. This enzyme is the first to be encountered by food when it enters the mouth, and it begins the process of starch digestion that then continues in the gut.People usually have two copies of each gene, but in some regions of our DNA there can be variability in the number of copies a person carries, which is known as copy number variation. The number of copies of AMY1 can be highly variable between different people.
Researchers from Imperial College London, in collaboration with other international institutions, looked at the number of copies of the gene AMY1 present in the DNA of thousands of people from the UK, France, Sweden and Singapore. They found that people who carried a low number of copies of the salivary amylase gene were at greater risk of obesity.
Parkinson’s missing link
A new chemical messenger that is critical in protecting the brain against Parkinson’s disease has been identified by scientists at the University of Dundee.
The research team, led by Wellcome Trust Senior Clinical Fellow Dr Miratul Muqit, had previously discovered that mutations in two genes – called PINK1 and Parkin – lead to Parkinson’s.
Now they have made the unexpected discovery about the way the two genes interact, which they say could open up exciting new avenues for research around Parkinson’s and offer new drug targets. The results of their research are published in Biochemical Journal.
“Understanding the fundamental mechanisms of how brain cells die in Parkinson’s is likely to uncover new insights into how to treat this progressive disorder,” said Dr Muqit.
Skin cancer warning
Mutations in a specific gene are responsible for a hereditary form of melanoma according to new research from the Wellcome Trust Sanger Institute.
Every year in the UK, almost 12,000 people are diagnosed with melanoma, a form of skin cancer. About 1 in 20 people with melanoma have a strong family history of the disease. In these patients, pinpointing the genetic mutations that drive disease development allows dermatologists to identify people who should be part of melanoma surveillance programmes.
The team found that people with specific mutations in the POT1 gene were extremely likely to develop melanoma. These mutations deactivate the POT1 gene that protects the ends of our chromosomes from damage.
Dr David Adams, co-senior author from the Wellcome Trust Sanger Institute said, “With this discovery we should be able to determine who in a family is at risk, and in turn, who should be regularly screened for early detection.”
In other news…
Carla McKinnon and the The Sleep Paralysis Project are celebrating their win at the CineGlobe International Film Festival at CERN. They picked up the award for Best Documentary for the film Devil in the Room.
Congratulations also to Luke Alphey, recipient of a Wellcome Trust Translation Award and chief scientific officer of Oxford-based biotechnology company Oxitec, who has won BBSRC’s 2014 Innovator of the Year award.
This Image of the Week comes courtesy of Wellcome Trust researcher Professor Andy Waters Director of the Wellcome Trust Centre for Molecular Parasitology (WTCMP) that participates in the Wellcome Trust Liverpool Glasgow Centre for Global Health (WTLGCGH). This week he’s been in Kenya with Prof Paul Garside, also from WTCMP and WTLGCGH . Professor Waters sent us this short report about their visit…
Last year Professor Paul Garside, Head of Immunobiology and member of the WTCMP in Glasgow, spent two periods of three months in Africa. He was researching and building links with two medical research centres, the KEMRI-WT Centre in Kilifi, Kenya and the Malawi Liverpool Wellcome (MLW) Centre in Blantyre Malawi.
The trips proved so successful at identifying common interests, such as applying some of the approaches to autoimmune disease that are Paul’s expertise, that they prompted a recent visit to Glasgow by Dr Francis Ndungu. Dr Ndungu is a Senior Researcher at KEMRI-WT and his visit allowed further assessment of whether the investigation of non-communicable disease (such as diabetes, rheumatoid arthritis and stroke) might reveal how they influence, or can be influenced, by communicable diseases such as malaria.
This week Paul and I visited the centres to try to take the interactions even further. We spent four days talking to different researchers in KEMRI-WT to continue to identify potential collaborations. Then we went slightly further afield to Pwani University in Kilifi, a new and expanding university that has research links with KEMRI-WT, and enjoyed a very enthusiastic exchange with the leading officials there. We left with the commitment to run an advanced training summer school together with KEMRI-WT in 2015.
The photo above shows KEMRI-WT driver, Benson Chai, and was taken on our visit to the Junju malaria cohort south of Kilifi. We participated in the regular briefing meeting held by Juliana Wambua with the field workers.
This particular meeting was held ahead of the intensive bleeding programme that accompanies the rains and increased malaria transmission. The cohort have agreed to allow the children of the village to give small amounts of blood to allow workers at KEMRI-WT to assess the levels of malaria and the intensity of its transmission. They will also genotype the parasites in each sample and characterise the individual’s immune responses to the parasite.
By repeating these studies over years it is possible to build a picture of time of an individual’s case history and identify trends in the whole population. This is only possible through good communication and openness that instills the whole enterprise with mutual trust.
This atmosphere was very evident at the meeting we attended. The villagers are fully behind this programme as they clearly see the need to combat malaria. They are kept informed of how they are helping the bigger research programme by regular visits from the researchers who explain their work.
This was one of an intensive series of meetings and lectures with many staff at KEMRI-WT and nearby Pwani University that aim to build closer research ties for WTCMP and Glasgow University with institutions in the region. Collaborative research and training is important to the goal of translating basic and applied research into a greater understanding of the actual field situation and developing measures that might help combat the disease.
For more information on this work listen to Prof Garside’s podcasts from his original visit to Kilifi in 2013.
The Wellcome Trust recently published details of how much it spent on open access publishing in the year 2012-2013 in an attempt to make the debate around the costs of open access publishing more evidence-based. The data we released fuelled much discussion online and Robert Kiley, Head Digital Services at the Wellcome Library, gives an update…
At the Wellcome Trust we are keen proponents of openness and transparency so we published details of our spending on open access publishing, (as reported by UK institutions and the Trust’s Major Overseas Programmes who are in receipt of an open access block grant) for 2012-13. Within a few hours of releasing this data we were pleased that the web community were working to enhance and normalise it. The version now available through Google Docs is far richer than the original dataset, and includes additional data elements such as DOI’s, licence terms and impact factor.
As well as enriching the data, crowdsourcing has highlighted examples where publishers have not, for whatever reason, made articles freely available, and where biases in the publishing system are leading to very high open access charges. These are both issues that we want to address head on.
Are publishers doing what they are paid to do?
Publishing the data provided the opportunity for anyone to check that articles, for which an article processing charge (APC) had been levied, were freely available under an open access model, in line with our requirements. Inevitably, with a dataset of over 2000 articles, published by 94 different publishers, problems have been identified. These include:
- Content remaining hidden behind a publisher pay-wall;
- Content freely available on the publisher site, but not available in PMC/Europe PubMed Central;
- Missing, incorrect, or contradictory licence information
- CC-BY licensed articles still linked to sites such as the Copyright Clearance Centre, where readers may be charged for re-using open content.
Prior to releasing this data, we analysed all the university APC returns and emailed the relevant publishers in cases where the content was not freely available in PMC. In summary we contacted 20 publishers in relation to 150 articles (approximately 7% of the total number of articles for which an APC had been paid).
In the majority of cases these papers are now available in PMC, though it did highlight a number of issues such as articles which were still “in press” (and thus not formally published), publishers saying they had not been paid, and in the case of one publisher, not having established a workflow to push content to PMC. In all cases we are following up these queries.
At this point in time we have not systematically looked at the licence statement for every article, not least as the CC-BY requirement only applied to research articles submitted after 1st April 2013. However, when we repeat this exercise next year, this element will be checked.
What does the data show?
In headline terms the Wellcome Trust spent approximately £3.9 million on APCs for 2126 articles in the year 2012-13. The average APC was around £1821, whilst the median cost was £1837.
Further analysis shows that the average APC levied by the traditional subscription publishers (e.g. Elsevier, Wiley, NPG) is significantly higher than that charged by the born-digital open access publishers, like PLOS.
This finding is in line with the recent study by Bjork and Solomon which concluded that the average APC in a hybrid journal – that is a journal which offers an open access option for individual articles, while continuing to operate via the subscription mode – was found to be almost twice that for a born-digital full open access journal ($2,727 compared to $1,418).
As 74% of articles in the 2012-13 dataset were published in a hybrid open access journals, we are actively considering the policy options (put forward in the Bjork/Solomon study) through which funders can help ensure that the rapidly growing open access market delivers high-quality services and value for money for the research community.
Elsevier: a case study
As much of the comment regarding the APC data set has been directed at Elsevier, we have looked in more detail at this data and found that:
- Elsevier is the single biggest publisher of Wellcome-funded research, publishing 422 (20%) of the articles listed in this dataset. The second biggest publisher was PLOS, with a total of 305 (14%) articles, and Wiley was third, publishing some 271 (13%) articles.
- Of the 422 Elsevier papers in this dataset, all but six (1.5%) are freely available at ScienceDirect. Elsevier are investigating why these six articles have not been made open access, but have confirmed that if articles for which an APC has been paid are not freely available, then they will rectify this and reimburse the institution which made the payment.
- An additional eight papers are also not available from PMC and Europe PMC. Elsevier have investigated and confirm these do not yet appear in PMC for a variety of reasons (some to do with authors, others to do with Elsevier systems, some to do with PMC/NLM systems). These papers will be deposited shortly.
We expect every publisher who levies on open access fee to provide a first class service to our researchers and their institutions. We recognise that subscription-based publishers are actively developing their systems (see this article) to accommodate the open access business model and we urge them to makes these changes as quickly as possible. Even though there are only a small number of articles that the Wellcome Trust has paid to be open access that have remained behind a pay-wall, this is not an acceptable situation in any instance.
The bigger issue concerns the high cost of hybrid open access publishing, which we have found to be nearly twice that of born-digital fully open access journals. We need to find ways of balancing this by working with others to encourage the development of a transparent, competitive and reasonably priced APC market.
Finally we would like to extend many thanks to all those who have enriched our data and highlighted the problems. Crowdsourcing analysis of this data has proved to be highly effective and truly in the spirit of the open access thinking of the Wellcome Trust. With you, we will continue to monitor this space to ensure that our open access requirements are fully adhered to.
The Wellcome Trust Science Writing Prize 2014 launches today and to help inspire your entries we’re publishing a series of “How to” blogs here on the Wellcome Trust blog. Over the next few weeks we’ll be covering a range of topics, including how to conduct an interview, how to write a feature, and how to pitch to editors. The prize is run in association with The Guardian and The Observer and so start us off, and to help you in your search for the perfect story for your entry, The Guardian’s Science Correspondent Ian Sample shares his tips on how to write a news story from a research paper.
Most journalists want to break exclusives, but a lot of what scientist journalists write is based on the latest findings published in academic journals. So here are some guidelines on how to write a great news story from a research paper.
1. Find a good paper
Thousands of scientific papers are published each week. The majority will not make good news stories. Look for work that is entertaining, fascinating, important or controversial. Ask yourself: will anyone care? Be brutal about this. Move on if the answer is no.
2. Read it
You cannot cover a paper properly without reading it. The abstract will give the barest essentials. You need to read the introduction for context, the discussion and conclusions for take-home messages. Check the methods. Was the experiment well designed? Was it large enough to draw conclusions from? Find weaknesses and flaws. You will probably need help to work out how fatal they are. Spend time on the results. Have the authors omitted key data? Look at odds ratios, error bars, fitted curves and statistical significances. Are the results robust? Do they back up the scientists’ conclusions? Remember: nematodes, fruit flies and mice are not humans, and what happens in a Petri dish won’t necessarily happen in a person. Read the supplementary material too. You will find gems.
3. Vested interests
Check for conflicts of interest. These should be declared at the end of the paper, but make your own checks too. Plenty of scientists have financial links with companies. The reader might want to know about them.
4. Get context
Science builds on science. Know the previous studies that matter so you can paint a fuller picture. If your story is about chimps in Guinea using cleavers and anvils, you might mention the different tools that chimps in the Republic of Congo use for termite fishing.
5. Interview the authors
Write from the paper alone and your news story will be dull. Interviews with authors will give you the colour to tell a story. How did the face transplant patient react when they looked in the mirror? What possessed the authors to study spiders on cocaine? How did it feel to unearth the remnants of an ancient hearth, knowing a Neanderthal sat in the same spot 40,000 years ago?
Get them to explain their results and justify their conclusions. What do the results mean in plain English? What do they not mean? Ask your questions in simple language to get answers you can quote. Run phrases you might use past the authors, so they can warn you of howlers. Do not ask multi-part questions: you will not get full answers.
Remember that papers can take months to appear in journals, so find out how the work has moved on since the work was submitted.
Think about whom you want to interview. First authors are generally the graduate students or postdocs who did all the work. Last authors are often senior scientists. On a good day, a senior author will give you the clearest explanation, the perfect quote, and the richest context. On a bad day, they will have no recollection of the paper their name appears on.
6. Get other scientists’ opinions
Send the paper to a handful of experts to check. You will find people in the paper’s references, or on Google Scholar. Chat about the paper on the phone. Some scientists will email you thick paragraphs of reaction. You might salvage a sentence or two, but email makes for clunky quotes: people do not speak the way they write. Ask your expert if the work looks sound or flakey. What does it add? What is the striking result? Will it be controversial? What fresh questions does it raise? Comments from other scientists will always improve your story. They will also save you from writing a story you wish you had never touched.
7. Find the top line
You’ve read the paper, interviewed the authors and discussed the work with other experts. Now you need to find the top line. One option is what drew you to the paper in the first place. But there will be others. Go over your interviews. What stood out as most fascinating, alarming, amusing, or important? Does it make for a stronger angle? Bear in mind that the story you should tell your readers might not be the story the authors want you to tell your readers.
8. Remember who you are writing for
The reader may be clever and curious about the world. But do not assume they are scientists, or that they have time to read boring, unimportant or incoherent stories. Make your story clear and informed. Science can be hard enough without the technical terms, so use simple words. Do not patronise the reader. Respect them and be honest. Make them glad they read you.
9. Be right
Don’t write a story that is wrong. This is harder than it sounds. Most scientific papers are wrong, thanks to poor study designs, author biases, small sample sizes and other problems. So don’t make things worse by introducing errors of your own. Check everything. Mistakes leave readers confused and misinformed. They will undermine your credibility too. Call a shrew a rodent and your soricid story is ruined.
10. Write well
Reporters often pick the same papers to cover. Why should anyone read you? You must have something to add. Make an effort to get the details that readers want to know. And learn how to write well. Find a clear path through the story and build one paragraph after another in logical order. Stick to one idea for each paragraph. Read Strunk and White until you can hear them tutting as your type. Even the shortest stories can be memorable in the hands of a good writer.
In a nutshell:
• Speak to the authors and get independent comment from scientists in the same field
• Get your facts straight
• Patronise your readers
• Mistake fruit flies, mice or Petri dishes for people
Find out more about the Science Writing Prize and how to enter by visiting the prize pages on the Wellcome Trust website. The competition is open from today and you’ve got until 11th May 2014 to submit your entry for the prize. The Wellcome Trust is committed to supporting the next generation of science journalists.
The Wellcome Trust Science Writing Prize 2014 is held in association with the Guardian and the Observer.
This week the winners of the Access to Understanding competition were announced at an event celebrating communication of scientific research. Competition entrants were challenged to take a cutting-edge research paper and explain it to a non-special audience, covering what the research entailed and why it matters. One of the papers selected for translation into ‘plain English’ was put forward by the Wellcome Trust, and we extend our congratulations to Aiden Maartens from the Gurdon Institute, University of Cambridge, for making the top three with his summary. Here’s his article…
Malaria claims a million lives a year, a majority of which are children, and threatens the lives of billions more within its tropical ranges. It is caused by Plasmodium falciparum, a parasite that uses mosquitoes as a way of getting in to and out of humans. Initial infection from the bite of a carrier mosquito is followed by the parasite’s massive proliferation and colonisation of the host’s blood, causing a suite of debilitating symptoms and providing a parasitized food source for the next mosquito. In the absence of a vaccine, prevention and treatment remain our only effective weapons against malaria. Today, the most effective treatment regime relies heavily on artemisinin, a compound from an Asian herb that effectively targets the parasite within red blood cells. But, as was the case for previous anti-malarial drugs, the spectre of artemisinin-resistant P. falciparum strains is rising. Worryingly, as there is currently no clear fall back to artemisinin, a global spread of resistance will seriously harm our ability to tackle the disease.
The research of Miotto, et al. was stimulated by the observation that resistance to artemisinin, and indeed some of its forebear drugs, appears to originate in the same part of the world: the remote mountains of western Cambodia. To tackle the question of why drug resistance originates here, the researchers sought clues within the parasite’s genome. They had previously developed a technique to isolate P. falciparum DNA directly from the blood of infected patients: a blood sample is taken, white blood cells removed (this removes a lot of the human DNA content which can complicate analysis), and DNA extracted and sequenced using modern sequencing technology. For this work they do not require the parasite genome sequenced in its entirety; rather, they seek sufficient coverage to allow reliable identification of variability between samples.
The researchers collected samples from infected patients in West Africa and Southeast Asia, including four sites in Cambodia, one in the east and three in the west. A global survey of the genetic data revealed that the Asian and African populations have distinct patterns of genetic variation, consistent with their geographical isolation. Within the Asian sample, the story was a little more complex. Samples from western Cambodia were notably distinct from those in eastern Cambodia and Thailand. The western Cambodian populations were also ‘structured’, that is, the population was split into subpopulations, each with their own distinct genetic signatures. The subpopulations were also relatively inbred, lacking in genetic diversity, which is often a signature of a recent expansion from a small, homogenous population. Crucially, the researchers were able to show that the subpopulations that predominate in western Cambodia showed artemisinin resistance, as infected patients responded poorly to treatment. Thus, while the distinct subpopulations of P. falciparum in western Cambodia are genetically distinct, they present the same problem: artemisinin resistance.
The beauty of these kinds of genomic studies is that as well as just looking at the variation between groups across the genome, on a global scale, we can zoom in and focus on the individually varying regions to ask whether these parts do anything relevant. The researchers made the important observation that the western Cambodian subpopulations harbour a number of genetic changes associated with drug resistance, including alterations to genes that control the entrance of molecules into the cell. One of the subpopulations even harboured mutations in genes involved in preventing mutations, raising the intriguing possibility that a general increase in mutability of the genome may provide more drug resistance mutations.
Identifying the source of emerging drug resistance, both in terms of geography and underlying genetic causation, is a critical task if we are to control its spread, hence the importance of this work for malaria control. The fact that there are multiple, independent artemisinin-resistant subpopulations shows that there are many routes for a parasite to become resistant. In practical terms the genetic signatures within the resistant strains can be used as biomarkers for artemisinin resistance in any sample of P. falciparum DNA, allowing health authorities to monitor its spread. Furthermore these genetic signatures will add to our biological understanding of how the parasites evolve to resist the drug.
We are still however left with our opening question: why Cambodia, specifically why western Cambodia? The authors propose a number of potential contributory factors, including the potential higher mutation rate, heavy use of drugs and local isolation of the populations (favouring inbreeding) due to the remoteness of the region. General features of host-parasite interactions are thus married with particularities of the region to provide a potent reservoir of drug resistance. Whatever the underlying causes, the next imminent step will be containment of these variants to prevent their global spread.
This article describes the research published in Nature Genetics in 2013 in a paper entitled: Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia. Meet the Trust-funded researchers on the front-lines, making a last stand against malaria drug resistance. Read ‘How malaria defeats our drugs’ by Ed Yong on Mosaic.
The Access to Understanding competition is run by Europe PubMed Central and the British Library. You can find out more about the competition and read the other entries on the Access to Understanding website.
Image credit: (blood sample) Sotiris Zafeiris, Wellcome Images
Four major UK research funders have released their joint response to a statement from the Expert Advisory Group on Data Access (EAGDA), on the issue of the re-identifiability of participants from genomic research studies. Natalie Banner, Policy Officer at the Wellcome Trust, explains why this issue is becomingly increasingly important.
When individuals participate in consented research studies, researchers are duty bound to protect their confidentiality as far as possible. Much genomic research relies on using large-scale aggregate datasets, which are anonymised, to establish which genes may be associated with different diseases. If any potentially identifiable data are made available for other researchers to access, there are strict legal restrictions in place stipulating how the data can and cannot be used. Such safeguards are designed to reduce the risk of participants being re-identified from research data, which would be a breach of confidentiality.
With advances in bioinformatics, an explosion in the volume of data, and an increasing push towards sharing data, there are growing possibilities for linking datasets in order to seek out and answer new research questions. To take just one example, linking data on the incidence of particular diseases, genomic markers, and socioeconomic indicators may reveal new insights into the complex relationship between aspects of health, genomics and environment.
However, linking data sets raises a challenging ethical and practical issue for participant confidentiality: the risk of jigsaw re-identification. With only one or two pieces of information, very little can be tied to particular individual and the possibility of actually identifying a person within the mass of aggregated data is remote. But when data from multiple sources is available, it may, in certain circumstances, allow a more complete picture of an individual to be pieced together. This could result in some confidential information being linked to an identifiable person. A paper on genomics published in Science last year demonstrated how it could be technically possible to link data in this way. The authors developed a complex methodology that involved linking open access genetic sequence data, information from publicly available genealogy databases that link surnames with specific genetic markers on the Y-chromosome, and public demographic records. The team successfully triangulated the identities and genomes of up to 50 participants from a research study, the 1000 Genomes Project. Importantly, while the participants themselves had given consent for their data to be openly and freely used, linking a genome to an individual has implications for their biological relatives as well, and future generations with whom they will share genetic characteristics.
Although the method used by the authors succeeded only in a highly specific set of circumstances, the paper alerted funders, researchers and institutions to the technical possibility that anonymised genomic data could, in principle, be subject to re-identification through linkage with other data sources. It’s important to realise that for the purposes of biomedical research, linking any research data to a name is neither necessary nor desirable: researchers want to know how different genes, diseases, environmental factors and so on relate to one another, not who has what condition. To continue the jigsaw analogy, they are much more interested in finding many pieces of the same shape or size from lots of different individuals than they are in putting together a complete picture of a single person. But if the risk of building such a picture is there, we need to mitigate it as strongly as possible.
In light of this, EAGDA conducted research last year into the issue of identifiability in UK research studies involving or linking to genomic data, seeking to establish whether there was a risk of participants being re-identified and steps that funders and study leaders could take to mitigate this risk. This culminated in a series of recommendations to EAGDA’s funders, the MRC, ESRC, CRUK and the Wellcome Trust. These recommendations centre around issues of consent, risk assessment, controlling access to data and enforcing sanctions against anyone found to have deliberately attempted to re-identify individuals from research data.
It would be naïve to presume that data can ever be 100% secure: there are going to be risks, but we believe that with good governance and management, and constant vigilance for the kinds of issues EAGDA has alerted us to, these can be managed. Given the recent public concerns over access to and the use of primary care records through the Government’s care.data scheme, it has never been more important for biomedical and health researchers to be transparent in how and why they use data, upfront to participants and their families about the risks involved and robust in the governance systems they use to control access to research data.
At the Wellcome Trust we’re continuing to work with EAGDA and the other funders to mitigate the risks of re-identification from the data our researchers generate and analyse. Our work cannot proceed without the generous participation in research from individuals all over the UK and beyond: it is our duty to push the boundaries of medical research whilst protecting and respecting their confidentiality as far as we can.
You can read the statement and response on the EAGDA section of the Wellcome Trust website.
Image credits: (Top) Peter Artymiuk, Wellcome Images, (Lower right)Adrian Cousins, Wellcome Images