Oxford Medicine July 2010

Oxford medicine THE NEWSLETTER OF THE OXFORD MEDICAL ALUMNI OXFORD MEDICINE . JULY 2010

Saving Oxford Medicine The Medical Sciences Division in collaboration with the Bodleian Library is embarking on an ambitious project designed to create a lasting archive of the personal papers of the most important Oxford medical doctors of the 20th and 21st centuries. The aim is to ensure the scientific legacy of this golden period for Oxford medicine is preserved for the benefit of future researchers, and to help Oxford explain and communicate the great contribution of its medical scientists.

Since its earliest days, when great commentaries on Hippocrates and Galen were given by the early donors, the Bodleian Library has counted medical manuscripts among its most important collections.

For over four hundred years, the Library has acquired the medical manuscripts of other collectors (such as Kenelm Digby), and has enriched its medical holdings with the personal and working papers of Oxford Faculty — including, for example the papers of Sir Henry Wentworth Acland, Regius Professor of Medicine at Oxford 1858–94 — as well as the papers of other medicine-related organisations, such as the Oxford Medical Club.

That giant of Oxford Medicine, Sir William Osler (1849–1919) was an habitué of, and major donor to, the Bodleian and was given special privileges as a reader. Osler presented it with (among more obvious donations of books and manuscripts) a wonderful clock that still strikes the most melodious tones on the half-hour. The story of Oxford as a major player in world medicine can also be told in part by the Bodleian’s Library of Commonwealth and African Studies, which looks after the papers of many individuals engaged in colonial medical service, the many medical missionary organisations based in Oxford, as well as significant institutional archives, such as the Overseas Nursing Association.

The readers of this publication hardly need to be reminded that over the past twenty or thirty years the University's Medical Sciences Division has grown to be one of the world’s greatest centres for medical research and teaching, and is today the largest of the University's five academic divisions. But the preservation of the personal

and academic papers of the great medical doctors who made that spectacular growth possible has not happened in a strategic way, and the papers of some major medical players have been lost.

The Bodleian and the Medical Sciences Division now intend to rectify this situation with a major project which will aim to raise awareness of the issue among the medical community, undertake a thorough survey of potential archives, and begin the process of establishing a major resource which documents the rise of Oxford’s medicine. The project will also provide access to the materials via the internet (as well as in the Bodleian itself), establish the basis for an ongoing collecting of papers, and lay the foundations for exhibitions, publications, websites and other ways of communicating with both the Oxford Medical Alumni and the general public about the extraordinary story of Oxford medicine.

Currently the papers created by the Oxford Medical Faculty are distributed among departments located on several sites around Oxford, and are also located in the homes of retired Faculty members — whether in paper form or in digital form, on personal computers. This represents a significant proportion of the records of contemporary and recent medicine in Oxford, and poses a preservation challenge to the University.

Fortunately the Bodleian has one of the most experienced archival teams in the world, and has the ability to manage a project on this scale. The Library is keenly aware that more must be done to ensure that archives documenting contemporary and recent medical research at Oxford will be preserved and made accessible to future historians alongside the Library's historic holdings. Physical collections are vulnerable in the context of new building projects and the unending and necessary quest for staff and lab space, as for example in the case of a small but important collection identified at the Dunn School of Pathology. But we are also concerned about components of this material that exist only in digital forms and are therefore vulnerable to physical decay and technological obsolescence.

David Weatherall

Contents A New Course in Biomedical Sciences

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Letter from the President .3 In the news . . . . . . . . . . . . . . .4 Patients' Experiences of Health and Illness . . . . . . .7 The Human Genome Project – 10 years on Obituaries Events

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The initial project has three complementary strands and will run over 18 months: • To survey the records and archives held by retired and working Oxford faculty, in order to identify archives of enduring value (in traditional and born-digital mediums), and to bring these into the Library's collections so that they may be preserved and made available for future research. This work will build on earlier efforts undertaken at the Bodleian.1 • To highlight the growing archive via a web portal. The portal would also be used to bring attention to new accessions made by the Library through the first strand of the project and to raise awareness of the importance of preservation among current medics.

• To begin the processing of important medical archives with that of Sir David Weatherall, the distinguished clinician and medical scientist and former Regius Professor of Medicine.

The project will be governed by an advisory board to assist the Library in targeting its contemporary collecting appropriately, with members from the Medical Sciences Division and from the History of Science community in Oxford.

The Project has received initial financial support, and is now seeking grants and donations from individuals. The initial project is estimated to cost £150,000 and so far £75,000 has been raised. We are confident of further funding from other sources, and are therefore appealing to

OMA members to help us raise £30,000 over the next two years.

Any members of the Oxford Medical Alumni who might be interested in supporting this project — at any level — are invited to contact either Richard Ovenden (Associate Director, Bodleian Library: richard.ovenden@ bodleian.ox.ac.uk) or Dr. Ken Fleming (kenneth.fleming@medsci.ox.ac.uk).

With your support we are confident of raising the remaining funds and beginning the project before the end of 2010 and in accordance with University practice, this also provides an equal opportunity to donate to your College. Donations can be made online at the University of Oxford online store (www.oxforduniversitystores.co.uk), select ‘product catalogue’ and then ‘Oxford Medical Alumni’.

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Paradigm project http://www.paradigm.ac.uk; Cairo project http://cairo.paradigm.ac.uk

Richard Ovenden and Ken Fleming

New course in Biomedical Sciences Oxford University will be offering a new course in Biomedical Sciences for students entering university in 2011. The course is one of only a small number of new undergraduate offerings made by Oxford in recent years.

The new interdisciplinary course is a successor to the Physiological Sciences and Psychology and Physiology courses, and will cover how cells, organs and systems function in the human body, to provide a modern education in molecular, cellular and systems biology and neuroscience. Students will have the opportunity to specialise as they progress through the course, ultimately graduating with either a BA in Neuroscience or a BA in Cell and Systems Biology.

Dr Robert Wilkins, course director for the Biomedical Sciences degree, said: ‘It's been exciting to develop something in which the possibilities for specialisation are so varied. We've built a course that provides an excellent foundation in basic biomedical science and then offers students real choice in the subjects that they study after that. It offers training in biomedical science for the twenty-first century that will be relevant for so many subsequent career paths.’

The course has been designed so that students acquire an understanding of biomedical science, and can then go on to specialise in the topics that

interest them most through a number of course pathways. Dr Wilkins notes: ‘One of the advantages of the course is that it is hugely flexible: two degree pathways are available to students with multiple second year modules offered to shape their choice and equip them for whichever specialist option they select. We've built a course that provides an excellent foundation in basic biomedical science and then offers students real choice in the subjects that they study after that.’

As the course progresses, students are increasingly encouraged to relate the course knowledge to scientific research. All students will have the opportunity to obtain firsthand research experience by joining one of the University’s research laboratories to work on an experimental research project of their choosing. While students on the new course will have access to lectures and practical training in a wide variety of fields, the core of the degree will remain Oxford’s unique tutorial system. Students in their first year will be introduced to systems science through a ‘Behaviour, Brain and Body’ module, and to cell biology thanks to a ‘Cells, Molecules and Genes’ unit. They will also have classes in essential physical, mathematical and statistical concepts.

Starting in the second year, students will be given the chance to choose from a number of modules, covering select topics in biochemistry and genetics, pathological processes, neuroscience and psychology, and pharmacology. By the third year, students will have chosen with which degree they wish to graduate, and will study a further range of specialised options accordingly. These can include topics ranging from infection and immunity to specialised neuroscience topics. The final term of the second year is set aside for the laboratory research project.

OXFORD MEDICINE . JULY 2010 / 3

Letter from the President

The Annual Meeting has always been a great focus for Medical Alumni and has always been well attended. This year was no exception and we had one of the highest attendances that I remember. That may well have been due to the topic of the meeting which was to celebrate about 700 years of medical teaching in Oxford. I said a little about that in the last edition of Oxford Medicine and so will not repeat it.

However, we had three superb talks from Eric Sidebottom, Colin Blakemore and Fiona Caldicott. Eric, as always, was amusing and informative about the development of the preclinical School from the time that Sir Henry Acland became Regius Professor of Medicine to the final acceptance by the University that a Clinical School should be established. The latter was triggered by medical students being ‘evacuated’ from London to continue their clinical studies during World War 2 and, of course, by the large benefaction of Lord Nuffield to set up the academic clinical units.

Colin spoke eloquently about the remarkable contributions made by Sir Charles Sherrington to the understanding of neuro anatomy and physiology, much of which was totally new to your gastroenterologically minded President, and to the many neurophysiologists that he trained. Some of them were still teaching in Oxford when I was a preclinical student and it was a great privilege to have had that almost first-hand connection with such a great scientist and mentor.

Having been delayed for hours in the Middle East on his way back from Singapore, Professor Blakemore had only a couple of hours to arrive home and then give the lecture in such a fresh and stimulating way. We were most grateful. Then Dame Fiona Caldicott gave a fascinating insight into some of the female medics that have enhanced Oxford medicine over the years. It was a beautifully illustrated account and was an exceptionally good Oxford Society Lecture. On a lighter note, Simon Smail gave a most entertaining talk on the clinical students’ Christmas pantomime that subsequently became Tyngwyk. Many of his slides brought back many happy memories and we now have a copy in the archives along with a disc of many clips and photographs of past performances prepared by the indefatigable Dr Fred Wright who for some many years held the post of ‘His Luminosity’. Relevant to our history, Dr Ken Fleming talked about a new initiative that he is pursuing with the Bodleian Library which is to create a medical archive. Ken and Richard Ovenden from the Bodleian have kindly contributed an article about this for this issue so that our Alumni can be fully involved and informed.

Our other major activity of the year was the medical brunch held at the Waldorf Hotel in New York as part of the biennial North American Reunion held by the University. We had invited Professor Michael Bliss from the University of Toronto to talk about ‘Osler in Oxford’. Many of you heard him give a similar talk at an OMA meeting about 7 years ago and some of you will have read his outstanding biography of Sir William Osler. It was a superb lecture and he included with slides, photographs and anecdotes of Osler never previously seen. We were joined by members of the New York Osler Society and it was a pleasure to welcome them. Dr Marty Edelstein, their President, had arranged for a group of students from Johns Hopkins

to sing a song that had been composed for the farewell dinner of Osler at the Waldorf just prior to his sailing for England and then Oxford in 1905. It was sung to that famous tune by Thomas Arne, elaborated as a theme and variations by Beethoven, and now sung as ‘God save our gracious Queen’. It was a great contribution to the brunch. My thanks go to Marty Edelstein and to Dr Don Chambers (University of Illinois Chicago) who got the whole thing organised, following a message from Jayne Todd that all flights had been cancelled because volcanic ash had closed Heathrow. So when I walked into the Waldorf on Sunday morning, there was that look of having seen a ghost and I was surplus to requirements! Fortunately I had been in Crete for another meeting and had been able to get a direct flight from Athens to New York. It was quite a surreal experience on the following morning to be at the North American Office of the University together with the Chancellor, Pro-Vice Chancellors, Heads of Houses and lots of other distinguished members of the University who were all stranded by the ash. Rumour has it around Wellington Square that none of us were missed that week!

At the annual business meeting in March I am delighted to report that we have a new executive committee. John Morris has become Vice-President as from Oct 1st, Bernadette Lavery has become Secretary, John Reid has taken over as Treasurer, and Amanda Salisbury stays on the committee to coordinate reunions. Richard Maxwell, who has served as treasurer for many years, is also staying on as he represents General Practice and is also living outside Oxford. It is a pleasure to welcome them and I am most grateful for their help and ideas. I have also come to the end of my 3 years of office but thought that it was a good idea for the health and vigour of the Association that there should be a change of President. I was elected to stay in post until the end of this academic year and Peggy Frith will take over from Oct 1st. I am delighted that she will be at the helm and I leave the post with full confidence for the future. It has been a great privilege to have been given the honour of leading OMA over the last 3 years and I am most grateful for the support of the Executive, the Medical School and all the Members of OMA. As ever, especial thanks go to Jayne Todd, our Administrator, for all the hard work.

Finally, I hope that you all have the date of the Osler Lecture in your diaries – Saturday September 25th, 11.00am at the Said Business School. Professor Kay Davies will be the Osler Lecturer and will use the power of modern genetics to illustrate how knowledge of genetic mutation can not only lead to better understanding of disease pathogenesis but also to allow new therapies to be devised. She will of course base this on muscular dystrophy and the dystrophin gene. Full details are given elsewhere in this issue, including registration for lunch after the lecture. I very much hope to see many of you there.

Professor Derek Jewell

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People in the News Four Oxford University researchers have been elected as Fellows of the Academy of Medical Sciences. The new Fellows are Professor Lars Fugger, Professor Antony Galione, Professor Ian Hickson and Professor Patrik Rorsman. Professor Sir John Bell, Regius Professor of Medicine at Oxford and President of the Academy of Medical Sciences commented upon the election of four Oxford University researchers as Fellows of the Academy of Medical Sciences, ‘Our new Fellows illustrate the wealth of experience and diversity of talent amongst the UK’s research community. I look forward to working with these skilled scientists to ensure their strengths across academia and industry are used to promote basic science discoveries, innovative healthcare and the rapid translation of research into patient benefits.’

Lars Fugger is a professor of neuroimmunology in the Department of Clinical Neurology at the University of Oxford. His research investigates the causes of multiple sclerosis. Genetic and environmental factors play a role in the disease, and Professor Fugger’s group is interested in understanding the molecular basis for these associations. The researchers’ goal is to use the knowledge from these studies to develop new drugs for the treatment of multiple sclerosis. Professor Fugger has also been awarded the largest European prize for multiple sclerosis research at a ceremony in Stuttgart, Germany.

Professor Antony Galione is head of Oxford’s Department of Pharmacology.

His work has been instrumental in elucidating new calcium signalling pathways in the cell. Calcium signalling plays a vital role in the body, coordinating and controlling processes as diverse as heart contraction, nerve growth, control of appetite, regulation of the immune system and insulin secretion by the pancreas. Professor Galione’s discoveries have implications for our understanding Professor Ian Hickson is Deputy Director of the Cancer Research UK Oxford Cancer Centre in the Department of Medical Oncology. His research focuses on genetic changes in cancer cells that are important in driving the growth of tumours. Armed with this knowledge, his team aim to develop new therapies to prevent or cure certain types of cancer. Professor Hickson was also elected as a Fellow of the Royal Society in June 2010.of cell regulation in health and disease.

Patrik Rorsman is professor of diabetic medicine in the Oxford Centre for Diabetes, Endocrinology & Metabolism at Oxford University. Professor Rorsman has been at the forefront of research on hormone-secreting cells in the pancreas for more than 20 years.

The work is highly relevant to the understanding of the causes and treatment of type 2 diabetes.

Professors Peter Ratcliffe and Nick White are w inners of Canada Gairdner Awards for 2010 Professor Nick White, who is director of the Mahidol-Oxford Tropical Medicine Research Unit in Bangkok, is to receive the 2010 Canada Gairdner Global Health Award – the first major international award that recognizes individual contributions to health in the developing world. Professor Peter Ratcliffe, the Nuffield Professor of Medicine at Oxford, is named a winner of a Canada Gairdner award together with William Kaelin Jr of the Dana-Farber/Harvard Cancer Center in Boston and Gregg Semenza of The Johns Hopkins Institute for Cell Engineering in Baltimore.

They have all played roles in identifying how cells in the body monitor and respond to oxygen levels.

Professor Dame Valerie Beral, Professor of Epidemiology, Director of the Cancer Research UK Epidemiology Unit and Fellow of Green Templeton College, was made a DBE for services to science in the New Year Honours List. A major focus of her research is the role of reproductive, hormonal and infectious agents in cancer. She is Principal Investigator for the Million Women Study and leads the international collaborative studies of breast, ovarian and endometrial cancer. She has published widely on the incidence of cancer in people infected with HIV, and is principal investigator of the International Collaboration on HIV in cancer, which brings together worldwide data in order to determine whether HIV infection increases the risk of cancer.

1974 Professor Peter Rubin, BM BCh, chair of the General Medical Council, was awarded a Knighthood in the Queen's Birthday Honours List. We extend many congratulations.

1975 Graeme Rocker received the Roger Bone award from the American College of Chest Physicians for leadership/advances in end of life care. (He remarks that he would have liked to have ‘shown up in my lovely DM gown’ for the presentation). He is lead editor in the OUP specialist handbook series entitled ‘End of life care in the intensive care unit: From advanced disease to bereavement’.

1998 Stephen Hoole was granted leave to supplicate for DM 4 February 2010.

2010 Danie l S tubbs, current medical student, was the first recipient of the Meakins McClaran Medal 2010 on 30 June 2010.

This new award is made for outstanding overall performance of a student graduating with the degrees of BM, B.Ch. (Oxon). Proxime accessit was given to Jonathan Wordsworth (2010). The Oxford Clinical School is grateful to Professor Jonathan Meakins, former Nuffield Professor of Surgery, and to Dr Jacqueline McLaran for donating and presenting this award.

OXFORD MEDICINE . JULY 2010 / 5

Oxford research in the news Bed nets to keep out mosquitoes and new drugs could outw eigh the effects of global warming. A study published in the journal Nature casts doubt on the widely held notion that warming global temperatures will lead to a future intensification of malaria and an expansion of its global range.

The research, conducted by the Malaria Atlas Project (MAP), a multinational team including Oxford University researchers and funded mainly by the Wellcome Trust, suggests that current interventions could have a far more dramatic – and positive – effect on reducing the spread of malaria than any negative effects caused by climate change.

A steady stream of modelling studies have predicted that malaria will worsen and its range will spread as the world gets warmer. Last year the Malaria Atlas Project produced a new map of modern-day malaria risk, giving researchers a unique opportunity to examine the effects that climate change may have had on the disease. The new research compared this modern-day map with a historic reconstruction of malaria at its assumed peak, around 1900, and measured changes in the disease risk since that time. Although it is widely known that malaria has receded from many areas where it was previously endemic, such as the United States and much of Europe, the researchers were able to measure for the first time the extent of this recession and show that even in tropical areas the intensity of transmission has declined substantially this century.

The team compared the increases in malaria predicted by global warming scenarios with the actual declines of the 20th century.

Importantly, they also gauged the efficacy of different disease control measures when set against the possible adverse effects of rising temperatures and concluded that interventions such as insecticidetreated bed nets or modern antimalarial drugs can potentially outweigh the effects of global warming as much as tenfold.

‘When we looked at studies measuring the possible impact of bed nets or drugs, it was clear that they could massively reduce transmission and counteract the much smaller effects of rising temperatures,’ said Dr Simon Hay, who leads the MAP group in Oxford.

‘Malaria remains a huge public health problem and the international community has an unprecedented opportunity to relieve this burden with existing interventions. Any failure in meeting this challenge will be very difficult to attribute to climate change.’

A report of the research, entitled, ‘Climate change and the global malaria recession’, is published in Nature.

Genetic link to infectious disease susceptibility found Genetic variants that increase susceptibility to several infectious diseases — including tuberculosis and malaria — have been identified by researchers from Oxford and Singapore.

The variations in DNA sequence identified by the scientists occur within a single gene involved in the body’s immune response to infectious disease. With greater understanding of the role

of the gene implicated, it is hoped the findings could one day lead to better therapies and vaccines.

Environmental factors such as malnutrition and poor hygiene can account for a large proportion of an individual person’s susceptibility to infectious diseases, but it’s clear that this is not the whole story.

Studies of twins and adopted persons indicate that genetics also plays a role.

The team from the Wellcome Trust Centre for Human Genetics at Oxford University, along with colleagues from Singapore’s Agency for Science, Technology and Research (A*STAR) and National University Health System (NUHS), analysed genes from over 8,000 people at clinical sites in Malawi, Kenya, Vietnam, Hong Kong and The Gambia, over a period of 5 years.

In particular, they were looking for genetic variants that might contribute to susceptibility to tuberculosis, malaria and serious bacterial infections of the blood, or bacteraemia.

Their findings, published in the New England Journal of Medicine, reveal a striking association with a gene called CISH and increased risk of susceptibility to these infectious diseases. CISH encodes a protein that plays a role in dampening down messaging signals between cells of the immune system.

A set of five different genetic variants was identified within the CISH gene. Within the population studied, having just one of these variants increased susceptibility to disease by 18% compared with somebody who does not have any ‘risk’ variants.

‘That is a substantial effect size for a single gene,’ commented Dr Fredrik Vannberg of the Wellcome Trust Centre for Human Genetics.

Professor Adrian Hill remarked that ‘The results tell us is that CISH is well worth following up with more research to understand better how the immune system responds to these infectious diseases, and how this can contribute to disease risk,’.

One variant in particular (labelled -292) accounted for most of the genetic association with disease. Studies carried out in Singapore showed that blood cells from healthy Chinese volunteers carrying the -292 variant had lower levels of the CISH protein overall than individuals with the normal variant. This suggests that CISH exerts a significant genetic influence on our immune response.

Examples of w riting needed for new Alzheimer’s study Dr Celeste de Jager of the OPTIMA project are asking people with and without Alzheimer’s disease to come forward with examples of their writing as part of a study to identify changes in language use that occur with the condition.

‘We’re encouraging people to go to their attics, rifle the back of drawers and search through piles of paperwork, to wherever they keep their old diaries, letters and notebooks. We’re looking for writing over a span of three decades, but we only need examples totalling around 1000 words per decade. People are welcome to suggest material from family and friends as well, including those that have passed away,’ adds Dr de Jager. ‘The only condition is that the writing should be in full sentences rather than notes, such as shopping lists.

Anyone wishing to get involved with the study should go to www.medsci.ox.ac.uk/optima or telephone OPTIMA on 01865 231270.’

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The team will use computer software to analyse the hundreds of writing examples. These methods will be able to pick up subtle changes in language use over time that can be associated with the onset and progression of Alzheimer’s disease, rather than normal agerelated changes in vocabulary and word usage. It is hoped that the analysis could lead to tests that allow early diagnosis of the condition before any symptoms are apparent. It could also lead to sensitive measures of language use that suggest the likely speed of disease progression and help guide treatment.

This computer-based approach has already been used to analyse language use in the novels of Iris Murdoch and the parliamentary speeches of former Prime Minister Harold Wilson. ‘Changes in Iris Murdoch’s language use can be identified in her last novel before anyone was aware of any symptoms of her Alzheimer’s disease, and it is possible to detect more subtle changes in the penultimate book, which she was writing at least two years earlier,’ says Dr Garrard.

Retina implants: location is key The first UK trial of a promising new retinal implant technique is to be led by Professor Robert MacLaren of the Nuffield Laboratory of Ophthalmology. The technology, developed by the firm Retinal Implant, AG, involves implanting a device underneath a patient's retina. The device itself is light sensitive, with a 1,500 pixel array, and is stimulated by the natural image focused by the eye — eliminating the need for an external camera (typically mounted on spectacles). Retinal implants hold particular promise for the treatment of retinitis pigmentosa (RP) a form of inherited retinal degeneration affecting approximately 200,000 people worldwide that typically causes severe vision problems in adulthood. The clinical trial using the technology, which will take place at the John Radcliffe Hospital, is due to start later this year.

New cancer biomarker may herald personalised medicine Scientists at Oxford University have led a study that shows how simple diagnostic tests to identify which patients will respond to which cancer drugs can be developed, potentially ushering in a new era of personalised cancer medicine.

Professor Nick La Thangue of Oxford University, who led the research together with colleagues at the MD Anderson Cancer Center at the University of Texas, Houston, confirm their approach works in results published in the journal PNAS. They show that a specific protein can be used as a ‘biomarker’ to identify which patients with a rare type of non-Hodgkin lymphoma would benefit from a new class of cancer drug. ‘This is the first report of a biomarker that predicts how a patient’s cancer will respond to a cancer drug. The presence or absence of the biomarker can now be used as a diagnostic test to identify which patients will benefit from this drug.

The researchers used a whole-genome screen to identify those genes active in CTCL cells that govern whether the cancer cells respond to the drug SAHA or not. The screen works by silencing each gene in turn to assess its effect on how well the drug works. HR23B was found to determine the CTCL cells’ sensitivity to SAHA. The scientists report that HR23B works as a biomarker in a clinically relevant setting. The presence of HR23B in biopsies from patients with CTCL predicted who would respond to the treatment 71.7% of the time.

With this first demonstration of a predictive biomarker for a cancer drug, the approach using a whole-genome screen can be done again

and again to find biomarkers for different cancers and different drugs.

The hope is that the identification of new biomarkers can become routine.

The research was funded by Cancer Research UK, the UK Medical Research Council, Leukaemia & Lymphoma Research and the Association for International Cancer Research in the UK, and the European Commission.

A simple and cheap w ay of making v accines stable – even at tropical temperatures – has been demonstrated

by Dr Matt Cottingham and other scientists at the Jenner Institute at Oxford and Nova Bio-Pharma Technologies.

The British technology has the potential to revolutionise vaccination efforts, particularly in the developing world where infectious diseases kill millions of people every year, by removing the need for fridges, freezers and associated health infrastructure. The work, funded by the Grand Challenges in Global Health partnership with other funds from the Wellcome Trust, is published in the journal Science Translational Medicine.

Preparing vaccines that do not need refrigeration has been identified as one of the major unsolved problems in global health.

Vaccines on sugar-stabilised membranes could be packaged with syringes ready for use.

Matt Cottingham and principal investigator Professor Adrian Hill carried out the proof-of-concept study, showing that vaccines they are developing could be stabilised for months using Nova’s patented technology, called the Hypodermic Rehydration Injection System (HydRIS). The team demonstrated it was possible to store two different virus-based vaccines on sugar-stabilised membranes for 4–6 months at 45°C without any degradation. The vaccines could be kept for a year and more at 37°C with only tiny losses in the amount of viral vaccine re-obtained from the membrane. If most or all vaccines could be stabilised at high temperatures, it would not only remove cost, more children would be vaccinated.

The method involves mixing the vaccine with the sugars trehalose and sucrose. The mixture is then left to slowly dry out on a simple filter or membrane. As it dries and the water evaporates the vaccine mixture turns into a syrup and then fully solidifies on the membrane.

The thin sugary film that forms on the membrane preserves the active part of the vaccine in a kind of suspended animation, protected from degradation even at high temperature. Flushing the membrane with water rehydrates the vaccine from the membrane in an instant.

Dr Peter White, Nova’s managing director, said the work by Oxford University demonstrated one successful application of Nova’s patented HydRIS technology platform and that Nova has already successfully stabilised a wide If you have new s: for range of viral and conventional vaccines.

‘This new technique of drug delivery is one of inclusion in Oxford medicine we will be delighted to the most exciting developments in the British include it. Items should be pharmaceutical and biotechnology industries, sent to — especially as it can be used for highly unstable jayne.todd@medsc.ox.ac.uk. products, for instance vaccines for malaria.’ Isis Innovation, Oxford University’s technology The editor reserves the right transfer company, is working with the to edit, or not publish any items sent. inventors to put a commercial strategy in place for the development of the technology.

OXFORD MEDICINE . JULY 2010 / 7

Patients' Experiences of Health and Illness — www.healthtalkonline.org Being diagnosed with cancer or other serious or life threatening disease sometimes propels people into doing extraordinary things.

They climb Kilimanjaro; sail the Atlantic; cycle across Europe; or walk round Britain. When I was diagnosed with breast cancer 15 years ago, even as a GP with 25 years experience I remember being struck by a sudden dreaded and overwhelming sense of isolation. Even though I had the hard facts, I had no idea how it would actually affect me and my life. I wanted to hear the first hand stories of others who had been through the same thing.

It was also at a time when medicine was changing dramatically: ‘evidence based medicine’ with randomised clinical trials was beginning to guide treatment options: choice was becoming a buzz word: committees had to include one patient representative. But for the health information industry the role of patients’ experiences still lagged far behind. It was OK for the media to ‘grab a quote’ or focus on only one wonderful or terrible experience as an illustration — with the result that unhelpful stereotypes and partial experiences were presented as the norm. Yet for each disease or health issue, as I knew from general practice, the experiences of individual patients differed enormously at every stage and in almost every way.

The DIPEx project (Database of Individual Patient Experiences) therefore began from a chance meeting whilst I was ‘convalescing’ (now much neglected in our macho 'get back to work a.s.a.p' culture), with an old colleague, Andrew Herxheimer, founder of Drug and Therapeutics Bulletin, who had had similar feelings after having a knee replacement. Together we wanted to provide a video and audio Database of People's Personal Experiences together with evidencebased information about the illness and treatment options — also linked to other relevant resources. How could we then collect these experiences and make them freely available to those that needed them?

A standard questionnaire would elicit only information of the ‘patient satisfaction’ variety and not about the whole experience: ticking the boxes was easy, but few people were willing or able to write freely about their experiences. The internet and the revolution in communication and information technology that it offered appeared to us to be a solution. Face to face narrative video or audio interviews of willing participants and qualitative analysis, using social science methods, could be used to explore people’s experiences. By focusing both on what people said and how they told their stories (instead of asking pre-defined questions) the researcher could then build a picture of the issues that mattered to people.

The challenges were many. First was funding, and ethics approval to allow us to recruit through NHS facilities. Then the TV companies we wanted to work with on the website had to be persuaded that interviews would be ‘better’ if a researcher with a camera visited patients at home rather than using a film crew or bringing participants into a studio. The initial mock up of www.dipex.org, was introduced by Jenni Murray and had interviews of two women with breast cancer. These interviews were then linked to appropriate and relevant information on the subject. This mock up helped us get start-up funding and employ our first proper qualitative researcher to collect men’s experiences of prostate cancer. From a group around my kitchen table we became a research group in the department of primary care at Oxford University, and in 2001 established the DIPEx charity.

Uniquely for the time the DIPEx project uses systematic qualitative research for each condition to gather the experiences of a broad range of 30–50 patients from different backgrounds across the UK.

Each illness or health issue has been a separate research project guided by a multidisciplinary advisory panel, and taking about 13 months to complete. The interviews are analysed, and the main themes summarised and put on the website with illustrative clips from the patients interviewed. Each subject module has around 25 summaries and 250 video and audio clips of Ann MacPherson and Jon Snow patients talking.

The site is therefore intended to overcome the inadequacies of other resources for health information on the internet especially those which include patient stories — by using the same degree of rigour in the collection and analysis of the narrative interviews as is expected of evidence based medicine.

Now, almost 10 years on, and with £6m from the Department of Health/NHS, CRUK, Wellcome Trust, British Heart Foundation, other charities and individual donations, we have interviewed over 2000 people, have sections on 60 different illnesses or health issues, either ‘up’ or ‘in preparation’ on the renamed www.healthtalkonline.org site. Subjects include cancers, heart disease, living with dying, women’s health, men’s health, experiences of carers, neurological conditions and pregnancy. Well known people, including Jenni Murray, Jenny Agutter, Clive Anderson, John Bayley, Sir Jonathan Miller, Hugh Grant and Antony Worral Thompson have recorded video introductions to individual illnesses.

A sister site launched in 2006 — www.youthhealthtalk.org — has young people talking about their health and illness concerns, including sexual health, teenage cancer, epilepsy and diabetes. Importantly the www.healthtalkonline.org site is also used to teach health professionals and medical students about patient perspectives.

New initiatives include the development of International DIPEx, collaboration with projects already underway with colleagues in Japan, Spain, Australia, Germany and Korea. This will allow for comparative studies of patients experiences from different countries. With the University, Green Templeton College and DIPEx charity we are planning to establish a new Health Experiences Institute (HEXI) on the new Radcliffe Infirmary site.

We have been awarded a 5 year NIHR programme grant to explore the health related consequences for patients of being able to access other people’s experiences of illness online. This work (qualitative, experimental and pilot trials) is being run from the Oxford department in collaboration with colleagues in Warwick, Northumbria, Sheffield and Stirling and will produce evidence about when and how patients’ experiences should be presented in health websites.

DIPEx has won many awards and has been accredited by the NHS. It gets 2 million hits and 80 thousand individual users per month.

With over 3000 classified medical conditions, prevention issues of smoking cessation, substance abuse and many more social issues such as ‘parenting’ — many more challenges remain, including the need for regular updating. So the project remains challenging, exciting and, thanks to the generous participants, a never ending source of insights into how people manage health and illness in their lives.

Ann McPherson

8 / OXFORD MEDICINE . JULY 2010

Human Genome Project — 10 years on ‘It’s hard to think back and remember how we worked then. We were scrabbling around in the dark,’ says Professor Mark McCarthy of the Oxford Centre for Diabetes, Endocrinology and Metabolism recalling how research on the genetic causes of disease had to be carried out before the human genome was sequenced.

The first draft sequence of the human genome was announced at the White House 10 years ago this June by Bill Clinton, with the promise that it would lead to new ways to prevent, diagnose and treat disease.

Mark McCarthy, who is also at the Wellcome Trust Centre for Human Genetics is the ideal person to explain what has happened since researchers got their hands on the DNA code and where we are now, 10 years on. Mark’s research aims to identify genes involved in diabetes and obesity, and he has been a leader in international collaborations to use the latest genotyping technology to advance our knowledge in this area.

Genetics of diabetes & obesity One in ten people either has diabetes now or will get it in future, making it a global health challenge now and in the coming decades. ‘Not everyone exposed to our increasingly sedentary lifestyles becomes overweight,’ says Mark, ‘meaning obesity is the result of a combination of nature and nurture, the effects of genes and the environment. In diabetes we’ve found just short of 40 genes associated with an increased risk of the condition. For obesity, the number’s similar. For diabetes, some of these genes are involved in cell cycle regulation and so may help in maintaining the cells in the pancreas that produce insulin.

Perhaps some people are blessed with more or better islet cells in the pancreas. The evidence from the genes identified for obesity supports the involvement of the part of the brain involved with appetite and the feeling of satiety. It seems that subtle effects in the neural circuitry in the brain that controls what and how much we eat are involved here.’

Sequencing the genome Once the first human genome had been sequenced, an obvious next step was to understand the genetic origin of variation between people – to find the 1 per cent of the genome that differed between people and where it was located. This could now be attempted in a comprehensive, systematic way across the 3 billion letters in the human DNA code. Two international collaborative efforts involving many hundreds of scientists, the SNP Consortium and the International HapMap Project, mapped the locations of common single-letter changes in the DNA code of different people. With that powerful knowledge in hand, it became possible to see if any of these differences in individual genetic makeup could explain people’s predisposition to common diseases like cancer, heart disease and diabetes.

Scanning for genes and disease The result was a new industry of big, international studies that scanned the whole genome of thousands of people using the latest technology. The studies checked the large number of sites where individual differences were now known to occur, to see whether common genetic variations could be associated with a particular disease or condition. And this huge effort has been very successful.

‘Close to 1000 sites of genetic variation have now been associated with common diseases, such as diabetes, heart disease and cancer,’ Mark says. ‘That is way more than we might have expected and it has given us insights into many diseases. At the same time, the results

have also been surprising in that the variants we’ve identified don’t explain more than a minority of the genetic basis for disease, and it has proved harder than we imagined to translate the results of these studies rapidly into new biological insights.’

The fact that, after all these studies, most of the genetic basis for common diseases still remains unknown has led to the concept of ‘missing heritability’. For example, despite almost 40 genes having been connected to diabetes and another 40 to obesity, in both cases the identified gene regions account for only around 10 per cent of the known risk that is inherited of developing these conditions.

‘There has been a lot of discussion about the 'missing heritability', comparing it to dark matter in physics – something that we know must be there but haven’t discovered yet,’ says Mark. ‘There are many possibilities for what makes up that missing heritability.’

The most likely, he says, is that less common or rare variants in the DNA code – which would not arise often enough to be picked up in genome-wide screens – have big impacts. Although rare, some of these variants would be connected with a much greater increased risk of disease over those found so far, and help to account for that missing heritability. And the search is now on.

New technology, new studies Advances in sequencing technology mean it now should be easier to look for these rare sites and test them systematically for association with common diseases — cancer, heart disease, or even schizophrenia, for example.

Rather than scan the genome as before, checking individual locations (albeit many thousands of them), the aim is now to sequence all of the DNA for thousands of people — with and without disease — and find genetic differences linked with various conditions.

The 1000 Genomes Project is already sequencing the genomes of different people to provide a more complete understanding of sequence variation between individuals than we have had so far. It’s sequenced around 300 people so far. But as the technology improves almost month by month, even larger projects become possible.

‘It took 10 years, $3 billion and many scientists around the world to sequence the first human genome,’ Mark explains. ‘Huge technological changes in the capacity to generate data means a handful of people can now generate a genome in a week for maybe $30-40,000. But these figures are almost out of date as soon as you write them down.'

‘New studies that compare whole genome sequences should be able to pick up common and rare variants in a way that has not been possible to date. There is optimism that this will nail the missing heritability. The first efforts to do this on a large scale are now beginning or being planned.’

Mark McCarthy is part of a new transatlantic consortium of researchers that is setting out to sequence the whole genomes of 3000 people: 1500 with diabetes and 1500 without.’

‘This will be a large effort. 3000 people is ten times the size of any dataset currently available,’ he says. ‘We calculate that the project will allow us to detect variants that are present in 1 in 100 people that are associated with diabetes.'

‘Previously, we’ve done very well at detecting variants present at a level of 1 in 10 people, but there will be many more variants present at lower frequencies that that.’How soon this new knowledge will translate into new genetics-based medicines?'

‘That’s the big open-ended question. It is very easy to talk about possibilities for new treatments and underestimate the time it takes.

But we can take hope where rare mutations causing diabetes have been identified – mutations that may be responsible for perhaps 2 per cent of diabetes cases. It has been possible to use that information to come up with new approaches for diagnosis and treatment for these rare types of diabetes.’

‘It is not out of bounds that we could do something similar with the information we obtain in these new sequencing studies,’ says Mark.

Professor Mark McCarthy

OXFORD MEDICINE . JULY 2010 / 9

Obituaries ERNESt DONALD ACHESON 17th September 1926 – 10th January 2010 “One of the most difficult things in medicine is to hear the right tune when the wrong one is being sung loudly”. Donald Acheson’s aphorism was first voiced when diagnosing the constrictive pericarditis of a patient long treated by a cardiologist as simple congestive heart failure. But it would have been equally apt when as Chief Medical Officer he recognized that given the mores of the times the real threat of AIDS in Britain was not an American-style epidemic but an African one.

Ernest Donald Acheson was born on September 17th 1926 to a Protestant family in Belfast, the son of Captain Malcolm King Acheson MC MD, a specialist in public health. His mother Dorothy Josephine née Rennodson was the daughter of a Tyneside shipbuilder. The family predilection for public health emerged also in Donald’s older brother Roy, a graduate of the early years of Oxford’s Clinical Medical School, who became Professor of Community Medicine at Cambridge. As acknowledged in his memoirs, an important influence on Donald Acheson’s childhood was his Roman Catholic nurse. Her caring idiosyncrasies contributed to his lifelong tolerance of human diversity despite a recognition of the corrosive influence of deeply rooted prejudices — “the social lesion” as he was to call it.

He was educated at Merchiston Castle School in Edinburgh and moved on in 1944 to read medicine at Oxford. His chosen College, Brasenose, was occupied temporarily, and some said paradoxically, by the Intelligence Corps, so the young Acheson had to endure the privations of wartime Christ Church where the first wine ever to touch his Protestant lips was a 1934 Chateau Margaux. His tutor Percy O’Brien duly imbued him with the Oxford ideal of education by guided personal study and enquiry rather than lectures, a tradition doomed to become unfashionable in the triumph of red-brick didacticism in medical education.

He interrupted conventional Clinical training at the Middlesex Hospital for experience in domiciliary obstetrics from the Rotunda Hospital in Dublin. This early exposure to the appalling consequences of extreme poverty and sociopolitical complacency inured him to later experience in the war-torn Balkans. As junior doctor at the Middlesex, Acheson’s experiences included committing Winston Churchill’s Private Secretary to a lunatic asylum, and being duty doctor during The Great Smog of London in 1952. The Clean Air Act and other reforms precipitated by the smog were to have an effect on life in the Metropolis and other large British towns as fundamental as those following the Great Stink of 1858. Again, the link between public conditions and personal health would not have been overlooked by a future Chief Medical Officer.

National Service as an acting Squadron leader in the Royal Air Force Medical Branch was followed by the then necessary qualification for an ambitious young doctor of the BtA (Been to America). He served as Chief Resident at the Maimonides Hospital in Brooklyn and on secondment to the Charity Hospital in New Orleans before a year of research on Armed Services medical records in Washington DC. For this last, to his considerable amusement, he had to be sworn in as a Federal Marshal of the USA. Here he began his groundbreaking work on the epidemiology of chronic inflammatory bowel disease and of

multiple sclerosis. He returned to England intending to train in gastroenterology with Francis Avery Jones who, deplorably, reneged on his promise of a post. With more discernment, Nuffield Professor of Clinical Medicine Leslie Witts invited him to Oxford where as a superb clinician in a department of superb clinicians he progressed to medical tutor and to May Reader. With the support of Witts and Sidney Truelove, Acheson set up the Oxford Record Linkage Study, a proof of the immense value of systematized health service data for generating and exploring hypotheses of aetiology and pathogenesis of both common and rarer diseases. Other exemplary studies by Acheson at this time included the discovery, with Ronald Macbeth, of “furniture makers’ cancer” of the nasopharynx. With perhaps a touch of Irish combativeness, Acheson also took on The Medical Establishment by publishing a devastating critique of the Membership examination of the Royal College of Physicians. The College’s President, Sir Robert Platt, was definitely Not Amused, but more enlightened spirits in the College accepted the justice of the criticism and initiated a long and reiterative process of reform to make the examination both fairer and more valid.

In 1967 Acheson was simultaneously offered a Professorial Fellowship at Brasenose and the post of Foundation Dean at the proposed new medical school at Southampton. Uncharacteristically he dithered, with the result that the national press reported his appointment to both jobs before he finally decided on Southampton.

It was not until 1988 that Brasenose forgave him with an Honorary Life Fellowship.

Under Donald Acheson’s guidance Southampton medical school introduced new approaches to the selection and education of students. Early exposure to patients, and inclusion of a fourth year research project, were quickly imitated at other schools. Selection of students without interview has survived less creditably into the age of computer-generated and plagiarized curricula vitarum. In 1979 Acheson gave up the post of Dean in order to become Director of Southampton’s MRC Unit in Environmental Epidemiology, where with Professor Martin Gardner he conducted research on asbestos that led to a ban on asbestos imports and to the introduction of more stringent safety standards.

In 1981 he was chairman of a study group on primary healthcare in inner London which produced a report with radical recommendations for reorganisation of family doctors, hospitals, surgeries and community nursing. Two years later he was appointed CMO. As an uncompromising idealist and brilliant medical scientist Donald Acheson cannot always have been comfortable in the company of politicians and civil servants. Nor did he always receive the support and information he needed from other government departments more concerned with defending their own interests than with the common good. He was also to endure the start of the process of politicisation of the Civil Service, which has so greatly reduced the influence and numbers of scientifically literate members of government departments.

None the less he never spoke ill of his political masters and only once, in a premature assertion of the safety of BSE-infected beef, was his scientific caution suborned by politicians’ expediency.

10 / OXFORD MEDICINE . JULY 2010

Despite the difficulties he proved himself a highly effective CMO and in BSE and AIDS faced two of the most daunting challenges in the history of public health. AIDS was first identified among American homosexuals and intravenous drug users. When the disease appeared in Britain, there were middle-class dinner parties where selective mortality of drug addicts and promiscuous homosexuals was viewed, if not with enthusiasm, at least with equanimity. Acheson, however, recognized that in the post-pill and cheerfully condom-less Britain of the 1980s heterosexual lechery presented the greater danger of an African style epidemic. The government’s “safe sex” campaigns that he instigated varied in style and effectiveness but served the nation well.

After retirement as CMO Donald Acheson continued public service, notably with his report on inequalities in health, and his work as WHO’s Special Representative to the “Former Republic of Yugoslavia”.

As the latter, he had to cope with the horrific consequences of political cynicism and administrative incompetence of a very high order. (“Some ass in Geneva” thought Sarajevo was in the tropics and sent a shipment of anti-malarials to relieve the besieged and starving city).

With his formidable intellect, emotional control, and thoughtful reticence, Acheson was sometimes misjudged by casual acquaintances as cold and aloof. Those who had the privilege of knowing him better saw his dominant characteristic as a wide compassion. He could be angry at injustice, and he knew a knave or a fool if he met one, but to honestly confused and bungling humanity he always showed practical concern and scrupulous courtesy. He is remembered with affection as well as respect.

Donald Acheson was appointed KBE in 1986. He was a past president of the Association of Physicians of Great Britain and Ireland and of the British Medical Association. He was the recipient of honorary degrees from many Universities, though not, to its shame, Oxford. He was twice married, with a son and five daughters (one deceased) from his marriage to Barbara Mary Castle, which was dissolved in 2002. He was married in that year to Angela Judith Roberts, with whom he had one daughter. He died on January 10th 2010 aged 83.

Professor Sir John Grimley Evans

JOAN AuStOKER 13th August 1947—19th January 2010

Dr Joan Austoker was a brilliant communicator to the public of the importance of early detection of cancer through screening, whose writings reached millions of homes. She wrote much of the public guidance that was crucial in helping women to consider the benefits and limitations of screening.

cancers and for the NHS prostate cancer risk management programme for GPs and patients.

She conveyed the complex biology in an accessible way that encouraged many people to accept their invitation for screening and have their condition diagnosed before it became lifethreatening. The present Department of Health National Awareness and Early Detection Initiative is the product of her work over the past two decades.

She wrote the first material for surgeons, The Guidelines for Surgeons in Breast Cancer Screening; she was part of the team which created the CRUK Cancerstats factsheets and she researched the psychological effects of screening on women.

In 1991 she founded the Cancer Research UK Primary Care Education Research Group and immediately found herself caught in the public storm around breast self-examination, which trials had shown to be ineffective in cutting the death rate from breast cancer.

Austoker had a parallel career as a Reader in public health and primary healthcare at the University of Oxford and wrote about 100 papers; the ones in the British Medical Journal on cancer prevention in primary care were also published in book form.

Austoker was one of the chief advocates of the “breast awareness” technique whereby woman were encouraged to monitor changes to the shape and condition of their breasts over a longer period rather than just checking periodically for lumps.

Abroad, she was involved in projects at the National Cancer Institute in the US and on the Continent she wrote the chapters on communication in the EU breast cancer, cervical and bowel cancer screening guidelines. She was leading the communication work on HPV testing and vaccination in the latest cervical cancer control programmes.

She convinced ministers and the new Chief Medical Officer about the benefits of “breast awareness” and ensured that information on breast awareness could be published quickly in the face of heightened public interest. As a result of her work the technique came widely into use and death rates from breast cancer were reduced.

Austoker produced information packs for GPs about the breast and cervical screening programmes in the late 1980s, and for the new bowel cancer screening programme which began in 2006. She also produced an information pack for women at high genetic risk of certain

Austoker was born in South Africa and took a first-class honours degree in biochemistry at the University of the Witwatersrand in 1968. She studied for her PhD in biochemistry at University College London in 1972. She took an MA in science and health education at Chelsea College in 1981. She is survived by four sons.

Dr Joan Austoker, public health expert, was born on August 13, 1947. She died of a splenic haemorrhage on January 19, 2010, aged 62.

OXFORD MEDICINE . JULY 2010 / 13

RONALD CARL ALAN PEARSON 1st June 1953—8th July 2008 Carl Pearson encompassed within his medical career a diversity of research, teaching and clinical experience, in this country, the USA and in Tanzania. He has died aged 55 from metastatic kidney cancer.

He was born and educated in the North of England, where his father was a GP for a small colliery village. The family was very medically biased and although initially attracted to Law, he changed to Medicine after A level studies in the humanities, when he found he was being excluded from family conversations about medicine. He passed the 1st MB examination at St Thomas’s Hospital and then went up to Trinity College, Oxford in October 1971, to read Physiological Sciences. Early on in his medical studies, he developed a passionate interest in the function of the brain, which was encouraged by his tutor in neuroanatomy, Dr T.P.S Powell. In his final year, with some temerity, he approached Dr Powell to enquire about the possibility of delaying clinical studies to enrol for a research degree in neuroanatomy and was gratified to be awarded an MRC postgraduate research studentship.

There followed a rigorous three years’ training in traditional research methods in neuroanatomy with a series of papers, culminating in the award of the degree of D.Phil. On entry into clinical medical studies in Oxford in 1977, he took to clinical work and patient contact with alacrity, enjoying immensely all opportunities to talk to patients.

Contemporaries at Oxford will probably remember him best of all however, immersed in a game of bridge in Osler House, chuckling wickedly over a winning hand; and for his portrayal of Dr Sidney Truelove, the eminent physician, to whom Carl bore an uncanny resemblance, at the medical student Tyngewick Pantomime of 1979.

He loved clinical work and therefore some were surprised when on graduating in 1980, he announced his intention to return to Tom Powell’s laboratory, to continue with his research, teaching and demonstration of anatomy and neuroanatomy, initially as a University demonstrator and subsequently as a Wellcome Research Fellow. This was a very productive research period, with many contributions to the knowledge of the development of Alzheimers Disease. During this time he also became very popular as a college tutor, with a prodigious reputation for lucid lecturing and tutorial style, which continued throughout his university career. He received many tutorial appointments amongst the Oxford colleges, but valued most highly his association with Corpus Christi College, as Research Fellow (1983-7).

The Wellcome Fellowship permitted the chance of working abroad, and thus in 1986-7, he enjoyed a highly productive year in the laboratory of Professor Sol Snyder, in the department of neurosciences at Johns Hopkins University Medical School in Baltimore, USA. Here he developed the technique of quantified in situ hybridisation of the brain, which consolidated his research reputation and led to a string of papers and collaborations, in which he was ever generous. He returned from the USA to an appointment as Senior Lecturer at St Mary’s Hospital Medical school in London and soon after, was appointed as Professor of Neuroscience at Sheffield University, at the age of 35. His collaborative style and infectious enjoyment of the science attracted a stream of medical and scientific postgraduate students to work in his laboratory, who all obtained the degrees they enrolled for and who always displayed their loyalty. He continued in Sheffield as legendary teacher; the lucidity of his style was undimmed by the burgeoning numbers in the lecture theatres and

was undoubtedly aided by his grounding in the humanities.

Carl made significant contributions to clinical neuroscience in three areas. Firstly, with Tom Powell, he made substantial discoveries regarding connectivity in the brain, particularly of the cholinergic pathways, which at the time were emerging as central to understanding the pathogenesis of Alzheimer’s disease. Secondly, working with clinical colleagues in Oxford, he was the first to describe clearly how Alzheimer’s disease spreads within the human brain, and to hypothesise how the process might begin.

The key paper he published on this subject in 1985 has become a citation classic, and ensures that his name will never be forgotten in this field. Thirdly, following his return from his sabbatical year in Johns Hopkins, Carl was the first in UK to use molecular techniques for the study of gene expression in the human brain, and to apply them productively to the study of Alzheimer’s disease. The latter studies were conducted at St Mary’s Hospital Medical School in London in the late 1980s, where there was a remarkable concentration of emerging names in clinical neuroscience, all of whom would go on to eminence elsewhere.

The 1990s were difficult times for those engaged in research and teaching in the universities, and Carl felt the compromises were unacceptable and would not permit standards of teaching and research to be diminished. In hindsight, it was perhaps a mistake that he accepted the Chair of Neuroscience in Sheffield, since the exceptional productivity and research environment which he had created at St Mary’s could not be recreated, and the increasing administrative and teaching burdens diminished his ability to do research of the quality and originality of which he was capable. By 1999, it was clear that he felt the need of a radical change of direction in his career.

By chance, he noticed an advertisement in the BMJ for teachers of undergraduate physiology and anatomy in the newly created Kilimanjaro Christian Medical College (KCMC) in Tanzania. A totally different sabbatical year then followed in 2001, spent giving his expertise in teaching undergraduate medical students in the developing Third World medical school, for which he retained a great affection thereafter. Carl would have been the first to admit that he gained more from Africa than he had given-a common experience amongst those who have worked in Third World countries. The sabbatical year gave time for reflection on the possibilities of a radical career change and he returned to England resolved to resume a career in clinical medicine, which he did in August 2002.

He took house jobs Medicine and Surgery in Hull, where he was remembered for his meticulous and, by then, old-fashioned attention to all his patients, with no care for clockwatching. Despite being then aged 50, he completed his preregistration year without a single day off sick.

Considering his background, it would have been a natural choice to consider pathology or neuropathology to complement his research

12 / OXFORD MEDICINE . JULY 2010

activity. However the contact with patients had been too attractive.

His gregarious nature, humour, excellent approach to patients and his strong moral and socialist principles made General Practice a natural choice. He was delighted to be accepted on the training program for General Practice in the North East, where again, he fulfilled a series of rigorous junior training posts with aplomb. He obtained a position as General Practitioner in Sunderland, where he spent the last 18 months of his working life, amongst the happiest and most fulfilling periods of his entire career. It gave him great pleasure to be awarded the MRCGP in April, an award which his daughter received on his behalf. He continued his interest in teaching and was glad to give tutorials in neuroanatomy to a young medical student friend during the final few weeks of his life.

A generously hospitable and sociable Yorkshireman, Carl loved good wine, cricket and brass bands. He played the cornet brilliantly, receiving his initial training as a boy in the Salvation Army. As an undergraduate, he was a founder member of the Broad Street Stompers jazz band, which was later reprised in his clinical years as the Tyngewick Band and in recent years as the St Georges Pantomime Band. He was also a proud member of the Morris Motors Concert Band, playing under the baton of Sir Harry Mortimer in the mid 1970s. A man of strong Christian faith, he became a confirmed

Anglican in 1997, and devoted much time and energy to his local church, St George’s, Jesmond, serving as Church Warden from 1997–2000. On returning from Tanzania in 2001, he established a fund for sponsorship of medical education in KCMC, which, to date, has put 6 students through the medical course and is still going strong.

He met Enid, a fellow medical student in November 1971, during their first term at Oxford; they married in 1975 and he was an unfailingly loyal supporter of her career in Obstetrics and Gynaecology. They have one daughter, Grace, aged 15, who also does pantomime.

Ronald Carl Alan Pearson, M.A., D.Phil. (Oxon), B.M. B.Ch., M.R.C.G.P., F.R.C.Path.; born 1st June 1953, Middlesbrough; educated at Barnard Castle School, County Durham, St Thomas’s Hospital Medical School (1st M.B.), Trinity College Oxford and Oxford University Medical School; Professor of Neuroscience, University of Sheffield (1989-2001) and lately, General Practitioner in Sunderland and Newcastle upon Tyne; died 8th July 2008,Newcastle upon Tyne, aged 55, from metastatic renal carcinoma; married Enid Michael in 1975; one daughter, Grace.

Enid Michael

MICHAEL C SPENCER 1926 – June 2008 Michael left school at 15 to work in an accountant’s office.

Following his first week’s holiday from full time work at a Baptist Missionary Society Summer School in August 1943 he decided to become a missionary. While continuing his full time job he managed in 5 months to organise his application and finance from grants and scholarships and get accepted on the premedical course at St Catherine’s Society, as it was then known starting in January 1944. In two terms, having not been to school for 18 months, he succeeded in obtaining a place on the medical course. “It is difficult to recount exactly the steps that changed me, in five months, from an aimless youth into a highly motivated individual with, what must have seemed to most observers, totally unrealistic aims.” Oxford was and remained for him the most inspiring institution and place. The memoirs he left his family show just what his time there and the people he met either as fellow students or as teachers meant to him.

From Oxford he went on to clinical studies at The Middlesex Hospital.

After house jobs in Medicine, Surgery and Obstetrics he went to Antwerp to study for the Diploma in Tropical Medicine and Hygiene where in addition to learning French he developed a life long interest in Flemish art and history.

He spent 5 years in the Belgian Congo where he was joined by his fiancée Philippa and was married without a single close acquaintance or friend present. There, working very much on his own with Philippa’s support he carried out his medical duties in fairly primitive surroundings carrying out major surgery such as repair of vesicovaginal fistulae having first administered spinal anaesthesia himself.

Back in England as a GP assistant he could not finance a partnership, though he had offers, so he and Philippa moved to Australia on the £10 scheme where he practiced as a GP in the remote NSW town of Carcoar.

Later he moved to New Zealand to work as a GP in Timaru where he helped develop a department of Respiratory Medicine. Following the death of a daughter the family eventually moved back to England.

Here after a short spell in Birmingham he settled down to spend the rest of his working life in Leiston, Suffolk not far from his roots.

Throughout his life he and Philippa kept open house to visiting students from foreign lands initially through the British Council and subsequently other agencies. Christmas was never a family only affair. A great many of these people and the friends from all over the world have kept in touch and visit whenever they are in England.

Michael was fascinated by history, science and natural history. He was keen on the green movement enjoyed cycling, walking and camping in his camper-van touring the whole of Britain and Europe.

His religious views gradually waned. He became disillusioned with some aspects of organised religion and adopted a more humanist approach as he read and learned about developments in science, especially genetics and the evidence behind evolutionary theory.

The stroke that was to lead to his death occurred whilst on a trip to the West Country in his campervan. It was fitting that he was able to be brought to his burial in his campervan, in the cardboard coffin he had desired, to be buried in a wood not far from his home in Chichester.

He leaves a wife, Philippa, five children and eleven grandchildren.

Michael C Spencer; b. 1926 matric. 1944 St Cathrine’s d. June 2008 aged 82 following a stroke.

Stephen Spencer

OXFORD MEDICINE . JULY 2010 / 15

DR JOHN MICHAEL tALBOt 29th March 1944—25th September 2009

MA, BM BCh, Oxon.(1968), FRCGP (1997).

Born 29th March 1944

for his patients, and was a wise, much loved and respected doctor and colleague. He was a trainer for 15 years and an Examiner for the MRCGP for 11 years. In 1997 he was made a Fellow of the RCGP in recognition of his contributions to general practice.

Died 25th September 2009 from Carcinoma of the Prostate.

General Practitioner. The Health Centre, Coker Close, Bicester, Oxfordshire.

John Talbot was awarded a scholarship to study medicine at Pembroke College and the Radcliffe Infirmary in Oxford and qualified in 1968. After house officer and SHO posts at the Radcliffe Infirmary, he spent a year as a Paediatric Registrar in in South Africa. He returned to this country and entered General Practice in Bicester in 1972. He was always committed to providing a high standard of care

He was a keen sportsman: he rowed and played rugby for his College, and later enjoyed shooting, sailing and meting with his friends. His greatest pleasure in life was his wife, children and a growing number of grandchildren, and his greatest concern during his long illness was for their care.

He is survived by his wife Lyn, six children and ten grandchildren.

Charles Talbot and Theo Schofield

With sadness…

Laslo C Antal; matric. Keble 1957, d. 30 March 2010. Born 10 April 1936 General practitioner. Escaped from Hungary in the 1950s Antal shot for Britain in 1976 Olympic Games and was Britain’s representative on the Olympic Medical Committee. Vice President of the National Small-bore Rifle Association, and was awarded NSRA’s Gold Medal for his services to shooting.

Jennifer Bates; matric. St Hugh’s 1956, d. 5 March 2010, aged 72.

Humphrey B Calwell; matric. Lincoln 1944, d.8 April 2009, aged 84.

John (Kenneth) Kw ok-Hoe Chong; matric. Christ Church 1952, d.

May 2009, aged 80.

Philip R Clay ; matric. Trinity 1941, d. 3 October 2009, aged 86.

Alexander C. Crampton Smith; q. Edinburgh 1941, d. 20 March 2010 aged 92. Following distinguished war service he obtained a house surgeon post at the Radcliffe Infirmary, Oxford, training in the Nuffield Department of Anaesthetics under the first Nuffield Professor, Sir Robert Macintosh, then moved to London before returning to Oxford in 1951 as a consultant anaesthetist, with a specific role to provide anaesthesia for thoracic surgery. In 1965 he became the second Nuffield Professor of Anaesthetics until retirement in 1979. A full obituary will follow.

Roger AB Drury; matric. Trinity 1940, d. 3 June 2009, aged 86.

Consultant Pathologist, Plymouth General Hospital. Consultant Pathologist, Plymouth General Hospital Thomas G Duggan; matric. Merton 1933.

Alan S Gardiner; matric. Keble 1945, d.17 October 2009, aged 81

Joseph E Hawkins; matric. Worcester 1934, d. 6 October 2008, aged 94. Born March 4th, 1914, in Texas. Graduated from Baylor University in 1933, returning 50 years later as Distinguished Visiting Professor, to teach anatomy. He attended Oxford as a Rhodes Scholar, leaving with a Bachelor’s Degree in 1937. He was awarded his Ph.D. in medical sciences in 1941. Later he returned to Oxford to complete the M.A. in 1966 and D.Sc. degree in 1979.

Joe Hawkins spent the war years at Harvard, where he exposed his own ears in the very earliest experimental research on the effects of intense sound on human hearing. The studies set a benchmark for all later research on noise trauma but also left the experimenters with permanent hearing loss. He explored the auditory and vestibular effects of the newly discovered aminoglycoside antibiotics at the Merck Institute for Therapeutic Research, and in 1963 joined the University of Michigan and the newly founded Kresge Hearing Research Institute upon the invitation of its director, Merle Lawrence.

Here he added novel behavioural assessments to his studies on ototoxicity. He continued his interest in noise trauma and defined the role of stria vascularis and vasoconstriction. Finally, his attention turned to auditory and vestibular changes with aging. He became Emeritus Professor in 1984. His recent years were devoted to one of his great hobbies, researching and writing on the history of otolaryngology.

He was a student of many cultures and languages: lecturing in three languages, conversing in six, and reading eleven. He would modestly admit, though, that his reading of Greek, Russian, and Icelandic required the use of dictionary.

Edmund N Hay ; matric. Exeter 1953, d. 6 December 2009, aged 75.

Trained as a respiratory physiologist in Oxford and worked for the MRC with Kenneth Cross, Geoffrey Dawes and Elsie Widdowson for some years before moving to Newcastle to get a grounding in paediatrics in 1968. He returned briefly to London in 1973 as a consultant to set up a respiratory intensive care service at Great Ormond Street Hospital,

14 / OXFORD MEDICINE . JULY 2010

London, but returned to Newcastle in 1977. Epidemiology and the conduct of controlled clinical trials were his main research interests.

James H Lewis; Trinity 1929 On qualifying, James Howard Lewis ("Howard") joined the Royal Air Force. Early postings included Basra and Aden, but for most of the war years, and until independence, he served in India, eventually becoming officer commanding the RAF hospital in Cawnpore and later Barrackpore. After postings in the UK, he was sent in 1954 to the US Academy of Aviation Medicine at Randolph Air Force Base, Texas, for one year. On his return to the UK, he was posted to the Institute of Aviation Medicine, Farnborough, and later became a commanding officer.

He subsequently became deputy director of aviation medicine; his last posting was to the Second Allied Tactical Air Force in Germany. On his retirement from the RAF, he worked as a medical officer with the Civil Aviation Authority for 10 years, until 1975. A polymath, he had a long, active, and happy retirement, the last 30 years of which were spent in Wales, the land of his birth. Predeceased by his wife of 67 years, Jeanne, and his daughter, he leaves two sons and six grandchildren.

Former medical officer Civil Aviation Authority and group captain Royal Air Force (b 1910; q Oxford/Charing Cross 1936; MA, DPH), d 23 April 2008.

Alexander Grant MacIntyre; matric. Brasenose 1951, d. 19 August 2009 aged 80. Alexander MacIntyre was born in Lucknow in 1930. He attended the University of Toronto before coming to Oxford on a Commonwealth Medical Scholarship in 1951. He held various resident and consultant posts in neurosurgery at Liverpool hospitals and also university post-graduate posts in Oxford, Heidelburg, Paris (Sorbonne), Boston (Harvard) becoming FRCS(Ed) before returning to Canada in the 1970s. Whilst at Oxford he was captain of the Oxford University Ice Hockey team. When he returned to Canada, MacIntyre joined a practice in Alliston in 1970. Outside his practice, he continued to play hockey and baseball, he also skated, rollerbladed and skied — all into his late 70s. After retiring, MacIntyre actively participated in the PRRC and taught future physicians during the annual Rural Health Day held in Alliston for University of Toronto first year medical students.

Michael R Mole; matric. Pembroke 1962, d. 4 October 2009 aged 67.

Michael Richard Mole studied medicine at Oxford and the Middlesex.

After qualifying, he worked in the ear, nose, and throat, accident and emergency medicine and plastic surgery at Frenchay Hospital, Bristol, followed by obstetrics and gynaecology at the Royal Devon and Exeter Hospital. From 1973 until his retirement due to ill health he worked as a general practitioner in Exeter. His special interest was medical hypnosis, which he used to help patients to deal with various issues. He died as a result of a prolonged illness on the 4 October 2009 leaving his second wife, Sheila; daughter, Marie-Solene; and son, Alex.

Ayub K Ommay a; matric. Balliol 1954, died on 10 July 2009 aged 79 at his home in Islamabad, Pakistan, of complications from Alzheimer’s disease. Neurosurgeon, and internationally known expert on brain injuries and inventor of a device that facilitates treatment of brain tumours. Rhodes Scholar at Balliol in 1956 he trained as an amateur boxer, rowed for Balliol and was a member of the Ice Hockey team. Known as the “singing neurosurgeon,” Dr. Ommaya was a trained opera tenor who often sang before and after surgery, to the delight of patients and their families and his hospital colleagues.

Gillian Parker; matric. St Anne’s 1943, d. 11 March 2010 aged 85, from ovarian and then peritoneal cancer. General practitioner.

Michael J Piachaud; matric. Lincoln 1967, d.10 February 2009, aged 61 SEE BMJ Former consultant psychiatrist in learning disability and honorary senior lecturer Imperial College (b 6 June 1948; q Oxford 1973; MA, FRCPsych), died from lung cancer on 10 February 2009.

Michael A H Russell born 9 March 1932; matric. University 1952, died 16 July 2009 at the age of 77 from a heart attack. Psychiatrist and public health scientist, Russell was born in Cape Town, South Africa. After studying medicine at Oxford, where he won a half-blue for swimming, he did his clinical training at Guy's. Russell was a psychiatrist in training at the Maudsley when he chose the topic of cigarette smoking for his research thesis in 1967. Based on his review of what was then fragmentary research literature, he concluded in a 1971 paper that the drug nicotine was the motivating force underlying smoking behaviour. He made the study of the interacting pharmacological and psychological determinants of tobacco dependence his life's work. His research led to the 1988 report of the US Surgeon General, Nicotine Addiction, which finally brought recognition that cigarette smoking is a classic drug dependence. Russell is probably best known in the cessation field for a non-pharmacological intervention. In 1979 he published a trial examining the effectiveness of brief advice to quit smoking given by GPs in the course of routine consultations. Russell moved towards the concept of an integrated district smoking cessation service, in which routine delivery of advice and pharmacological therapy in primary care was combined with intensive clinic support. That vision has now been realised in the NHS. Klaus F R Schiller; matric. Queens 1945, d.9 July 2010, at the Churchill Hospital in Oxford from complications following treatment for primary amyloidosis. An obituary will follow.

Patrick L Strong; matric. Wadham 1950, d.3 January 2010, aged 79.

William H Taylor b 26 April 1924; matric. Christ Church 1942, d 23 February 2008 aged 86 Former consultant chemical pathologist Liverpool Royal Infirmary James Watt KBE; d.28 December 2009, aged 95. Medical DirectorGeneral of the Royal Navy, 1972-77.

Richard L Woodhead b 1941; matric. Queens 1960, died from acute leukaemia on 7 November 2009. Richard Leslie Woodhead ("Dick") qualified in 1966 and was consultant physician with an interest in acute poisoning in Bradford from 1975 to 1997.

Orlando Harold Warw ick, b 1915, matric. Christchurch 1936, aged 94, died Oct. 21 2009.

BA from Mount Allison University, Rhodes Scholar MA in Physiology from Oxford University and MD from McGill University. Warwick interned at the Royal Victoria Hospital in Montreal before joining the RCAF, postgraduate work at the Royal Victoria Hospital, Royal Cancer Hospital, and Brompton Chest, internal medicine in Montreal and taught at McGill University. In 1961 became Dean of the Faculty of Medicine at Western and Vice-President of Health Sciences (1965–1972). He became a Member of the Order of Canada in 1990.

David P Winstanley; matric. Trinity 1943, d.15 April 2010, aged 85.

Pathologist.

We are anxious to include information about the lives of those who have died and would welcome submissions. These will, where space allows, be published in Oxford medicine. Otherwise they will be placed in the obituaries section of our website www.medsci.ox.ac.uk/oma

OXFORD MEDICINE . JULY 2010 / 15

OMA Events SEPtEMBER 2010 40 PLuS YEARS — REuNION FOR tHOSE ENtERING tHE OxFORD CLINICAL SCHOOL BEtWEEN 1964 AND 1968 A reunion is being held on 24 and 25 September 2010 for those who entered the Clinical School at Oxford between 1964 and 1968. The reunion is being coordinated by Professor John Reid johnlreid@btinternet.com. Invitations have been sent — if you have not received yours then contact Professor John Reid or Jayne Todd 01865 221690 jayne.todd@medsci.ox.ac.uk The reunion has been timed to run in parallel with the first day of the University Alumni Weekend so that people can enjoy the programme of events the University is offering whilst being able to meet up with colleagues from their student days.

John is anxious to meet up with as many old friends as possible so do make every effort to come. The reunion will include a walking tour of Oxford, an afternoon of short talks and a formal dinner at Green Templeton College.

50 PLuS YEARS — REuNION FOR tHOSE READING MEDICINE At OxFORD IN 1954 A 50th reunion is being held on 1st October 2010 for those who read medicine at Oxford in 1954. The reunion is being coordinated

by Dr John B Wood. Invitations have been sent — if you have not received yours then contact Jayne Todd 01865 221690 jayne.todd@medsci.ox.ac.uk . The reunion will comprise a short talk on Oxford medicine followed by a reception and then dinner at Magdalen College. It is hoped that there will be the opportunity for an informal buffet lunch on the following day.

2010 OSLER LECtuRE The 2010 Oxford Osler Lecture will be given by Professor Kay Davies on “Therapy for Muscular Dystrophy in the New Genetics Era” on Saturday 25 September 2010 at 11.30am at the Said Business School, Park End Street, Oxford. Free admission to the lecture is by pre-booked ticket only. Lunch for Oxford Medical Alumni will be held at the Said Business School after the lecture, £10 per head. Please note that there is no parking of any kind available at the Said Business School.

This lecture is part of the programme of events which comprise the Oxford University Alumni Weekend. To attend ONLY this lecture and/or the lunch which follows alumni must obtain their tickets from: Jayne Todd, OMA, Medical Sciences Office, John Radcliffe Hospital, Oxford, OX3 9DU Telephone 01865 221690 RSVP by 10 September 2010.

If you wish to take part in any of the other parts of the 2010 alumni weekend programme then you must register either through the alumni weekend website www.alumniweekend.ox.ac.uk or by using the booking form which is obtainable from the Alumni Office, University Offices Wellington Square Oxford OX1 2DJ To attend ONLY this lecture and/or the lunch which follows alumni should either: book tickets for the lecture (free) and/or the lunch (£10 per person) using the form below or: from 5 July you are encouraged to book tickets and pay for lunch online at www.medsci.ox.ac.uk/oma/events/2010-events 2010 Osler Lecture Booking Form Your name...........................................................................................Your guest’s name.............................................................

Address.............................................................................................................................................................................................

Postcode ...........................................................................................................................................................................................

Telephone ............................................................................................Email ..................................................................................

If you wish to take part in any of the other parts of the 2010 alumni weekend programme then you must register either through the alumni weekend website: www.alumniweekend.o

Please specify any special dietary requirements

x.ac.uk or by using the booking form which is

Cheque for £ .................................(GBP) payable to ‘Oxford University’.

OR from 5 July you are encouraged to book tickets and pay for lunch online at www.medsci.ox.ac.uk/oma/events/2010-events Bookings close on 31 August 2010 at the latest — we cannot accept telephone bookings: An early response would be most appreciated.

Please return this form to: Jayne Todd, OMA, Medical Sciences Office, John Radcliffe Hospital, Oxford OX3 9DU Telephone 01865 221690 Email jayne.todd@medsci.ox.ac.uk

obtainable from the Alumni Office, University Offices Wellington Square Oxford OX1 2DJ

Contacting OMA Address: Oxford Medical Alumni Medical Sciences Office John Radcliffe Hospital Oxford OX3 9DU Email: jayne.todd@medsci.ox.ac.uk Website: www.medsci.ox.ac.uk/oma Enquiries: 01865 221690 Fax: 01865 750750

OMA Events for 2011 APRIL 2011 The 2011 Oxford Medical Alumni Symposium will take place on 2 April at the Medical Sciences Teaching Centre in the University Science area.

The theme of the Symposium is ‘The New Professors’ .The Symposium will be followed by the Annual Dinner which will be held at Wadham College.

REuNIONS Invitations will be sent to those graduating from the Oxford Clinical School in: 1969-72 (40 years), 1985-87 (25 years) 2000-02 (10 years) It would be most helpful if the Osler House President, Secretary and Treasurer, the Tyngewyck Director or producer and the editors of the Oxford Medical School Gazette for these years could make themselves known to Jayne Todd jayne.todd@medsci.ox.ac.uk 01865 221690 as soon as possible.

AuStRALIA 2011 In 2011 a series of reunions will be held for Oxford Medical Alumni living and working in Australia and New Zealand. Details are being developed – if you would like to receive further information about this please email jayne.todd@medsci.ox.ac.uk as soon as possible.

SEPtEMBER 2011 The 2011 Oxford Osler Lecture will be given during the weekend of 16-18 September 2011. This lecture is part of the programme of events which comprise the Oxford University Alumni Weekend.

NORtH AMERICA 2012 The next North American Reunion will take place in the Spring of 2012. Further information will be available shortly.

More information on Oxford university alumni events can be found at www.alumni.ox.ac.uk

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Oxford medicine is produced by the Medical Informatics Unit, NDCLS, University of Oxford. Telephone +44 (0)1865 222746.

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