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Improving Lives: 150 Years of UK Medical School Achievements | 1 150 Years of UK Medical School Achievements

improving lives 2 | Improving Lives: 150 Years of UK Medical School Achievements

MEDICAL SCHOOLS COUNCIL

The Medical Schools Council is the representative body for the UK’s 32 medical schools. It works to ensure that the UK – and indeed the world – benefits from the contributions of the hugely talented teams of doctors, student doctors and colleagues who are working in medical schools to improve patients’ lives. To that end, we present here a selective overview of the impact – nationally and internationally – of individuals and teams who have worked in the UK’s medical schools, universities and hospitals over the past 150 years. Their efforts have not only transformed the quality and quantity of our lives, but have immeasurably changed society for the better.

Katie Petty-Saphon Executive Director, Medical Schools Council October 2008 Improving Lives: 150 Years of UK Medical School Achievements | 1

CONTENTS

Introduction: 150 years of innovation 2 The body: Understanding the heart and circulation 4 Nerves and the 5 | Tackling cardiovascular disease 6 6 | Diet and health 7 | The Krebs cycle 7 Structural engineering 8 Surgery and transplantation: Surgical strike 10 | surgery 11 Stem cells 12 | Replacement parts 12 | Plastic surgery 13 : Death on demand 13 UK Life Nobel Prizes 14 Infection and immunity: Resisting invaders 16 | Diagnostics 17 Calming immunity 17 | HIV 18 | Monoclonal antibodies 18 Tropical 19 An inside view 20 at large: Doctor as detective 22 | DNA and medicine 23 IVF and PGD 23 | Effective healthcare 24 | Cognitive behavioural therapy 24 Social factors 25 | Genes and cancer 25 Perspectives: Future challenges 26 UK Medical Schools 28 2 | Improving Lives: 150 Years of UK Medical School Achievements INTRODUCTION The modern era of UK medical schools began in the mid-19th century. It is difficult to be certain which medical school can lay claim to being the UK’s oldest – although has the first record of a medical graduate in 1312. St Andrews University’s Foundation Charter issued in 1412 lists the subjects to be taught as ‘divine human law, medicine and the liberal arts’ and Aberdeen appointed the UK’s first medical professor in 1497 – indeed, Scotland was an early focus of medical education. was teaching medicine by the 16th century (albeit with a maximum of four students) but medical schools did not truly blossom until the when schools were established in Belfast, , , , , , Manchester, Newcastle, Sheffield and Wales. Thus the modern era of the medical school can be dated to the mid-19th century. It was not until a century later, when the Todd Report led to a wave of new schools in the , that their numbers increased significantly. With further expansion in the and early 21st century, the UK now has 32 medical schools as well as three partner schools in Derby, Durham and Lancaster. The Victorian boom owes much to the professionalisation of medicine during the 19th century. By setting up its own education systems, codes of conduct and forms of governance, medicine established its authority as the trusted agency for protecting health and curing disease – a counterpart to the assorted quacks, charlatans, snake-oil salesman and others to whom members of the public might otherwise turn. Medical education was crucial to this professionalisation. It ensured that only suitably able candidates could enter the profession. It also, of course, provided a way for aspiring to acquire the necessary skills, knowledge and behaviour. Crucially, though, from the Enlightenment on, medicine had ceased to be a static, backward-looking discipline. New knowledge was constantly being acquired. So, as well as acquiring existing knowledge, physicians were also generating new knowledge of their own. Sometimes they may have been 150 years of motivated by their own innate curiosity, a desire to understand better the natural world. Often, they were driven by medical innovation needs, to be able to do more for patients. Improving Lives: 150 Years of UK Medical School Achievements | 3

New knowledge donor system owe their origins The Victorian era was a time of explosive growth in to the tireless work of doctors. understanding of the body and of the of disease. Internationally, British doctors are The emergence of germ theory transformed thinking about working in numerous developing infections. The development of anaesthetics revolutionised countries, aiming not just to deliver medical care where it is surgery. Key physiological concepts were established. So, as needed but also to develop the well as being centres in which established knowledge was capacity of countries so they are passed on from generation to generation, medical schools better equipped to tackle their were hotbeds of discovery and innovation. The speed of own health problems. advance could be breathtaking. Within months of Roentgen’s In the UK, doctors are delivering discovery of X-rays, for example, a radiology unit had been the and established at Glasgow. programmes that help keep the public healthy. They are also at Why were medical schools able to be such drivers of change? the forefront of surveillance for Partly it was down to the nurturing of enquiring minds, Social roles, must go along with it – it is the appearance of new threats essential in both science and medicine. political influence literally our life in their hands. to health or the re-emergence A record of success Dietary deficiencies are now Partly, though, it also recognises of old ones. By feeding into rare. Organ transplants routine. Doctors have traditionally been The past 150 years have seen Perhaps most significantly, though, the juxtaposition of a long history in which physicians the policy-making process, Previously unimaginable recognised as the archetypal huge improvements in length medical delivery and academic endeavour created an have worked or campaigned for doctors can ensure that the surgical procedures are an pillars of society, a position and quality of life. environment in which research could be allied to the realities the public good. country is prepared for the everyday occurrence. Chronic reinforced by polls confirming new challenges to health that Life expectancy has leapt conditions such as diabetes, of disease and medical needs. Even now, while research that they remain the most trusted It was doctors who identified will inevitably appear. from 40 to 76 for men and if not cured are often at least in medical schools is often curiosity-led, it is rooted in the group in UK society – the latest the links between smoking and from 42 to 81 for women, adequately managed. potential for medical intervention. poll reveals that 90% of people disease and led public health Above: Doctors have played a and continues to increase trust them to tell the truth campaigns against smoking. crucial role in creating the blood These advances were driven by five hours every day. Hence research in medical schools spans a spectrum, from (compared with 78% for judges, It was doctors who promoted transfusion service. by a new awareness of the highly goal-oriented studies that seek to improve healthcare 44% for civil servants and 18% legislation to enforce wearing Infant mortality has been causes of ill-health and in the short term through to more speculative work that may for politicians). of seatbelts, which has saved slashed – from more than the development of new thousands of lives. Invaluable 100 to fewer than 5 deaths interventions to prevent take decades or more to come to fruition. And that balance is In part this reflects the intimate important: too much focus on the here and now and the flow resources such as the blood per 1000 live births. or treat disease. While nature of the doctor–patient transfusion service and organ challenges still remain, the of medical innovations will dry up; too much emphasis on blue relationship and the trust that Women were not allowed first 150 years have been a skies and patients will never derive any benefits. on the Medical Register period of sustained success. 150 years ago – but now While the links with medical service delivery are obvious, Scientific training has also proven invaluable in the growth of make up 58% of the Above: Newborn baby the importance of the connections with university academic population-based studies and randomised clinical trials. As well undergraduate population. in incubator. networks should not be underestimated. The rise of as shedding light on key public health issues, such work has and vaccines in the early years of the 20th century provided established an evidence base to support rational healthcare have turned many infectious new routes by which knowledge could be translated into delivery and policy making. diseases into distant medical benefits. So too has the emergence of molecular memories. The roll call of winners, and the stream of other in the late 20th century. Engineering has contributed innovations emerging from UK medical schools, is testament to hugely to the development of medicine, particularly imaging the success of this model. Medical schools are not just training technologies and replacement parts. Crucially, it took medically the doctors of tomorrow – they are also laying the foundations qualified individuals to spot the potential of new technologies of the medicine these doctors will deliver. and to devote the time and energy to turn them into tools of widespread practical value. 4 | Improving Lives: 150 Years of UK Medical School Achievements The heart Modern medicine has been founded on an ever-increasing understanding of the and circulation human body in health and disease. Blood and its circulation has been widely By the 1850s, the function of most of recognised as a fundamental aspect of life – the major organ systems of the body indeed, perhaps the fundamental aspect: had been discerned, yet the ability of the lack of a beating heart spelt death. doctors to tackle even the most common Not surprisingly, then, the heart and circulation have figured conditions was strictly limited. The next strongly in the development of modern medicine. 100 years, however, saw a remarkable The pulse has been central to medical practice for centuries. flourishing of understanding, as the cellular The electrical innovations of the late 19th century were soon being applied to provide a more systematic assessment of and biochemical nature of physiological heart function. processes were unravelled. In 1872, while studying for his Doctor of Science degree (in With this growth in understanding came electricity) at St Bartholomew’s Hospital, Alexander Muirhead attached wires to a feverish patient’s wrist in order to record his a vastly improved ability to intervene in heartbeat. Later, Augustus Waller, working in St Mary’s Hospital disease. Nowhere was this change more in London, was the first to tackle the heart systematically from dramatic than in two fundamental life an electrical standpoint. Making ingenious use of a toy train, his electrocardiograph (ECG) machine produced a trace that processes – the cardiovascular system was projected onto a moving photographic plate. This allowed and the dietary basis of health. a heartbeat to be recorded in real time. Ironically, Waller could see little clinical application for his work – unlike Thomas Lewis at University College London, who pioneered the use of ECG in clinical settings, founding a field crucial in cardiology to this day. The pumping action of the heart was also yielding to intensive study. In 1915, at University College London made the important discovery that the amount of blood pumped by the heart depended on the volume entering its chambers on relaxation – the so-called ‘law of the heart’. Such insight provided a basis for understanding the nature the body of heart failure. Improving Lives: 150 Years of UK Medical School Achievements | 5

1848 1913 of his career at UCL. Alfred Baring Garrod at King’s Thomas Lewis at University Digitally enhanced image of a model human heart. Katz discovered that College London, who coined College London introduces were the term ‘rheumatoid arthritis’ the electrocardiogram released in discrete packages, and suggested use of lithium (ECG) into clinical practice, or ‘quanta’, at to treat mental illness, discovers laying the foundations of (a term introduced by increased levels of uric acid in electrocardiography. the blood of patients with gout. Sherrington). His work earned 1915 him a Nobel Prize in 1970. 1855 Ernest Starling at University Thomas Addison at Guy’s College London describes the A further step forward came Hospital describes Addison’s ‘Law of the Heart’, an important in 1975 when Hans Kosterlitz disease, a skin condition step towards understanding in Aberdeen discovered caused by destruction of heart function and the nature that the brain produced the adrenal glands. of heart failure. molecules which bound to opioid receptors – the so- 1923 called endogenous opioids John MacLeod, a graduate of or endorphins. He went on to Aberdeen University, is awarded a share of a Nobel Prize with show their importance in pain Nerves and The nature of nerve Fraser Grant Banting for the perception, opiate addiction, the nervous system transmission remained discovery of insulin. learning and memory. controversial in the early 20th Many key aspects of nervous 1952 century, with two opposing More recently, attention has system function have been at University camps: the electrical and focused on functional imaging, revealed by UK researchers. College London discovers the chemical. The issue was revealing insight into the brain the quantal release of Following a varied scientific and largely resolved, in favour in action. The UK again remains neurotransmitters at synaptic medical education in London of the chemical camp, by at the forefront of the field 1858 terminals, for which he receives and Cambridge, Charles , who with groups such as Ray Dolan Henry Gray, a Lecturer in a Nobel Prize in 1970. trained at Cambridge and and colleagues at UCL and Anatomy at St George’s Hospital Sherrington established his Medical School, publishes 1953 University College London career in Liverpool and, later, Hugo Critchley at Brighton Gray’s Anatomy, probably the Sylvia Simpson and James Oxford. Sherrington – possibly (UCL) and discovered and Medical School. most famous medical textbook Tait at the Middlesex Hospital the only Nobel Laureate to the of all time. isolate the The great advances in our play football for Ipswich Town – . aldosterone. understanding of the nervous was hugely influential in 1867 How chemicals could trigger system in the 20th century led mid-1950s By the post-war years, ultrasound was emerging as a developing the modern , who studied electrical impulses was to a whole host of treatments at York and Cambridge, invents Inventive work on heart potentially valuable imaging technique in medicine. It rapidly idea of the nervous system brilliantly explained by Andrew based on pharmacological the clinical . Just pacemakers and plastic heart found application in cardiology, while Aubrey Leatham, as an integrated system for Huxley and in manipulation of nerve 3 inches in length, it is a vast valves by Leon Abrams of the controlling the body’s actions. with the assistance of Graham Leech, pioneered the use Cambridge, who developed impulses – from beta-blockers improvement on its predecessor, Queen Elizabeth Hospital and Birmingham Medical School of sound-based imaging, echophonocardiography, mathematical models to to antidepressants. The which was more than a foot long. Sherrington shared the 1932 leads to their widespread use at St George’s Hospital. Nobel Prize with , describe the dynamics of nerve remarkable progress in brain 1891 internationally. who studied medicine at impulses. Their Nobel Prize imaging promises to deliver Myxoedema is first treated New therapies also began to appear. The artificial pacemaker Barts and, while in Cambridge, was awarded in 1963. equally significant advances in successfully, using an extract 1955 has saved many lives. The idea of using artificial electrical psychiatric and psychological of sheep’s thyroid gland, by Sheila Sherlock, pioneer of carried out landmark studies The behaviour of individual stimulation goes as far back as the pioneering work of characterising the electrical conditions that are a growing George Murray at Newcastle’s hepatic medicine and first neurones was also the focus of professor of medicine at behaviour of isolated nerve cause of ill-health and distress. Royal Infirmary. Aberdeen’s John Alexander MacWilliam, who in 1889 Bernard Katz, a German-born London’s published his findings on human heart stimulation. Later, cells. He also helped to develop biophysicist who, after working Above: Colour-enhanced image 1905 School of Medicine, publishes the ‘sensory map’ in the brain. the inventive work on heart pacemakers and plastic heart with Hodgkin and Huxley of two myelinated nerve fibres. The first hormone, , Diseases of the Liver and in Cambridge, spent much is discovered at University Biliary System. valves by Leon Abrams of the Queen Elizabeth Hospital and College London by the Birmingham Medical School in the mid-1950s led to their . 1958 widespread use internationally. Aubrey Leatham at 1906 St George’s Hospital, On the drug front, the development of beta-blockers by Sir Charles Sherrington with Graham Leech, publishes landmark is the first to use James Black and ACE inhibitors by (see page 9) findings on nervous echophonocardiography, provided enormous benefits. system function while at publishing a landmark Liverpool. He later moves paper in the Lancet. to Oxford and is awarded a Nobel Prize in 1932. 6 | Improving Lives: 150 Years of UK Medical School Achievements

1961 1995 Cardiovascular disease The UK’s first professor of James Shepherd and Another consequence of nutrition, John Yudkin of King’s colleagues publish With people living longer, smoking and eating high-fat diets, modern life is the dramatic rise the West of Scotland in obesity. The physiological College London, publishes coronary heart disease and related conditions were the UK’s The Slimmer’s Cookbook, Coronary Prevention basis of this condition is being the first scientifically based Study, the first biggest killers. clarified, thanks to the work book on slimming. demonstration that of researchers such as Stephen statins protect middle- One consequence was a significant shift towards cardiovascular O’Rahilly and colleagues 1969 aged men with high disease , and large-scale trials of treatments or in Cambridge, who in 1997 Propanolol, the levels preventive measures. Researchers at Oxford (coordinated by world’s first beta- and no history of identified defects in the blocker, is launched, heart attack. Peter Sleight), for example, showed that the ‘clot-busting’ drug for the hormone leptin thanks to the insights streptokinase, in combination with , constitutes the most that cause obesity in children. of James Black. 1997 Stephen O’Rahilly and colleagues effective acute treatment following a heart attack. Steve Bloom at Imperial, 1970 in Cambridge identify single- The Heart Protection Study, led by Rory Collins and Richard meanwhile, has identified Graham Russell in Sheffield gene defects causing obesity in hormones signalling a sense discovers the mechanism of children, providing key insight Peto, advocated widespread use of cholesterol-lowering drugs, of ‘fullness’ and is developing action of bisphosphonates, into the nature of obesity. such as statins, even to those with only a minor risk of heart pharmaceutical mimics that drugs used to treat osteoporosis, attack or . The cost of such an initiative, they calculated, might suppress appetite. Paget’s disease and malignant 1998 Hormones became a mainstay Another promising lead, being bone disease. Researchers at Oxford, would be outweighed by the savings made on treatment. of medical treatment in Hormonal disorders have been pursued by Jonathan Seckl coordinated by Peter Sleight, the 20th century, following show that a combination of For those with acute coronary heart syndromes, Keith Fox known about for centuries and colleagues in Edinburgh, 1972 extensive work on natural David Brock in Edinburgh finds aspirin with streptokinase is the – diabetes was described is based on steroid hormone from Edinburgh led studies precisely defining individual risk of steroid hormones. The husband that increased alpha-fetoprotein most effective acute treatment in the 11th century. While in adipose tissue, heart attack and death and established the role of antiplatelet and wife team of James and in the mother’s bloodstream is after a heart attack. doctors did have some early which may underlie the harmful therapies such as clopidogrel in reducing mortality. Sylvia Tait (nee Simpson) at the associated with spina bifida and success – George Murray at cardiovascular complications anencephaly, leading to prenatal 1999 Middlesex Hospital was notable Newcastle’s Royal Victoria of obesity. screening tests. The Heart Protection Study, Although heart disease remains a major killer, mortality rates for the isolation of aldosterone, Infirmary successfully treated led by Rory Collins and Richard are falling. Patients are more likely to survive a heart attack part of the renin–angiotensin The impact of genetics is also 1974 Peto, advocates widespread use myxoedema using an extract and enjoy good quality of life afterwards. system, in 1953. being seen. For example, a Graham Teasdale and Bryan of cholesterol-lowering drugs, of sheep’s thyroid gland in 1891 collaboration led by Andrew Jennett in Glasgow develop even to those at low risk, as costs – the modern era really began In 1989, David Barker in Hattersley and colleagues the Glasgow Coma Scale, the would be outweighed by savings in 1905, when William Bayliss suggested that from Peninsula College of standard method for assessing on treatment. and Ernest Starling at UCL the roots of later-life metabolic the conscious state of a patient. Colour-enhanced image of red blood cells leaking out Medicine and Dentistry and discovered the first hormone, conditions such as high blood 2006 of a ruptured blood vessel. Mark McCarthy and his team secretin. They introduced the pressure or diabetes might lie 1975 Andrew Hattersley in Oxford has been dissecting and colleagues term ‘hormone’ to describe in the prenatal environment. Hans Kosterlitz in Aberdeen the genetic causes of different discovers endorphins and goes from Peninsula the general class of substances In times of scarce nutrition, the types of diabetes. One on to show their importance College of that could act without physical metabolism of a foetus might consequence has been that in pain perception, opiate Medicine and connections between tissues. be programmed for survival in hundreds of children can now addiction, learning and memory. Dentistry establish a nutrient-poor environment. that patients with The medical value of this area be treated with tablets, freeing However, if food is plentiful, 1975 the most common was vividly demonstrated by them from a lifetime of insulin this stores up First ACE inhibitor launched, genetic cause of John MacLeod, a graduate injections. problems in later life. This thanks particularly to the work neonatal diabetes of Aberdeen University, who of John Vane. could be treated influential ‘Barker hypothesis’ Above: Neuroendocrine cells (light received a share of a Nobel with tablets, has received much attention blue) in the human small intestine. Prize in 1923 for showing that 1989 freeing hundreds with populations living longer odo at, metus. extracts of pancreas could David Barker in Southampton of children from a in food-rich environments. proposes the ‘Barker hypothesis’ lifetime of multiple control the symptoms of – that poor maternal nutrition insulin injections. diabetes. The active principle programmes a foetus for survival was later identified as insulin. in a nutrient-poor environment. 2007 Paul Thornalley and colleagues 1995 in Warwick discover that Jonathan Seckl and Brian Walker thiamine (vitamin B1) deficiency in Edinburgh identify steroid in diabetes is linked to abnormal hormone metabolism in adipose metabolism in the kidney, tissue as a possible cause of leading to trials of thiamine cardiovascular complications supplementation to prevent linked to obesity. vascular complications in diabetes. Improving Lives: 150 Years of UK Medical School Achievements | 7

Diet and health Adolescent male and female children with rickets, from around 1901.

As well as energy, our diet provides a suite of other molecules that are essential to life – the full range of which has gradually been identified over the past 100 years. The early 20th century saw a profound change in medicine, with the emergence of the field of biochemistry and the realisation that disease could result from defects in biochemical processes. A key figure in this shift was Archibald Edward Garrod, the first director of Barts’ Medical Clinic, who is generally considered the father of metabolic medicine. He also made the link with the emerging area of genetics, realising that some metabolic conditions could be inherited – coining the term ‘inborn errors THE KREBS CYCLE food is metabolised in most living cells – subsequently of metabolism’. A protégé of Frederick named the Krebs cycle in his Gowland Hopkins was A second pivotal figure was Frederick Gowland Hopkins, who honour. This core biochemical German-born biochemist pathway is found in nearly after studying in London moved to Cambridge and established . Krebs emigrated every living , from its first department of biochemistry. He realised that diet was from Germany in 1933, to avoid bacterium to human. providing many trace elements, or vitamins – insight that led persecution by the Nazis, to a share of a Nobel Prize in 1929. and moved from Cambridge Hans Krebs was awarded the to Sheffield in 1945. 1953 Nobel Prize in Further discoveries came thick and fast. Through studies or Medicine for his work. on dogs kept in the dark and fed a restricted diet, Edward In Sheffield, he carried out a remarkable series of Above: Melanoma cells Mellanby, the first Professor of in Sheffield, experiments that revealed growing in culture. established that rickets could be prevented by treatment with the biochemical processes cod liver oil. He went on to contribute to the discovery of the by which carbohydrate in role of vitamins such as vitamin D, the active principle in cod liver oil. Following the work by on vitamin C In 1965, at Leeds discovered that poor synthesis, for which he received the Nobel Prize for nutrition and vitamin deficiency, particularly of folate, in in 1937, the pioneering Birmingham paediatrician Leonard pregnant mothers was a risk factor for malformations of the Parsons was, in 1932, the first to use synthetic vitamin C spine and brain such as spina bifida. Folic acid supplements to treat scurvy in children. are now recommended for pregnant women. Later, in 1972, David Brock in Edinburgh noted that high levels of a foetal Vitamins were integral to the nutritional standards established protein (alpha-fetoprotein) in the mother’s bloodstream were by Robert McCance and in Cambridge, associated with spina bifida and anencephaly, leading to the who drew up guidelines on the nutritional needs of the first widely used prenatal screening tests. population in wartime Britain – a time when the health of the population was remarkably good. Their iconic monograph, The recognition of the importance of dietary factors has almost The Nutritional Composition of Foods, became the standard eliminated several conditions from the UK. Scurvy and rickets work on nutrition. are seldom seen, while spinal deformities are on the decline. The potential ill-effects of modern diets were highlighted by John Yudkin of King’s College London, who identified a link between sugar intake and coronary heart disease. The UK’s first professor of nutrition, in 1961 he wrote The Slimmer’s Cookbook, the first scientifically based book on slimming. 8 | Improving Lives: 150 Years of UK Medical School Achievements structural engineering

Klug went on to discover ‘zinc fingers’, characteristic protein STRUCTURAL structures that bind different DNA sequences with high specificity. There is growing interest in the design of novel Knowing the structure of large biological zinc finger proteins to interfere with gene activity in disease states. Clinical trials are underway in which a tailored zinc molecules has opened up the prospect of tailored finger protein is used to turn on a growth factor to stimulate pharmaceuticals. blood vessel formation in peripheral arterial disease. In 1962, Watson, Crick and Wilkins were awarded a Nobel Another highly complex ‘molecular machine’ is the Prize for the discovery of the DNA double helix. But they ATP synthase, the structure of which was solved were not the only UK researchers receiving a Nobel Prize by John Walker – yet another member of LMB who has been that year – so too did and , awarded a Nobel Prize (Chemistry 1997). This remarkable who were awarded the chemistry prize for their work multimeric protein structure generates the cell’s ‘energy on the three-dimensional structure of proteins. currency’, ATP, driven by a stream of protons. Max Perutz established the Laboratory of The structure of another important biological (LMB) in Cambridge and supervised the PhD studies of macromolecule – immunoglobulin – was determined Watson and Crick. With John Kendrew, he pioneered the by Rodney Porter, who worked at the National Institute use of X-ray crystallographic approaches to study protein of Medical Research, St Mary’s Hospital Medical School structures, working initially with the blood proteins and Oxford. With , he correctly proposed haemoglobin and myoglobin. that antibodies form a characteristic Y-shape. Perutz was inspired by the father and son team of , While it took Dorothy Crowfoot Hodgkin 35 years to William and , the latter being head of determine the sequence of insulin, protein structures can the Cavendish Laboratory in Cambridge. He also built now be determined in a matter of weeks or months. Indeed, on the work of Dorothy Crowfoot Hodgkin, who, under recent years have even seen high-throughput approaches the supervision of J D Bernal, was the first to apply X-ray adopted, with international initiatives such as the Structural diffraction to the study of proteins. She solved the structures Genomics Consortium, partly based in Oxford. of , vitamin B12 (for which she was awarded a Nobel Prize in 1964) and, most momentously, insulin – The SGC is working out the structure of a range of medically after 35 years’ toil. important human and parasite proteins. Crucially, an understanding of how a protein’s structure is linked to its Cambridge continued to excel in innovative structural function opens up the prospect of designing molecules studies. Another protégé of J D Bernal, to interfere precisely with a target protein. moved to Cambridge, combining electron microscope and crystallographic approaches to structure determination. He was able to look not just at single proteins but molecular aggregates – such as virus particles and complexes of Above: Growing crystals DNA and protein and how they wrapped into nucleosome of a DNA repair protein core particles. This work led to the award of a Chemistry bound to DNA. Nobel Prize in 1982. Improving Lives: 150 Years of UK Medical School Achievements | 9 structural engineering

Launched in 1969, propanolol was spectacularly rational drug design successful. Moreover, it led to profound changes in understanding of mechanisms of heart disease. Structural biology is a key technique in rational Arguably his greatest legacy, though, was in defining the paradigm for modern pharmaceutical research: drug design, which has already given us important start with a clinical problem, define its mechanisms, medications and is the basis of modern medicine. investigate the potential of small molecules to interfere For centuries, drug development was an empirical process with these mechanisms in a desirable way. – some successful drugs were developed but it was rarely clear how they worked. As an understanding of human physiology and biochemistry has improved, drugs can be SERVING AN ACE specifically tailored to interfere with a biological process – The paradigm can clearly be seen in the work of John Vane, rational drug design. whose research led to the development of ACE inhibitors UK scientists played key roles in the early stages of this (blood pressure-lowering drugs that act on angiotensin- new approach to drug development. A central figure converting enzyme, ACE). A chemistry graduate from was James Black, who trained at St Andrews and Dundee Birmingham, Vane moved into pharmacology at Oxford before working in industry for ICI and Wellcome. Black and later at the Royal College of Surgeons, testing the developed analogues that were structurally similar to effects of peptides isolated from the venom of a Brazilian and bound the histamine H2 receptor but did pit viper on ACE. This led to the first ACE inhibitor, . not trigger a cellular response. These ‘receptor antagonists’, Vane is perhaps best known, however, for working out such as cimetidine, inhibited gastric acid secretion and the mechanisms of action of aspirin, which turned out to be revolutionised the treatment of peptic ulcers. an inhibitor of synthesis. This understanding, Similarly well conceived was his pioneering work on beta- which led to a Nobel Prize in 1982, has underpinned the blockers. In the late 1950s, the standard way to treat angina widespread use of aspirin as a blood thinner. Indirectly, and ischaemic heart disease was thought to be by boosting it also led to a new class of anti-inflammatory agent, the supply of blood to the heart by vasodilators. Black turned non-steroidal anti-inflammatory drugs (NSAIDs), which the issue on its head, reasoning that slowing heart rate target the same processes but are designed to have fewer would also protect the heart from reduced supply. side-effects on the gut. He drew upon a new theory that the effects of adrenaline, The examples of Black and Vane also illustrate how which boosted heart rate, were mediated by a specific productive links between academia and industry can receptor, the beta-receptor. Then at ICI, Black worked create that benefit millions the world over. with medicinal to invent a beta-blocking drug, eventually coming up with propanolol, the first successful beta-blocker – for which he was awarded a Nobel Prize Above: Molecular model in 1988. of the testicular form of angiotensin I-converting enzyme. 10 | Improving Lives: 150 Years of UK Medical School Achievements Surgical strike Few areas have undergone such remarkable change during the past 150 years as surgery. The skill of surgeons came to the fore thanks Once the poor relation of medicine, in to two advances: anaesthesia and the control the 19th century surgery was losing its of infection. traditional association with the ‘barber– may be best known for linking the spread of surgeons’ and becoming a highly skilled to contaminated water, but he has a second claim to fame profession within medicine. Surgery is as the first medical professional to anaesthetise a reigning monarch. At the suggestion of James Young Simpson – now one of the most sophisticated the Edinburgh professor who discovered the anaesthetic medical disciplines. properties of chloroform – and James Matthews Duncan, Snow administered chloroform to Queen Victoria when she A significant factor was the introduction of was in labour with her last two children. anaesthesia in the mid- to late 19th century, If pain relief was a crucial advance in surgery so too was which afforded surgeons precious time to control of infection. In the mid-1800s, post-operative infection perform more sophisticated operations. killed almost half of all patients undergoing major surgery. Pasteur, Koch and others were developing the ‘germ theory’, At the same time, progress in infection that infectious disease was caused by . , Regius Professor of Surgery at Glasgow, made control meant that patients were far more the connection with wound sepsis and began to clean wounds likely to survive surgical intervention. and dress them using a solution of carbolic acid. In 1867, he was able to announce that his wards at the Glasgow Royal Infirmary The 20th century saw many innovations, had remained clear of sepsis for nine months. from reconstructive surgery to minimally In 1877, Lister moved to King’s College London, going on invasive techniques. to carry out pioneering brain surgery, improving mastectomy procedures, and developing a method of repairing kneecaps Then, in the second half of the 20th century, with metal wire. the ability to control tissue rejection The following decades saw many advances in surgery. spawned remarkable growth in the field In the 1880s, for example, the Birmingham Professor of Surgery of transplantation. Lawson Tait laid the foundation of modern gynaecology, including procedures for ectopic pregnancies which greatly increased survival. Tait did much to promote the idea of surgical removal of affected tissue. Similarly influential was Berkeley Moynihan, a graduate of , whose book Abdominal Operations secured him an international reputation. Later, figures such as , a surgeon at Barts between 1946 and 1949, developed surgery important ideas on surgical interventions for breast cancer and transplantation and radium implantation. Improving Lives: 150 Years of UK Medical School Achievements | 11

1853 1946 A modern surgical team at work. BRAIN SURGERY Alexander Wood Geoffrey Keynes, a surgeon at develops the hypodermic Barts, develops important ideas syringe, experimenting on the surgical removal of breast with a hollow needle cancer and radium implantation. British doctors have made key contributions to deliver morphine to to the development of brain surgery. treat neuralgia. 1949 At St Thomas’ Hospital, London, The modern era of brain surgery began with the realisation 1853 Harold Ridley of King’s College John Snow is the first performs the first cataract that the brain was functionally compartmentalised – different medical professional to extraction combined with an regions were responsible for controlling different parts of the anaesthetise a reigning artificial lens implantation, body. Although German Fritsch and Hitzig first monarch, administering pioneering surgery that would chloroform to Queen Victoria restore the sight of millions demonstrated this experimentally in 1870, it had already been during the birth of her last around the world. surmised by John Hughlings Jackson of London Hospital two children. Medical School. 1953 1876 at University Jackson, a graduate of St Andrew’s, was the first to suggest William Macewen in Glasgow College London discovers that mental abnormalities were caused by structural damage carries out groundbreaking immunological tolerance, the brain surgery to treat abscesses foundation for transplantation to the brain. He was particularly interested in , which and cancer. biology; he is awarded a Nobel affected both his wife and cousin, and drew an association Prize for this work in 1960. 1877 between epileptic convulsions spreading through the body Joseph Lister moves to King’s 1962 and electrical discharges spreading across the brain. College London and is the first John Charnley at Manchester to carry out an operation under carries out the first successful Jackson was a big influence on David Ferrier, an Edinburgh antiseptic conditions, driving total hip replacement. graduate working at King’s College Hospital. Ferrier carried out huge change in surgical practice. the experimental work confirming Jackson’s theories. 1883 The medical implications of Ferrier’s work were profound. In Birmingham, surgical pioneer Lawson Tait carries If brain functions were localised, a patient’s symptoms would out the first surgical removal of provide clues to the location of brain abnormalities. Following fallopian tube to treat ectopic this thinking, in 1876 Glasgow graduate and Lister disciple pregnancy, an approach that has subsequently saved many lives. 1962 William Macewen predicted that a young boy had an abscess in Oxford clones a Heart surgery was advanced by innovators such as Russell on his frontal lobe. However, his family refused permission 1905 frog, the first adult mammal to Brock from King’s College London, who in 1948 pioneered for Macewen to operate, and the boy died. At post-mortem, Berkeley Moynihan, a graduate be cloned. of Leeds School of Medicine, mitral valve surgery, as well as inventing new instruments to Macewen’s diagnosis was shown to have been correct. publishes Abdominal Operations, 1963 treat congenital heart defects. When Macewen did get to test his conclusions on patients, establishing his international Michael Tunstall in Aberdeen he met with dramatic success. reputation for surgical develops ‘Entonox’, a nitrous In the , Michael Tunstall in Aberdeen improved control excellence. oxide/oxygen mixture for pain of pain relief in labour by developing ‘Entonox’, a mixture of In recent years, a new form of brain surgery – deep brain relief in labour. nitrous oxide and oxygen still in use today. stimulation – has been developed for Parkinson’s disease 1966 patients who no longer respond to drug treatments. This The association between The late saw a major advance, with the emergence of approach owes much to the work of Alan Crossman in dermatitis herpetiformis (a minimally invasive (keyhole) surgery, carried out for the first Manchester and neurosurgeon Tipo Aziz in Oxford, who in blistering condition of the skin) time in the UK by Alfred Cuschieri in Dundee. Most surgical and intestinal abnormalities 1991 established that it reversed Parkinson’s symptoms in procedures are now minimally invasive. is first made by Marks and animal models. Some 30,000 patients have now been treated, Shuster in Newcastle; small- In Sheffield, Alan Johnson showed that surgical interventions and the technique may also be of benefit in other conditions, bowel changes in dermatitis herpetiformis are later identified could be compared with the same rigour and objectivity including chronic pain and depression. 1930 The first successful corneal as coeliac disease. as pharmacological interventions in randomised control graft is performed, after 1972 trials, in a pioneering study comparing conventional with nearly a decade of work by Andrew Wyllie and colleagues the ophthalmic surgeon laparoscopic surgery. in Aberdeen describe and Tudor Thomas of Cardiff Royal name apoptosis, programmed Infirmary. cell death. 12 | Improving Lives: 150 Years of UK Medical School Achievements

REPLACEMENT PARTS Prosthetic heart valve implantation.

The idea that tissues or organs could be transferred between people, or other animals and people, has a long history. Yet most early experiments failed miserably, because of the recipient’s rejection of donor tissue. Some success was achieved in the eye, however, which is protected from the host’s immune response. In 1930, the first successful corneal graft was performed, following nearly a decade’s work by the ophthalmic surgeon Tudor Thomas at Cardiff Royal Infirmary. And in 1949, at St Thomas’ Hospital, London, Harold Ridley of King’s performed the first cataract extraction combined with artificial lens implantation, pioneering the surgery that would restore the sight of millions of people around the world. Stem cells One hope is that stem cells facilitating research on disease will be able to repair damaged mechanisms. Stephen Minger A discovery from 25 years ago The explosive growth in transplantation owes much to the tissue (or stimulate the body’s at King’s, for example, has is turning out to have immense development and testing of novel immunosuppressive own repair mechanisms). created several such embryonic medical potential. Anthony Mathur at Barts, lines, including one compounds by researchers such as Roy Calne in Cambridge. In 1981, (then for example, is carrying out carrying the most common He was using drugs such as aziothioprine in kidney transplants, in Cambridge, now in Cardiff) a clinical trial to test stem cell causing cystic fibrosis. but it was his clinical work confirming the value of cyclosporine was, with Gail Martin in the USA, treatments for heart failure. that turned an experimental technique into a routine procedure. A particularly exciting goal the first to culture embryonic It may also be possible to is to understand the genetic stem cells. Evans went on to engineer new tissues – Calne worked with Roger Williams of King’s College London and cellular programmes develop key techniques for Magdi Yacoub and colleagues on the UK’s first liver transplants (Williams was later responsible that control pluripotency – manipulating mouse , at Imperial have developed for George Best’s liver transplant). UK heart transplants were including the role of genes for which he received a share prototype heart valves based such as Nanog, named after pioneered by Magdi Yacoub of Imperial College, who went of a Nobel Prize in 2007. on stem cells. the mythological Celtic land on to perform more heart transplants than any other surgeon. Engineering of mice is a valuable To obtain embryonic stem cells, of the immortal, Tir na nOg, tool in medical research, researchers turn to somatic which was discovered by Ian The clinical side of transplantation owed much to the ever- particularly for developing cell nuclear transplantation – Chambers and Austin Smith growing understanding of the immune system and its mouse models of disease. And a technique pioneered in the in Edinburgh. Nanog is one response to foreign tissue. A crucial contribution was made research on stem cells is offering UK. In the 1960s, John Gurdon, of a handful of genes that, many exciting new therapeutic by Peter Medawar, who studied at Birmingham and UCL, then in Oxford, was the first collectively, can reprogramme opportunities. and whose research revealed key insights into the nature of to clone a mammal – growing cells into a pluripotent state. ‘tolerance’ to transplanted tissue – recognised by the award Embryonic stem cells are an adult frog by transferring The considerable advances of a Nobel Prize in 1960. exciting because of their a nucleus from a differentiated being made in understanding pluripotency – their ability cell into an egg which had had the mechanisms controlling cell Medical innovations remain important, however, including to turn into any of the many its own nucleus removed. fate, and experience from early the development by a team at Birmingham of the ‘split liver’ cell types of the body. New This technique was famously clinical trials, are combining technique, enabling one liver to be transplanted to both treatments may also emerge used by Ian Wilmut and to make stem cell therapy one from research on adult stem an adult and a child. Keith Campbell in Edinburgh of the most exciting areas of cells. Generally, these cells to clone Dolly the sheep. modern medicine. A further key development has been the development of are more restricted in the types In humans, this approach of cells they can develop into, Above: Human embryonic stem prosthetic body parts, notably the total hip replacement can also be used to generate but are easier to obtain. cell (gold) growing on a layer pioneered by John Charnley at Manchester and the Oxford a supply of cells all sharing of supporting cells (fibroblasts). Knee, developed by John O’Connor and John Goodfellow the same genetic defect, in 1976. Many thousands of children have benefited from cochlear implants, first launched in in 1989. Improving Lives: 150 Years of UK Medical School Achievements | 13

1974 and colleagues in Cambridge begin studies of cell death (apoptosis) in the nematode worm C. elegans.

1978 Roy Calne in Cambridge begins clinical trials on cyclosporine, a new drug preventing organ rejection. Success is an important step towards routine .

1979 David Lane in Dundee discovers the tumour suppressor p53.

1981 Martin Evans in Cambridge cultures embryonic stem cells for the first time. Apoptosis: Central to this system is p53, 1987 Death on demand discovered by David Lane In Sheffield, Alan Johnson in Dundee. The ‘guardian of Understanding how cells shows that surgical interventions the ’, p53 monitors commit suicide is leading can be compared with the DNA for damage, triggering same rigour and objectivity as Plastic surgery Gillies insisted that their with new horrors: combustion the way to new treatments treatment should be of highly inflammable aviation apoptosis when problems pharmacological interventions British doctors were pioneers for cancer. concentrated at one location fuel left many pilots with are detected. in in randomised control trials, of reconstructive surgery for in a pioneering study – converting an old mansion horrific burns. In 1972, Andrew Wyllie and the p53 gene often lead injured servicemen. comparing conventional house near Sidcup, Kent. colleagues in Aberdeen to cancer – indeed, p53 With new techniques being with laparoscopic surgery. War is a major driver of described and named the mutations are found in Unusually, Gillies drew pioneered, McIndoe’s patients medical innovation. process by which cells around half of human cancers. 1989 together a multidisciplinary became known as the ‘Guinea Reconstructive surgery, for deliberately and carefully The Nottingham Cochlear team, including artists, dentists, Pig Club’. As well as physical Many insights into the example, was transformed dismantle themselves. Implant Programme is radiologists and anaesthetists injuries, McIndoe paid equal molecular mechanisms of during the First and Second A professor of Greek in established and provides as well as surgeons. They were attention to the potential apoptosis have come from the first UK child with a World Wars – primarily thanks Aberdeen suggested responsible for numerous psychological damage, studies of the nematode cochlear implant. to two New Zealanders ‘apoptosis’, for ‘falling off’, innovations, including the integrating patients into local worm C. elegans, including working in the UK: Harold as in leaves from a tree. development of endotracheal town life and emphasising those of John Sulston in 1991 Gillies and Archibald McIndoe. Alan Crossman in Manchester anaesthesia by Ivan Magill. the value of psychological Apoptosis is important for Cambridge, who received a share of a Nobel Prize in 2002. and Tipo Aziz in Oxford show Born in Dunedin in 1882, Gillies also placed great rehabilitation. removing cells in development that deep brain stimulation Gillies studied medicine in importance on the (it creates the space between Warfare generates many Many agents targeting the corrects symptoms of Cambridge before qualifying psychological welfare our toes, for example) but Parkinson’s disease in an medical challenges, from apoptosis pathway in cancer at Barts. A posting to France of soldiers. it also has a crucial role animal model. unusual injuries to large are now in development. in 1915 converted him to facial in preventing cancer – it This concern was also notable numbers of casualties. 1996 surgery, and returning to the eliminates damaged and Above: Confocal microscope in New Zealander Both Gillies and McIndoe Dolly the sheep is UK, he persuaded the Army potentially dangerous cells. image of a nematode worm Archibald McIndoe. A cousin are notable not just for cloned by Ian Wilmut to establish a treatment centre If this process is disrupted, (C. elegans). of Gillies, McIndoe studied remarkable surgical success and Keith Campbell at Aldershot for troops with cells can multiply out medicine in New Zealand. but also the enlightened and in Edinburgh. facial injuries. of control. He arrived in the UK in 1930 humane way in which they 2003 The horrors of the Somme and secured a position in cared for patients. Ian Chambers and Austin Smith the plastic surgery department in Edinburgh identify a key soon made it obvious that Above: Photographs of plastic at Barts. pluripotency gene, Nanog. Aldershot’s facilities were surgery cases at the King George hopelessly inadequate, as At the start of the Second Military Hospital, 1916–1918. 2004 soldiers flooded back to World War, McIndoe moved to Stephen Minger at King’s College with horrific facial the Queen Victoria Hospital in London is the first to bank an injuries caused by shrapnel East Grinstead. He was faced line in the and sniper fire. Crucially, UK’s national stem cell bank. 14 | Improving Lives: 150 Years of UK Medical School Achievements

1902 (P/M): Transmission of 1922 (P/M): Heat production in muscle 1923 John Macleod (P/M): Discovery of insulin 1929 1932 Frederick Gowland Hopkins (P/M): Edgar Adrian, Charles Sherrington Discovery of vitamins (P/M): Function of neurones (C): 1936 Fermentation of sugar by yeast Henry Dale (P/M): Chemical transmission of nerve impulses 1937 Albert Szent-Györgyi (P/M): Chemistry of cell respiration Norman Haworth (C): Since Ronald Ross received the UK’s first Nobel Structures of carbohydrates Prize in 1902, scientists based or trained in 1944 the UK have been regular recipients of these Herbert Gasser (P/M): prestigious awards. While the Physiology or Functions of single nerve fibres Medicine Prize recognises work of significant 1945 1946 clinical importance, the Chemistry Prize has often , , Hermann Muller (P/M): Production of mutations by X rays also been awarded for achievements that have (P/M): Discovery of penicillin significant implications for medicine. 1947 Robert Robinson (C): 1956 Synthesis and analysis of alkaloids Cyril Hinshelwood (C): Chemical kinetics of 1951 metabolic reactions Max Theiler (P/M): Transmission of yellow fever 1957 Alexander Todd (C): 1952 Chemistry of nucleotides , Richard Synge UK life science (C): Invention of partition 1958 chromatography (C): Protein sequencing 1953 Hans Krebs (P/M): Discovery of 1960 the (Krebs) cycle Peter Medawar (P/M): Acquired immunological tolerance 1962 Nobel Prizes John Kendrew, Max Perutz (C): Protein structures Improving Lives: 150 Years of UK Medical School Achievements | 15

1962 1977 , , (P/M): (P/M): 1970 Peptide hormones in the brain Double helix structure of DNA Bernard Katz (P/M): 1978 1963 Quantal release of neurotransmitters Peter Mitchell (C): John Eccles, Alan Hodgkin, 1972 Biological energy transfer (P/M): Mechanisms Rodney Porter (P/M): across membranes of nerve impulse transmission Structure of immunoglobulins 1979 1964 1975 (P/M): Development Dorothy Crowfoot Hodgkin (C): (C): of computed tomography (CT) X-ray crystallography of proteins of enzyme reactions 1980 1968 Frederick Sanger (C): Gobind Khorana (P/M): DNA sequencing methods Elucidation of the genetic code 1982 Aaron Klug (C): Structure of nucleic acid–protein complexes 1982 John Vane (P/M): Activities of and role of aspirin

1984 KEY Georges Köhler, César Milstein (P/M): White: Nobel laureates whose main body of work Development of monoclonal antibodies was carried out in the UK. 1988 Yellow: Nobel laureates who received significant James Black (P/M): scientific training in the UK. Principles of drug treatment Only Chemistry Prize winners whose work is 1993 of major relevance to the life are (C): included here. Site-directed mutagenesis C: Chemistry 2003 P/M: Physiology or Medicine (P/M): Development 1993 of magnetic resonance imaging Richard Roberts (P/M): Discovery of ‘split genes’ 2006 Roger Kornberg (C): 1997 Mechanisms of transcription John Walker (C): Structure and mechanism of ATPase 2007 Martin Evans, (P/M): 2001 Introduction of specific modifications , (P/M): in mice by use of stem cells Regulators of the 2002 Brenner, John Sulston (P/M): Genetic regulation of 16 | Improving Lives: 150 Years of UK Medical School Achievements Resisting invaders Throughout human history, human life has been blighted by infectious disease. The origins of germ theory are generally credited With the emergence of ‘germ theory’ in the to Louis Pasteur, but British doctors were quick mid-19th century, it became clear that many to spot the medical possibilities of this new way lethal diseases were caused by microbes – of thinking. and could be prevented. Foremost among them was Joseph Lister. A dedicated medic – he spent three months of his honeymoon visiting So began the fightback against infectious medical centres on the Continent – Lister reasoned that microorganisms, first with aseptic techniques, chemical treatments could be used to rid wounds and surgical then antibiotics. These advances have saved instruments of contaminating microbes. His use of carbolic acid and obsession with cleanliness radically transformed surgery. countless lives. Antiseptic approaches prevented people from being infected. Infectious diseases remain a serious problem But if they did acquire infection, there was very little doctors in the developing world, though even here could do. That all changed with the revolutionary development of antibiotics. new drugs are becoming available to treat In 1928, while working at St Mary’s Hospital, part of Imperial diseases such as malaria. College, Alexander Fleming noticed that were not growing around mould colonies that had appeared on plates left exposed to the atmosphere. He went on to discover that the active compound from his mould, penicillin, killed several disease-causing bacteria. However, he struggled to grow the mould and extract penicillin. Turning the promise of penicillin into reality fell to a group of Oxford researchers, including Ernst Chain, Howard Florey (who shared a Nobel Prize with Fleming) and Norman Heatley, who made crucial contributions – including the inspired use of bedpans from the to grow the mould. Antibiotics are arguably the greatest ever advance in medical infection history. Their clinical value was confirmed by the Oxford team and others, including Mary Evans and Wilfred Gaisford at Dudley Road (now City) Hospital Birmingham, who ran clinical trials of the sulpha M&B 693 (sulphapyridine) for the treatment of lobar pneumonia. This antibiotic was used to treat and immunity when he contracted pneumonia in 1942. Improving Lives: 150 Years of UK Medical School Achievements | 17

1832 John Snow enrols at Newcastle’s medical school shortly after it opens in 1832, moving on to London to complete his degree. In 1854, he makes the connection between water and cholera transmission, halting a cholera epidemic in London’s Soho.

1867 1945 Joseph Lister, Regius Professor Howard Florey, Ernst Chain of Surgery at Glasgow University, and Norman Heatley, working announces that his wards at the Sir William Dunn School have remained clear of sepsis of in Oxford, for nine months – testament demonstrate the therapeutic to the success of his aseptic value of penicillin and develop procedures. ways to mass produce it, ushering in the age of antibiotics. Calming immunity Their work is a notable 1894 example of translational Patrick Manson, the father 1951 The immune system has In Cardiff, Anthony Campbell research: taking a laboratory of , suggests evolved to defend us from develops a novel biomedical finding – that TNF is a key that malaria is transmitted by microbial and other threats, mosquitoes. assay technology based on mediator in inflammation but sometimes it turns on chemiluminescence instead of – and then developing and traditional radioactive labels; the body’s own tissues, testing targeted therapies, the technique is now used causing a range of helping to steer a drug in over 100 million clinical autoimmune conditions. through the drug laboratory tests per year. approval process. A better understanding 1951 of the mechanisms of this In Southampton, Stephen Frederick Heaf in Cardiff immunological friendly fire Holgate has adopted an publishes his work on a multi- can suggest new therapeutic puncture screening procedure analogous approach to options, as exemplified by for immunity to TB, subsequently A 96-well robot dispensing a liquid into a 384-well dish. block the action of the key the work of Marc Feldmann known world-wide as the inflammatory antibody 1902 and Ravinder Maini at Imperial ‘Heaf test’. IgE, leading to innovative Ronald Ross, who studied College. They targeted a key biological approaches to medicine at Barts and later 1952 signalling molecule, tumour Diagnostics treat respiratory conditions worked at the Liverpool School James Riley in Dundee discovers necrosis factor (TNF), which such as asthma. of Tropical Medicine, is awarded that histamine is stored in mast As well as treatment, diagnosis of infections can be crucial, had been identified by Gordon a Nobel Prize for his work cells, work that underpins much helping to guide therapy. In 1951, Frederick Heaf in Cardiff Duff’s group in Sheffield, Above: A thermogram revealing confirming that mosquitoes subsequent pharmacological developed a multi-puncture screening procedure which developing new therapies rheumatoid arthritis of the hand. transmit the malaria parasite. and allergy research. for rheumatoid arthritis and revealed whether someone had been exposed to TB. It 1928 1965 other autoimmune diseases. subsequently became known world-wide as the ‘Heaf test’ Alexander Fleming, Jenny Best of , and Jangu and was in use in the UK for 50 years. makes his famous discovery Banatvala at Several centres have made substantial contributions to of penicillin while working in King’s College the Inoculation Department London detection methods, including Anthony Campbell In Cardiff at St Mary’s Hospital. develop a whose assay technology based on chemiluminescence instead technique for of radioactive labels is now used in over 100 million clinical 1939 rapid diagnosis and detection Mary Evans and Wilfred Gaisford of rubella, leading to the first laboratory tests per year, while in Birmingham, Gary Thorpe and at Dudley Road (now City) characterisation of rubella virus Tom Whitehead pioneered similar tests to detect antioxidants Hospital Birmingham by electron microscopy. and test water purity. begin clinical trials of the sulpha antibiotic M&B 693 1969 In the 1960s, Peter Sneath in Leicester developed - (sulphapyridine) for the In response to an outbreak of treatment of lobar pneumonia. hepatitis that claims 11 lives, based methods for studies of microbial taxonomy and Ken Murray in Edinburgh identification, ultimately leading to miniaturised biochemical develops the first diagnostic test systems now used in virtually every hospital or diagnostic test for hepatitis B virus and later the first HBV . laboratory worldwide. 18 | Improving Lives: 150 Years of UK Medical School Achievements

1973 1989 George Stevenson in David Strachan from the Illustration showing the structure of an HIV particle. Southampton isolates the first London School of Hygiene and molecularly defined human Tropical Medicine proposes the anti-cancer antibodies, leading ‘hygiene hypothesis’, that lack of to the development of DNA exposure to infections in early vaccines for cancer. life underlies the recent rise in asthma and allergic responses. 1975 César Milstein and Georges 1992 Köhler in Cambridge develop Marc Feldmann and Ravinder a method for mass producing Maini at Imperial College develop monoclonal antibodies, leading treatments to block tumour to a Nobel Prize in 1984. necrosis factor, leading to new therapies for rheumatoid arthritis and other autoimmune diseases.

1997 Stephen Holgate, Southampton, pioneers anti-IgE therapy for asthma, leading to the application of innovative biological approaches to 1976 treat respiratory diseases. The World Health Organisation announces that smallpox 1990s has been eradicated, thanks to Researchers at the London Monoclonal Early medical use was a concerted effort in which School of Hygiene and Tropical antibodies hampered by the fact that Allan Watt Downie at Liverpool Medicine show in randomised monoclonal antibodies were controlled trials that First created in the 1970s, has played an important role. based on mouse antibodies, nets impregnated with monoclonal antibodies are and hence seen as ‘foreign’ insecticides can block the invaluable in research and 1982 by patients. A significant Tony Pinching and Jonathan spread of malaria. increasingly being used step forward was made by Weber of Imperial College therapeutically. establish the first UK cohort 2002 Greg Winter and colleagues, studies of people with HIV. Mike Malim and his team at The exquisite selectivity of also at LMB, who replaced King’s College London discover HIV antibodies makes them ideal key mouse structures in the 1983 a human gene that inhibits HIV antibodies with their human infection, opening up a new tools in many areas, from Herman Waldman in Cambridge In the 1980s, a new devastating viral infection appeared: detection and diagnosis to counterparts – creating develops Campath-1 therapeutic avenue of anti-HIV research. blocking of specific protein ‘humanised’ antibodies monoclonal antibody, forerunner HIV/AIDS. Researchers in the UK made several important 2005 that now form the basis of alemtuzumab. contributions in the early days of this new epidemic. activity. In 1975, their use The and Infection exploded when César Milstein of therapeutic monoclonal Robin Weiss at University College London identified CD4 1984 Unit at and Georges Köhler at the antibodies. Robin Weiss at University College opens, integrating the study of as the cell surface receptor for HIV and developed the first Laboratory of Molecular basic immunology, microbiology This new class of therapeutic London identifies CD4 as test for antibodies to the virus, used to identify those infected. Biology (LMB) in Cambridge and . is becoming increasingly the cell surface receptor for developed a way of mass- HIV and develops the first common, as researchers At Imperial College, Tony Pinching and Jonathan Weber producing identical antibody serological test for the virus. 2006 target molecules specifically The WHO recommends use established the first UK cohort studies of people with HIV molecules – monoclonal implicated in disease 1985 of artemisinin combination in 1982, which generated important information on the antibodies. therapies, developed by processes. Examples include In Birmingham, Gary Thorpe progression of the disease. trastuzamab (Herceptin), and Tom Whitehead pioneer Nick White and colleagues in One medical use is in cancer the development and Oxford, for treatment of malaria. Although effective drugs exist, there is still an urgent need treatment, using antibodies alemtuzumab (the humanised form of Campath-1) and commercialisation of enhanced for more and better treatments. Research continues into HIV targeted against structures chemiluminescence, used in 2006 found on cancer cells. An early monoclonal antibodies Irwin Mclean in Dundee blood-borne disease analysis at several centres, including King’s College London, where example was the ‘Campath-1’ against tumour necrosis discovers that mutations of and water purity testing. Mike Malim and his team recently discovered a human gene factor (see page 17). the fillagrin gene are present monoclonal antibody, that inhibits HIV infection, opening up a new avenue of specific for T cells, which 1986 in many cases of eczema and Above: Herceptin breast cancer Greg Winter in Cambridge asthma, providing new targets anti-HIV research. was developed by Herman drug, molecular model. develops techniques to for treatment of these Waldmann and colleagues in humanise monoclonal common diseases. Meanwhile, groups such as that of Andrew McMichael in Cambridge to treat forms of antibodies. Oxford are attempting to understand the nature of the immune leukaemia and lymphoma. response to HIV and to develop effective vaccines. Improving Lives: 150 Years of UK Medical School Achievements | 19

Although malaria was banished from many regions in the Tropical medicine 20th century – including England – it remains a serious A mosquito (Anopheles stephensi) in flight with its abdomen full of blood. global threat to health. Several effective drugs have been The roots of tropical medicine lie in the UK and rendered next to useless because the malaria parasite has developed resistance. it continues to be a field in which the UK excels. Yet there have recently been encouraging signs of progress. The field of tropical medicine was strongly influenced by Randomised controlled trials run by researchers at the London the UK’s imperialistic excursions overseas in the 19th century. School of Hygiene and Tropical Medicine have shown that Tropical diseases exacted a heavy toll on troops and bednets soaked in insecticide are effective and cost-effective government administrators stationed abroad. counters to malaria transmission. Their widespread use could A key figure was Patrick Manson, who trained originally in save the lives of 400 000 young African children every year. Aberdeen and made numerous discoveries about the causes In a significant advance, Nick White and colleagues in Oxford, and spread of tropical diseases. He helped to set up what is working in Thailand and Vietnam, have pioneered the use of now the London School of Hygiene and Tropical Medicine. artemisinin combination therapies for malaria, using derivatives Possibly Manson’s greatest contribution was to suggest that of an ancient Chinese herbal remedy. Use of these drugs has mosquitoes were responsible for the spread of the malaria dramatically cut deaths from malaria in South-East Asia and, parasite – a supposition proved by his protégé, Ronald Ross. globally, are the World Health Organisation’s recommended Ross received the UK’s first Nobel Prize in Physiology or drugs for malaria. Medicine in 1902. A medical student at Barts, Ross spent most of his career at the Liverpool School of Tropical Medicine.

Postcard: to be worn as a veil, early 20th century. Malaria parasites in a mosquito midgut. 20 | Improving Lives: 150 Years of UK Medical School Achievements an inside view Being able to see inside the living body has X-ray imaging is also at the heart of CT (computed revolutionised medicine. tomography) scanning, developed by Godfrey Hounsfield at EMI in the UK and the US For most of history, doctors were unable to see inside Allan McLeod Cormack. By taking a series of ‘slices’ the living body, relying instead on outward signs of illness, through the body, CT imaging provides a three- poring over its emanations, or interpreting the pulse. dimensional view of body structures. The 20th century saw a flourishing of techniques for visualising living tissue, greatly extending medicine’s Hounsfield tested his device on a preserved human diagnostic abilities. brain and a fresh cow’s brain, before in 1971 trying it out on a patient – a patient with a cerebral cyst. The beginning of this new era can be traced back to This work, carried out in conjunction with Jamie Wilhelm Roentgen’s discovery of X-rays in 1895. Ambrose at Atkinson Morley’s Hospital in Wimbledon, Remarkably, just months later John Macintyre, a nose part of St George’s, was a crucial step in adapting the and throat specialist in Glasgow with a particular interest technology for medical practice. in music – he also made phonographic recordings of famous singers and musicians – had opened the world’s In 1972 the first commercial CT scanner was pressed first radiology department. He presented his first X-ray into service by Ian Isherwood and Godfrey Hounsfield images to the Royal Society in London in 1897. in Manchester, with machines also being installed at Glasgow and the Institute of Neurology in London.

Above: Interior of the X-ray department at the Hospital for Cancer and Allied Diseases, 1934. Improving Lives: 150 Years of UK Medical School Achievements | 21

Below: MRI reconstruction of the brain, skull and face. Below: Foetus ultrasound at 24 weeks. Below: Positron emission tomograph of the brain.

MRI: Magnetic attraction Ultrasound: PET: From structure to function X-rays were not the only tool being used to visualise the Engineering meets medicine CT, MRI and ultrasound have provided a wealth of information living body. Great interest was being shown in the use A further imaging technology, ultrasound, also owes much on body structures and structural abnormalities. Recently, of magnetic resonance imaging (MRI), based on the effects to UK researchers – in particular, Ian Donald in Glasgow. this structural insight has been complemented by a growth of strong magnetic fields on molecules in the body. A former RAF medical officer and graduate of St Thomas’, in functional information that can be obtained from the The development of MRI owes much to Peter Mansfield, Donald arrived in Glasgow in 1954 with, in his words, living body. a physicist at Nottingham. Imaging of the body was “a rudimentary interest in radar… and a continuing One key technology is positron emission tomography (PET), made possible by the mathematical tools developed childish interest in machines”. Despite much scepticism championed by John Mallard. The strength of PET signals by Mansfield – an advance that led to a share of a Nobel he was convinced that echo sounding, or sonar, had from the body depends on metabolic activity, so PET imaging Prize in 2003. great medical potential. can reveal differences between structures that may be As with CT, the technology development was In 1955, Donald visited local boilermakers Babcock & physically similar but very different in character – such as accompanied by clinical input. A crucial figure in this Wilcox, at the behest of one of the directors, husband of a cyst versus a cancer. regard was John Mallard of Aberdeen, whose practical a grateful patient. Two cars made the journey, their boots PET is now used for cancer detection and monitoring of innovations did much to turn MRI into a viable medical full of clinical samples. These were studied using an responses to treatment, as well as for recording brain activity tool. In 1980, his team produced the first clinically useful industrial ultrasonic metal flaw detector – along with and tracing metabolism in the body. The availability of new image of a patient. a large steak as control sample. forms of radiolabelled metabolite may significantly increase Working with Tom Brown from the engineering firm its potential medical uses. It may provide a way to diagnose Kelvin & Hughes, Donald refined the technologies for early stages of conditions such as Alzheimer’s disease. abdominal imaging, proving its worth with a series of The brain is also the target of a spinoff of MRI, functional spectacular diagnoses – including that of a woman with MRI, which can be used to assess regional brain activation. a history of fibrosis who was admitted with a suspected It is based on the finding that blood flow in the brain increases myoma. Ultrasound imaging revealed that she was with neural activity – a discovery actually made by Charles actually pregnant. She went on to have a healthy baby. Sherrington in the 1890s. By 1958, Donald had published the world’s first ultrasound fMRI is now widely used in research to identify areas of the brain images of the foetus, and foetal imaging became one of active as particular tasks are undertaken, providing fascinating the technology’s main applications. insight into the brain function. The technique is also revealing what may be going wrong in conditions such as schizophrenia, autism and attention deficit hyperactivity disorder. 22 | Improving Lives: 150 Years of UK Medical School Achievements DOCTOR AS DETECTIVE

Identifying the causes of diseases and how they are spread are fundamental steps towards prevention, and they often call for highly honed investigative skills. One of the earliest and best known examples is that of doctor John Snow, an early student at Newcastle’s medical school, who made the connection between water and cholera transmission in 1854. He studied a cholera outbreak in Soho, London, and by mapping each case of disease, pinpointed a water pump on Broad Street as the likely source of contamination. By preventing the pump from being used, he also managed to halt the epidemic. at large In 1894, the first UK Public Health lab was founded by Sheridan Delepine of Manchester. Delepine also successfully A doctor is principally concerned tracked down the causes of a poisoning outbreak in Derby with the health of his or her patients. in 1902, tracing its origins to a consignment of contaminated pork pies. Diagnosis and treatment of each Monitoring of disease outbreaks in populations can also individual patient is at the heart of provide vital information on how a disease is spread within medical practice. a community. An early example was the meticulous work of , a graduate of Leeds Medical School, who Sometimes, though, physicians have followed an epidemic of catarrhal jaundice in Wensleydale, the opportunity to have an even tracing the entire epidemic to one child and establishing the broader beneficial impact, by helping long incubation (26–35 days) of the disease. Pickles’s careful and precise recording, published in his book Epidemiology in a to safeguard public health. Country Practice, provided a model for practice-based research. The role of the doctor here can be Perhaps the most famous epidemiological study, though, significantly different – searching was that of Richard Doll, who with Austin Bradford Hill of the London School of Hygiene and Tropical Medicine, showed for the roots of disease outbreaks, that smoking caused lung cancer and increased the risk of identifying potential threats to health, heart disease. In the 1950s, the prevalence of lung cancer was or influencing health or social policy. rising inexorably, yet its causes remained a mystery. A popular idea was that road building might be to blame. Through these kinds of activities, Ironically, it was through studies of general practitioners who doctors are not only protecting the smoked that Doll and Hill were able to link lung cancer to public from health dangers that are smoking. They confirmed the finding in other populations, ultimately leading to a profound change in attitudes to smoking known about but also helping to and providing the evidence for a raft of public health measures. identify where the problems of the future may lie. Improving Lives: 150 Years of UK Medical School Achievements | 23

Contaminants in the water supply, from a scientific Single-gene disorders were report into the cholera epidemic of 1854. soon being unravelled by new technologies – greatly helped by the , to which the Sanger Institute at Hinxton made a major contribution. More common conditions – where genes and environmental factors combine to enhance the risk of disease – have proved trickier to unpick. Within the past two years, this situation has changed dramatically, with a flurry of papers from the Wellcome Trust Case Control Consortium – a partnership between 24 leading UK groups – revealing a host of genes linked to a range DNA and medicine of genetics. As well as IVF and PGD prenatal genetic testing of common diseases, from providing molecular for parents known to be at The second half of the 20th diabetes to Crohn’s disease. The birth of Louise Brown explanations for biological risk of having children with century saw a flourishing of in 1978 was a landmark in phenomena, the new field In general, psychiatric serious genetic conditions. DNA-based science, the fruits reproductive medicine. provided a suite of tools for conditions have proven Alan Handyside, Robert of which are beginning to be studying living systems. a tougher nut to crack. Winston and colleagues harvested in medicine. Infertility is common. There have been some pioneered the use of new In medicine, a major goal has For many couples the The discovery of the double successes, such as a possible DNA methods to identify been to determine the role solution lies in IVF (in vitro helix structure of DNA by schizophrenia risk factor, harmful mutations in the genes play in disease, harking fertilisation), first achieved James Watson and Francis DISC1, identified by David cells of very early embryos back to Archibald Edward in humans in 1978 by Patrick Crick in Cambridge, aided Porteous and colleagues – preimplantation genetic Garrod’s ‘inborn errors of Steptoe, who trained at by Maurice Wilkins and in Edinburgh. diagnosis (PGD). metabolism’. In the modern King’s College London and Rosalind Franklin at King’s St George’s Hospital Medical Moreover, Doll and Hill’s work laid the foundations of modern era, pioneering work was done Although not of immediate In 2006, doctors at Guy’s College London, is often School, and Cambridge by David Weatherall in Oxford, medical benefit, identification and St Thomas’ Hospitals epidemiological practice, an area of profound importance heralded as the beginning of physiologist Bob Edwards. whose group dissected the of these genes opens up developed a modified to today’s public health. a new era in science. Equally More than a million babies causes of thalassaemias, blood valuable new avenues of procedure, preimplantation auspicious, though, were the worldwide have now been Evidence of the power of epidemiological approaches can disorders caused by mutations research for therapeutics. genetic haplotyping. elucidation of the genetic born via IVF. in haemoglobin genes. This technique can identify be seen in the success of initiatives such as Bristol’s Avon code (to which Francis Crick, Above: The DNA double helix. more mutations than Longitudinal Study of Parents and Children (ALSPAC, also with , made Genetic diagnostic tools As well as enabling couples conventional PGD. known as the ‘Children of the Nineties’), which began with important contributions) and emerging from the work have to have the children they so desperately want, IVF has also the development of DNA been widely adopted globally. Above: Oocyte during in vitro 14 000 pregnant women in 1991 and 1992. It has provided opened up the possibility of a wealth of information on the determinants of infant health sequencing technologies In , for example, testing fertilisation. by Fred Sanger. for carrier status has reduced and development. the number of affected The emerging field of children almost to zero, And looking forward, the UK BioBank project, which is ‘molecular biology’ dovetailed even though haemoglobin collecting health and lifestyle information from 500 000 people with the traditional discipline mutations are common. aged 40–69, in collaboration with centres throughout the UK, will provide valuable information on the causes of disease in middle and later life. 24 | Improving Lives: 150 Years of UK Medical School Achievements

Effective healthcare Blood transfusion during the Second World War.

The UK’s medical infrastructure also owes much to the products of its medical schools. Our highly effective national blood transfusion service, for example, is in large part due to the efforts of Geoffrey Keynes, a surgeon at Barts between 1946 and 1949. The UK was at the forefront of transfusion services, launching a national service in 1946. Two years later, the National Health Service itself was established – a process in which Henry Cohen (later Lord Cohen of Birkenhead) in Liverpool played a crucial role. Cohen was an exceptionally talented and teacher, and through his Cognitive Notably, the success of close association with Aneurin Bevan, the Minister of Health, behavioural therapy CBT has been confirmed in he made a significant contribution to the planning of the NHS. randomised controlled trials, A ‘talking therapy’, cognitive providing a firm evidence On the international stage, Allan Watt Downie, Professor of behavioural therapy (CBT) base for their wider rollout offers a validated non- Bacteriology at Liverpool for over 20 years, provided expertise across the NHS – including pharmacological approach and practical assistance to the World Health Organisation in its a £173 million expansion of for a range of disabling efforts to eradicate smallpox, which was achieved in 1976. talking therapies announced conditions. in 2007. In the latter part of the 20th century, the concept of evidence- CBT is a way of addressing Work continues to test based medicine gained ascendancy, emphasising the ability distinctive thinking and the value of CBT in a wide of medical research to identify effective (and cost-effective) behaviour patterns that range of conditions, including negatively impact on a treatments. The randomised controlled trial has become the schizophrenia, being studied patient’s mental state. Over gold standard by which therapies should be judged and has by, for example, Doug the past 20 years, theoretical shown the value of numerous treatments now in routine clinical Turkington in Newcastle models have been developed and David Kingdon in use, including statins and ‘clot-busting’ drugs (see page 6). for different conditions and Southampton, and pain, used to create successful Other approaches have also yielded important information, the focus of Simon Morley interventions. however – including longitudinal studies which pinpointed in Leeds and others. The first CBT treatment babies sleeping on their front as a significant risk factor for The computerised delivery approved by NICE was sudden infant death syndrome. of CBT also holds great developed by Chris Fairburn promise. Beating the Blues for Edzard Ernst at Peninsula Medical School has championed the and colleagues in Oxford The saw the continuation of large-scale clinical trials in depression and FearFighter for eating disorders such as primary care, such as those led by Tony Kendrick and Paul rigorous appraisal of complementary and alternative medicines. for phobias, developed by bulimia nervosa. Researchers Little, involving a network of hundreds of general practitioners groups at the Institute of Evidence-based approaches to medicine have been such as David Clark and in Southampton, David Mant in Oxford and Ann-Louise Psychiatry, have both received energetically promoted by Iain Chalmers, who worked at the Anke Ehlers at King’s College Kinmonth in Cambridge. In Keele, Elaine Hay has shown how NICE approval. London School of Hygiene and Tropical Medicine and Oxford London have shown that CBT multidisciplinary health professional teams can use randomised before establishing the Cochrane Collaboration. The drive for is effective in post-traumatic Above: Talking therapies controlled trials to identify effective primary care for people stress disorder, helping are effective treatments a rational basis for healthcare provision across the UK led to with common chronic disabling conditions such as back pain survivors of the Omagh for depression. the creation of the National Institute for Health and Clinical and osteoarthritis. bombing in Northern Ireland, Excellence in 1999. among others. Improving Lives: 150 Years of UK Medical School Achievements | 25

1854 1950s SOCIAL FACTORS Chart showing temperature and mortality of London for John Snow makes the Richard Doll in Oxford and Austin every week of 11 years, 1840-50, and 11-year average. connection between water Bradford Hill of the London and cholera transmission. School of Hygiene and Tropical Medicine show that smoking An important role of doctors has been 1894 causes lung cancer and increases to highlight the health consequences of The first UK Public Health the risk of heart disease. laboratory is founded by social inequities. Sheridan Delepine of 1967 Manchester. Based at London School of Even before the advent of the welfare state in 1948, Hygiene and Tropical Medicine, Dugald Baird, Professor of Obstetrics and Gynaecology at 1919 the original Whitehall Study Aberdeen, was highlighting the association between social Ethel Manson, a former Matron begins; it uncovers a strong link at Barts, succeeds in her between mortality and lower circumstances and maternal and foetal health, promoting campaign for the state grades in the Civil Service. policies to reduce perinatal mortality, particularly among registration of nurses. Manson is the poor, and to encourage planned parenthood. widely regarded as the founder 1967 of professional nursing and as Cicely Saunders, of King’s Also influential was Douglas Black, a graduate of St Andrews a visionary, with ideas half a College London, founds century ahead of her time. the hospice movement and and Professor of Medicine in Manchester. While on devotes her life to ensuring that secondment at the Department of Health, he prepared what 1934 terminally ill people can die became known as the ‘Black Report’, the first major publication Henry (later Lord) Cohen with dignity and without pain. becomes Chair of Medicine on the relationship between poverty and disease. Despite at Liverpool; an exceptionally 1978 reputedly being suppressed by the incoming Conservative talented physician and teacher, Patrick Steptoe, a graduate of Government led by , it later became a his close association with Aneurin St George’s, is instrumental in Bevan, the Minister of Health, work leading to the first ‘test bestselling paperback and laid the foundations for much enables him to make a significant tube’ baby, Louise Brown, further work on the impact of social inequalities on health – contribution to the planning of born on 25 July 1978. still an issue, with male life expectancy differing by 10 years the National Health Service. 1984 between affluent areas of London and Manchester. 1939 in Leicester William Pickles, a graduate of develops the techniques for Further evidence of the impact of social factors in health Leeds Medical School, publishes DNA fingerprinting and DNA has come from the Whitehall study, led by Michael Marmot his book Epidemiology in a profiling, which are now used all medical consequences. initially at the London School of Hygiene and Tropical Medicine Country Practice, detailing his over the world in forensic science As the case of trastuzamab observations of an epidemic to assist police detective work and later at UCL. Looking at mortality rates among civil (Herceptin) illustrates, the of catarrhal jaundice in and to resolve paternity and servants aged 20–64, the study found a clear link between causes of breast cancer will Wensleydale. immigration disputes. civil service grade and mortality – those on the lowest grades dictate whether a therapy will work. 1940s 1997 were more likely to die early. Dugald Baird in Aberdeen The campaign of More generally, the growing highlights important role of of Leeds to outlaw chemical On a global stage, Alastair Hay of Leeds has been highly awareness of the links between social circumstances on maternal weapons is successful, with influential in his campaign for chemical agent disarmament, genes (or their products) and and foetal health, introducing the creation of the Chemical enshrined in the Chemical Weapons Convention adopted risk of disease (and responses the term ‘perinatal’. Weapons Convention, since adopted by 182 countries. by 182 countries. Having seen the effects of Agent Orange to drugs) is ushering in the in the Vietnam War, he has campaigned tirelessly against field of pharmacogenetics or 2001 the use of chemical and biological agents in warfare. personalised medicine. While The world’s first male fertility still in its infancy, treatments home test is developed in tailored to individuals’ genetic Birmingham Medical School, Genes and cancer the breast cancer gene BRCA2 make up will undoubtedly in conjunction with the (isolated by Mike Stratton and company Genosis. Numerous genes have been become more common in colleagues at the Institute of linked to cancer, including the coming decades. 2007 Cancer Research). MEN2 (causing multiple In a newly built Clinical Research Above: Colour-enhanced image 1946 endocrine neoplasia, identified Increasingly, it appears that of a breast cancer cell. Facility and Trials Unit, University Geoffrey Keynes, surgeon of East Anglia Medical School by Bruce Ponder in Cambridge), cancer is genetically highly at Barts between 1946 and p53 (discovered by David Lane complex. Crucially, this is coordinating a £4 million trial 1949, is instrumental in the to determine the effectiveness in Dundee; see page 13), and complexity has important establishment of a national of a screening programme for blood transfusion service. osteoporosis among 12 000 subjects in seven UK centres. 26 | Improving Lives: 150 Years of UK Medical School Achievements FUTURE CHALLENGES

Despite the major achievements of the past 150 years, significant challenges remain. Many diseases remain difficult to treat, including Alzheimer’s disease and other conditions that affect people in later life – which are growing in importance as the population ages. perspectives New therapies would also be valuable in other areas, including UK Medical Schools continue to psychiatric conditions and management of chronic pain. have an important role to play in Although infectious diseases are not the major killers they used safeguarding public health. to be (in the UK at least), there is no cause for complacency. Antibiotic-resistant bacteria are a medical headache and new antibiotics are urgently needed. Globally, around two new human infections are appearing each year, mainly as pathogens jump species from animals to people. As HIV, SARS and avian flu illustrate, these infections can be highly dangerous. There is a need for ongoing surveillance to identify emerging threats, as well as for research to develop new and better treatments or vaccines. Recent years have seen an alarming rise in obesity and associated health problems. Excessive weight gain is now common in young people, storing up potential health problems in later life. As a result, some fear that the century- long rise in life expectancy may stall or even decline. On the international front, while some progress is being made, diseases such as HIV/AIDS, malaria and tuberculosis continue to kill millions every year. Even where infectious diseases are being brought under control, countries are beginning to feel the impact of the ‘diseases of affluence’ as heart disease, diabetes and so on take their place. The developing world will also bear the brunt of climate change. But the UK will not escape its impact. The country can expect a future of increasingly turbulent weather, including heat waves and more severe weather events such as storms and floods. Respiratory complaints are likely to rise, particularly in cities. Food-borne diseases may well become more common. Improving Lives: 150 Years of UK Medical School Achievements | 27

More generally, the spiralling costs of healthcare are challenging The biology of ageing is another exciting area. With evidence the economic models on which medical care has been based growing that accumulating damage to cells underpins many The preparation of samples for DNA sequencing. for the past 50 years. Developing new, safe and effective drugs of the diseases of later life, intervening in these processes could is becoming an increasingly expensive occupation, and much prevent a range of conditions. thought needs to be put into ensuring that the public can More generally, disease prevention is emerging as a key aspect continue to gain access to the fruits of medical progress over of public health. Many factors associated with healthy longevity the coming years. have now been identified. Other dietary and behavioural information may be augmented by pharmacogenetic tests Opportunities or genetic tests that identify risk factors for common diseases and suggest options for avoiding ill-health. It is feasible that On the other hand, there are plenty of reasons to be optimistic supplements – dietary or pharmacological – could play an about the future of medicine. The genetic revolution is increasing role in keeping people healthy rather than treating transforming the way biomedical research is carried out. them when they fall ill. The Sanger Institute, which led the UK’s contribution to Another major opportunity lies in the gathering, sharing the Human Genome Project, is now generating 10 billion and analysis of health-related information. Large-scale base pairs of sequence information – the equivalent of three epidemiological studies are already generating important human – every day. And productivity is continuing findings. The UK has a great advantage in the shape of the NHS, to rise exponentially. and developing effective systems to draw on population data This information is underpinning research into human biology has to be a high priority. and unearthing new leads for drug development. It is helping Realising the benefits of the revolutionary changes in doctors dissect disease and offer treatments based on biomedical research of the past 50 years will call for some underlying causes rather than generic symptoms. significant shifts. There is a widespread realisation – across the Pharmacogenetics, the use of drugs tailored to individuals’ world – that more effort is needed to turn laboratory advances genetic make-up, is slowly infiltrating clinical practice. An early into practical medical innovations – the so-called ‘translational example is the use of genetic tests to identify those at risk research’. There is unfortunately no easy way to turn new of side-effects from antiretroviral drugs used to treat HIV knowledge into new products, and driving the process infections. The clinical impact of pharmacogenetics is likely forward will have to involve major investment in people to be gradual, but it is already changing drug development, and facilities – a requirement that has been recognised and enabling companies to focus at earlier stages on responsive is being implemented. populations. It may also lead to new uses for old drugs, So what of the doctor of the future? Increasingly he or she will which have been shelved because of adverse reactions be contributing both to treating illness and preventing disease; in a subsection of the population. working locally but networking nationally (or internationally); Progress in stem cell science is hugely exciting, particularly with listening to informed patients as well as dispensing advice the growing understanding of pluripotency – the ability of cells and medicines. Medicine has been transformed over the past to generate all the other cell types of the body. There is a real 150 years, and doctors have adapted too. Yet the principles prospect that adult cells could be converted into pluripotent that have governed doctors’ behaviour and the importance stem cells, which could be used as a source of new cells for of the trusting, therapeutic relationships with patients remain tissue repair or regenerative medicine. In fact, a significant as valid today as they were a century and a half ago. Whatever challenge is to balance the urge to rush towards clinical changes occur over the next 150 years, doctors will undoubtedly application with the need to understand stem cells better, be helping to drive and implement them in a way that benefits outside and inside the body. the public. 28 | Improving Lives: 150 Years of UK Medical School Achievements uk medical schools

Medical School Council Member Date Established Aberdeen Professor Mike Greaves 1497 Barts and the London Professor Sir Nicholas Wright 1123 as St Bartholomew’s, 1785 as the London Hospital Medical College Birmingham Professor Ian Booth 1825 Bristol Professor Peter Mathieson 1833 Brighton and Sussex Professor Jon Cohen 2001 Cambridge Professor Patrick Sissons 1975 Cardiff Professor Mike Owen 1893 (University of Wales, 2004 Cardiff) Dundee Professor Irene Leigh 1967 East Anglia Professor Sam Leinster 2000 Edinburgh Professor Sir John Savill 1720 Glasgow Professor David Barlow 1637 Hull York Professor Ian Greer 2001 Imperial Professor Steve Smith 1997 as Imperial (1834 as Westminster and as Charing Cross) King’s Professor Robert Lechler 1561 as St Thomas’ Keele Professor Richard Hays 2004 Leeds Professor David Cottrell 1831 Leicester Professor David Wynford-Thomas 1975 Liverpool Professor John Caldwell 1834 London School of Hygiene and Tropical Medicine Professor Nick Black 1899 Manchester Professor Paul O’Neill 1874 Newcastle Professor Chris Day 1834 Nottingham Professor 1966 Oxford Professor Alastair Buchan 1312 Peninsula Professor Sir John Tooke 2000 (Chair, Medical Schools Council) Queen’s Belfast Professor Patrick Johnston 1849 Sheffield Professor Tony Weetman 1828 Southampton Professor Iain Cameron 1969 St Andrews Professor Hugh MacDougall 1413 St George’s Professor Peter Kopelman 1752 Swansea Professor Rhys Williams 2004 UCL Professor Ed Byrne 1828 Warwick Professor Yvonne Carter 2000 with Leicester/2007 independent Improving Lives: 150 Years of UK Medical School Achievements | 29

Image credits: Front cover: villi in small intestine, S Schuller/Wellcome Images (WI); contents: antique anatomy, iStockphoto.com/mstroz; p. 2: antique anatomy, iStockphoto.com/mstroz; p. 3: blood bag, WI; baby in incubator, iStockphoto.com/RapidEye; p. 4: body, iStockphoto. com/Eraxion; p. 5: heart, Gordon Museum/WI; nerves, D Furness/ WI; Gray’s Anatomy, WI; anatomy model, iStockphoto.com/mevans; p. 6: pill, iStockphoto.com/ryasick; man on scales, A Sieveking/WI; syringe, iStockphoto.com/Plainview; blood vessel, A Weston/WI; neuroendocrine cells, S Schuller/WI; p. 7: melanoma cells, P J Smith and R Errington/WI; children with rickets, WI; p. 8: crystals: B O’Hara and R Savva/WI; p. 9: molecular model: K R Acharya/WI; p. 10: surgeon, Rubberball Productions; p. 11: surgery, iStockphoto.com/rafost; syringe, iStockphoto.com/milosluz; corneal graft, iStockphoto.com/milosluz; frog, iStockphoto.com/Captainflash; p. 12: embryonic stem cell, A Cavanagh/WI; heart valve surgery, iStockphoto.com/beerkoff; p. 13: plastic surgery, RAMC Muniment Collection/WI; nematode worm, D Becker/WI; sheep, iStockphoto.com/GlobalP; p. 14: molecular model, iStockphoto.com/cdascher; p. 16: bacterium, D Gregory and D Marshall/ WI; p. 17: robot, iStockphoto.com/red moon rise; p. 17, thermogram, WI; mosquito, Audio Visual, London School of Hygiene and Tropical Medicine/WI; , D Gregory and D Marshall/WI; rubella virus, Medical Art Service, Munich/WI; p. 18: smallpox, WI; HIV, Medical Art Service, Munich/WI; herceptin, T Evans/SPL; p. 19: mosquito net, WI; malaria parasites, H Hurd/WI; mosquito, H Sturrock/WI; p. 20: X-ray department, WI; head X-ray, iStockphoto.com/Gewitterkind; p. 21: MRI scan, M Lythgoe and C Hutton/WI; ultrasound scan, iStockphoto. com/mathieukor; PET scan, WI; p. 22: baby, iStockphoto.com/1joe; p. 23: water contaminants, WI; DNA, P Artymiuk/WI; oocyte, M I Walker/WI; p. 24: blood transfusion, RAMC Muniment Collection/WI; psychotherapy, iStockphoto.com/Bliz; p. 25: mortality report, WI; breast cancer cell, A Weston/WI; blood bag, WI; p. 26: baby, iStockphoto. com/Rais; p. 27: researcher, WI.

Editorial: Ian Jones, Isinglass Consultancy Limited. Design: Jag Matharu, Thin Air Productions Limited.

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