Establishing the Vision, and the Reality in 1945

A Brief History of the Institute of Child Health

1852: The Hospital for 1866 1910: Postgraduate Medical Background Sick Children (HSC). courses at HSC expanded • Lectures for undergraduates and 1853 Pupils at the hospital for bedside tuition. postgraduates in the hospital. Smallpox vaccination 1878 made1854 compulsory • The School of Nursing established at The Hospital for Charles West publishes his book Sick Children. Florence“How Nightingaleto nurse sick in children” the Crimea; 1857-61 1884-87 Pasteur describes origin of bacteria; • Lecture theatre and course prospectus at The Hospital for Sick Children. birth 1880-83of germ theory of 1895 Pasteur develops vaccines against • The Hospital for Sick Children Medical Koch discovers tubercule bacillus chicken pox, cholera and anthrax. School established; approved by and cholera bacillus the Royal Colleges of and Surgeons First Dean; Dr F.G. Penrose. Founder — Charles West 1900 First Dean — Dr F.G. Penrose By the turn of the century progress

infection, its channels and preventative 1941: Board of Management of HSC began to discuss “new concept” of preventative applied to children. included identification of causes of and Koch), Anaesthesia (Lister), methodsRadiography of containment (Reuntgen) (Pasteur 1942 (March): HSC Subcommittee meets and makes recommendations 1905 1. Preventative and curative work c) Practice of preventative with a Dean, a Professor, • Applied Psychology Bordet and Gengou isolate should be concerted by closer whooping cough bacillus cooperation between public health hospital is a convenient centre Puberty and Delinquency. services and children’s hospitals. methods for which a children’s part-time teachers and Home discipline, School life, e) Preventative paediatrics to be infant welfare, special clinics accommodation. 1911-12 2. Preventative paediatrics furthered taught in three divisions: by setting up: forie. treatment growth disorders, of prematurity, endocrine • Applied • Applied Physiology Infant Welfare Centre and National Insurance Act; disease and nutrition. An Immunology Clinic, an Vitamins become known; Diet, Growth, Endocrines, other clinics should be set up those who will be engaged in the d) A “School of Preventative in liaison with an obstetric a) preventionA teaching departmentof disease in to children instruct Paediatrics” should be hospital for the teaching of Tuberculosis notification compulsory established in ante- and neonatal hygiene. 1924 ie. nurses, health visitors, parents Clothing, Exercise, Play, Climate, etc. with BCG vaccine nursery staff and nursery schools) Members of the subcommittee CalmettHSC and Research Guérin inject Appeal children plus(for hygieneGeneral andPractitioners. mothercraft), Manchester Guardian (28.1.1924)

for research into b) Active encouragement 1926 Discovery of penicillin by preventative medicine. 1942 (May) Sir Alexander1928 Fleming • First satisfactory iron lung (Drinker respirator) for London, London County Council and BritishInformal Postgraduate approaches Medicalto University School. of Sir Lancelot Mr Thomas Dr R.S. Lightwood Dr W.W. Payne Dr W.G. Wyllie • It was strongly felt that “it was Barrington-Ward Twistington Higgins treatment1930-40 of poliomyelitis General trend toward indroduction partessential of a larger to keep Medical it as a GreatSchool”! Ormond 1945 (13 February) of local authority health centres and scholl health and dental services • UniversityStreet scheme states and that not theto be school a minor • Mr H. Claughton, Principal of the wrote to Lord 1932 cannot be formed until after the war. Senate and Court of the University HSC are given a Drinker Respirator 1942 (November) Southwood to confirm that the of an Institute of Child Health “as a • centralhad approved activity the of theestablishment university”. 1935 to “The London School of Paediatrics” Administration of and appointments discussed with the above authorities Introduction of sulphonamides used plus Holborn Borough Council. 1945 (June) especially to combat tuberculosis • 1938 Southwood Building opened introducing single-patient 1943-44 Advertisement placed for a which was taken up by Dr (later Sir) cubicles to HSC • Nuffield Professor of Child Health Health”. Funding discussed with the Director of the Institute. Definite title now “Institute of Child who also became 1940 Mass production of penicillin University and the Nuffield Trust. and, later, other antibiotics 1944 (July) Dr Alan Moncrieff 1942 • Beveridge Report on Health And so the Institute was born. and Social Services in HSC offer accommodation including Accommodation for students at HSC an office, lecture room and common rooms for men and women students. Content researched and written by Raymond J Lunnon MPhil HonFRPS HonFIMI RMIP, Archivist, Institute of Child Health The First Steps 1945 – 1964

A Brief History of the Institute of Child Health

1945 1949 1959 Medical Background • University approves ICH as part Building Appeal of British Postgraduate Medical goes public under 1945 Year was taken up making Federation and its incorporation chairmanship of Sir Hugh Beaver. administrative, financial and academic arrangementsst for the • Child Study Centre. First course on 1 under the Companies Act, 1948. Institute to start work officially First vaccine for influenza January 1946. • Reorganisation starts. Pilot scheme for research into of Professorial 1948 1946 Dr GH Newns Growth and Development started. Medical Unit. succeeds National Health Service is established • • Dr Wyllie Child Health with a grant of £100,000. Building Appeal reachs £100,000. as Dean. Nuffield Foundation endows Chair in Building Committee appointed and Dr W G Wyllie • Marks Kennedy Trust donate £40,000 (Dean of for a lecture theatre in the building. 1952 the Hospital • Medical School) TeachingDevelopment HSC Policy& QEH, planned Clinical forGenetics, appointed first Paulirregular Zoll develops heartbeat the first 1962/67 – departments include: cardiac pacemaker to control Dean of ICH. 1955 Preventitative Paediatrics, Growth • Pathology and Museum, Enzymology, • Medical Illustration, Mental 1953 Academic Board formed with Dr history of ICH, the Province of Natal & Development, Child Psychology, Clerkships introduced. Considered to be a milestone in the WG Wyllie as Chairman and Clinical Centre was opened on 26th May by • Retardation, Professorial Departments. Teaching facilitites (HSC Outpatient for South Africa. James Watson and Francis Crick at Strong criticism over poor Outpatient MR GP Jooste, High Commissoner Cambridge University publish the • 1961 unable to rebuild until 1954). Watson,structure Crick, of andthe DNAMaurice molecule Wilkins Department demolished in 1938 and for ICH staff to lecture. • UNICEF Grant for Course for Teachers Expansion in international demands in Paediatrics ($50,000). • ICH Teaching staff now 1 Professor, or Medicine in 1962 1950 1 Reader, 4 Lecturers and over • share the Nobel Prize for Physiology 80 Honorary Lecturers in 38 Child Study Centre to Institute. • Site purchased for Model Welfare Growth Research transferred from • • 1954 Conduit and Guilford Streets) – specialisms at HSC. • Dr RS Illingworth and Dr R E Centre (bomb site on corner of Lambs Nuffield Trust fund Neonatal Research houses have 8 years to run on leases. researchDr JM Tanner started joins in staff1949. of Child Unit for five years (£55,000). Dr AP Norman Assistants to the Professor. Study Centre to continue long-term Dr. Joseph E. Murray performs Bonham Carter (above) appointed appointed Deputy 1963 between identical twins • Lecturers in Child Welfare and the first kidney transplant Director of ICH. Public Health and Recognised 1956 • Building Appeal wound up with teachers appointed. • Students ability £500,000 total achieved. • • 1955 • Weekly Child Health Conference. in English now • to communicate Nuffield Foundation mark Lord grant to endow a Chair in Paediatric Dr AP Norman conducts research Nuffield’s 80th birthday with a • polio vaccine Surgery (£80,000). into asthma. RobertsDepartment FRS. of Genetics inaugurated considered a prime facilities considered for The Hospital for Jonas Salk develops the first • Clinical Genetics Research Unit funded under the Direction of Dr JA Fraser requirement. Pickering Committee Report; combined • Sick Children, Institue of Child Health, 1951 The National Hospital for Nervous • and Dr Cedric Carter, Deputy Director. 1962 Research Committee established. by MRC; Dr JA Fraser Roberts, Director Diseases and Institute of . • Director, Dr Alan Moncrieff consolidates • New Cardiac Research Unit set up; • • Professor Alan Research projects at discussion stage. links with Africa with second visit. directed by Dr BGB Lucas and First oral polio vaccine (as an Moncrieff resigns. Doctors returning from war services Dr Cedric Carter ensuingand from year. the Commonwealth enrol • Hospital Lecture Theatre opened alternative to the injected vaccine) 1952 Mr DJ Waterston. (right) takes over as in numbers as postgraduates for the (88 seats). Already the need for Director of Clinical • a 200-seat theatre envisaged. 1964 Genetics Unit. • First BPMF Course for 1947 First full-time physiologist appointed. General Practitioners. • Twice-weekly ward rounds organised for postgraduate students at HSC and • First vaccine for measles Lord, appointed. First full-time librarian, Miss WH 1964 • Queen Elizabeth Hospital. 1953 • Professor Alan Moncrieff awarded KBE. Number of students threatens to • Plans to erect an Institute building • become unmanageable - 168 Full • Model Welfare Centre and School fronting Guilford Street and transplantation. • People of Durban, South Africa Clinic – building starts. time and 104 Part time. interconnecting with Province of Pilot scheme for research into organ and the Province of Natal donate • Appointments1958 £106,880 to establish a Model Child Natal Centre. Welfare Clinic and Health Centre at • Building Fund Appeal for £220,000. Dr JF Soothill appointed Head of Professor Andrew Wood Wilkinson the Institute. Department of Immunology. was appointed Professor in • Paediatric Surgery • Monthly research meetings start. 1948 Finanical outlook for next • Freehold of Nos. 26 to 33 Guilford quinquennium – not promising. 1964 • Street purchased by University. • ICH and Institute of Education Professor Otto H Wolff succeeds as Library transferred from HSC. set up Child Study Centre at the Foundling Hospital Nurseries in 1958 Nuffield Professor of Child Health Professor JPM Tizard was • appointed Professor of Child Health • 1954 Coram’s Fields. no increase in UGC grant for 5 years. and Neonatal Medicine Children to collaborate on teaching • Financial expansion at a standstill - andQueen research. Elizabeth Hospital for • Professor JM Tanner was appointed New Outpatient Department opened facilities for teaching. Teaching resources now fully extended Professor Child Health and Growth in Hospital; greatly improved New ICH Building begins construction - serious accommodation problem.

Content researched and written by Raymond J Lunnon MPhil HonFRPS HonFIMI RMIP, Archivist, Institute of Child Health New Building Opens 1965 – 1984

A Brief History of the Institute of Child Health

1966: Her Majesty The Queen 1975 1979 1968 • Fund Raising Policy Review; Department of Professor JF Soothill was appointed opens new Institute Building a professional fund-raiser Paediatric Nephrology set up under Professor TM Barratt Professor of Immunology appointed for first time. Professor RM Hardisty was appointed Open Day held with many visitors including donors and supporters of the Institute. • Children’s Research 1976 Fund and Mr Hugh Professor of Haematology • Mr Leolin Price QC succeeds Dr Professor AE Claireaux was annual grant of appointed Professor of Histopathology Leslie Farrar-Brown, who had been £25,000Greenwood to foster make research associated with the Institute since plus other support grants. inception. Professor Barbara E Clayton was • appointed Professor of • First bone marrow transplantation HealthSub-Committee Service. to report on the in a child performed at GOSH. Chemical Pathology Royal Commission on the National • Child Health Research Appeal Trust 1981 (CHRAT) launched. 1972 • • Institutes visits ICH. Professor JA Dudgeon was appointed Morris Committee on Postgraduate Dean formulates proposals to relieve • Gold Medal of the Children’s Hospital the serious financial situation; Professor of Microbiology redundancies, early retirements The Hospital for Sick Children and and increased income from outside Professor V Dubowitz Instituteof Philadelphia of Child awarded Health. jointly to sources to be implemented. No Hospital was appointed Professor of • departments to be closed. Paediatrics and Neonatal, Hammersmith Medicine Defects identified in Cardiac Wing; • Honorary Fellowship of the Institute 1978 completion delayed four years. conferred upon Mr Hugh Greenwood. • HM the Queen Mother inaugurates 1974 Queen Square House. Professor June K Lloyd was appointed • HRH the Duke of Edinburgh opens the 1982 Professor of Paediatrics • Professor OH Wolff succeeds Professor Perinatal Building at Hammersmith. Professor JP Graham was appointed appointed Nuffield Professor of Child Psychiatry – the • Professor of Paediatric Professor JA Dudgeon as Dean. Walker Chair of Child Pyschiatry Surgery in succession • Professor JPM Tizard knighted. to Professor AW Neonatal Medicine transferred to the Wilkinson BritishDepartment Postgraduate of Paediatrics Medical and School 1966 1970 • 1975 • • Proposals for change in the structure • Departments and at . Professor F Macartney was appointed building Wolfson Centre (£85,000). of the London Teaching Hospitals. Medicine awarded to Dr DC Morley. Chair of Immunology King Faisal International Prize in Professor of Paediatric Cardiology Wolfson Foundation make grant for Greenwood, long-standing benefactor. • CHRAT reaches £2,147,504. • Dr KS Holt appointed Director of • ICH Research Fund reorganised – named in honour of Mr Hugh Wolfson Centre. Professor C O Carter was appointed Professor of Clinical Genetics planned fund raising campaign to set 1983 1967 up Endowment Fund of £1,000,000. • Honorary Fellowship of the Institute 1971 conferred upon Dr IAB Cathie, • longstanding supporter of ICH. 1977 block at QEH - the Hayward Building. • • Plans submitted for new research Professor AD Patrick was appointed • Wolfson Centre - building starts. Institute celebrates its Silver Jubilee Wolfson Foundation Grant of £69,000. Wolfson Centre extension starts; with a Conversazione and Open Day with each department exhibiting Professor of Enzymology 1969 examples of research and teaching. 1984 1981 • National Foundation for Crippling 1972 • Rosen van Rosenstein Award given Professor JT Harries was appointed (£250,000). • ICH and Institute of Neurology • Professor of Gastroenterology Disease make grant for research negotiate lease of land to build Queen to Professor JM Tanner. • HRH The Duchess of Kent opens Square House (Phase 1 building). Minister of Health approved more • CHRAT reaches total of £2,910,719. Mr Hugh Greenwood OBE and Dr J • Tropical Child Health Unit located in remedial works to Cardiac Wing. Cathie Wolfson Centre, Coram’s Fields. • University Grant now partially related to research support. became ICH Honorary Fellows Coram’s Fields. The Hugh Greenwood 1974 Department of immunology 1983

Professor JA Dudgeon Professor Professor DC Morley was appointed succeeds Dr GH Newns Catherine Professor in Tropical Child Health (Dean since 1949). Peckham • Dr GH Newns created Dean 1984

• Teaching Aids at Low Cost (TALC) Emeritus. Professor Catherine S Peckham was appointed Professor of for distributing audiovisual and otherbecomes teaching charitable aids tofoundation developing countries. Paediatric Epidemiology Professor Professor June K Lloyd was appointed • June for a Cardiac Wing K Lloyd succession to Professor Wolff Outline planning permission given. Nuffield Professor of Child Health in

Content researched and written by Raymond J Lunnon MPhil HonFRPS HonFIMI RMIP, Archivist, Institute of Child Health A Period of Growth 1985 – 1994

A Brief History of the Institute of Child Health

1985 1989 1985 Professor BD Lake was appointed HRH Princess Royal’s visit; TALC success • CHRAT now funds nine postgraduate physicians in specialist fields of adult Professor MA Preece was appointed • Professor Philip J Graham succeeds Professor of Histochemistry studentships. medicine and may other professional Professor of Child Health and Growth Professor Otto H Wolff as Dean. CHRAT funding; more courses; Wishing Well Appeal • Many and varied courses now groups. • HRH Princess Anne, Chancellor of Professor R A Risdon was appointed run for: paediatricians, general • Wishing Well Appeal endows Chair in the University of London, visits the Professor of Histopathology practitioners, social workers, health International Child Health. Institute and addresses the students visitors, psychologists, speech and staff at the commencement of • Professor June K Lloyd appointed DBE. therapists, physiotherapists, the first course for Teachers and Planners in Community-Based 1986 Rehabilitation run by the Tropical Professor Marcus E Pembrey was Child Health Unit. appointed Mothercare Professor of • Teaching Aids at Low Cost (TALC) 1990 Paediatric Genetics becomes largest worldwide distributor of low cost slides and New Dean; closer HSC integration; new structure Professor Roland Levinsky was appointed books on child health for teachers and health workers everywhere. • Professor Roland J • New academic structure bridging Levinsky (right) succeeds ICH and HSC departments allowing Hugh Greenwood Professor of Immunology • Income from an expanded Professor Philip J closer integration of activities. teaching programme, together with Graham as Dean. 1987 economies, helps to balance costs. • ICH now structured into five divisions • Joint Strategic Planning each containing several units with Sir John Hogg appointed Honorary • The Sir Clavering Fison Visiting Group convened to research themes proposed for Fellow of the Institute in recognition of his Professorship; funded by Fison plc. consult and cooperate next five years: molecular basis longstanding services as Treasurer • The Wellcome Trust funds new between HSC and ICH. of single gene disorders; vascular Lectureships in Immunology and • External review by BPMF enables ICH and transplantation biology; Genetics. to take critical look at research strategy developmental biology, growth • The Iris Fund sponsor a non-clinical and the long-standing departmental and dysmorphology; immunity and 1988 infection; neurosciences. Senior Lectureship, in the Department structure with a view to beneficial Professor John Deanfield was appointed of . realignment to facilitate interdisciplinary Professor of Cardiology research along defined themes. Professor Brian Neville was appointed Professor of Paediatric Neurology, succeeding Professor Holt and takes charge 1992 of reorganised Department of Neurology and 1986 Developmental Paediatrics • Research grant applications now upon Dr Robin Winter, co-creator 1989 subject to “peer group review”. of the London Dysmorphology Cardiac Wing; Alternative Funding Model ResearchResearch grants growth; database DevelopmentalDatabase. Together Biology with his MRC- Unit Professor David Gadian was instituted. Review and improvement funded team, fetal medicine will be appointed Professor of Physics • Cardiac Wing wards and research Income from research grants and of research grant applications one subject of research together laboratories available. teaching continues to increase. Prince increases success rate by 35%. with the Obstetric Department of (jointly with Hunterian Institute) • New diploma courses in Paediatric Fahd bin Slaman endows a Research University College Hospital and Surgery, Child & Adolescent Fellowship in the Department of Middlesex School of Medicine. Nephrology (£200,000). The Sports 1991 Psychiatry, new one-day and other • New academic unit of Developmental Council makes a substantial five-year short courses started. Biology, funded by part of the Wishing Dr MW Turner was appointed grant. CHRAT continues finance for Well Appeal, has Professor Peter • New scheme for Clinical Fellowships important research and its investment Thorogood as Head together with an started. company, the Child Health Research was appointed entire research team of eighteen scientists. ProfessorProfessor SG of MolecularHaworth Immunology • University funding for the Institute now Investment Trust Company, is Professor of Paediatric Cardiology less than 30% of its total revenue. continued for a further seven years. • Senior researchers appointed to investigate fields including: gene Professor DJ Hatch was appointed Professor expression in early mammalian development; European treatment trials for HIV Infection; respiratory of Paediatric Anaesthesia, endowed by Smith 1987 epidemiology; molecular Industries as the Portex Chair of Paediatric haematology; medical audit and ProfessorAnaesthesia, Hatch was the appointed first in the Head UK of the health services research; molecular pathology and behavioural sciences. Respiratory Medicine Portex Unit of Paediatric Anaesthesia and • Major initiative to improve the image • New Academic Plan: prospect • Links to be established with European Professor J Fabre, Head of the Division of both the BPMF and ICH on all fronts. of establishment of Chairs in • Eighteen new clinical and basic centres and help establish postgraduate of Cell and Molecular Biology was International Child Health and research staff join ICH as result of medical education in Eastern Europe. appointed The Vandervell Chair • Laboratory space expanded in the of Paediatric Cardiology Cardiac Wing and development of Virology; New MSc course in Wellcome programme and transfer • Continued expansion of PhD Morespace on Ground Labs; Floor of Province New AcademicMother and Child Health; New Plan Sub- team from Hunterian Institute. Title of studentships – more than ninety are of Natal Building vacated by Department of Radiology. Reader in Clinical Genetics conferred now registered. District Health Authority. • Grants and Gifts now cover 75% of 1992 • Wolfson Foundation finance major ICH annual expenditure. Professor Peter Thorogood was refurbishment of two floors of the • Leukeamia Research Fund make appointed to the newly-established Chair of Institute Building. grant to fund Chair in Haematology 1993 and Oncology, plus supporting staff, for next ten years. Professor DevelopmentalJames V Leonard Biology was appointed Professor of Metabolic Medicine • A new academic unit of Molecular schools and suggests ICH should Medicine has been formed, headed merge with University College in the Mrs Caroline Bond, Lady 1988 Molecularby Dr Peter Scambler, Medicine; and includes Tomlinsonnext five years. Review Callaghan and Dr G Piller his research team of eleven scientists • Research and Development Director to research the genes involved in Dr at Department of Health initiates became ICH Honorary Fellows George syndrome and other related review of research in London’s cardiac defects, plus establishing a SHAs and Institutes. ICH and GOS • European Collaborative Study on • Courses for MRCP (Paediatrics) somatic-gene therapy programme. 1993 Paediatric Aids (Department of and the Diploma in Child Health research teams highly placed, either Professor Al Aynsley-Green appointed to Epidemiology). commenced. • New research initiatives and equal to national or amongst beset Commercial Funding; Research successes appointments not in place at time internationally, 80% being in the • Mothercare pls pledge funding for • Noteworthy research achievements of UFC Research Review (four latter category. Professor A Todd-Pokropek was appointed next decade for Mothercare Unit of include: completion of a national years ending June 1992). Results the Nuffield Chair of Child Health Paediatric Genetics. iuunidation survey; discovery of the • London Implementation Group Professor of Medical Physics were therefore disappointing, but recommends strengthening the • KabiVitrum fund major project in chromosomal defect in Angelman understandable. Public Health and syndrome (Department of Genetics); ICH/GOS multi-specialty paediatric Child Growth in Department of Epidemiology receive high awards. centre, and paediatrics as the Growth and Development with identification of mannan binding protein as a causative factor in • New method of rating for Higher Royal Free, University College 1994 Middlesex/University College. Education Funding Council for and Middlesex Hospitals to be opsonization defect (Department of was appointed • Wolfson Foundation fund Child results in reduction of amalgamated with GOS. Professor Robin Winter Immunology). Professor of Clinical Genetics and Health monitoring Unit in Department HEFCE funding for ICH. • Professor Al Aynsley Green succeeds of Epidemiology (£300,000). • Professor June K Lloyd awarded the Rosen van Rosenstein Medal for • Tomlinson Review of London Professor Roland Levinsky as • MSc Course in Community service to paediatrics. Medicine recommends that medical Director of Clinical Research and Professor DavidDysmorphology H Skuse appointed to the Paediatrics inaugurated. colleges merge with multi-faculty Development for GOS. Chair of Behavioural Sciences

Content researched and written by Raymond J Lunnon MPhil HonFRPS HonFIMI RMIP, Archivist, Institute of Child Health 50th Anniversary 1995 – 1999

A Brief History of the Institute of Child Health

1995 1998 1995 Professor Robin Winter was appointed HRH Princess Royal’s visit; UCL affiliation Professor of Clinical Genetics and Professor Paul Brickell was appointed to • The Institute of Child Health • The Wellcome Trust Building was • The completion of the building with Dysmorphology celebrated its 50th Anniversary on 7 officially opened on 30 January its emphasis on attractive circulation February 1995 with a Scientific Open The University of London conferred the 1998 by Sir Roger Gibbs, Chairman and exhibition areas marked a the Chair of Molecular Haematology Afternoon commencing with a visit by of the Wellcome Trust, and by Sir significant step in the Dean’s Wellcome Building official opening on HRH The Princess Royal, Chancellor Robert Clarke, Chairman of the stated intention of improving the Professor Marilyn Monk title of Professor of Molecular Embryology of the University of London. The Special Trustees for Great Ormond environment, thereby both retaining, Sir A Tippet Chancellor viewed an historical Street Hospital, following a Scientific and attracting, good staff to work in exhibit showing the developments Symposium which also included an the Institute. became ICH Honorary Fellow that had taken place in the Institute Inaugural Lecture by Professor John 1996 since 1945 and several displays Deanfield, Professor of Cardiology. depicting the current research work Professor Peter Scambler was appointed of the Institute. An anniversary Professor of Molecular Medicine cake was cut by the Princess and The Wellcome Trust Building new facilities Professor Robin Callard was appointed the Dean in front of a capacity audience in the Kennedy Lecture Professor Sue Malcolm was appointed Professor of Immunology Theatre. This event was followed by Professor of Molecular Genetics the inaugural lecture by Professor Robin Winter, the newly appointed Professor Sally McGregor was appointed Professor of Clinical Genetics and Professor of Child Health and Nutrition Dysmorphology. Afterwards, visitors Professor Stephan Strobel was appointed toured the research departments of Professor of Paediatrics and Clinical the Institute • Later that year on 31 July 1995, Professor Bryan Winchester was Immunology the Institute severed its long- the University of London and, on 1 August 1995, became affiliated with standing relationship with the British Professor Alan Lucas was appointed University College London. appointed Professor of Biochemistry Postgraduate Medical Federation of Professor of Paediatric Nutrition Professor Andrew Copp was appointed

Glaxo Wellcome Chair of 1996 Professor Alan Lucas was appointed Developmental Neurobiology Professor of Paediatric Nutrition Professor David Beach was appointed

established Hugh and Catherine Stevenson • The full merger with UCL attainable levels of international as the firstChair Chairholder of Cancer Biology. of the newly- took place on 1 August 1995 excellence in virtually all others”. This following the passing into law dramatic improvement in the quality Professor Philip J Graham, Professor of the University College Act. assessment grade was greeted with D Landon, Syliva Countess of Limerick FullThis Act alsoUCL provided formerger; the a greatRAE sense of Gradeachievement by staff 5 CBE, Mr N K Maitland, Professor E O R Institute of Neurology and mixed with relief that the Institute’s Reynolds, Professor Sir Michael Rutter, the School of financial well-being was assured Sir Hugh A Stevenson, Mr Michael J Medicine to merge with the College for another four years until the next Todhunter, Mr Leolin Price, Mr R C

in the next few years, thus creating assessment at the turn of the century. Thornton and Professor Otto Wolff the potential for the creation of the • This year also saw the establishment foremost medical school in the UK. of the Glaxo Wellcome Chair of became ICH Honorary Fellows • The general reorientation of the Developmental Neurobiology Institute’s research programmes to which Dr Andrew Copp was 1997 begun in 1990, had been accelerated appointed. Further distinction was Professor Usha Goswami was appointed after the disappointing outcome brought to the Institute by the award of the 1992 Research Assessment of a clinical professorship by the 1999 to the first Chair of the Cognitive Exercise conducted by the Higher MRC to Professor Alan Lucas, whose Sir Robert Clarke and Sir Brian Hill Education Funding Council for Child Nutrition Group had transferred Developmental Psychology England. It was pleasing, therefore, to the Institute in March 1996 that the 1996 Assessment, based • In September 1996, Professor David • On 1 September 1999, Professor • Professor Levinsky became ICH Honorary Fellows on research published up to 31 Beach FRS, was formally appointed Roland Levinsky, was appointed (right) was 1998 March 1996, resulted in an overall as the first Chairholder of the newly- UCLas Vice-Provost Vice-Provost for Biomedicine for at Biomedicine; succeeded as New Dean ICH Dean assessment of Grade 5, indicating Professor John Deanfield was appointed established Hugh and Catherine UCL after serving as Dean of the of the Institute by Professor of Cardiology “Research quality that equates to Stevenson Chair of Cancer Biology, Institute since October 1990. During Professor David S was Professor Levinsky’s tenure, the Latchman, formerly Professor Annette Karmiloff-Smith appointed to the newly established Chair Institute’s research and teaching Director of the activities increased enormously Windeyer Institute and its academic standing as at UCL. Professor Marc de Leval was appointed of Cognitive Development. 1997 Professor of Cardiothoracic Surgery a leading centre of paediatric • In October, the research and education was Quality Assurance Professor Peter Clayton was considerably enhanced. This growth Agency (HEFCE) carried out a appointed Professor of Paediatric was made possible by a major Subject/Programme Review, joint Metabolic Disease & Hepatology capital redevelopment programme with the Institute of Ophthalmology, Professor Peter Milla was appointed which was funded by a number of the following Institute MSc/ Professor of Paediatric Gastroenterology of charitable sources and also by Diploma programmes: MSc in & Nutrition • During the course of 1997, the was constructed on the site of the additional HEFCE funds obtained as Clinical Paediatrics; MSc/Diploma in ResearchInstitute and Hospital’s themes joint redefined;old Kennedy Lecture Theatre and Professor Michael Dillon was appointed a result of the dramatic increase in Community Disability Studies; MSc in research themes were redefined as included a replacement theatre with Professor of Paediatric Nephrology the Institute’s research assessment Community Paediatrics; MSc/Diploma follows: Biochemical and Nutritional state-of-the-art audiovisual facilities, Wellcome Trust facilities completed rating from 3 in 1992 to 5 in 1996. in Mother and Child Health; Diploma Professor Christine Kinnon was appointed Sciences; Cancer; Cardiorespiratory a new “baby” theatre named “the New developments extended in Systematic Reviews Methodology. Sciences; Congenital Anomalies; Leolin Price Lecture Theatre” after throughout the decade and created These programmes were subjected Infection & Immunity; Neurosciences Leo Price (right), the last Chairman Professor of Molecular Immunology. state-of-the-art laboratories, as well to rigorous assessment processes, and Mental Health; Population of he Institute’s Committee of as additional teaching and office including peer observation of Health Sciences. By the end of Management (1976-1996), and a 1999 accommodation. teaching, and were awarded a score the 1996/97 financial year, over number of other teaching/conference Professor Faraneh Vargha-Khadem of 23 out of a maximum of 24 points. £12m had been raised in the form facilities. The upper floors of the was appointed Professor of of research grants to support building house the non-laboratory work in these themes, more than research activities complementing Commemorating the Leolin Price Lecture Theatre Professor Janet Stocks was appointed Developmental Cognitive Neuroscience quadrupling the total research grant the laboratories located in the Main Professor of Respiratory Physiology income received a decade earlier. Building and the Cardiac Wing. Professor Tim Cole was appointed • The Institute’s pressing Professor of Medical Statistics accommodation problems arising Professor Robert Anderson was appointed from this rapid expansion were Professor of Paediatric Cardiac Morphology relieved in September 1997 when Professor Andrew Redington the new Wellcome Trust Building, was appointed Professor of Congenital funded partly by the Wellcome Trust Heart Disease (£4.25m) and the Special Trustees of Great Ormond Street Hospital Professor David Latchman was appointed Children’s Charity (GOSHCC) (£2.5m), was opened. The building Sir John Pattison to the Chair of Human Genetics ICH Honorary Fellow became

Content researched and written by Raymond J Lunnon MPhil HonFRPS HonFIMI RMIP, Archivist, Institute of Child Health 2000 – 2004

A Brief IntoHistory of the theInstitute New Millennium of Child Health

2000 2002 2000 Professor Martin Koltzenburg was Royal Visit for 150 year anniversary; appointed Professor of Pain Research Professor Renzo Guerrinin was appointed •Queen’s The ICH was Anniversary awarded Prize:• ConsultantPhilip rheumatologistUllman Wing; Dr Kevin Professor of Paediatric Neurology the prestigious Murrey has set up the first ever • GOSH/ICH, together with the CentreQueen’s Anniversaryof Excellence in Juvenilecentre ofDermatomyositis research excellence in Institute of Education’s Social Professor was appointed Prize for Higher and juvenile dermatomyositis thanks Science Professor of International Child Health Further Education to the support of Jack and Eileen Newborn Screening ProgrammeResearch Centre in recognition of it’s Hayes whose son Cathal suffered Unit, take the Professor Agostino Pierro was appointed world-class training from the condition. helm of the and research. The UK National • Professor David Beach, Hugh Nuffield Professor of Paediatric Surgery ICH was commended Newborn Professor Adrian Woolf was appointed and Catherine Stevenson Chair Professor of Nephrology for its major role of Cancer Biology, shared the Screening in training the next 23rd Bristol-Myers Squibb Award Programme generation of children’s doctors and for Distinguished Achievement in Centre. for its nationally and internationally landmark discoveries in cell biology • ICH International Symposium on renowned research. The award was and tumour development. Child Health in the 21st Century held 2001 officially announced on November as part of GOSH’s 150th anniversary. 16 at a special ceremony at St. • Professor Andrew Tomkins, Director Professor John Harper was appointed James’ Palace. of the Centre for International Child • Professor Carol Dezateux appointed Health, was awarded the Royal to Chair of Paediatric Epidemiology • The new Philip Ullmann Wing Society of Tropical Medicine and and leads Millennium Cohort Study ProfessorProfessor Isky of Paediatric Gordon wasDermatology appointed was opened for business in 2000. Hygiene’s George MacDonald medal. • Her Majesty the Queen visited (MCS), a national collaboration, using The state-of-the-start five-storey face-to-face interviews to study the building houses seminar rooms and GOSH/ICH as part of the start in life of almost 19,000 babies ProfessorProfessor Mary-Louise of Paediatric Newell Imaging was conference facilities – including celebrations to mark the hospital’s 150th anniversary and visited the born during 2000 and 2001 across appointed Professor of the Roland Levinsky seminar room the UK. named in honour of the former cardiac intensive care unit and the Dean – plus office and laboratory Camelia Botnar laboratories. Paediatric Epidemiology was space for researchers including a Professor Christine Power appointed new metabolic laboratory shared by and Public Health various disciplines. The new wing Professor of Epidemiology was funded to the tune of £2.4 million 2003 by the Philip Ullmann Trust and the GOSHCC Special Trustees. 2002

Professor Christine Hall was appointed • Professor Andrew Copp, Professor • Professor Peter Scambler becomes Professor of Paediatric Radiology of Developmental Neurobiology Deputy Director (Research). becomes Dean of the Institute. • Partnership with the Children’s Trust, Professor Ian Hann was appointed New• Professor Davidappointments; Goldblatt appointed Tadworth. Partnerships Opening of the Harrison Director of Clinical Research and Research Centre at the Children’s Trust. and Oncology Development. Professor of Paediatric Haematology Professor Robert Surtees was appointed Professor of Paediatric Neurology

Professor Adrian Thrasher was appointed

ProfessorProfessor Marco of Paediatric Londei Immunologywas appointed

ProfessorMr Andrew of Autoimmunity Fane ICH Honorary Fellow 2001 became RAE 5* Award; London IDEAS; Gene 2003 Professor Andrew Copp Professor David Goldblatt Professor Peter Scambler Therapy Facilities; National Director Professor Robin Ali was appointed

for Children’s Healthcare Services ProfessorProfessor ofAlan Human Connelly Molecular was appointed Genetics • The Institute received 5* for its • The Government appointed Professor 2004 Professor of Biophysics research, the highest mark available, Al Aynsley-Green as the first National in the Research Assessment Exercise Director for Children’s Healthcare Professor David Goldblatt was appointed (RAE) conducted by the Higher Services, tasked with modernising Education Funding Council of NHS and social care services for • Dr Philip Beales published landmark • Members of the Developmental England. This means that most of its children and adolescents. ProfessorProfessor of VaccinologyNigel Klein andwas Immunologyappointed papers in Nature Genetics and Cell Cognitive Neuroscience and research has been judged to be of Professor of Infectious Disease on the Bardet biedl syndrome. Radiology and Physics Units, led international significance. Landmark papers; Prince of Wales’ Chair • Professor Pete Scambler continued by Professor Faraneh Vargha- • London IDEAS Khadem and David Gadian, his ground-breaking publications on and Immunology was appointed (Innovation, Professor David Muller Fraser’s syndrome. published striking findings on the Dissemination, brain representation of language in Evaluation and • Dr Atul Singhal and Professor Alan children who had undergone major ProfessorProfessor David of Taylor Biochemistry was appointed Application Strategy Lucas demonstrated in brain surgery early in life. for genetics across that breast-fed infants have a • Professor the community): lowered risk of later coronary heart Brian Neville Professor of Paediatric Ophthalmology the Government disease, and suggested a mechanism (right) became announced the for this important effect. the Prince of creation of a Genetics Knowledge Park Professor Al • Dr David Osrin 2004 Articles Wales’ Chair based in London, one of five across Aynsley-Green and Professor of Childhood was Effect of a participatory intervention with women’s groups Professor Raoul Hennekam the UK, to be led by the ICH Dean Anthony on birth outcomes in : cluster-randomised controlled trial Epilepsy. appointed Professor of Clinical Genetics Lancet 2004; 364: 970–79 Dharma S Manandhar, David Osrin, Bhim Prasad Shrestha, Natasha Mesko, Joanna Morrison, Kirti Man Tumbahangphe, Suresh Tamang, Professor David Latchman. The role of See Comment page 914 Sushma Thapa, Dej Shrestha, Bidur Thapa, Jyoti Raj Shrestha, Angie Wade, Josephine Borghi, Hilary Standing, Madan Manandhar, Costello Mother and Infant Research Anthony M de L Costello, and members of the MIRA Makwanpur trial team Activities (MIRA), PO Box 921, Kathmandu, Nepal Summary This new (Prof D S Manandhar FRCP, B P Shrestha MSc, Background Neonatal deaths in developing countries make the largest contribution to global mortality in children K M Tumbahangphe MSc, younger than 5 years. 90% of deliveries in the poorest quintile of households happen at home. We postulated that a the knowledge parks is to accelerate S Tamang BSc, S Thapa MSc, community-based participatory intervention could significantly reduce neonatal mortality rates. published their D Shrestha BSc, B Thapa BSc, J R Shrestha MPH); International Perinatal Care Unit Methods We pair-matched 42 geopolitical clusters in Makwanpur district, Nepal, selected 12 pairs randomly, and (D Osrin MRCP, N Mesko MSc, randomly assigned one of each pair to intervention or control. In each intervention cluster (average population professorial J Morrison MSc, J Borghi MSc, 7000), a female facilitator convened nine women’s group meetings every month. The facilitator supported groups Prof A M de L Costello FRCP) and through an action-learning cycle in which they identified local perinatal problems and formulated strategies to Centre for Paediatric address them. We monitored birth outcomes in a cohort of 28 931 women, of whom 8% joined the groups. The application of new information from the Epidemiology and Biostatistics findings from (A Wade PhD), Institute of Child primary outcome was neonatal mortality rate. Other outcomes included stillbirths and maternal deaths, uptake of Health, University College antenatal and delivery services, home care practices, infant morbidity, and health-care seeking. Analysis was by London, 30 Guilford Street intention to treat. The study is registered as an International Standard Randomised Controlled Trial, number position has London WC1N 1EH, UK; and Dysmorphology Institute of Development ISRCTN31137309. Professor Martin Elliott was appointed Studies, Falmer, Brighton BN1 9RE, UK (H Standing PhD); and Findings From 2001 to 2003, the neonatal mortality rate was 26·2 per 1000 (76 deaths per 2899 livebirths) in field of genetics within the NHS. Nepal Administrative Staff intervention clusters compared with 36·9 per 1000 (119 deaths per 3226 livebirths) in controls (adjusted odds ratio Nepal in The College, Kathmandu, Nepal (M Manandhar PhD) 0·70 [95% CI 0·53–0·94]). Stillbirth rates were similar in both groups. The maternal mortality ratio was 69 per Correspondence to: 100 000 (two deaths per 2899 livebirths) in intervention clusters compared with 341 per 100 000 (11 deaths per been funded Prof Anthony Costello 3226 livebirths) in control clusters (0·22 [0·05–0·90]). Women in intervention clusters were more likely to have Professor of Cardiothoracic Surgery [email protected] antenatal care, institutional delivery, trained birth attendance, and hygienic care than were controls.

Lancet, which Interpretation Birth outcomes in a poor rural population improved greatly through a low cost, potentially sustainable • A specialist laboratory to facilitate and scalable, participatory intervention with women’s groups. through the Introduction project—an uncontrolled before-and-after study—was Of the world’s 4 million annual neonatal deaths, 98% implemented in a poor rural population of 15 000 people occur in developing countries.1 Infant and child with little health-system infrastructure. The project revealed a mortality rates have declined, notably through better worked with women’s groups to encourage participatory clinical trials of gene therapy control of diarrhoea, pneumonia, and vaccine- planning for mother and infant care,6–8 and showed a fall preventable disease, and the importance of the newborn in perinatal mortality rate from 117 to 44 per 1000 births generosity of period has increased. In , neonatal mortality now over 3 years. In India, the SEARCH group reported a non- 2 was appointed accounts for up to 70% of infant mortality. Most randomised controlled study from a rural population of Professor Richard Hayward perinatal and neonatal deaths happen at home, and 80 000 in Gadchiroli, Maharashtra.9 The intervention startling 30% many could be avoided with changes in antenatal, entailed training of traditional birth attendants, health for children with rare immune delivery, and newborn care practices.3 However, primary education, and a new cadre of supervised village health and secondary health-care systems have difficulties in workers who visited newborn infants at home, identified the National reaching poor rural residents, and a potentially effective warning signs, and managed sepsis with antibiotics. After Professor of Paediatric Neurosurgery perinatal health strategy must recognise this reality. In 3 years the neonatal mortality rate had fallen by 62%. Makwanpur district, Nepal, for example, 90% of women Replication and scaling up of this exciting community- reduction in give birth at home, and trained attendance at delivery is based model presents policy makers with some deficiencies was opened with joint uncommon.4 challenges, particularly because of the need for a new We are unaware of any randomised controlled trial of cadre of community health worker to deliver injectable Centre for Young People with Epilepsy community-based strategies to reduce neonatal mortality, antibiotics at home. a shortfall that indicates the absence of information on Community participation has long been advocated to demand-side interventions.5 Two studies have made build links between primary services and their users,10–12 funding from ICH, GOS and the infant mortality important contributions in this area. Bolivia’s Warmi and to improve service quality.13–15 However, the evidence and the Special Trustees of Great 970 For personal use. Only reproduce with permissionwww.thelancet.com from ElsevierVol 364 September Ltd. 11, 2004 Professor Sheilz Wirz was appointed national Jeans for Genes Appeal. after the Ormond Street Hospital. introduction of a Professor of Disability Studies as well as the low-cost intervention to improve the • Professor Annette Karmiloff-Smith new Director of Learning and Teaching standard of hygiene during childbirth was awarded CBE in the Queen’s and in the care of very young babies. Birthday Honours List. Professor Roland Levinsky Gene Therapy Laboratory an ICH Honorary Fellow became

Content researched and written by Nicole Hofmans, Executive Officer, UCL Institute of Child Health and David Smithson, Senior Designer, UCL Health Creatives Collaboration 2005 – 2009

A Brief History of the Institute of Child Health

2005 2008 2005 Professor Gudrun Moore was appointed as Wolfson Centre for Gene Therapy; Grant Success Professor of Clinical and Molecular Genetics • The Wolfson Centre for Gene Therapy, Professor Philip Beales was appointed funded by The Wolfson Foundation Professor of Medical and Molecular Genetics was opened in early March. Professor Adrian Thrasher (below) and • RAE rating: In RAE 2008, ICH was • A team led by Dr Renee McCulloch was appointed colleagues are awarded the Descartes • Grant successes (raised over £22m in Professor Charles Newton RAEpart of a UCLRating; return to UoA4 inBRC Opening;and Dr Finella Craig Somers succeeded in Professor of Paediatric Neuroscience Research Prize 2005: European research grants and contracts); MRC which 70% of staff were rated as a national competition to establish Initiative in Primary Immunodeficiencies. Grant awards to Professors Faraneh of international quality (4*, 40%; an academic unit of children’s Vargha-Khadem, Janet Stocks and CRF Opens; UCL Genomics forms 3* 30%). In addition, ICH’s return palliative care. Alan Lucas and two large grants from was scored as 100% 4* for both DFID to Professor Anthony Costello. 2006 Environment and Esteem indicators. Professor Tony Charman was appointed Centre for Paediatric Epidemiology and Biostatistics ProfessorProfessor of MehulNeurodevelopmental Dattani was appointed Disorders Professor of Paediatric Endocrinology • Professor Professor Fenella Kirkham was appointed Dezateux (right) Professor of Paediatric Neurology and team were awarded an MRC Centre for Paediatric Epidemiology 2007 and Biostatistics,

which establishes Professor Francesco Muntoni was appointed Professor of Paediatric the first centre dedicated to population health Neurology and head of the Dubowitz research in children. ProfessorNeuromuscular Tessa Crompton Centre was appointed

ProfessorProfessor Peter of Experimental Hammond Immunologywas appointed

2006/2007 • Opening of the • The highly successful ICH ProfessorProfessor of Computational Brent Taylor Biology Great Ormond Microarray Centre, headed by Dr Centre for Childhood Infectious Diseases Opens; Street Hospital/ICH Mike Hubank, merged with the two unit of General and Adolescent Paediatricsjoins Specialist Biomedical other main UCL microarray centres the Institute and leads the new academic nd in the Division of Infection and 2 MRC Centre; Groundbreaking papers Research Centre Professor Helen Cross was appointed (BRC) focused on Immunity and the Wolfson Institute Professor of Paediatric Neurology. • 2nd MRC Centre: Professor Martin • Opening of the Hugh and Catherine children’s health. for Biomedical Research. Together they form UCL Genomics which now Koltzenburg, together with Professor Stevenson Centre for Childhood The Centre is led Professor Bobby Gaspar was appointed Mike Hanna and Professor Francesco Infectious Diseases and Immunology, by Professor David operates as a single service across Muntoni were awarded funding from donations by Hugh and Goldblatt (right). three sites, drawing on a wealth of technical expertise and running to establish the MRC Centre for Catherine Stevenson and the GOSH • Opening of the Somers Clinical ProfessorProfessor of Ruth Paediatrics Gilbert and was Immunology appointed experiments across three major Neuromuscular Diseases (IoN and ICH). Special Trustees. Research Facility (CRF) at GOSH, microarray platforms, Affymetrix, built with the support of a generous Vol 445 | 11 January 2007 | doi:10.1038/nature05383 Agilent and Illumina. donation by Mrs Phyllis Somers. ProfessorProfessor Catherine of Clinical Law Epidemiology was appointed Centre for ARTICLES Neuromuscular Diseases Thymosin b4 induces adult epicardial Professor of Public Health and Epidemiology progenitor mobilization and • Groundbreaking papers in Nature on neovascularization 2009

1 1 1 2 2 2008 stem cell technology to develop new Nicola Smart , Catherine A. Risebro , Athalie A. D. Melville , Kelvin Moses , Robert J. Schwartz , Kenneth R. Chien3 & Paul R. Riley1

therapies for retinal degeneration (Dr Cardiac failure has a principal underlying aetiology of ischaemic damage arising from vascular insufficiency. Molecules that regulate collateral growth in the ischaemic heart also regulate coronary vasculature formation during embryogenesis. Here UCL Partners; Baby Biobank; HDBR; MCADD Professor Helen Cross was appointed Jane Sowden and Professor Robin we identify thymosin b4 (Tb4) as essential for all aspects of coronary vessel development in mice, and demonstrate that Tb4 stimulates significant outgrowth from quiescent adult epicardial explants, restoring pluripotency and triggering differentiation of fibroblasts, smooth muscle cells and endothelial cells. Tb4 knockdown in the heart is accompanied by as the Prince of Wales’ Chair of Ali (Institute of Ophthalmology) and significant reduction in the pro-angiogenic cleavage product N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP). Although • ICH becomes part of UCL Partners, injection of AcSDKP was unable to rescue Tb4 mutant hearts, it significantly enhanced endothelial cell differentiation from Childhood Epilepsy on the enhancement of blood vessel adult epicardially derived precursor cells. This study identifies Tb4 and AcSDKP as potent stimulators of coronary vasculogenesis and angiogenesis, and reveals Tb4-induced adult epicardial cells as a viable source of vascular progenitors a new Academic Health Sciences growth in diseased heart muscle (Dr for continued renewal of regressed vessels at low basal level or sustained neovascularization following cardiac injury. Tb4 is a G-actin monomer binding protein implicated in reorgan- Equivalent phenotypes were observed in embryos from three inde- Centre, in which UCL is joined by its ization of the actin cytoskeleton, a process fundamentally required pendent Tb4shRNAflox transgenic lines. Variation in phenotype Professor Atul Singhal was appointed Paul Riley). Further paper in Nature for cell migration. We previously identified Tb4 as a putative effector between Tb4shNk and Tb4shMlc embryos could be attributed to of Hand1-mediated cardiac morphogenesis1. More recently Tb4 was variability in the timing and level of Cre-induced recombination four closest, research-active NHS elevated to a potential therapeutic target (http://www.regenerx.com/ (Supplementary Fig. 3a–f). Mutant embryos were categorized into Professor of Childhood Nutrition Biotechnology by Dr Paolo de Coppi wt/home/index) in terms of its ability to minimize cardiomyocyte mild, moderate and severe phenotype classes (Supplementary Table loss after myocardial infarction2. Here we reveal an essential role for 1), and the severity of phenotype correlated directly with the extent trusts: GOSH, UCLH, Moorfields and Tb4 in regulating all three key stages of cardiac vessel development of knockdown of Tb4 protein (Supplementary Fig. 1b). There was demonstrating the therapeutic (vasculogenesis, angiogenesis and arteriogenesis), and identify the no effect on expression of the closely related b-thymosin, Tb10 adult epicardium as a potential source of vascular progenitors which, (Supplementary Fig. 1c), suggesting that the RNAi was specific, the Royal Free. when stimulated by Tb4, migrate and differentiate into smooth mus- although potential off-target effects cannot be unequivocally ruled potential of a stem cell population cle and endothelial cells. The ability of Tb4 to promote coronary out at this stage. vascularization both during development and in the adult enhances Examination of Tb4shNk and Tb4shMlc embryos during devel- cardiomyocyte survival and contributes significantly towards Tb4- opment revealed no apparent phenotype at embryonic day 8.5 in the amniotic fluid of the fetus induced cardioprotection. (E8.5), despite reported expression of Tb4 in the developing heart from E8.01 (data not shown). By E10.5, however, there were clear Cardiac-specific knockdown of Tb4 indications of pericardial oedema in severely affected embryos that can replace damaged cells in a To investigate a role for Tb4 during heart development and to pro- (Supplementary Fig. 4a–c). At E12.5, Tb4shNk mutant embryos 2009 vide insight into the mechanism by which the peptide mediates adult had epicardial defects manifesting as abnormal surface nodules and cardiac repair, we generated mouse embryos with heart-specific Tb4 haemorrhaging (Supplementary Fig. 4d,e), before any obvious mor- variety of organs. deficiency using a novel strategy of transgenic conditional RNA phogenetic defects within the myocardium (Supplementary Fig. 4g, interference (RNAi; illustrated in Supplementary Fig. 1a). Floxed h). Severely affected Tb4shMlc embryos at E12.5 had, in addition to • The Baby Biobank was launched Tb4 short hairpin RNA (Tb4shRNAflox) mice were crossed with epicardial defects, severe leftward displacement of the heart with two strains of Cre-expressing mice: Nkx2-5CreKI (designated respect to the embryonic midline, and showed early signs of necrosis Professor was Tb4shNk), which directs Cre expression throughout the majority of (Supplementary Fig. 4f). with £1.6m funding from Wellbeing cardiomyocytes3,4, and MLC2vCreKI (designated Tb4shMlc), which Detailed analysis of Tb4shNk embryos at E14.5 (Fig. 1) revealed a directs Cre expression specifically to ventricular cardiomyocytes5. thin non-compacted myocardium and partially detached epicardium appointed Tb4shNk embryos were also observed to have thymic defects (Supple- mottled with surface nodules (Fig. 1b, e). The ventricular myocar- of Women and is led by Professor mentary Fig. 2a, b) consistent not only with Cre expression driven by dium of Tb4shMlc embryos was markedly pale and necrotic, with an Nkx2-5 in the developing thymus3 (Supplementary Fig. 2c), but also extended outflow tract and detached epicardium (Fig. 1c, f). The with the thymus representing an obvious source of Tb4. epicardial defects observed at E12.5 and E14.5 in both Tb4shNk Gudrun Moore and Professor Lesley

1Molecular Medicine Unit, UCL Institute of Child Health, London WC1N 1EH, UK. 2Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, Nuffield Professor of Child Health USA. 3Massachusetts General Hospital Cardiovascular Research Center, Boston, Massachusetts 02114, USA, and the Department of Cell Biology, Harvard Medical School, and the Professor Christine Kinnon Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA. Regan (). 177 © 2007 Nature Publishing Group Deputy Director (Education) became

Vol 444 | 9 November 2006 | doi:10.1038/nature05161 Professor Simon Heales was appointed the ARTICLES LETTERS • The Human Developmental Biology Resource (HDBR) received five-year first Professor of Clinical Chemistry Retinal repair by transplantation of photoreceptor renewal funding (£2.1m) from the Professor Lyn Chitty was appointed Isolation of amniotic stem cell lines with potential precursors MRC and Wellcome Trust. The HDBR Professor of Genetics and Fetal Medicine

for therapy R. E. MacLaren1,2*, R. A. Pearson3*, A. MacNeil1, R. H. Douglas4, T. E. Salt5, M. Akimoto6{, A. Swaroop6,7, J. C. Sowden3 & R. R. Ali1,8 is led by Professor Andrew Copp and Paolo De Coppi1,3, Georg Bartsch, Jr1,3, M Minhaj Siddiqui1, Tao Xu 1, Cesar C Santos1, Laura Perin1, Gustavo Mostoslavsky2, Ange´line C Serre2, Evan Y Snyder2, James J Yoo1, Mark E Furth1, Shay Soker1 & Professor Susan Lindsey (Newcastle Professor Therese Hesketh was appointed 1 Anthony Atala Photoreceptor loss causes irreversible blindness in many retinal correctly oriented within the ONL and had morphological features diseases. Repair of such damage by cell transplantation is one of typical of mature photoreceptors (Fig. 1a, b). Stem cells capable of differentiating to multiple lineages may be valuable for therapy. We report the isolation of human and rodent the most feasible types of central nervous system repair; photo- As a population of cells in the P1 retina could integrate and dif- University) and it the UK’s only fetal Professor of Global Health amniotic fluid–derived stem (AFS) cells that express embryonic and adult stem cell markers. Undifferentiated AFS cells expand receptor degeneration initially leaves the inner retinal circuitry ferentiate into photoreceptors when transplanted in the immature 5 extensively without feeders, double in 36 h and are not tumorigenic. Lines maintained for over 250 population doublings retained intact and new photoreceptors need only make single, short syn- retina, we transplanted P1 cells (,8 3 10 cells per eye) into the long telomeres and a normal karyotype. AFS cells are broadly multipotent. Clonal human lines verified by retroviral marking were aptic connections to contribute to the retinotopic map. So far, subretinal space of adult GFP-negative wild-type mice. By contrast tissue bank, enabling studies of gene 1,8 induced to differentiate into cell types representing each embryonic germ layer, including cells of adipogenic, osteogenic, myogenic, brain- and retina-derived stem cells transplanted into adult retina to previous reports , we found that transplanted cells could migrate HDBR have shown little evidence of being able to integrate into the into the ONL of adult recipients (see also Supplementary Fig. 1). The endothelial, neuronal and hepatic lineages. Examples of differentiated cells derived from human AFS cells and displaying speciali- 1–4 http://www.nature.com/naturebiotechnology outer nuclear layer and differentiate into new photoreceptors . cells integrated in proportionately similar numbers to those trans- expression in relation to genetic was appointed zed functions include neuronal lineage cells secreting the neurotransmitter L-glutamate or expressing G-protein-gated inwardly Professor Paul Riley Furthermore, there has been no demonstration that transplanted rectifying potassium channels, hepatic lineage cells producing urea, and osteogenic lineage cells forming tissue-engineered bone. planted into the immature retina (300–1,000 cells per eye; N 5 6) and cells form functional synaptic connections with other neurons in had the morphological characteristics of mature photoreceptors Human Developmental the recipient retina or restore visual function. This might be (Fig. 1b–e). Virtually all integrated cells were rod-like, as expected disease and birth defects. Professor of Molecular Cardiology because the mature mammalian retina lacks the ability to accept 5,9 Amniotic fluid is known to contain multiple cell types derived from antigen c-Kit (CD117), the receptor for stem cell factor8 (Supple- given the developmental stage of the donor cells . Cone-like profiles and incorporate stem cells or to promote photoreceptor differenti- the developing fetus1,2. Cells within this heterogeneous population can mentary Table 1 online). We used immunoselection with magnetic were occasionally observed (Fig. 1e). The site of injection seemed to ation. We hypothesized that committed progenitor or precursor be crucial because, as noted by others2, there was no integration give rise to diverse differentiated cells including those of adipose, microspheres to isolate the c-Kit–positive population from many cells at later ontogenetic stages might have a higher probability of 3–6 within the ONL in either P1 (N 5 12) or adult (N 5 18) recipients Biology Resource muscle, bone and neuronal lineages . We now describe lines of amniocentesis specimens and found that these cells can be readily success upon transplantation. Here we show that donor cells can after intravitreal injections. broadly multipotent AFS cells, and use retroviral marking to verify expanded in culture as stable lines, termed AFS cells. We have integrate into the adult or degenerating retina if they are taken Fusion between transplanted and host cells has been proposed as that clonal human AFS cells can give rise to adipogenic, osteogenic, routinely established clonal AFS cell lines with a typical doubling Professor Neil Sebire was appointed from the developing retina at a time coincident with the peak of an explanation for the apparent plasticity of stem cells10–12. To evalu- myogenic, endothelial, neurogenic and hepatic lineages, inclusive of all time of about 36 h and no need for feeder layers. Sub-confluent cells 5 rod genesis . These transplanted cells integrate, differentiate ate this possibility, we transplanted P1 GFP-positive cells into adult embryonic germ layers. In this respect, they meet a commonly show no evidence of spontaneous differentiation. However, under into rod photoreceptors, form synaptic connections and improve transgenic mice that ubiquitously expressed cyan fluorescent protein Nature Publishing Group Group Publishing Nature 200 7 accepted criterion for pluripotent stem cells, without implying that specific inducing conditions AFS cells are able to give rise to lineages Professor of Paediatric and visual function. Furthermore, we use genetically tagged post- (CFP) (Cba-cfp1/1)13. Confocal scans of integrated cells showed that © they can generate every adult tissue. representative of the three embryonic germ layers. mitotic rod precursors expressing the transcription factor Nrl GFP and CFP signals were not co-localized in any of the retinas Neurons, hepatocytes and osteoblasts are among the cell types for We used flow cytometry to assess markers expressed by human AFS (ref. 6) (neural retina leucine zipper) to show that successfully studied (N 5 8; Supplementary Fig. 2a). Cell fusion might result in • The UK Collaborative Study of which improved stem cell sources may open up novel therapeutic cells (Supplementary Fig. 1 and Supplementary Methods online). integrated rod photoreceptors are derived only from immature multinuclear cells12,14, but here integrated cells had only a single applications. For each of these examples we show that AFS cells can Five clonal lines gave similar results. The cells were positive for Class I post-mitotic rod precursors and not from proliferating progenitor nucleus. DNA labelling of GFP-positive donor cells with bromo- yield differentiated cells that express lineage-specific markers and major histocompatibility (MHC) antigens (HLA-ABC), and some or stem cells. These findings define the ontogenetic stage of donor deoxyuridine (BrdU) confirmed that these nuclei originated from Newborn Screening for Medium acquire characteristic functions in vitro. In addition, we present initial were weakly positive for MHC Class II (HLA-DR). The AFS cells cells for successful rod photoreceptor transplantation. donors (Supplementary Fig. 2b). Therefore, it seems unlikely that studies indicating that AFS cells induced toward particular lineages were negative for markers of the hematopoietic lineage (CD45) and of We assessed the transplantation potential of immature mouse ret- cell fusion occurred in our experiments. can generate specialized cells after implantation in vivo. We show that hematopoietic stem cells (CD34, CD133). However, they stained inal cells, taken from the early postnatal period at the peak of rod The population of cells derived from the P1 retina comprises a Chain Acyl Dehydrogenane Deficiency Developmental Pathology 5 AFS cells directed to neural lineage differentiation by exposure to positively for a number of surface markers characteristic of mesench- photoreceptor genesis (postnatal day (P)1) . At this age, the retinal mixture of proliferating progenitors, post-mitotic precursors and Professor Andrew Taylor was appointed nerve growth factor (NGF) are able to widely engraft the developing ymal and/or neural stem cells, but not embryonic stem (ES) cells, microenvironment should be favourable to promote the differenti- differentiated cells that do not yet express the markers of mature mouse brain in a manner similar to that observed previously for including CD29, CD44 (hyaluronan receptor), CD73, CD90 and ation and integration of transplanted cells within the outer nuclear photoreceptors5. We sought to determine which of these integrated (MCADD) was launched, led by 7 5,9,10 neural stem cells . In addition, we document the formation of tissue- CD105 (endoglin) . Human AFS cells also were positive for layer (ONL). Furthermore, transplanted cells have a higher probabil- into the ONL. We examined the developmental time window for engineered bone from printed constructs of osteogenically differen- stage-specific embryonic antigen (SSEA)-4 (ref. 11), a marker expressed ity of integration if recipient and donor retinas are at equivalent obtaining donor cells that successfully integrate after transplantation. 5 tiated human AFS cells in immune-deficient mice. by ES cells but generally not by adult stem cells. The AFS cells did not stages of development. Neural retinal cell suspensions (,2 3 10 Cells were taken from embryonic day (E)11.5, E16.5, P1–P15 or adult Professor Carol Dezateux and funded express other surface markers characteristic of ES12,13 and embryonic cells per injection) from P1 transgenic mice, expressing a green fluor- GFP-positive donors and transplanted by standardized subretinal RESULTS germ (EG) cells14, SSEA-3 and Tra-1-81. Some lines were weakly escent protein (GFP) gene under the control of a chicken b-actin injections (see Methods) into adult wild-type recipients. Cells Clonal stem cell lines from amniotic fluid positive for Tra-1-60. Over 90% of the cells expressed the transcription promoter (Cba-gfp1/2)7, were transplanted into the subretinal space derived from E11.5 retinas, the latest stage that consists almost by the Department of Health and Professor of Cardiovascular Imaging Approximately 1% of the cells in cultures of human amniocentesis factor Oct4, which has been associated with the maintenance of the of GFP-negative wild-type littermates. Three weeks after transplanta- entirely of proliferating progenitors5,9 (Supplementary Fig. 3), sur- Professor Carol Dezateux, specimens obtained for prenatal genetic diagnosis express the surface undifferentiated state and the pluripotency of ES and EG cells15. tion, substantial numbers of cells (10–200 cells per eye; N 5 10 eyes) vived after transplantation, but in all cases failed to integrate had migrated into the recipient neural retina. Most (.95%) were (N 5 12) (Fig. 2a). Similarly, cells derived from adult retinas survived National Screening Committee. Every for Population Health Sciences and Head of 1Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1094, USA. 1Division of Molecular Therapy, University College London Institute of Ophthalmology, 11–43 Bath Street, London EC1V 9EL, UK. 2Vitreoretinal Service, , 162 2Children’s Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA. 3These authors contributed equally to this work. City Road, London EC1V 2PD, UK. 3Developmental Biology Unit, University College London Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK. 4Henry Wellcome newborn baby in England will now be Correspondence should be addressed to A.A. ([email protected]). 5 Theme Leader Laboratory for Vision Sciences, Department of Optometry and Visual Science, City University, Northampton Square, London EC1V 0HB, UK. Division of Visual Science, University 6 7 Received 27 July 2006; accepted 20 November 2006; published online 7 January 2007; doi:10.1038/nbt1274 College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK. Department of Ophthalmology and Visual Sciences and Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48105, USA. 8Molecular Immunology Unit, University College London Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK. {Present address: Translational Research Center, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan. offered a screening test for MCADD, a *These authors contributed equally to this work. Health was awarded a CBE in the New Years 100 VOLUME 25 NUMBER 1 JANUARY 2007 NATURE BIOTECHNOLOGY 203 © 2006 Nature Publishing Group serious inborn error of metabolism. the MRCHonours Centre for of services Epidemiology to science for Child

Content researched and written by Nicole Hofmans, Executive Officer, UCL Institute of Child Health and David Smithson, Senior Designer, UCL Health Creatives Awards & Restructuring 2010 – 2014

A Brief History of the Institute of Child Health

2010 2012 2010 Professor Persis Amrolia UK specialist centres; DoH funding Birth Cohort Study; New Director; was appointed Professor of Professor Jugnoo Rahi • The Louis Dundas Centre for • Hugh Stevenson received a Transplantationwas appointed ProfessorImmunology of Children’s Palliative Care became knighthood in the Queen’s birthday HEFCE fund Centre for Research the first unit in the UK devoted to Honours List. Hugh and his wife Professor Lucy Wedderburn research and education in children’s Catherine are long-standing wasOphthalmic appointed Epidemiology Professor of terminal illness. Myra Bluebond- benefactors to the Institute. in Rare Disease in Children Langner was appointed the first • A team led by Professor Terence • In September • £10m HEFCE award to establish Professor Jonathan Wells True Colours Chair in Palliative Care Paediatric Rheumatology Stephenson, Nuffield Professor of Professor Andrew a Centre for Research into Rare was appointed Professor of Anthropology for Children and Young People. Child Health, was awarded £4.6m Copp stepped down Disease in Children, in partnership and Paediatric Nutrition Donations came from the Dundas over five years by the Department of as ICH Director and with GOSH and GOSHCC. Professor Kathy Pritchard-Jones family, True Colours Trust, Charles Health to establish a Policy Research Professor Rosalind was appointed Hugh & Catherine Stevenson Wolfson Charitable Trust, Marie Unit (PRU) for the Health of Children, L Smyth FMedSi Chair of Paediatric Oncology Curie Cancer Care and the Raisa Young People and Families. The (right) appointed Gorbachev Foundation. Professor Myra Bluebond-Langer PRU’s aim is to provide evidence for as Director and was appointed True Colours Chair • Professor Kathy Pritchard-Jones policy and practice, so as to promote Professor of in Palliative Care for Children and is appointed Hugh and Catherine the health and well-being of children, Child Health. Young People Stevenson Professor of Paediatric young people and families. Oncology. The Stevenson Chair • Professor Faraneh • In October the HRH The Princess was endowed more than ten years Vargha-Khadem Royal opens the Newlife Birth ago, and is one of many generous Defects Research Centre led 2011 (right) received donations that Hugh and Catherine by Professor Andrew Copp and Professor Russell Viner pump-priming was appointed Professor of have made to ICH. Kathy joined November saw the opening of The support from the Adolescent Health ICH earlier in 2010 and holds a joint Provost of UCL to Arthritis Research UK Centre for appointment with UCL Partners Adolescent Rheumatology, co-led by Professor Jane Sowden develop a Centre was appointed Professor of (where she is Cancer Lead) and for Developmental Professor Lucy Wedderburn. the North London Cancer Network, Cognitive Neuro- which she directs. • The Centre for International Health Sir Cyril Chantler and Professor Lewis Spitz science (CDCN). Developmental Biology and Genetics and Development became a separate Institute of Global Health with the Faculty of Population Health Sciences. became2012 ICH Honorary Fellows 2011 Professor Maria Bitner-Glindzicz was appointed Professor in Clinical 2013/2014 and Molecular Genetics Wolfson Centre opens; BRC renewed; Professor Stephen Hart was appointed Professor of Population Health Sciences created Molecular Genetics Professor Rodney Scott • ICH/GOSH Biomedical Research • ICH becomes one of the founding was appointed Professor in Centre renewed for another 5 years. members of the Faculty of Population Paediatric Neuroscience • Professor Health Sciences, created as part of Athena SWAN & NIHR awards a restructuring of the UCL School Professor Chris O’Callaghan Christine • Professor Smyth instigates • Improvement in grant incomes from of Life and Medical Sciences. The was appointed Professor of Respiratory Kinnon (right) AHSCrestructuring ofsuccess; the Institute’s CHR£22m CIOper annum formed;(2011-12) to £50m Faculty brings together the entire life and Paediatric Medicine was appointed Units/Themes and with the senior (2013-14) Professor Rosalind L Smyth Vice-Dean for course of human health. management team, visits top • Athena SWAN Silver Award received was appointed Professor of Child Health Education within • Sir Cyril Chantler, former Chief of the international children’s research – a recognition for the good work at & ICH Director the Faculty GOSH Trust Board, and Professor centres around the world. ICH to address the gender balance of Population Lewis Spitz, former Nuffield • Research-led teaching further and the development of academic Health Sciences Professor of Surgery, were awarded developed with new growing careers for both men and women. and the Institute ICH Honorary Fellowships (below). 2013 educational portfolio in CPD courses launched two Professor John Anderson and new MSc/Dip in Paediatric new Masters level was appointed Professor of Physiotherapy and a new pathway for courses in cell & Paediatric Gastroenterology. gene therapy and child & adolescent Professor Paul Gissen mental health. • UCLPartners application for re- Experimentalwas appointed Paediatric Professorial Oncology designation for the AHSC successful. • Opening of the completely Research Associate refurbished Wolfson Centre in • Child Health is one of the six clinical Professor John Achermann Mecklenburgh Square, the Institute’s academic programmes. was appointed Professor of first dedicated teaching and Paediatric Endocrinology • Professor Peris • Excellent results for ICH in HEFCE conference room resource. Professor Mary Fewtrell Amrolia (right) REF2014 exercise, where ICH was appointed Professor of is awarded one research constituted to >43% of Paediatric Nutrition of five nationally UCL’s outputs being rated as “world- awarded NIHR leading” and the Institute submitted a Professor Nick Greene Research staggering 15 Impact Case Studies. was appointed Professor of Professorships for his work in stem Professor Jenny Morgan cell therapies was appointedDevelopmental Professor Neurobiology of Cell Biology in 2013, The following year Professor Paolo de Coppi (right) • Citation impact suggests ICH/ 2014 Professor Torsten Baldeweg was similarly GOSH publications are top in the was appointed Professor of successful in world compared with other leading obtaining this award for his work international children’s hospitals. Professor Christopher Clark in regenerative medicine and • Institute launches new five-year Developmental Cognitive Neuroscience oesophagus reconstruction. strategy with five programmes in was appointed Professor of • The Child Health Research Charitable Developmental Biology & Cancer Professor Paolo de Coppi Incorporated Organisation (CHR (led by Professor Andrew Copp), was appointedImaging and Biophysics CIO) was formed by merging the Developmental Neurosciences (led by Professor Francesco Muntoni), of Paediatric Surgery General Charitable Trust (GCT), Nuffield Professor The Child Health Research Appeal Genetics & Genomic Medicine Professor Khalid Hussein Trust (CHRAT) and The Bill Marshall (led by Professor Philip Beales), was appointed Professor of Memorial Fund (BMMF). Infection, Immunity, Inflammation Paediatric Endocrinology and Physiological Medicine (led Professor Mark Peters by Professor Adrian Thrasher), was appointed Professor of Paediatric Population, Policy & Practice (led and Neonatal Intensive care by Professor Catherine Law) and one Professor Shamima Rahman cross-cutting theme in Rare Diseases was appointed Professor of Paediatric (led by Professor Bobby Gaspar). Metabolic Medicine

Professor Philip Stanier was appointed Infection, Developmental Genetics Immunity, Population, Developmental Biology and and Genomic Inflammation & Policy and Biology and Genetics Neurosciences Cancer Medicine Physiological Practice ProfessorProfessor Alastair of Craniofacial Sutcliffe Developmental was appointed Medicine Professor General Paediatrics Rare Diseases Professor Angie Wade was appointed Professor of Medical Statistics

Content researched and written by Nicole Hofmans, Executive Officer, UCL Institute of Child Health and David Smithson, Senior Designer, UCL Health Creatives