ISSUE 65 DECEMBER 2010

Reflections on cloning
An interview with John Gurdon

Grand designs
The SGC’s 1000th protein structure released

Past presents
Christmas books from Henry Wellcome

Wellcome News
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All images, unless otherwise stated, are from the Wellcome Library. Copies of images can be obtained through Wellcome Images (images.wellcome.ac.uk).

Editorial
Elion, who worked for over 30 years at the Wellcome Research Laboratories in North Carolina. They pioneered ‘rational drug design’ – investigating specific molecular targets for potential drugs – and their achievements included the first ever treatment for leukaemia and the first immunosuppressive agent, used for organ transplants. Their work was rewarded with the 1988 Nobel Prize in Physiology or Medicine. It is rare for an organisation to have a single transformative moment. But the Trust had one in February 1986, when it floated the Wellcome Foundation on the stock market. Over the next 15 years, it sold all the shares and became fully independent. With the proceeds of the sales, it could diversify its assets, allowing extraordinary growth. In 1988 its asset base was £3.4 billion; today it is around £13bn. Annual spending on research was on average £28m in the 1980s; today, it is around £600m – a more than 20-fold increase. So these are the bare bones of the story, but what they do not show are the personalities that the Trust has worked with. For we have been privileged to be associated with and to support the work of many superb scientists. Henry Foy, the Trust’s first scientific employee, studied malaria in Greece in the 1930s – and was captured by bandits at one point while collecting mosquitoes – then moved to Kenya. His research team eventually evolved into our Major Overseas Programme in Kenya. The sheep studies of Graham ‘Mont’ Liggins led to the now standard treatment of giving steroids to women in premature labour, to help the lungs of preterm babies. Ralph Lainson, funded by us since 1964, has transformed our understanding of leishmaniasis in South America. Sir John Sulston led the UK contributions to the Human Genome Project. Nick White’s pioneering studies of the drug artemisinin have led to its wordwide adoption in treatment for malaria. We plan a range of activities and publications for 2011 to mark this anniversary and expand upon some of these individual stories, and I hope that you will join with us in celebrating 75 extraordinary years.

The Wellcome Trust

We are a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests. www.wellcome.ac.uk This is an open access publication and, with the exception of images and illustrations, the content may, unless otherwise stated, be reproduced free of charge in any format or medium, subject to the following constraints: content must be reproduced accurately; content must not be used in a misleading context; the Wellcome Trust must be attributed as the original author and the title of the document specified in the attribution. The views and opinions expressed by writers within Wellcome News do not necessarily reflect those of the Wellcome Trust or Editor. No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. ISSN 1356-9112. First published by the Wellcome Trust, 2010. Wellcome News is © the Wellcome Trust and is licensed under Creative Commons Attribution 2.0 UK. The Wellcome Trust is a charity registered in England and Wales, no. 210183. Its sole trustee is The Wellcome Trust Limited, a company registered in England and Wales, no. 2711000 (whose registered office is at 215 Euston Road, London NW1 2BE, UK).
PU-4737.4/14.2K/11-2010/MB Cover: Professor Sir John Gurdon. See page 12.

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This document was printed on material made from 25 per cent post-consumer waste & 25 per cent pre-consumer waste.

In 2011, the Wellcome Trust will be 75 years old. We usually focus on our current activities and future plans, so this is a refreshing opportunity for us to reflect on the Trust’s history and evolution into what it is today. It is a fascinating story, of how a charitable foundation with only one asset – Sir Henry Wellcome’s pharmaceutical company, which was insolvent by 1947 – came to be fully independent and able to take a world-leading role in funding research. The story of the origin of the Trust is well known. On Wellcome’s death in 1936, the share capital of his company, the Wellcome Foundation Limited, was vested in the Wellcome Trust. Income from the capital would be used to advance medical research and understanding of its history. As Wellcome pointed out in his will, “With the enormous possibility of development in chemistry, bacteriology, pharmacy and allied sciences…there are likely to be vast fields opened for productive enterprise for centuries to come.” Less well known are the struggles of the Trust’s early years. So complex were Wellcome’s affairs and diverse enterprises – and the need to pay enormous estate duties – that the Trust’s income was fairly low in its first 20 years, and its total charitable expenditure for the period was £1.2 million. The company struggled through World War II and the demands of postwar reorganisation. During the 1950s and 1960s, the Trust’s funding tended to focus on buildings, laboratories and equipment – notably electron microscopes. From the mid-1960s, it began to focus more on personal grants to individual scientists, and its funding grew markedly – as between 1966 and 1986, annual sales of the Wellcome Foundation grew from £32m to over £500m. Most of this growth was owing to the astonishing success of George Hitchings and Gertrude

Sir Mark Walport Director of the Wellcome Trust

WellcomeNews | Issue 65

In this issue
Funding
Obesity drug enters clinical trial Scurvy, shark bites and shipwrecks Senior Research Fellows update 6 7 7

2 12
News
Join the High Society Book Prize winner announced Awards for Trust photographers 2 3 4

Research

8
Features
Indian initiatives Changing fates: Sir John Gurdon Henry Wellcome’s Christmas gifts 5 12 16 Shaping up: the SGC’s 1000 protein structures 8

Plant fibres and Crohn’s disease Genes linked to asthma Dissecting macular degeneration Making liver cells in the lab

10 11 14 14

Noticeboard

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7 16
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News
Get a taste of high society Join us to celebrate 75 extraordinary years
On 25 July 1936, Sir Henry Wellcome died, aged 82. His will, which he had signed four years before, vested the entire share capital of his company, the Wellcome Foundation Limited, to create the Wellcome Trust on his death. This means that 2011 is the Trust’s 75th anniversary. Throughout 2011 we’ll be organising a series of events and activities to celebrate the thousands of achievements made over the last 75 years. Keep an eye on our publications and www.wellcome.ac.uk to find out what’s in store, and how you can be part of the celebrations.

‘Dr Syntax’ experimenting with laughing gas. Thomas Rowlandson, after William Combe. Late 18th/early 19th century.

The role of mind-altering drugs in history and culture is explored in High Society, Wellcome Collection’s latest exhibition (open until 27 February 2011). Challenging the perception that drug use is a modern phenomenon, the exhibition shows how mind-altering drugs have been used in many ways throughout history: as medicines, sacraments and status symbols, to investigate the brain, inspire works of art or encounter the divine, or simply as an escape from the experience of being ourselves. It also

demonstrates how psychoactive drugs as common as alcohol, coffee and tobacco have all been illegal in the past. Several events accompany High Society, including discussions of drugs in history and culture, and evidence-based drug policy. And in February 2011, you can also look forward to a special two-day event on drugs in Victorian Britain, examining drugs in literature and culture, the temperance movement and the origins of drug control. www.wellcomecollection. org/highsociety

All in hand

Sir Mark makes no. 2 in science ‘Power 100’

Steel replacement hand in Wellcome Collection, c.1890.

Congratulations to the Trust-associated scientists named in the inaugural Times Eureka ‘Power 100’ list of the most influential people in British science, published in October. Top of the pile is Sir Paul Nurse (right), incoming President of the Royal Society
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and Director of the Trust-backed UK Centre for Medical Research and Innovation. But a close second is our own Director, Sir Mark Walport (left). There are also several names associated with the Wellcome Trust Sanger Institute: Professor Sir John Sulston, the Institute’s first Director and pioneer of the Human Genome Project, is at number 6 and Fred Sanger himself is number 22. Professor Mike Stratton, the new Director of the Institute and one of the world’s leading cancer researchers, is number 36. Also featured are geneticist and Wellcome Trust Governor Professor Kay Davies (29) and the cancer scientist Professor Peter Ratcliffe (60).

Our hands are critical parts of our bodies, central to the objects we create and key in our physical interaction with the world. These amazing appendages were celebrated in a special Friday-night spectacular at Wellcome Collection in November. This event featured everything from the dexterity of surgery to palm and graphology readings, and talks on the evolution of left- and right-handedness. Other highlights included performances by Andrew Dawson, a physical theatre practitioner whose show, The Articulate Hand, received a Trust Arts Award in 2009. If you missed that, you can still catch the Wellcome Library’s exhibition on the hand, which uses the Library’s unrivalled collections to explore some extraordinary stories of the hand’s cultural significance and use in healing from history to the present day.

Time to reflect at the British Science Festival
following in the footsteps of Darwin. Read about their adventures on their blog (galapagoslive.wordpress.com). Elsewhere at the Festival, scientists from the Wellcome Trust Centre for Neuroimaging and colleagues reported that they have identified an area of the brain that is larger in people who are good at introspection – the ability to reflect on our own thoughts, emotions and behaviour, and one of the key aspects of consciousness. The study (Fleming SM et al. Science 2010;329:1541–3) found that differences in introspection seem connected to a small area of prefrontal cortex near the front of the brain. The team believes the findings might help us understand why and how brain damage can affect a person’s ability to reflect on their thoughts, and to develop appropriate interventions in situations such as helping patients adhere to their medication.

Trust YouTube channel breaks the 100 000 barrier

Galápagos wildlife. stockcam/iStockphoto

The British Science Festival took place at Aston University in Birmingham in September, and was the setting for several big Trust announcements. We declared the winners of our Survival Rivals competition. The students, from St Cyres School in Penarth, Wales, travelled to the Galápagos Islands in October,

And the winner is…
The second Wellcome Trust Book Prize has been won by Rebecca Skloot for her book The Immortal Life of Henrietta Lacks. The result was announced at an awards reception at Wellcome Collection in November. The book tells the story of a poor tobacco farmer whose cancer cells, taken without her knowledge, became one of the most important tools in medicine. Clive Anderson, comedy writer and presenter, chaired the judging panel, which included philosopher A C Grayling, author Maggie Gee, historian Michael Neve and scientist and presenter Alice Roberts. Skloot beat off strong competition from a varied shortlist featuring both factual accounts and gripping novels, including work by Lionel Shriver, Tim Parks and others. Launched in 2009, the £25 000 Prize highlights outstanding works of fiction and non-fiction on the theme of health, illness or medicine. The 2011 Prize is now open for submissions. www.wellcomebookprize.org

Chronic pain, appetite, ageing, dwarfism – the contents of our YouTube channel are as eclectic as the research and activities we fund. Earlier in the year, we were thrilled to find that the fruits of our two full-time film makers had been viewed over 100 000 times. And – at the time of going to press – the total views of the Trust channel now top 130 000. Recent additions include ‘Learning to Fly’ (below), a film about Professor Dame Linda Partridge and her team at King’s College London’s Institute of Healthy Ageing, who are working with fruit flies to try to understand the precise mechanisms underpinning Alzheimer’s disease. All of these films are free to view, share and embed, so visit www.youtube. com/wellcometrust to find out more.

Dartford marks Wellcome connection
The town of Dartford’s connections with Sir Henry Wellcome began in 1890, when he moved his pharmaceutical business’s production base to a site there. Now, the town has commemorated these links by erecting a bandstand, which, after public consultation, has been named after Wellcome. Part of Dartford Borough Council’s plans to regenerate the town’s Central Park and restore it to its Edwardian splendour, the new bandstand is situated close to Acacia Hall, which for many years served as a site for social events for employees of the Wellcome business. With Wellcome Trust assistance, the bandstand played host to a series of traditional concerts over the summer. On 24 August it was the setting for a ceremony to mark the historic connection between Dartford and the Wellcome business. A time capsule, which contained items pertaining to both Henry Wellcome and Dartford, was buried beneath the bandstand. Attendees included staff from GSK (formed by the merger of Glaxo Wellcome and SmithKline Beecham in 2000) and Ross MacFarlane, representing the Trust.
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Dartford Borough Council

News
Awards recognise outstanding photography
Our congratulations to Wellcome Library photographers Dave Sayer and Ben Gilbert, who have scooped prizes at the Institute of Medical Illustrators annual awards. Dave, who’s also behind the photography that graces the pages of Wellcome News, won a gold award for his photograph of George Nuku at Wellcome Collection’s Skin exhibition. Dave captured George, an artist, with the Maori display case George created for the exhibition (near right). Dave was also given a bronze award for his chilling photograph of an engorged female sand fly (far right), the vector for visceral leishmaniasis – a potentially fatal tropical disease. Ben was presented with a bronze award for his striking photograph of a 19th-century wax embryo (below), recognising his excellent use of technique. www.imi.org.uk

Telling stories in science: report out now
In December 2009, 84 delegates from 22 countries met in Bangalore, India to participate in the second Wellcome Trust International Engagement Workshop: ‘Telling Stories’. Health researchers, artists, educationalists, drama and development practitioners came together to share their personal experiences and discuss lessons and ideas about engaging the public with science and why narrative matters in doing so. A full report of the meeting is now available for download: www.wellcome.ac.uk/tellingstories

Trust and others team up to drive open access
The Wellcome Trust is one of ten leading organisations from the higher education and research sectors that have joined forces to drive the implementation of open access in the UK. Open access is a part of a movement toward more openness and transparency in universities and the public sector. It promises significant benefits for universities and the UK economy as papers, educational resources and data are more widely available to support teaching, research and innovation. The ten organisations will form the UK Open Access Implementation Group and will coordinate evidence, policies, systems and guidance to make open access an easy choice for authors and one that benefits all universities. The group will also promote a deeper understanding of the opportunities that open access offers for the UK to maintain its worldwide reputation and impact. www.jisc.ac.uk/openaccess

Trust Chairman hosts dinner in Japan
At the sixth Science and Technology in Society forum in Kyoto, Japan, Trust Chairman Sir William Castell hosted a special dinner for African ministers responsible for research. The event, held in early October, introduced guests to the many Trust activities throughout Africa and explored the opportunity and barriers to building research capacity across Africa. The forum brought together over 1000 global leaders from policy, business, science and the media to discuss the progress of science and technology. www.stsforum.org

TELLING STORIES: HOW THE PUBLIC CAN ENGAGE WITH SCIENCE
Bangalore 2009 Conference Report

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nicepix25216 on Flickr

Indian initiatives
scibak/iStockphoto

In July, the Trust’s Director, Sir Mark Walport, accompanied David Cameron on a trip to India. The Prime Minister could not have had a better guide to medical research in India, with the Trust funding several innovative initiatives there. Mun-Keat Looi presents a quick guide to some of our activities.

MSD–Wellcome Trust Hilleman Laboratories
A joint venture between the Trust and Merck & Co., Inc., the Hilleman Laboratories combine the best of the business and not-for-profit sectors to develop and deliver vaccines for lowincome countries. Named after pioneering vaccine scientist Dr Maurice Hilleman, the Laboratories will provide key expertise in developing new vaccines and optimising existing ones – expertise usually available only within large companies. They will also work with vaccine manufacturers to ensure that production can be scaled up and that the vaccines are affordable. As well as developing new vaccines in areas of unmet need, the Laboratories will also look to optimise existing vaccines. Since the September 2009 launch, work has been progressing on the Laboratories in earnest. The CEO, Dr Altaf Lal, and other senior staff have been appointed and their offices established in Delhi. Once operational, research will focus initially on improving Merck’s RotaTeq vaccine against rotavirus gastroenteritis by making the vaccine more stable at different temperatures, while Hilleman’s international Strategic Advisory Committee, chaired by Dr David Heymann (former Assistant Director General of the World Health Organization), will examine future priorities. www.hillemanlaboratories.in

programmes. The aim is to support the most promising researchers at three specific career stages: early, intermediate and senior. The Alliance has so far awarded eight early-stage project grants, ten intermediate fellowships and ten senior fellowships. www.wellcomedbt.org

the five London institutions that make up the Wellcome Trust Bloomsbury Centre for Clinical Tropical Medicine. Network partners, which include research groups across India and in Pakistan, Bangladesh and Sri Lanka, share skills and knowledge to try to improve the prevention and control of chronic disease in South Asia.

R&D for Affordable Healthcare for India
This initiative looks to bring together researchers from the public and private sectors, largely working in India, to develop innovative new devices, diagnostics, medicines and vaccines. Announced during Sir Mark’s visit, this £45 million partnership between the Trust and the Indian Department of Biotechnology follows a successful pilot scheme. The initiative has a number of awards in the pipeline in areas such as cardiovascular disease, tuberculosis and ophthalmology. One such project is a collaboration between the LV Prasad Eye Institute in Hyderabad and the University of Sheffield to develop and use new biocompatible materials for a stem-cellbased therapy to restore sight where the cornea has been damaged by chemical injury or burns. The initiative’s funding committee has made five awards to date, with others to come. www.wellcome. ac.uk/techtransfer/india

Indian Programme Awards
For many years, the Trust has supported research on the Indian subcontinent on a wide variety of topics in the history of medicine, such as public health, epidemics and historical epidemiology, and the interaction of Western and traditional systems of medicine. To build on this, this year saw the launch of the Indian Programme Awards. This scheme will provide up to five years of flexible support for medical humanities researchers in India. The aim is for grantholders to act as a ‘hub’ of research and training activities in medical history and humanities for their own region or state and develop local collaborations across several disciplines, enabling a more fruitful dialogue between the humanities, public health workers and policy makers.

Debating Matters
In 2009, in partnership with the British Council, we took the ‘Debating Matters’ competition to India. This brings together students from all backgrounds to debate topical scientific issues. An extended Society Award from the Trust saw the competition run for a second time in January 2010 with a final in Delhi, and a third competition will run in 2011. www.debatingmatters.com/ projects/debating_matters_india/

Wellcome Trust–DBT India Alliance
A five-year, £80 million initiative between the Trust and the Indian government’s Department of Biotechnology, the Alliance seeks to strengthen Indian biomedical sciences through a series of fellowship

South Asia Network for Chronic Diseases
In 2008, Professor Shah Ebrahim was granted a £4.5 million Strategic Award to establish the South Asia Network for Chronic Disease, a collaboration between the Public Health Foundation of India and

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Funding
Obesity drug enters clinical trial
A promising anti-obesity drug has entered its first phase I clinical trial. With funding from our Seeding Drug Discovery initiative, Professor Steve Bloom and his team at Imperial College London have developed a novel, synthetic form of a gut hormone, pancreatic polypeptide, that naturally suppresses appetite. Their lead compound

Trust partners up to promote prevention
We have agreed to commit up to £2 million to the latest call for proposals under phase 4 of the National Prevention Research Initiative (NPRI) – a partnership of governmental departments, research councils and medical charities that aims to encourage and support research into preventing chronic disease. Dr Pat Goodwin, Wellcome Trust Head of Pathogens, Immunology and Population Health, said: “The Trust’s Strategic Plan 2010–20 recognises the need to support multidisciplinary research to understand the biological, social and environmental factors that influence lifestyle decisions and inform prevention strategies at the population as well as the individual level. The research supported under NPRI phase 4 will provide an evidence base to inform policy on interventions at the population level.”
Public health poster, 1946.

Support renewed for Kenya Programme
activities for the next five years. A collaboration between the University of Oxford and the Kenya Medical Research Institute, the KEMRI–Wellcome Trust Research Programme studies conditions such as malaria, bacteraemias, respiratory syncytial viral infections, HIV and malnutrition. A separate £1.2m award will establish a new link between the Programme and Muhimbili University in Dar es Salaam, Tanzania, focusing on research into sickle-cell disease.

was shown to cause a significant reduction in food intake and body weight in mice and entered human trials earlier this year. If successful, the proposed research may lead to a treatment within five to eight years. You can watch a video about this research (see stills above) at www. wellcome.ac.uk/obesitytreatment or www.youtube.com/wellcometrust

Kilifi District Hospital, Kenya. Mark Jones

Our Major Overseas Programme in Kenya continues to make important contributions to tropical medicine and has been awarded £32.5 million to support its

Awards to support genetics innovations
Back in July 2009, we opened the Health Innovation Challenge Fund to stimulate the development of innovative healthcare products, technologies and interventions. We have made the first awards and among those funded are two groups from the Wellcome Trust Sanger Institute. Dr Nigel Carter’s team received £10 million to improve the diagnosis of developmental disorders. They will build on the DECIPHER database – an online catalogue of genetic changes linked to symptoms – to create a more detailed resource and cheaper, more efficient diagnostic microarray tools for genetic testing. Meanwhile, Dr Peter Campbell and colleagues will use their £1.6m award to develop ways to identify DNA fragments from specific cancer tumours in a patient’s bloodstream. This could offer a way to monitor patient responses to treatment and to predict Anthea Sieveking relapses. www.wellcome.ac.uk/hicf
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Support to study cells
A pair of new Wellcome Trust awards will allow University of Oxford researchers to gain further insight into two important aspects of cell function. Professor Kim Nasmyth has received a £2.8 million programme grant to study cell replication, in particular how DNA segregates to opposite sides of the cell before it divides. Of key interest is cohesin, a protein complex previously identified in yeast studies. This research should improve our understanding of what causes a broad range of genetic disorders. Linked to this work, Professor Nasmyth and his colleagues have also been given a £3.8m Strategic Award to develop novel microscopes to help visualise how DNA moves during the segregation process. Meanwhile, a team led by Professor Peter Ratcliffe (pictured) has received a £1.3m programme grant to study

Senior Research Fellows latest
One achievement we’re particularly proud of is our role in the long-term career development of outstanding researchers, several of whom have recently received Trust Senior Research Fellowships. Dr Adele Marston was previously a Wellcome Trust Prize Student, a Travelling Fellow and a Research Career Development Fellow, and studies cell division at the Wellcome Trust Centre for Cell Biology in Edinburgh. Dr Heidi Johansen-Berg, who researches brain changes associated with learning and recovery from stroke at the University of Oxford, is also on her fourth award, as is Professor Nancy Papalopulu of the University of Manchester, who studies the development of neurons. Finally, Professors Sophie Scott and Greg Towers of University College London have received their third Trust awards to continue their research into the neurobiology of speech and molecular virology, respectively.

Robert Taylor

hypoxia – when cells are starved of oxygen. The team’s previous work has revealed much about how cells sense and respond to hypoxia. Their new research will look at the signalling molecules involved to understand better how cells respond in this situation. Such knowledge will guide the design of drugs for cardiovascular disease and cancer, in which hypoxia plays an important role.

Scurvy, shark bites and shipwrecks

New grants to research history of antipsychiatry movement
Until the 1960s, psychiatric patients were stigmatised as ‘ill’ and asylums were little more than prisons. A group of psychiatrists revolted, advocating more humane treatment. This was the beginning of the ‘anti-psychiatry movement’, which is explored in two new Medical History and Humanities grants. Professor John Foot of University College London is studying the Italian psychiatrist Franco Basaglia, a key figure who spearheaded the reform of Italian asylums. Meanwhile, Professor Howard Caygill and Dr David Reggio of Goldsmiths, University of London are investigating the factors that led to reform in Brazil, and how changes in France had an influence.

With Trust funding, the National Archives has opened up and made accessible over 1000 Royal Navy medical officers’ journals, compiled by Royal Navy surgeons and assistant surgeons who served on HM ships, hospitals, naval brigades, shore parties and on emigrant and convict ships from 1793 to 1880. The journals tell of ship life, including drunken rum-related incidents, venereal disease, shark bites, scurvy (above), tarantulas, gunfights, mutiny, shipwrecks, arrests and courtsmartial. www.nationalarchives.gov.uk/ surgeonsatsea

The National Archives

Corridor in High Royds Hospital, Yorkshire, formerly a Victorian lunatic asylum. By Paul Digby.

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Shaping up
In September, the Structural Genomics Consortium (SGC), an international public– private partnership that aims to determine three-dimensional structures of medically important proteins, announced the release into the public domain of its 1000th high-resolution protein structure. We’ve picked five structures from this 1000, which have been solved by researchers working in SGC laboratories around the world, and give you the lowdown on their structures and functions below. Find out more on all of the structures determined by the SGC, including additional ‘follow-on’ structures, at www.thesgc.org/structures.

Self-renewal in stem cells
STRUCTURE 1000: JMJD2C

The structure of JMJD2C was solved as a part of an SGC programme focused on epigenetic signalling. Epigenetics is the study of inherited changes in gene expression – how genes are switched on or off – that occur without a change in the DNA sequence. What does it do? JMJD2C is believed to be an important epigenetic regulator. Established functions include a role in mainaining self-renewal in stem cells as well as roles in cancer; changes in this gene are for example associated with oesophageal squamous cell carcinoma. Solved by: A team led by Prof. Udo Opperman, University of Oxford (paper to be published).

Regulating cell processes
STRUCTURE 870: TNKS2

TNKS2 belongs to a class of proteins, PARPs, that regulate key functions in the cell. Some, PARP1 and PARP2, are involved in repairing DNA damage, and are pursued as drug targets for development of new treatments for different types of cancer. What does it do? TNKS2 is involved in the control of several processes that are often misregulated in cancer cells. They are therefore also attracting significant interest as drug targets for cancer. Solved by: A team led by Dr Herwig Schüler, Karolinska Institute, Stockholm (J Med Chem 2010;53:5352–5).

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Making energy
STRUCTURE 764: PKM2

What does it do? PKM2 is a key metabolic enzyme involved in generating energy within cells. It has been linked to diseases related to both glucose and oxygen use, such as diabetes, and the development of blood vessels. PKM2 is typically found in lung tissue as well as all cells with high rates of nucleic acid synthesis, including all proliferating cells such as embryonic cells and especially tumour cells. Solved by: A team led by Dr Hee-Won Park, University of Toronto (Bioorg Med Chem Lett 2010;20:3387–93).

Unwinding DNA
STRUCTURE 868: RECQL IN COMPLEX WITH DNA

What does it do? RECQL is a so-called DNA helicase, a group of proteins that unwind and separate the two strands of the DNA helix to facilitate processes such as DNA replication, transcription and repair. The RecQ family of DNA helicases is conserved in organisms from bacteria to human: E.coli and yeast produce just one RecQ protein, whereas the human genome has five distinct family members. Mutations in the genes that produce these proteins cause genetic disorders that result in a high incidence of cancer and chromosomal instability, as well as gene-specific defects such as premature ageing and developmental defects. Solved by: A team led by Dr Opher Gileadi, University of Oxford (Biophys Chem 2010;149:67–77).

Controlling the cytoskeleton
STRUCTURE 989: SHIP2

What does it do? SHIP2 regulates the actin cytoskeleton in the cell and plays an important role in the control of insulin sensitivity. Genetic differences in the SHIP2 gene have been linked to type 2 diabetes, hypertension and obesity. The structure provides novel insights into enzymatic function and molecular recognition. Solved by: A team led by Prof. Pär Nordlund, Karolinska Institute, Stockholm (paper to be published).

Images courtesy of Dr Wen Hwa Lee, Structural Genomics Consortium

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Research
Human malaria began in gorillas, study shows
Researchers have recently shown that the most common form of human malaria – caused by Plasmodium falciparum – originated from infected gorillas, though it remains unclear when the disease jumped to humans. The finding contradicts earlier studies’ claims that the disease began in chimpanzees and bonobo apes. Using techniques developed for HIV analysis, scientists from the University of Alabama at Birmingham, the Wellcome Trust Sanger Institute and colleagues identified the malaria parasites infecting apes. They analysed over 2700 ape faecal samples collected from 57 field sites throughout central Africa. They found a nearly perfect genetic match between the human malaria parasite P. falciparum and those infecting wild gorillas. The parasite was widespread, with up to half of the apes in some communities were infected. It is not known whether infection causes malarialike disease in apes. “Like AIDS, malaria is of primate origin.

rowan.simpson on Flickr

Studies of the primate precursors of HIV have unravelled many aspects of AIDS pathogenesis. I expect the same to happen when the biology of the gorilla precursor of P. falciparum is compared to that of its human counterpart,” said Dr Beatrice

Hahn from the University of Alabama, who led the research.
Liu W et al. Origin of the human malaria parasite Plasmodium falciparum in western gorillas. Nature 2010;467(7314):420–5.

Can plant fibres help treat Crohn’s?
Fibres found in vegetables such as broccoli and plantain can prevent bacteria from penetrating cells of the gut, considered to be a key stage in the onset of Crohn’s disease, according to a study we have part-funded. People with Crohn’s disease have been shown to have higher numbers of a particular strain of E. coli sticking to the gut wall. The ‘sticky’ E. coli are capable of penetrating the gut wall via specialised cells called M cells. It is thought that this triggers an immune reaction and chronic inflammation, which causes the symptoms

Gene findings add to tall story
Hundreds of common genetic variants across the human genome influence adult height, according to a study of over 180 000 people. The research shows that these variants are not randomly distributed, but clustered around genes that have been linked to growth. The researchers from the GIANT Consortium, including teams from the UK, the USA, Iceland and the Netherlands, identified a total of 180 genetic variants that influence height. Yet they say this still only accounts for around 10 per cent of our inherited variation in height, showing just how complex the trait is. It’s estimated that over 80 per cent of the variation in height within a population is due to genetic factors, with the remainder influenced by the environment, such as diet.
GIANT Consortium. Hundreds of common variants clustered in genomic loci and biological pathways influence human height. Nature 2010;467(7317):832–8.

elena’s pantry on Flickr

Arthur Chapman on Flickr

that are associated with Crohn’s disease. In cell culture experiments and in samples of human intestinal tissue, the researchers found that soluble fibres from
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broccoli and plantain prevented E. coli from getting into M cells. In contrast, polysorbate-80, a common stabiliser added to processed foods, encouraged the movement of bacteria through the cells. This latter finding may offer a potential explanation for the association between Crohn’s disease and the ‘Western’ diet. The research was performed by researchers from the University of Liverpool working with biotechnology company Provexis. They are now conducting clinical trials to test whether a new plantain-based food product could be used to treat patients with the disease.
Roberts CL et al. Translocation of Crohn’s disease Escherichia coli across M-cells: contrasting effects of soluble plant fibres and emulsifiers. Gut 2010;59:1331–9.

Sleep apnoea linked to changes in brain structure
Obstructive sleep apnoea occurs when someone stops breathing while sleeping, because their airway at the back of the throat becomes blocked. This can lead to excessive sleepiness, increased risk of stroke and heart attack, and cognitive impairment. The changes in the brain that cause these cognitive effects are little understood, and studies into links between sleep apnoea and changes in brain structure have so far yielded conflicting results. Now, research from the UK and Australia has reinforced the idea that there are differences in brain structure between people with sleep apnoea and healthy controls, although more work is needed to understand how these differences affect brain function. For the study, 60 people with severe sleep apnoea were recruited from sleep clinics at the Royal Brompton and Charing Cross Hospitals in London and Austin Health, Melbourne, alongside 60 healthy controls. The researchers used magnetic resonance imaging to compare the volume of grey matter in the two groups. Compared with controls, people with sleep apnoea had significantly reduced amounts of grey matter in the temporal lobe and the cerebellum. The team concludes that these deficits could negatively affect motor processing and working memory – which could, in combination with sleepiness, impair the everyday tasks such as driving that suffer as a result of sleep apnoea. The condition is thought to affect around 2–4 per cent of younger adults and over 15 per cent of elderly people.
Morrell MJ et al. Changes in brain morphology in patients with obstructive sleep apnoea. Thorax 2010;65:908–14.

More genetic variants linked to asthma
A large international study that we partfunded has identified several genetic variants that increase susceptibility to asthma in the population. Researchers from the GABRIEL consortium – a collaboration of 164 scientists from 19 countries in Europe – along with other groups in the UK, Canada and Australia looked at DNA samples from 10 000 children and adults with asthma, and 16 000 non-asthmatics, to pinpoint differences in sequence. The seven locations they found contribute to asthma

Study uncovers genetic component to ADHD

Artwork illustrating neural development. Bill McConkey

Researchers have found the first direct evidence that attention deficit hyperactivity disorder (ADHD) has a genetic component. Scientists at Cardiff University found that children with ADHD were more likely than other children to have small segments of their DNA – known as copy number variants – duplicated or missing. They also found significant overlap between these segments and genetic variants implicated in autism and schizophrenia, providing strong evidence that ADHD is a neurodevelopmental disorder.

“We hope that these findings will help overcome the stigma associated with ADHD,” says Professor Anita Thapar, who led the study. “Too often, people dismiss ADHD as being down to bad parenting or poor diet. As a clinician, it was clear to me that this was unlikely to be the case. Now we can say with confidence that ADHD is a genetic disease and that the brains of children with this condition develop differently to those of other children.”
Williams NM et al. Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. Lancet 2010 [Epub ahead of print].

in more than a third of children with the disease. Strong environmental effects on asthma mean that these markers will not be useful for predicting asthma early in life, but the findings point the way towards better-targeted therapy. Childhood asthma, which can persist throughout life, is often linked to allergies, and it has been assumed that these can trigger the condition. Yet the study found that genes controlling the levels of immunoglobulin E (IgE) – elevated levels of which are associated with allergies – had little effect on the presence of asthma, suggesting that allergies are more likely to be a consequence of asthma than a cause. Professor Miriam Moffatt from Imperial College London, one of the study’s leaders, said: “This does not mean that allergies are not important, but it does mean that concentrating therapies only on allergies will not effectively treat the whole disease.”
Moffatt MF et al. A large-scale, consortium-based genomewide association study of asthma. N Engl J Med 2010;363(13):1211–21.

WellcomeNews | Issue 65 | 11 WellcomeNews | Issue 61 | 11

Changing fates: Sir John Gurdon
Professor Sir John Gurdon is the man who made cloning possible, pioneering nuclear transfer and the ‘reprogramming’ of the fate of cells. Yet, as he tells Mun-Keat Looi, he himself owes a lot to fate and luck.
Among the clutter of John Gurdon’s brightly lit Cambridge office sits a picture frame, displaying a small scrap of browning paper from an early school report. It reads: “I believe he has ideas about becoming a scientist…this is quite ridiculous…it would be a sheer waste of time, both on his part and of those who have to teach him.” Professor Sir John Gurdon is now a knight of the realm, a Fellow of the Royal Society, a former Governor of the Wellcome Trust and the scientist who kickstarted the field of cloning. That he should have so utterly disproved his schoolteacher’s assessment is testimony to his passion for science – and to an element of luck. “There’s a saying: ‘Luck favours the prepared mind’,” he says. “Ninety per cent of the time things don’t work, but when they do you have to seize the opportunity.”
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Change of direction Had history taken a different turn, John Gurdon wouldn’t even be a scientist. Educated at Eton, he was on course to study classics, only to receive a surprising offer from an Oxford admissions tutor who had neglected to fill all the places at his college. Fate, if a scientist believes in such things, led the young John to follow his childhood interests and read Zoology at Christ Church. A PhD followed in 1962, and there again fate intervened. Challenged with working on transplanting a nucleus from one cell to another, John successfully ‘cloned’ the South African frog Xenopus laevis from a tadpole’s intestinal cell (“a pivotal piece of luck,” he says) by transplanting the nucleus into an empty Xenopus egg cell. The result was an organism genetically identical to the tadpole before. This proved that cells can be ‘reprogrammed’ to start anew.

The discovery caused shockwaves around the scientific community, not least because a mere graduate student had disproved previously held dogma developed by more famous and established scientists. “In the 1950s, no one knew if all cells in the body had the same genes,” says John. “The hypothesis was that as cells grew they lost the genes they didn’t need.” His finding proved that cells all carry the same

The South African frog Xenopus laevis.

genes, with other factors telling the cell which to use. The biologist John Haldane dubbed John’s achievement ‘cloning’, borrowing a term from plant biology, and a new field was born. “If you take a skin cell nucleus and put it into an egg cell which has had its own genes removed, you can get a normal animal,” John explains. “The question then was: how can it do it?”

“Ninety per cent of the time things don’t work, but when they do you have to seize the opportunity.”
Get with the reprogram John’s current research, funded by three successive Wellcome Trust grants, focuses again on the Xenopus egg cell. His research group is working to tease out the molecules and mechanisms through which they reverse specialisation. If they can work this

the components of eggs are.” There are two things you need to do to reprogram a cell: reactivate suppressed genes and activate other genes. John says: “In a specialised cell, a lot of genes are switched off by suppressor molecules. We want to find out what these suppressors are and how the egg removes them in reprogramming. The other thing is when you start up an embryo, certain genes need to be activated – we want to identify these and how they work.” His great hope is that we can one day generate banks of replacement heart, brain, blood, skin or other cells that are grown from our own cells and thus avoid the problems of rejection and immunosuppression that come with current tissue and organ transplants. And, unlike new methods such as induced pluripotent stem cells, reprogramming of egg cells remains, Xenopus laevis egg cells. he says, the most “natural” method, harnessing an inherent property of egg cells and creating stem cells most amenable to clinical transplantation. Prospects for regeneration We sit in his ecletically decorated office on the second floor of the Gurdon Institute, formerly the Wellcome Trust– Cancer Research UK Institute of Cancer and Developmental Biology, renamed in his honour (“A great honour but a strange feeling…like a coded message that you should be dead but have failed to do so!”). John founded the centre in 1989 with his colleague Ron Laskey and chaired it for 12 years. “We started with two groups and now there are 18. It means we can have a greater diversity of work in roughly the same field. And being in Cambridge is hugely beneficial – if we want to do something there’s almost always someone nearby doing something like it.” The future of cloning and stem cells

excites him and, though realising the vision of regenerating entire organs is still some way away, John believes that regenerating individual cells is on the horizon. He points to the work of Professor Pete Coffey, Director of the London Project to Cure Blindness and Professor of Cellular Therapy and Visual Sciences, who has managed to regenerate retinal epithelial cells from stem cells to treat macular degeneration in mice. “Progress in replicating individual kinds of cells is really quite hopeful, and

treatments are feasible if you think of neurological diseases such as Parkinson’s disease where certain cells are defective. It’s difficult but it will happen.” At the age of 77, he is fuelled by the same curiosity and passion that took him to Oxford in the 1950s, work that still spurs him to arrive early in the lab. “I once asked Dame Miriam Rothschild [the British zoologist and author] what it is like when you reach an older age. She said to me: ‘You just have to focus more and more on what you really know about.’ So if you focus down, one can still get a lot done, even in your later years.” In that fateful school report, his teacher wrote that the young John “will not listen, but will insist on doing his work in his own way”. How fortunate. References
Gurdon JB. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol 1962;10:622–40. Gurdon JB, Colman A. The future of cloning. Nature 2000;402:743–6. Gurdon JB, Byrne JA. The first half-century of nuclear transplantation. Proc Natl Acad Sci USA 2003;100:8048–52. Gurdon JB. From nuclear transfer to nuclear reprogramming: the reversal of cell differentiation. Ann Rev Cell Dev Biol 2006;22:1–22. Gurdon JB, Melton DA. Nuclear reprogramming in cells. Science 2008;322:1811–5.

out, it may one day be possible to create an endless supply of embryonic stem cells from adult cells. “It’s remarkable that an egg cell – this single cell – has every instruction it needs to turn itself into a complex organism,” says John. “It knows how to go through this remarkable process; that is an amazing phenomenon. Yet there are very few people worldwide trying to work out what

WellcomeNews | Issue 65 | 13

Research
Pharma collaborations bear fruit
Two collaborations between Trustfunded researchers and pharmaceutical companies have yielded groundbreaking results. An international collaboration, including scientists from the Novartis Institute for Tropical Diseases, has developed a potent new drug candidate for malaria. Tests have shown that it can clear malaria in mice with a single oral dose. Meanwhile, researchers from GlaxoSmithKline have published detailed X-ray crystallography pictures that reveal how a new type of

Team finds mutation involved in macular degeneration
leads to the death of photoreceptor cells and thus loss of central vision. Professor Tony Day, Dr Simon Clark and Professor Paul Bishop found that the Y402H polymorphism of the CFH gene altered the function of complement factor H, a key protein that helps prevent damage to the body. This coding change reduces the protein’s ability to bind to the part of the retina where drusen accumulate, suggesting a potential mechanism through which age-related macular degeneration develops. The finding could help us develop new therapeutic strategies for treating or preventing the condition.
Clark SJ et al. Impaired binding of the AMD-associated complement factor H 402H allotype to Bruch’s membrane in human retina. J Biol Chem 2010;285(39):30192–202. Clark SJ et al. Complement factor H and age-related macular degeneration: the role of glycosaminoglycan recognition in disease pathology. Biochem Soc Trans 2010;38(5):1342–8.

Macular degeneration.

Researchers from the Wellcome Trust Centre for Cell-Matrix Research in Manchester have revealed more about how a particular genetic change significantly raises the risk of developing age-related macular degeneration. This disease, the major cause of blindness in the Western world, is preceded by the build-up of small yellow particles (drusen) in the retina. This

Linking lipids to coronary artery disease
Researchers from the Wellcome Trust Sanger Institute have shed further light on why lipids (fats) and the body’s lipid transporters are important indicators for coronary artery disease. Looking at the genomes and gene products of a sample of people in Finland, they found a correlation between a network of inflammatory genes and levels of lipids in the blood. Furthermore, the expression of the genes involved was so highly coordinated that they appeared to function as part of a single pathway, itself highly correlated with and reactive to lipid levels. The findings provide an insight into how lipids activate circulating immune cells, potentially contributing to coronary artery disease.

The new GSK antibacterial (yellow) latches onto the topoisomerase enzyme and prevents it from performing its function. Ben Bax

experimental antibiotic can kill bacteria that are resistant to existing treatments. The findings could help scientists to develop new antibiotics to tackle the bacteria responsible for many hospitaland community-acquired infections.
Rottmann M et al. Spiroindolones, a potent compound class for the treatment of malaria. Science 2010;329 (5996):1175–80. Bax B et al. Type llA topoisomerase inhibition by a new class of antibacterial agents. Nature 2010:466(7309):935–40.

An artery with thickened walls. Inouye M et al. An immune response network associated with blood lipid levels. PLoS Genet 2010;6(9):e1001113.

Researchers make liver cells to model disease
Scientists from the University of Cambridge have created diseased liver cells from a small sample of human skin, showing for the first time that stem cells can be used to model a diverse range of inherited disorders. Liver cells (hepatocytes) cannot be grown in the laboratory, which makes researching liver disorders extremely difficult. By replicating the organ’s cells, researchers can not only investigate exactly what is happening in a diseased cell but also test the effectiveness of new therapies to treat these conditions.
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A liver cell. University of Edinburgh

from people with genetic diseases are ‘cured’ and transplanted back. “We know that given the shortage of donor liver organs, alternative strategies must urgently be sought,” said Dr Tamir Rashid, lead author on the paper. “Our study improves the possibility that such alternatives will be found, either using new drugs or a cell-based therapeutic approach.”
Rashid ST et al. Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J Clin Invest 2010;120(9):3127–36.

It is hoped that this discovery will lead to individually tailored treatments and eventually cell-based therapy, where cells

Q&A: David Rubinsztein
some of the key pathologies you see in Parkinson’s disease. First, it’s plausible that since this extra α-synuclein does impede autophagy, then cells will be more prone to developing protein aggregates. Second, one of the common abnormalities in Parkinson’s disease is malfunction of the mitochondria within cells. Unhealthy mitochondria produce increased levels of reactive oxygen species, among other things, which are harmful to a cell. Since autophagy can selectively remove and degrade malfunctioning mitochondria, these will be more likely to accumulate when there is excess α-synuclein. the impaired autophagy caused by high levels of α-synuclein. What are the implications of your findings? Our data provide some plausible explanations for the cellular abnormalities you see in Parkinson’s disease. Certainly, too much α-synuclein is not a good thing. But the effects we see are only a partial block on autophagy, not a full block. The question is: is that significant? Over many decades of life, as is the scenario in Parkinson’s disease, I think it is likely to be of consequence. But autophagy is probably just one of the players in the orchestra regulating cellular health in Parkinson’s disease. Our data also tell us how disrupting some of the machinery involved in the early secretory pathway might have an impact on autophagy. However, some of our data suggest that disrupting other machinery involved in the early secretory pathway does not result in the same type of block in autophagy. So there may be some specificity to the way Rab1a works in this context. What’s next for your research? We need to understand how exactly α-synuclein is impairing Rab1a function. It is likely – on the basis of the Lindquist data – that if one impairs Rab1a function with α-synuclein you are also going to affect other aspects of cellular health. A molecular understanding of that will be challenging but useful. We also need to know how exactly Rab1a affects autophagy. That’s important not only from the disease perspective but also for understanding the relationship between signals coming from the early secretory pathway to autophagy, and the protein degradation in the rest of the cell. There are quite a few black boxes that need to be tackled there. What do you do outside of work? I’m a keen cellist and like listening to music. I also enjoy reading, particularly biographies.
Winslow AR et al. α-Synuclein impairs macroautophagy: implications for Parkinson’s disease. J Cell Biol 2010;190(6):1023–37.

Around one person in every 500 – some 120 000 people in the UK – develops Parkinson’s disease. Professor David Rubinsztein, a Wellcome Trust Senior Research Fellow at the Cambridge Institute for Medical Research, studies how genetic mutations lead to neurodegenerative diseases. A recent paper from his group revealed more about how certain mutations may cause toxicity in neurons in forms of Parkinson’s. What is α-synuclein? α-synuclein is a protein that is the predominant component of the clumps seen in neurons in Parkinson’s disease. Recent discoveries have shown that certain people have extra copies of the α-synuclein gene, and these people develop early-onset forms of Parkinson’s disease. What was the aim of your study? Our study looked at whether autophagy – a process through which cells engulf cytoplasm, organelles and protein complexes and deliver them for degradation – is abnormal when α-synuclein is overexpressed. This evolved from one of our earlier studies, which found that α-synuclein enhanced the aggregation of mutant forms of huntingtin [the protein associated with Huntington’s disease]. We later discovered that mutant huntingtin was degraded by autophagy. The question was: does α-synuclein block autophagy? What did you find? Increased levels of α-synuclein do indeed block autophagy. This could explain

Mitochondrion surrounded by cytoplasm. Dr David Furness

How does Rab1a fit into this? Rab1a was a clue that we got from a study by Susan Lindquist’s lab at the Whitehead Institute in the USA. It’s a molecule that helps to transport proteins when they are first produced (this is known as the early secretory pathway). Lindquist’s group found that Rab1a activity was impaired in a yeast model of Parkinson’s disease. They also found they could overcome some of the toxicity of α-synuclein in fruit-fly and cultured neuron models of Parkinson’s disease by overexpressing Rab1a. We tested whether decreased activity of Rab1a impaired autophagy. And indeed it did. Interestingly, we also found that if we overproduce Rab1a, it can counteract

WellcomeNews | Issue 65 | 15

You shouldn’t have…
Every Christmas from the 1890s until 1914, Henry Wellcome gave a book to the employees of his pharmaceutical business, Burroughs Wellcome & Co. Ross MacFarlane looked through the Wellcome Library archives to find out about some of these titles and what they might tell us about Henry and his feelings towards his staff, as well as attitudes of employers in Victorian and Edwardian times more generally.
Forget socks, handkerchiefs or dodgy toiletry kits – Henry Wellcome had a consistent approach to buying Christmas presents for his staff, giving books to each employee every year. But what kind of titles did he offer and what insights can these give us into Henry as an employer and as a man? Among the titles, there’s some fiction, a little poetry, numerous biographical works and at least one compendium. Most of the titles were popular at the time, but not all of them remembered in the 21st century. A clear theme from the titles is that of self-improvement and utility. Through examples of selfmade men promoting the virtues of hard work, Wellcome was not only giving role models to his staff but also commenting on his own journey from impoverished childhood in rural America to wealth and success in London. A journey made, of course, through sheer hard work. For example, in 1907 Wellcome gave as his Christmas book Samuel Smiles’s Life and Labour (1887). One of the bestselling authors of the late Victorian period, Smiles advocated social advancement through the virtuous acts of hard work, thrift and sobriety. He can even be seen as the forerunner of the various self-help guides
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JoeBiafore/iStockphoto

you find today. Even in Wellcome’s gift of 1911 – Cassell’s Book of Sports and Pastimes – there is a sense of practicality. This title (below)was full of advice on making, mending and healthy pursuits, which suggested to the staff as they unwrapped their gifts that even their spare time should be spent in a useful, practical manner. Another clear theme in Wellcome’s choices is his growing interest in Africa. By 1914, he had not only opened the groundbreaking Wellcome Tropical Research Laboratory in Khartoum but also carried out extensive archaeological excavations in Sudan (both activities he felt had practical philanthropic benefits to the local populations). This interest in Africa comes through in his 1914 gift, The Autobiography of Sir Henry Stanley, edited by Dorothy Stanley (Henry Stanley the journalist and explorer – another self-made man – was a close friend of Wellcome’s). It’s also evident in two other choices from the 1890s:

Fire & Sword in the Sudan and With Kitchener to Khartoum – two titles on the British Army’s derring-do in Sudan in the late 19th century. Of the more famous works of literature Wellcome gave, Henry Longfellow’s romanticised poem of Native American

His choice of Gulliver’s Travels is more intriguing: perhaps Wellcome saw in Gulliver’s adventures a lone individual pulling himself through against difficult odds?
life, The Song of Haiwatha, is suggestive of Wellcome’s childhood in rural Minnesota, growing up close to the Sioux. His choice of Gulliver’s Travels is more intriguing: perhaps Wellcome saw in Gulliver’s adventures a lone individual pulling himself through against difficult odds? So, Henry Wellcome’s choice of gift does offer a degree of insight into his interests and attitudes, and also how he wished to be perceived. His selections are very much of their time – as are, however, his thoughts on his staff. In 1910, Wellcome chose Charles Darwin’s The Voyage of the Beagle. But he chose it for male employees; women received copies of the Encyclopaedia of Needlework.

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Courses, conferences and workshops
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18–20 Working with the Human Genome Sequence Workshop Dubai, United Arab Emirates 20–25 Working with Pathogen Genomes Workshop, Instituto de Higiene, Montevideo, Uruguay 23–26 Genomic Disorders 2011: The genomics of rare diseases Conference GC 30–1 Apr Cellular Cytoskeletal Motor Proteins Biochemical Society–Wellcome Trust conference GC

May
8–14 Molecular Basis of Bacterial Infection: Basic and Applied Research Approaches Advanced Course GC 9–11 Working with the Human Genome Sequence Workshop GC 18–21 Nicotinic Acetylcholine Receptors 2011 Conference GC

HeLa cancer cells in metaphase, with microtubules of the cytoskeleton in white and the motor protein kinesin in yellow. William J Moore/University of Dundee

GC: Event takes place at the Wellcome Trust Genome Campus, Hinxton, Cambs. For information on Wellcome Trust Conferences, see www.wellcome.ac.uk/conferences. For information on Advanced Courses and Open door Workshops, see www.wellcome.ac.uk/advancedcourses.

February 2011
27–2 Mar Biomarkers for Brain Disorders: Challenges and opportunities Conference GC

June
20–24 EBI–Wellcome Trust Summer School in Bioinformatics 2011 GC

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