Capturing the Craftsman

Almost 70 years since World War II, a Master's student from the Department of Defence Studies has previewed her film which depicts a soldier heading into battle with the enemy, in an act that, ‘undoubtedly saved considerable casualties and damage', according to his commendation for the Military Medal.

Lt Col Anna-Lee Johnston, who is studying on the Defence Studies MA programme at the Joint Services Command and Staff College in Shrivenham, hosted a preview of the film Above and Beyond: The Craftsman at King’s with her partners from Ivory London. Among the invited audience was guest of honour, the subject of the film, Sergeant Wally Harris MM.

Sergeant Harris MM served with the Royal Electrical and Mechanical Engineers (REME) during World War II and is the only REME veteran to be given a gallantry award for direct enemy action. As an engineer Sergeant Harris was a non combat soldier who should never have gone into battle. With his unit of craftsmen, Sergeant Harris‘ task was to maintain self-propelled guns as 231 Brigade pushed through France and ultimately liberated Europe from the grip of Nazi Germany.

On 3 September 1944, with his unit stuck behind a column of vehicles that was backed up through the town of Mons-en-Pevelle, Sergeant Harris decided to go on ahead, through the village, to find an alternative route. As he made his way through the streets, he turned a corner and came face to face with a German 88mm artillery gun unmounting.

He had only a moment to make a decision that would affect his and the lives of many of his comrades.

Sergeant Harris takes on the enemy with a .30cal Browning machine gun, cannibalised on D-Day from a drowned Sherman, with his friend and colleague Cpl. Swann. It is a defining moment in both their lives.

Now, Sergeant Wally Harris’ story has been preserved in Above and Beyond: The Craftsman, by Anna-Lee and her collaborators, Rowland Kimber (Executive Producer), Richard Canavan (Executive Producer and Composer) and Peter King (Director) who have written Wally’s story directly from his first hand account.

Anna-Lee said: ‘Wally’s story is so special. We are so pleased to be able to tell it and preserve it. We must capture others like it while we still have the chance to be with people who actually experienced the Second World War. If we don’t record these remarkable accounts now, they will be lost to history forever.’

Wally, who is now 90, offered his military expertise to the production team and was on location, on Salisbury Plain, during filming to advise on the events that unfolded nearly 70 years ago.

Wally said at the preview: ‘History tells us about the Battle of Britain and what those brave lads did out there – ‘the few’ as Churchill called them. But what they did, defeating the Germans, made them realise that we were much stronger than they thought.’

Former Head of the Department of Defence Studies, Professor Matt Uttley, said before the screening: ‘This is such an important piece of oral history that must be preserved, so we can reflect on the past and inform the future.’

For further media information contact Anna Mitchell on 0207 848 3092 or at anna.i.mitchell@kcl.ac.uk.

For more information about King's see our 'King's in Brief' page.

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Leukaemia stem cell discovery

Blood cells

Researchers at King’s College London have discovered that leukaemic stem cells can be reversed to a pre-leukaemic stage by suppressing a protein called beta-catenin found in the blood.

They also found that advanced leukaemic stem cells that had become resistant to treatment could be ‘re-sensitised’ to treatment by suppressing the same protein.

Professor Eric So, who led the study at the Department of Haematology at King’s College London, says the findings, published today in the journal Cancer Cell, represent a ‘critical step forward’ in the search for more effective treatments for aggressive forms of leukaemia.

The role that beta-catenin plays in the development and drug-resistance of stem cells in acute leukaemia was previously unknown. This study, funded by the Association for International Cancer Research (AICR), Cancer Research UK and the Kay Kendall Leukaemia Fund, reveals its significance and highlights it as a potential therapeutic target that could allow selective eradication of leukaemic stem cells.

King’s scientists looked at leukaemic stem cells found in types of leukaemia that involve mutations of the MLL gene. This accounts for around 70 per cent of infant leukaemias and 10 per cent of adult acute leukaemias. The prognosis for this type of leukaemia in children is not good – only 50 per cent survive past two years after receiving standard anti-leukaemia treatment.

To understand how the disease develops, the King’s team carried out a series of experiments to look at how pre-leukaemic stem cells (which do not always develop into leukaemia) are different to leukaemic stem cells, which sustain the disease and are likely to be responsible for relapse. They carried out studies in mice, in cultured human cells derived from cord blood, and on human leukaemic cells obtained from two leukaemia patients.

The studies in mice showed that pre-leukaemic cells developed into leukaemic stem cells and induced leukaemia, in part by activation of beta-catenin. But suppression of beta-catenin in leukaemic stem cells reduced leukaemic cell growth, delayed the onset of leukaemia and reversed the stem cells to a pre-leukaemic stage. Furthermore, when beta-catenin was completely inactivated in mice with pre-leukaemic cells, the mice did not develop leukaemia, even though they carried MLL gene mutations.

Researchers then wanted to see how suppression of the beta-catenin protein impaired human leukaemic cells. They found that suppression of the protein in MLL leukaemic cells again diminished their ability to proliferate and renew themselves (an essential part of how leukaemia develops). This confirmed the important role of beta-catenin in the human disease.

The study also revealed a previously unrecognized critical function of beta-catenin in mediating drug resistant properties of leukaemic stem cells. Leukaemic stem cells can become resistant to treatment in some cases but, crucially, this study showed that suppression of beta-catenin in human MLL leukaemic cells made them sensitive again.

Professor Eric So, who led the study at King’s, said: ‘These results are extremely exciting and represent a critical step forward in the search for more effective treatments for this devastating form of leukaemia. The findings provide compelling evidence that this protein could be exploited to develop an effective therapeutic target for this form of the disease.

‘Most of the current anti-cancer therapies used to treat leukaemia attack healthy blood cells as well as cancerous ones. Interestingly, beta-catenin is not required for normal blood stem cells. So if we can specifically target beta-catenin in the bone marrow, we can have potentially a more effective and less toxic anti-leukaemia therapy that can efficiently eradicate leukaemic stem cells but spares healthy blood stem cells.

‘Much more research needs to be done before we can adopt this approach in treating people with leukaemia, but the findings of this study do look promising. We will now investigate the mechanisms behind these molecular changes to find out why beta-catenin is so important in the development of MLL leukaemia, and if we can apply the principle to other types of leukaemia.’

Dr Mark Matfield, AICR's scientific co-ordinator said: ‘The whole field of cancer stem cell research is relatively new, but this discovery has the potential to be one of the most useful in this rapidly-advancing area, because it shows us directly how a new treatment could be developed.’

Notes to editors

King's College London

King's College London is one of the top 25 universities in the world (2010 QS international world rankings), The Sunday Times 'University of the Year 2010/11' and the fourth oldest in England. A research-led university based in the heart of London, King's has nearly 23,000 students (of whom more than 8,600 are graduate students) from nearly 140 countries, and some 5,500 employees. King's is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King's has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.

King's has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.

King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit:

www.kingshealthpartners.org

The Association for International Cancer Research (AICR)

AICR is the largest Scottish-based cancer charity, currently funding 207 active projects, at a cost of £36,765,555. Of those, 91 are in the UK and 116 are overseas. They include 12 prostate and nine bowel cancer projects.

Twenty three countries currently hold grants from AICR. Those are: (Overseas) Australia 15; Belgium 1; Denmark 1; Finland 3; France 13; Germany 6; Greece 5; Hong Kong 1;India 1; Israel 4; Italy 25; Netherlands 20; New Zealand 1; Portugal 2; Singapore 1; Spain 9; Sweden 3; Switzerland 3; USA 2.

In the UK there are 67 in England; 1 in Northern Ireland; 21 in Scotland and 2 in Wales.

Since the charity was established in St Andrews, in Fife, Scotland, 30 years ago, its overall spend on research has totalled £137,957,566. That money has been spent on 1762 projects, throughout 32 different countries.

For more information on AICR please visit www.aicr.org.uk

The Kay Kendall Leukaemia Fund

The Kay Kendall Leukaemia Fund awards grants for research on aspects of leukaemia and for relevant studies on related haematological malignancies. Grants are awarded for first class research on innovative proposals, particularly those close to the care of leukaemia patients or the prevention of leukaemia or related diseases. Programme/Project grants are awarded twice yearly, and Senior, Intermediate, and Junior Fellowships of 3 – 5 years are awarded annually.  The Fund also considers support for capital projects that will have direct benefit to leukaemia patient care.  For more information please see Kay Kendall Leukaemia Fund website www.kklf.org.uk

About Cancer Research UK

• Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research

• The charity’s groundbreaking work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.  This work is funded entirely by the public.

• Cancer Research UK has been at the heart of the progress that has already seen survival rates double in the last forty years.

• Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.

• Together with its partners and supporters, Cancer Research UK's vision is to beat cancer.

 For further information please contact Emma Reynolds, Press Officer at King’s College London, on 0207 848 4334 or email emma.reynolds@kcl.ac.uk

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From Maxwell to Higgs: the history of physics

Professor John Ellis

King’s alumnus Peter Higgs, who first proposed the ‘Higgs Boson’ particle, joined forces last week with John Ellis, King’s Clerk Maxwell Professor of Theoretical Physics, in a public lecture to celebrate the history of modern physics.

Professor Ellis addressed more than 350 staff, alumni, prospective students and school pupils on the achievements of James Clerk Maxwell and Peter Higgs.

Peter Higgs, who studied physics at King’s from 1947 to 1954, was guest of honour and introduced Professor Ellis’ lecture. Higgs’ theory is currently being tested by CERN’s Large Hadron Collider near Geneva, where scientists recently announced they were a step closer to finding the theoretical particle.

James Clerk Maxwell was Professor of Natural Philosophy at King’s 150 years ago from 1860 to 1865. During his time here he demonstrated that magnetism, electricity and light were different manifestations of the same fundamental laws, taking a major step towards a theory unifying the forces of nature. He also made a major contribution to the first demonstration of colour photography and the understanding of colour vision.

Following a welcome by Professor Sir Rick Trainor, Principal of King’s, Professor Ellis took the audience on a journey through the history of physics and speculated on what the future for the discipline may hold.

His talk was followed by a question and answer session chaired by Ian Sample, Science Correspondent for The Guardian and author of Massive: The hunt for the God Particle.

For further media information contact Anna Mitchell on 0207 848 3092 or at anna.i.mitchell@kcl.ac.uk.

For more details about King’s see our ‘King’s in Brief’ page.

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Landmark breast cancer study

A new study could revolutionise the way women with breast cancer will be diagnosed and treated in the future by reclassifying the disease into 10 completely new categories based on the tumour’s genetic ‘fingerprint’.

The study suggests that doctors could one day predict survival more accurately based on these new categories or subtypes, and better tailor treatment to the individual patient.

The research, published in the journal Nature is the largest global gene study of breast cancer tissue ever performed – the culmination of decades of research into the disease.

Researchers from the Breakthrough Breast Cancer Research Unit at King’s College London were part of an international collaboration that gathered, and then analysed, the DNA and RNA of 2,000 tumour samples taken from women diagnosed with breast cancer between five and ten years ago.

The scientists classified breast cancer into at least 10 subtypes grouped by common genetic features that correlate with survival – this new classification could change the way drugs are tailored to treat women with breast cancer.

The team discovered several completely new breast cancer genes that drive the disease – these are all potential targets for the development of new types of drugs. This information will be available to scientists worldwide to boost drug discovery and development. 

The study reveals the relationship between these genes and known cell signalling pathways (the messaging networks that control cell growth and division) – this could pinpoint how these gene faults cause cancer by disrupting important cell processes. 

Prof Arnie Purushotham, a co-author of the paper from King’s, said:  ‘This is a huge step forward towards personalising the diagnosis and care of individual patients. In the future we’ll be able to diagnosis exactly which type of breast cancer a woman – and occasionally a man – has, and which types of drugs will work best.’

The next stage is to discover how tumours in each subgroup behave, for example how quickly they grow or spread. More research in the laboratory and in patients is needed to confirm the most effective treatment plan for each of the 10 types of breast cancer.

For further information please contact Emma Reynolds, Press Officer at King’s College London, on 0207 848 4334 or email emma.reynolds@kcl.ac.uk.

For more information about King’s see our ‘King’s in Brief’ page.

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Key gene in breast cancer development identified

Researchers at King’s College London have identified a gene involved in the development of breast cancer, which could lead to the earlier detection and treatment of the disease.

A new study, in collaboration with Institut d'Investigació Biomédica de Bellvitge (IDIBELL), has found that gene changes occur up to five years before the detection of breast cancer, paving the way for treatments aimed specifically at reversing changes in susceptible genes before cancer occurs.

Breast cancer is the most common cancer in the UK with around 50,000 people diagnosed each year.

Published today in Carcinogenesis, the study was based on a group of 36 identical twin pairs from TwinsUK, based at King’s, the biggest adult twin registry in the UK, where one twin had developed breast cancer and the other had not. Comparing DNA samples from each twin, collected before and after the diagnosis of breast cancer, as well as samples from breast tumours and breast cancer cell lines, the research team found significant chemical changes in around 400 sites in the affected twin. Of these, scientists identified the DOK7 gene was identified as most likely to be directly involved in the development of breast cancer. On average, these chemical changes took place five years prior to the diagnosis of breast cancer.

Identical twins such as those at TwinsUK are ideal for studies of this nature as theyshare 100 per cent of their genes. Therefore, any difference between twins is attributable to environmental factors or chemical changes to their genes. These chemicalchanges in the way genes are expressed is called epigenetics.

Crucially, the DOK7 gene identified in this study can be switched on and off epigenetically, says Professor Tim Spector from the Department of Twin Research & Genetic Epidemiology at King’s, who co-authored the research paper.

Professor Spector said: ‘The identification of the DOK7 gene offers possibilities for the prediction and treatment of breast cancer and other common illnesses such as diabetes, Alzheimer’s disease and arthritis. In the future screening of epigenetic changes in key genes followed by drug treatments could be commonplace. Our twin studies are a great way of detecting these small but important differences between sisters and we hope to explore many other diseases.’

Dr Manel Esteller, Head of Epigenetics at IDIBELL, said: ‘An epigenetic alteration associated with an increased risk of breast cancer can be detected in the sick twin before theclinical diagnosis.’ The next step for researchers will be identifying the exact function of the DOK7 gene.

Dr Esteller added: ‘We believe the DOK7 gene is a regulator of tyrosine kinases, an antitumor drug target already used for the treatment of breast cancer. If DOK7 performs this function, new studies to test drugs for tumours resistant to chemotherapy could take place in the future.’

Notes to editors

Professor Tim Spector is available for interview.

Please contact Jack Stonebridge, PR Coordinator at King’s College London, on 0207 848 3238 or email jack.stonebridge@kcl.ac.uk

View the Carcinogenesis paper.

For further information on King’s visit our ‘King’s in Brief’ page.

For more information on the Epitwin project visit the website.

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New TB treatment study

A microscope

A team of researchers, led by Professor Juraj Ivanyi at King’s, have identified potential new means to treat tuberculosis (TB). 

They have developed a monoclonal antibody which was found to offer protection against tuberculosis infection in experimental models when combined with interferon, a modulator of the immune system.

The study was carried out by researchers from King’s College London, University of Dundee, and St George’s, University of London, and the findings were published in the most recent edition of Journal of Immunology.

TB remains a recognised global emergency, claiming around two million lives across the world each year, and 2010 saw the largest number of new cases of TB in the UK for over a decade.

Approximately one-third of the world's population is infected with Mycobacterium tuberculosis, the bacterium responsible for this huge public health problem. Unfortunately, the BCG vaccine used in some countries does not protect against disease in all adults, and drugs need to be delivered for several months.

The problem has been compounded by a dramatic rise in TB strains displaying multiple drug resistance. As a result, new ways to prevent and control tuberculosis are urgently required, and the strategy developed by the London/Dundee teams paves the way toward a previously unexplored form of treatment.

With a team of collaborators, Dr Sucharitha Balu in Professor Ivanyi’s team at King’s produced the human monoclonal antibody, which is of the IgA type and can specifically recognise Mycobacterium tuberculosis. IgA antibodies are proteins normally used by the immune system to identify and neutralise foreign microbes like bacteria and viruses within the lungs and intestinal tract.

The human monoclonal antibody generated in the research is a homogeneous antibody preparation with the capability to specifically attach to the Mycobacterium tuberculosis bacterium and trigger immune processes that prevent bacterial growth. Although human monoclonal antibodies are widely used to treat various forms of cancer and inflammatory disorders, this is the first demonstration that they might have applicability against tuberculosis.

Dr Woof from the University of Dundee explained the need to develop new treatments and vaccines for TB, and the potential to develop this research further. 'The number of cases of TB remains very high, and so this is clearly a major problem,' she said. 'Across the world, there are millions of people falling victim to infectious diseases such as TB, so the implications of this research could be considerable'. 

'Antibodies exist as five different types in humans, with those of the IgG type already being used in some clinical treatments. Antibodies of the IgA type are slightly different. They possess properties that we believe may be important in governing how this IgA antibody works against TB infection'.

The study, funded in part by the Wellcome Trust and the Dunhill Medical Trust, was the result of a productive collaboration with each team bringing a different sphere of expertise. Professor Juraj Ivanyi at King’s is an international expert in tuberculosis research, while Dr Woof's team in Dundee brought experience in human IgA antibodies. Dr Reljic at St George’s has expertise and special facilities for experimental models of TB infection.

Several years of previous research by Professor Ivanyi, Dr Reljic and their collaborators at the HPA Salisbury and Palermo, Italy provided general ‘proof of concept’ for this sort of approach, while this study opens the road for translating it toward human application.

Professor Ivanyi is based at the Dental Institute at King’s, which has a long history of pioneering research into mucosal immunology and vaccines. He said: 'This study brings us much closer to finding new ways to treat tuberculosis, although further research is needed before we can begin to trial this approach in patients.

'I am excited about where this project can lead us in terms of potential new treatments for this devastating disease.'

Notes to editors

King's College London

King's College London is one of the top 25 universities in the world (2010 QS international world rankings), The Sunday Times 'University of the Year 2010/11' and the fourth oldest in England. A research-led university based in the heart of London, King's has nearly 23,000 students (of whom more than 8,600 are graduate students) from nearly 140 countries, and some 5,500 employees. King's is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King's has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.

King's has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.

King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: www.kingshealthpartners.org

For further information please contact Emma Reynolds, Press Officer at King’s College London, on 0207 848 4334 or email emma.reynolds@kcl.ac.uk

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