This article was first published in the Spring edition of Network.

Soldiers in the trenches, 1916

The complex and destructive nature of war has been a catalyst for some of the MRC’s greatest medical discoveries over the past century. Sarah Harrop reports.

The great war: infections and ingenuity

When the First World War broke out in 1914, the MRC was barely a year old, but it reacted quickly to focus research on the national war effort. Gangrene, caused by bacteria which thrive in oxygen-free conditions such as soil, was a particular problem for men fighting in the muddy trenches of France and Belgium during WW1. This horrifying condition causes living tissue to decay and die and was responsible for many limb amputations and deaths in soldiers whose wounds had become infected. But by the eve of Armistice Day in 1918, MRC researchers had managed to develop the first serum for the prevention and cure of wound gangrene, which contained anti-toxins against all three bacteria involved.

Desperate times also fuelled ingenuity. Ships bringing home the wounded had poor sanitary conditions, but antiseptics were in short supply. With MRC funding, British chemist Dr Henry Drysdale Dakin managed to work out a cheap way to produce large quantities of an antiseptic from sea water. ‘Dakin’s Solution’ reduced secondary infections in repatriated soldiers to almost zero.

Development of penicillin

Penicillin – the first broad-spectrum antibiotic – was discovered by chance by Alexander Fleming in 1928 when Penicillum mould contaminated his culture dishes and killed the bacteria growing there. But it wasn’t until 1940 that MRC-funded scientists Lord Howard Florey and Sir Ernst Chain managed to work out a way to scale up production of the compound to make it a viable antibiotic drug.

Realising the urgent need for penicillin to treat infections in wounded soldiers during the Second World War (WW2), the pair turned their department at Oxford university into a penicillin factory and carried out clinical trials at the city’s Radcliffe infirmary. The results helped persuade drug manufacturers in the uS to mass-produce the drug. By the time of the Normandy landings in 1944, penicillin was readily available to all servicemen who needed it.

From penicillin to ‘iraqibacter’

Today, multi-drug resistant bacteria are one of the greatest challenges faced by the medical community. At the university of Birmingham, Professor Mark Pallen has been carrying out MRC-funded research on a type of multi-drug resistant Acinetobacter bacterial infection, which is usually found in hospitals. Military patients returning from the Middle East are particularly susceptible to the bacterium, so much so that it used to be nicknamed ‘iraqibacter.’

“Patients who are critically ill are given lots of antibiotics, which decimates their natural balance of bacteria in the body. Acinetobacter gets into wounds and takes up a vacant niche,” Mark explains.

In 2008, Mark and colleagues published a study which proved that a particularly virulent outbreak had jumped from a military patient returning from Afghanistan to a civilian patient in an adjacent bed.

The MRC has funded him to carry out more detailed work on whole genome sequencing of Acinetobacter samples to look for tiny genetic variations – known as single nucleotide polymorphisms – that distinguish different bacterial isolates, and then use this information to piece together how the infection was transmitted from person to person, providing new insights into how multi-drug resistant infections can spread in hospitals.

Professor Janet Lord with Major Mark Foster at the Royal Centre for Defence Medicine in Birmingham (Copyright: John James)

Insights into trauma

The use of explosive shells for the first time on the frontline meant that surgeons began to see cases of traumatic shock – the body’s reaction to severe injury involving loss of blood. MRC researchers discovered that shattered tissues produce substances which hamper blood circulation, so they devised a blood substitute, gum acacia (derived from acacia tree sap) to restore lost blood volume. Blood for transfusion was difficult to preserve and transport, so this invention helped save many lives.

Nearly a century later, Professor Janet Lord, a principal investigator at the MRC Centre for immune Regulation in Birmingham, is also working to save the lives of those injured in conflicts. She’s studying the inflammatory response in severely injured soldiers sent home from Afghanistan, and using the findings to advance treatment of burns and trauma in the civilian population.

“When you’re exposed to acute trauma – for example burns, blasts or multiple amputations – there’s an immediate inflammation response, but also an anti-inflammation response,” she explains. “Inflammation is useful because it protects against infections and stimulates woundhealing. But if it doesn’t get turned off at the right time by the anti-inflammatory response, you can’t heal properly. We’re trying to understand what controls that yin and yang balance, and what dictates whether or not a patient makes a good recovery.”

She adds: “How well you recover from a burn is age-related; the older you are the less likely you are to recover. We think that’s to do with immune system changes that occur with age, in particular having fewer cells which promote inflammation and reduced functioning of cells that fight infections such as neutrophils and natural killer (NK) cells.

So we’re taking measurements from young patients flown in from Afghanistan and comparing them with elderly burns and trauma patients. It may be that if we can restore the pro- and antiinflammatory balance and improve function of these cells we can improve patient outcomes.”

Health and rationing

Maintaining the health both of soldiers and those supporting them with the war effort was of critical importance during WW2, and the MRC was called upon to make recommendations to the War Cabinet about nutrition that directly influenced the uK’s food policy.

In 1937, MRC scientists Dr Elsie Widdowson and Dr Robert McCance bravely experimented on themselves to test out the efficacy of proposed ration diets in the event of another world war. Over three months, they pushed their bodies to the limit, for example by climbing fells in the Lake District, to test the physical impact on their health of limited food supplies. Both were fit and well at the end of the experiment and the results were secretly passed to the War Cabinet, which was reassured that rationing in the general population would be safe.

The pair went on to make many lasting contributions to nutrition research; their book on the constituents of commonly eaten foods is now in its sixth edition and is still used by researchers today.

Futuristic findings: tissue regeneration and artificial vision

War continues to shape and inform medical research, particularly in the fields of surgery and regenerative medicine. Wing Commander Rob Scott, an ophthalmic surgeon at the Royal Centre for Defence Medicine in Birmingham, specialises in traumatic eye injuries sustained in war and has treated around 200 serious eye injuries over the past decade. Alongside US collaborators, he has developed the Brainport, an artificial vision device for people who have lost their sight. The device consists of a camera attached to a pair of spectacles which takes a pixellated picture of the outside world and translates the pixels into a tingling sensation via a ‘lollypop’ which sits on the user’s tongue. it allows a blind person to build up a picture of the world around them, and is so effective that users can distinguish between knives and forks on a table and even men’s and women’s toilet signs.

For those whose sight could still be saved by surgery, it is critical to intervene before the process of scarring begins, explains Rob: “Scarring is an absolute disaster for eye surgery because it changes the shape of the tissue. But if you can get something to regenerate instead, you don’t get scarring.”

Working with molecular neuroscientist Professor Ann Logan from the University of Birmingham, Rob and his research team are carrying out research on a substance derived from  amniotic  membranes  expelled by women during childbirth which has anti-inflammatory and antiscarring properties. They’re using the substance to encourage damaged optic nerve and retina tissue to regenerate into new tissue rather than forming scar tissue.

“I now supervise an MRC-funded PhD student who has found some of the main pathways that will allow the regeneration of damaged optic nerves. We’ve discovered a very simple way of ‘tricking’ cells into re-growing by reprogramming how their DNA is expressed to make it promote certain pathways. So actually by stimulating the regeneration of the nerves it prevents scarring. If we can get it to work in people, that would be a holy grail – we could make blind people see again.”

War is, unfortunately, always likely be a part of human existence, but medicine will continue to learn lessons from it to benefit health, as it has throughout the bloody conflicts of the last 100 years.

Sarah Harrop

Professor Lord, Professor Pallen and Wing Commander Scott are all part of the NIHR Surgical Reconstruction and Microbiology Research Centre in Birmingham.

This article was first published in the Spring edition of Network.

Andrew with his wife Madeleine and son Lucas (left), and the whole research team

Why did you enter the Max Perutz Science Writing Award?

A fellow PhD student at the university sent me the link and suggested I should apply. It made sense to write an article explaining the project in non-scientific terms as I was always being asked by friends and family what it was that I was doing. This was the perfect opportunity to distill my thoughts into a form that could be understood by everyone and that I could direct people to if they were interested. I never expected to end up winning the competition.

How did taking part in the competition and winning the award change your thoughts about science communication?

Having to sit down and write something without jargon made me look at my work in a different light. Trying to see something you are deeply involved in from a more distant and very different perspective can be quite challenging, but very refreshing. The question set to us was, “Why does your research matter?” Getting to the heart of that question meant engaging with the emotion that drives the work in the first place.

The whole process has made me appreciate good writers and their ability to present complex information in an engaging way. It has also encouraged me to write about the everyday scientific work I’m doing in Kenya in a manner that can be understood by friends and family.

Have you done any more science writing since you won and/or are you planning on writing in the future?

I really enjoyed the experience and would certainly like to do more. I’ve been writing scientific papers and a book chapter, but I’ve also been writing a blog with my wife that combines eye care and baking.

What would you say to encourage other MRC-funded researchers to take part?

The competition aside, going through the process of writing an article to explain your own work allows those closest to you to really understand what it is you do all day, as well as helping you think about why you’re doing it. It’s easy to forget about that in the hustle and bustle of daily life. Having been shortlisted we were invited to a science writing masterclass which was really valuable. And the publicity that follows should you win can be helpful in securing future funding and raising the profile of the work you are doing.

Do you have any tips for those planning on entering this year’s competition?

Try to engage the reader on a personal level. Try to tell a story rather than present facts. Link your opening paragraph to your concluding remarks. Avoid any jargon, unnecessarily long words or any terminology that may make the reader feel uncomfortable.

Get a couple of friends and your mum to read it, if they ask “What does that bit mean?” change it until no further explanation is needed. And enjoy it!

How has your research progressed since you won the award?

Since the award I’ve moved to Kenya to set up a project where we compare the smartphone apps I’m developing with normal equipment. Thanks to the publicity that came from my article being printed in Metro we’ve been able to generate more media interest including future BBC coverage. All this has been really for helping to share information about the research and how it’s developing. Ultimately it helps communicate a bigger message: that we can reduce unnecessary blindness.

Andrew will be one of the judges for this year’s Max Perutz Science Writing Award. He blogs, along with his wife, at Eye Bake – Kenya 

Photo 51 (Image credit: King’s College London)

Sixty years ago today a paper describing the structure of DNA was published in Nature. Photo 51 was important to Watson and Crick’s discovery, and is surely the most famous x-ray crystallography image in the world. But what do its shadows and cruciform spots actually mean? Katherine Nightingale met King’s College London Professor of Molecular Biophysics Brian Sutton for an explanation of both the image and its history.

When and where was Photo 51 taken?

It was taken in May 1952 by Rosalind Franklin and her PhD student Raymond Gosling at the MRC Biophysics Unit. Franklin, a biophysicist, had been recruited to the unit to work on the structure of DNA. The unit was then part of the King’s College campus on the Strand in London and was run by Sir John Randall, who had turned some of the university’s physics department over to studying biological problems. More literally, it was taken three floors down in the basement underneath the chemistry laboratories, below the level of the Thames.

The MRC Biophysics Unit moved to Drury Lane in the 1960s and later became the Randall Institute. I now work in its most recent incarnation — the Randall Division of Cell and Molecular Biophysics. So photo 51 is doubly significant for me: I’m an x-ray crystallographer so it’s part of my heritage in that respect, but all of us in the division are proud of this link with the work in the 1950s.

What is x-ray crystallography?

It’s a long-established method of determining the structure of molecules by bombarding them with x-rays — in fact it’s exactly 100 years since the first structures were determined by William Henry Bragg and his son William Lawrence Bragg. The molecules are in a crystal or otherwise ordered form, so when the x-rays bounce off the electrons in the molecule’s atoms, they scatter in a particular unique pattern ― just like photo 51 ― and you can use that pattern to infer the structure. These days we take thousands of images from different angles and digitally build up a 3D image of the structure.

How would it have been done in the 1950s?

The technique wouldn’t actually have differed too much, although it would have been a much more painstaking and time-consuming process. Franklin and Gosling used a very pure form of DNA and they became expert in pulling it into strands for analysis. Within each strand would have been a vast number of DNA helices lined up next to each other — you can’t image just one helix in its usual form because it’s too small. The DNA strand was fixed to a support and sealed in a camera, in front of a piece of x-ray film, and then exposed to x-rays for days at a time — you had to hope the sample didn’t move! Rather dangerously, hydrogen was bubbled through water and into the camera to stop the x-rays from bouncing off molecules in the air. The film was then developed and the patterns emerged before the researchers’ eyes. Raymond Gosling often speaks of the great excitement of developing the films in the King’s basement.

Brian Sutton in his office at King’s College London

So what are we actually looking at when we look at photo 51?

Photo 51 is an image of the more hydrated ‘B’ form of DNA. Franklin and Gosling had been experimenting with whether the humidity at which they kept the samples would affect the images. They had taken a series of images — photo 51 was taken at the highest humidity, around 92 per cent.

The darker patches indicate where the film has been repeatedly bombarded by diffracted x-rays from regular, repeating features within the molecule. The dark patches at the top and bottom of the picture, for example, represent DNA’s ‘bases’, the four parts of DNA which make up the genetic code — the patches are dark because there are so many bases all arranged in a regular fashion. You can work out the distance between bases in the structure by measuring the distance between the dark patches on the film and making a calculation based on how far the DNA sample was from the x-ray film and how it was orientated in the x-ray beam. In this case it’s 3.4 Ångstroms, a unit of measurement equivalent to 0.1 nanometre.

What about the cross shape of spots?

For people like Watson and Crick, who were already building models, this cross really spells out helix. Maurice Wilkins, who had worked on DNA separately from Franklin, showed this photo to Jim Watson when he came to visit and it really excited him — he raced back to Cambridge to the Cavendish Laboratory to tell Francis Crick about it. A lot has been said and written about that moment and some people think that Wilkins shouldn’t have shared the photo, but he had it legitimately as part of Rosalind’s papers (she was soon to leave for Birkbeck College) and he was keen that research on the structure progressed, particularly because he wanted the UK to beat Linus Pauling in the US to discovering the structure.

The reason that the cross indicates a helix is that the arms of the cross represent the planes of symmetry in a helix viewed from the side: the ‘zig’ and the ‘zag’, so to speak, of the turns of the helix. It’s difficult to see clearly, but there are ten blobs on each arm of the cross before you reach the large black patch at the top, and this tells you that there are ten bases stacked one on top of the other in each turn of the helix. In fact, one of the blobs is missing, the fourth if you count out from the centre of the pattern, and this indicates that one strand of DNA is slightly offset against the other.

If Franklin had all this information, why didn’t she suggest the structure?

Well, it’s difficult to say but one reason is probably that Rosalind had chosen to focus her attention on her x-ray photos of a less hydrated ‘A’ form of DNA, which appeared to show much more information and from which she hoped to calculate the structure directly, rather than build models. In fact, these photos of the ‘A’ form had revealed a key piece of information, namely that the two strands of DNA ran in opposite directions, although neither Rosalind nor the others had appreciated this, until Francis Crick realised its significance just before building the final model.

She didn’t turn her attention to photo 51 until early in 1953. You can see from her notebooks that once she did concentrate on it, she gleaned all the key information about the structure from it — I fully believe that given more time she would have cracked the structure. She was so close. Watson was surprised that she accepted the correctness of their model immediately upon seeing it — it must have been because she could see that it fitted so well with all of her evidence.

The 1953 model made at King’s, along with Maurice Wilkins and the workshop where the parts were machined (Image credits: King’s College London)

What happened after the structure was published?

Franklin was already working at Birkbeck College by the time the Nature paper came out. Of course Watson and Crick’s model was just that — only a model — so it needed to be verified. Wilkins built the first accurate model of DNA in the summer of 1953 and checked it against diffraction data such as photo 51. Of course the structure was right — it was too beautiful not to be.

Katherine Nightingale

Listen to the audio clip below to hear Brian Sutton talk about the second most famous model of DNA built in 1953.

For those of you who’d like a simple explanation of x-ray crystallography, we like this article in Metro.

Thank you to Craig Nicol at the MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh for taking the photographs.

Never underestimate your audience. Especially not when they are seven years old, dressed in a lab coat, with a pen poised over a clip board and ready to make a virus, remodel a city and extract some slimy-looking DNA from even slimier pea-juice.

The MRC’s Mini Scientists activity at the Edinburgh International Science Festival is usually booked out and feedback tells us that the kids, their parents and our dedicated volunteers all love taking part. But, after having run the activity for three years, I felt I wasn’t telling the audience the whole story.

A lot of medical research relies on flies, fish, frogs and mice. Most research institutes I know are linked to an animal house, but these research participants were invisible to our Mini Scientists. So this year I brought some in. With the help of the fish team at the MRC Human Genetics Unit (MRC HGU), Mini Scientists were joined by two tanks of zebrafish, a tiny tropical fish the MRC HGU uses in skin cancer research.

All the fish were ‘wildtype’, meaning they’re like the zebrafish found in the wild, rather than those genetically modified for research. The first shoal had spots and naturally ragged fins, while the second flicked and flashed their neat blue stripes. The MRC team used this spots-or-stripes difference between the shoals to start conversations about DNA, genetic variation, and how and why the fish are used in medical research. The kids looked at the fish during the three-minute break in the DNA extraction activity; never confuse pea juice with pee juice or at least one Mini Scientist will get the giggles.

The zebrafish in one tank were spotty, while in the other they were striped

We told the kids that zebrafish are used as models for humans, even though we don’t look much like each other. It only took a few moments of gazing into the tanks for the kids to start listing similarities between the fish and themselves, often accompanied by rolling ‘fish’ eyes and pouting ‘fish’ mouths. Then the questions started trickling out.

Can the fish see us through the glass? Are spotty fish more likely get to skin cancer because they already have round spots? Can I feed them? Do fish have ears? What can you actually learn from a fish that has anything to do with people? How do the fish get cancer? Have you ever seen a piranha?

The team used the kids’ questions as starting points to get to the message that by studying the fish, scientists can look for ways to treat skin cancer and other diseases in people. The Mini Scientists then turned back to their DNA extraction activity.

Ten days in and despite daily checks, the water in the tanks became worryingly cloudy. Then an expert popped in and told me why. The fish darting and twisting above the plants were displaying classic mating behaviour and the water was cloudy as a result. A quick change of water calmed things down a little.

The fish so excelled in breeding that they are now on their way to a primary school where pupils will find out the answer to the most frequently asked question: “If a stripy fish and a spotty fish have babies, are they spotty or stripy?” I’m not sure, so I’ll leave it to the Mini Scientists to find out.

Hazel Lambert

If you’d like to read more about Mini Scientists, visit this storify of pictures and tweets from the team.

A diffusion MRI scan of Charlotte’s own brain, showing three cross-sections. The colour-coding indicates the direction of the brain connections: blue connections travel between the top and bottom of the brain; green connections travel between the back and front; and red connections travel side-to-side.

The brain is one big network of chattering neurons, so what happens when, as in Parkinson’s disease, a part of that network breaks down? Charlotte Rae, a graduate student at the MRC Cognition and Brain Sciences Unit in Cambridge marks Parkinson’s Awareness Week by explaining her research, which looks at how brain connections fail in this debilitating disease.

When Helen wakes up each morning, she takes four different pills, and will take them again every three hours until she goes to bed. If she forgets, she finds it difficult to walk, notices her left arm shaking uncontrollably, and can’t speak properly. Helen has Parkinson’s disease, and to stave off these symptoms she will need to take her cocktail of medicines every three hours, every day, for the rest of her life.

Parkinson’s affects one in every 500 people, and is currently incurable. Unfortunately, while the physical symptoms are strikingly obvious, the causes of the disease are less clear.

We do know that in Parkinson’s patients brain cells, or neurons, that use a chemical called dopamine start to die. In healthy people a region deep within the brain, called the basal ganglia, uses dopamine to make and control movements. In people with Parkinson’s, the dopamine-using neurons in the basal ganglia are gradually lost as the disease progresses. This can happen in people as young as 40, although it is more common in those aged over 60. As the loss of these neurons continues, the symptoms get steadily worse. Patients find it increasingly difficult to perform even basic tasks like making a cup of tea or buttoning up a shirt.

Because the human brain is one big network of neurons, loss of dopamine cells in just one area can affect how the rest of the brain works. This means that in Parkinson’s disease, cells dying in the basal ganglia can have far-reaching consequences for how the whole brain functions and result in a spectrum of debilitating symptoms. As well as the movement difficulties, patients can also experience sleep problems, depression, and trouble with behavioural control.

I have been looking at how Parkinson’s disease affects these far-reaching connections between brain cells. To do this I use a technique called diffusion MRI scanning to produce maps of brain connections in living people, without the need to cut up and examine their brain tissue under a microscope. Diffusion MRI scans are collected on a doughnut-shaped brain scanner, with the patient’s head placed in the centre. The diffusion scans work by measuring the movement of water molecules in patients’ neurons, which gives us an indicator of how strong the brain connections are.

Handily for the patient volunteers, these non-invasive scans take only 10 minutes, meaning that we can gain new insights into the disease without them having to undergo lengthy or uncomfortable tests. And unlike MRI scans which measure brain activity, patients don’t need to perform a task while being scanned — they can have a nap instead.

Our results so far have shown that the brain connections in the frontal lobe, the part of the brain responsible for deciding on an action and planning it, are being degraded in Parkinson’s. When neurons in the basal ganglia die, the connections between the basal ganglia and frontal lobe are lost. This means that decisions about movements, processed in the frontal lobe, can’t get to the basal ganglia — which is crucial for making and controlling those movements.

The next step is to use the diffusion MRI technique to look at how the brain connections change over time as the disease progresses. If patients come back for repeat brain scans, then we can compare these over the years with their symptoms and build up an even clearer picture of how the brain is affected by this devastating disease.

One thing we do know is that when searching for treatments for Parkinson’s disease, researchers will need to focus not just on preventing neurons from dying, but also on the damage that occurs to the connections between them. The brain only works in harmony as a sum of its parts, so as researchers, we need to continue investigating how to get the whole brain network back in balance.

Charlotte Rae

Pictures by Haberdashery (http://www.haberdasherylondon.com/)

How can an exhibition encapsulate a century of modern medicine in a way that brings to life the sights, sounds and smells of science for both adults and children? This is the ambitious aim of the Strictly Science exhibition; which not only looks back at 100 years of discoveries as part of the MRC’s Centenary programme, but also aims to use this as a springboard to get people excited about science, and the possibilities of scientific discovery in the next 100 years.

The journey starts in 1913, the year in which the MRC was founded, with a salute to David Lloyd George, the Prime Minister whose 1911 National Insurance Act set the wheels in motion for the establishment of the organisation, primarily to curb the devastating effects of tuberculosis on the population. You can see posters showing how this was lauded as the ‘Dawn of Hope’ — the first time public money had been used for medical research.

Strictly Science’s ‘Yesterday lab’ encourages children to dip their hands into bowls of marmite and cod liver oil and recreate the recipes that researcher Harriette Chick developed to bolster vitamin D in the diet and help to cure the bone disease rickets.

Instruments such as Henry Dale’s clockwork kymograph, a simple black device he developed to measure the activity of muscles, looks deceptively primitive, bringing home that these researchers were making discoveries that changed the world without any of the technology that contemporary researchers rely on — and not an iPad in sight.

The simple idea of ‘how does our brain help us move’ provides the backbone for many of the experiments that form the ‘Today lab’, which is based on contemporary work at the MRC Clinical Sciences Centre. The Wii Balance Boards and motion capture suits are unnerving in their ability to analyse and mimic the effects of ageing on our bodies. Meanwhile, the BLINK game allows players to play the classic arcade game PONG solely with their eyes, a thrilling concept that offers exciting possibilities for people who don’t have the use of their limbs to interact with computers.

But where is all this going? The ‘Future lab’ provides a series of perspectives from researchers, commentators and children on their hopes and fears for science between now and 2113. Both the adults and children agree that science is unpredictable, though the kids are slightly more outlandish — can we ever rule out the possibility of a ‘giant radioactive killer baby’ or, perhaps more hearteningly, ‘a heart-healing ice lolly’?

Cathy Beveridge

The Strictly Science exhibition runs until 14 April 2013, 10.00 – 18.00, in the Exhibition Road foyer of Imperial College London, South Kensington.

(Image copyright: MRC Cognition and Brain Sciences Unit)

It’s pretty safe to say that these five sailors, shirtless as they are and with some sporting makeshift sweatbands, are being ‘cooked’ in the hot room of the MRC Applied Psychology Unit (MRC APU) in Cambridge, which became the MRC Cognition and Brain Sciences Unit in 1998.

This photo was published in a 1974 research paper, but the MRC APU first began using naval ratings as experimental subjects in 1961, testing them for two hours a day on a range of tasks and paying them an hourly honorarium for their troubles.

The work was carried out on behalf of the Royal Navy Personnel Research Committee, which was interested in how the sailors made decisions when under stresses such as extreme heat, noise, boredom and sleep loss, or strange atmospheric pressures.

“Once a fortnight you got a new group of six sailors and you could test them every day for two weeks, so basically you were given ten sessions, or nine if you were worried about the sort of demob-happy effect on the final Friday,” Professor Peter McLeod, who worked at the MRC APU from 1969 to 1983, told a Witness Seminar on the MRC APU in 2002.

A unit of naval ratings was stationed permanently in Cambridge to participate in experiments until it was closed in 1974. The closure was probably in part because research at the unit was shifting from testing the effects of extreme environments and situations to studying more everyday behaviours, such as language.

Housewives became a larger part of the group of subjects used in experiments, albeit it through a gradual transition. Dr Ivan Brown, who worked at the unit for 40 years, told the Witness Seminar: “I remember early on that there was a time when we tested both naval ratings and Cambridge housewives. I knew someone who lived across the road from the building we were in and he would leave in the morning as naval ratings came to get tested and, when he came home for lunch, they were apparently walking out as Cambridge housewives, and he wondered what on earth our research was doing to them!”

Katherine Nightingale

The MRC couldn’t do much of its work without the valued involvement of the public in research. To find out more, visit our public involvement webpages.

Iain Chalmers (Copyright: Ian Milne)

All trials registered, all results reported, a new campaign which the MRC is supporting alongside other research organisations, calls for the results of all clinical trials to be made public. Sir Iain Chalmers, Coordinator of the James Lind Initiative, says that longstanding biased under-reporting of clinical research must stop.

Successful conduct of clinical trials depends on many factors, but these studies are impossible unless patients agree to participate in them. For many patients the principal motivation for participating in clinical trials is the hope that they may receive better care, and perhaps more effective treatment. All participants in clinical trials, however, believe that their involvement will help to increase knowledge about the effects of treatments. They expect that people with health problems like theirs – and perhaps they themselves – will be able to make better informed treatment decisions in future as a result of their contributions to knowledge.

How come, then, that the research community, including research funders and regulators, have acquiesced for decades in the nonpublication of around 50 per cent of all clinical trials? Can this be characterised as anything other than a gross betrayal of the trust in researchers which motivated volunteers to participate in clinical trials in the first place? How many of them would have agreed to participate if researchers had told them “If the results of this trial don’t serve our academic or commercial interests we won’t make them public”?

After doing research on biased under-reporting of research 20 years ago, I raised these issues in an article published in the Journal of the American Medical Association entitled ‘Underreporting research is scientific misconduct’. The evidence that has accumulated over the subsequent two decades has made clear that the problem is widespread. It’s not only unethical and scientific misconduct; it is also simply a waste of precious research resources. As illustrated by numerous examples, under-reporting of research has led to harm to patients from exaggerated estimates of treatment benefits and safety, and built-in inefficiency in efforts to discover useful and safer treatments.

Until recently, the academics who have exposed biased underreporting of research have had little or no effect in persuading people with the power to do something about this scandal to put an end to it. It is true that — a decade or two after they had called for trials to be registered publicly at inception and a major drug company had beenfined for suppressing information about dangerous effects of one of its drugs — registration of trials slowly gathered momentum. Indeed, within the UK, it was the MRC that led the way in trial registration in the 1990s. However, the main consequence of trial registration has been to expose the massive extent of non-publication of clinical trials.

Yet only one medical professional organisation — the Faculty of Pharmaceutical Medicine — has so far declared non-publication to be unethical; the position of others remains unstated or ambiguous.

So what has happened to change the terms of the debate after a quarter of a century during which researchers, research funders, research regulators and politicians have failed to address the problem seriously? Two things. First, Dr Ben Goldacre, the award-winning medical journalist, published Bad Pharma — a book making clear to the public, using a mountain of evidence, why they should be concerned about the situation. In brief, his message is: ‘How can you or your doctor make an informed choice about which treatment to choose if half the relevant evidence has not been made public?’

Second, Sense about Science, an organisation campaigning to promote science to the public, has decided that non-publication of clinical trials is a stain on the public image of science, and that, after years of havering and disingenuous excuses for inaction, it must be confronted and dealt with. Following on its influential campaign to reform the English libel laws that were being used to silence scientists, Sense about Science’s new campaign — All trials registered, all trials reported — aims to achieve just what its title calls for. Sense about Science has invited those who agree with these principles to join the tens of thousands that have already signed the petition

To its great credit, the MRC was the first organisation to do so, with these words: “The MRC is pleased to sign up to this campaign and has, for many years, strongly supported the position that clinical trial results must be published in a timely manner. At the end of 2012, we made both the requirement to publish, and the need for MRC-funded researchers to share data, even more explicit: “Results of MRC-funded clinical studies (whether positive or negative) must be published within a reasonable period (generally within a year of completion) following the conclusion of the study.”

As the MRC admits, it would be surprising if, in its one hundred year history, there were no unreported or unpublished skeletons in its cupboards. While monitoring future adherence to its policy, therefore, the MRC should audit the trials it has funded. An audit of the publication record of studies funded by the Health Technology Assessment Programme has shown that 98 per cent of them have been reported. A similar finding from an audit of trials funded by the MRC would be very reassuring.

If action is not taken urgently by research funders and regulators, information on what was done and what was found in trials could be lost forever, leading to bad treatment decisions, unnecessary repetition of trials, and missed opportunities for good medical practice.

To find out more and sign the petition, visit the All Trials Registered, All Results Reported campaign web page.

This article was originally published in the Spring 2013 issue of Network.