Today's Neuroscience, Tomorrow's HistorySupported by a Wellcome Trust Public Engagement grant (2006-2008) in the History of Medicine to Professor Tilli Tansey (QMUL) and Professor Leslie Iversen (Oxford), this project recorded interviews with 12 prominent neuroscientists, between 2006 and 2008. On the completion of the interviews and their transcriptions, podcasts and visual clips were prepared which are now accessible by following the links below.
Neuroscience has been one of the key areas of biomedical science that the Wellcome Trust has fostered since its creation in 1936. Indeed the very first ‘fellowship’ grant awarded by the Wellcome Trust in 1937 was to Otto Loewi, who shared the 1936 Nobel Prize in Physiology or Medicine with Sir Henry Dale for their work on the elucidation of chemical neurotransmission.
This project aims to provide material resources about contemporary neuroscience to inform and stimulate present and new generations of neuroscientists, and for others, such as historians, journalists and policy-makers, engaged in the analysis, understanding and promotion of modern medical sciences.
SELECTION OF THEMES AND SUBJECTS
Constraints of finance and time have meant that it has been possible to interview only 12 neuroscientists, and difficult decisions had to be made about areas and individuals to include. Mindful of the Society for Neurosciences’ oral–history project, (see http://www.sfn.org/index.aspx?pagename=HistoryofNeuroscience_videos) we sought to avoid duplication with their subjects. After much discussion and consultation, we focussed on three major thematic groupings: neuropharmacology, psychiatry/neuropsychology, and neuroimaging, with four interviewees in each. This will inevitably exclude some major contributions to modern neuroscience, but we believe that the internal coherence achieved will enhance the material’s historical, educational and out-reach potential.
The interviewees, by the very nature of our purpose, are part of the distinguished elite of international science who have made outstanding contributions to neuroscience, and increased our understanding and awareness of ways in which the nervous system functions in health and disease. These are individual interviews in which the subjects were asked to reflect on their careers and the influences that have affected the problems they have tackled and the directions they have taken. Although inevitably centred on one person, the interviews are far-ranging and include discussions of, inter alia, where relevant, collaborators, technical support staff, clinical relevance, commercial relationships and funding mechanisms. Those interested in hearing many voices in broader discussions of modern medical sciences are directed, in the first instance, towards the Witness Seminar series at http://www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/
British scientists have played major roles in the development of understanding of how drugs work on the peripheral and central nervous system. Scientists such as Sir Henry Dale, Sir Bernard Katz, Marthe Vogt, Sir John Gaddum, and Sir John Vane were instrumental in elucidating the key role that chemical neurotransmitters and neuromodulators play in drug and hormone actions in the nervous system. The contemporary scientists chosen for interview were:
Geoffrey Burnstock has provided new insights about chemical neurotransmission in the autonomic nervous system where there are few specialised synapses, and transmitter release occurs from multiple points along a nerve fibre. For 30 years Burnstock pioneered an entirely new field of neuropharmacology known as “purinergic” based on his discovery that the purine derivatives adenosine and adenosine triphosphate (ATP) act as neurotransmitters or modulators in both the peripheral and central nervous system. This field has thrived in recent years with the discovery of multiple receptor subtypes. Currently major pharmaceutical industry efforts are developing new medicines for pain, cardiovascular disease and gastrointestinal diseases based on purinergic mechanisms. His work has had a major international impact, and in 2003 he was the most highly cited scientist in pharmacology and toxicology over the previous 10 years (Anonymous (2004) Geoffrey Burnstock: most highly cited scientist. Molecular Interventions 4: 192).
Salvador Moncada also pioneered new fields. As a student of Sir John Vane he helped discover how aspirin inhibits prostaglandin biosynthesis and at the Wellcome Research Laboratories he discovered the prostaglandin derivative prostacyclin, which suppresses blood platelet aggregation and is now widely used therapeutically. Moncada is best known for his research in the 1980’s which helped identify what was then described as “endothelium derived relaxing factor” as the simple gaseous chemical nitric oxide. His influential review of the field was one of the most highly cited papers of the 1990s, with more than 6,500 citations (Moncada, S (1991) Nitric oxide – physiology, pathophysiology and pharmacology Pharmacol Rev 43:109-142). Many believed that he should have shared the 1998 Nobel Prize for the discovery of nitric oxide. He has since collaborated with industrial partners to explore the development of therapeutic products based on nitric oxide pharmacology.
Ann Silver is internationally known for her pioneering work on acetylcholine in both the peripheral and central nervous system. In the 1960’s when many physiologists were sceptical about chemical neurotransmission in the central nervous system, Silver devised methods for measuring acetylcholine’s biosynthetic enzyme choline acetylase in small tissue samples, and produced histochemical methods which allowed choline acetylase and acetylcholine’s degrading enzyme acetylcholinesterase to be visualised in tissue sections (see e.g. Silver, A (1974) The biology of cholinesterases Amsterdam, North Holland Pub Co. ). Using these techniques she mapped cholinergic systems, which helped emphasise the importance of these pathways in brain areas central to cognitive and memory functions and laid the basis for the “cholinergic hypothesis” of Alzheimer’s disease. This in turn led to the development of acetylcholinesterase inhibitors as the only treatments currently approved for Alzheimer’s disease.
Alan North represents a new generation of British neuropharmacologists who have exploited the powerful tools of molecular biology to study drug actions. He trained in the University of Aberdeen under Professor Hans Kosterlitz, who in the 1970’s with John Hughes discovered the enkephalins, endogenous morphine-like chemicals. North was among the first to study enkephalins at a cellular level using microelectrode recording and other pharmacological techniques. He worked in the USA (Chicago, Boston, Oregon) and also as senior scientist in the Geneva laboratory of Glaxo/Wellcome (now GSK). He currently uses electrophysiological and molecular biological approaches to dissect the detailed structure and function of purinergic receptors – thus continuing the field pioneered by Burnstock.
These scientists have had a major impact in the application of rigorous scientific methods to the complex fields of psychiatry and neuropsychology. Their work has helped explain the higher functions of the human brain in terms of cognition and perception, and provide insight into what goes wrong in certain neuropsychiatric illnesses.
Uta Frith is a world expert in autism spectrum disorders. She was one of the first in the 1960’s to assess the alterations in brain function that underlie autism, at a time when the general view was that autism was an emotional disorder with a psychological basis. Frith believed that a specific neural fault was responsible for the abnormal mental development, and by psychological testing she probed the cognitive deficits of autism. In the 1980’s she co-developed a theory that suggested that autistic individuals lacked a “theory of mind”. This refers to the mind’s ability to think about itself and about the minds of other people, which is essential for engaging in complex social activity. Most recently she has applied brain imaging techniques to study the brain mechanisms that underlie 'theory of mind'.
Richard Gregory was Head of the Brain and Perception Laboratory at the University of Bristol and is internationally recognized for his new insights into the mechanisms underlying visual perception i.e. those that underlie our consciousness of the external world? Perception differs from vision, as Gregory vividly illustrated by studying a 52 year-old blind person who gained vision, determining the gradual development of useful vision, and the interpretation of the message transmitted from the eye to the brain. He suggested that perception depends very largely on knowledge derived from past experience and from ancestral, sometimes even prehuman, experience. The key notion is that brain descriptions are built from the world of objects, which give perception and intelligent behaviour. Perceptions are largely based on the past, but recognizing the present is essential for survival (A brief summary of some of his work is Gregory, R. (1997) Eye and brain: the psychology of seeing O.U.P.). In Bristol Gregory also founded “The Exploratory” the first hands-on science museum in the world – a model that has since been widely copied internationally.
Michael Rutter is a leading international figure in academic psychiatry. He has worked in the USA, University of Birmingham and for much of his career at the Institute of Psychiatry in London. His research has included the epidemiology of childhood psychiatric illnesses, longitudinal studies of school effectiveness, depression and attention deficit hyperactivity disorder. He has written extensively about childhood autism, including autistic “idiots savants”. He is well known for studying the interplay of nature and nurture in the development of childhood psychiatric disturbances, and devised objective measurements of the “deprivation index” in a child’s environment, showing that this correlated with the risk of developing antisocial behaviour, drug taking or criminality.
Elizabeth Warrington is a neuropsychologist whose work centres on how neural networks enable us to see, perceive, remember and discuss things. Her research has improved the accuracy of tests to diagnose and chart degenerative brain conditions, to track recovery, and to plan rehabilitation programmes. She has been influential in testing theories about cognitive psychology and is particularly known for work on long- and short-term memory, and the recognition that these systems operate independently - in parallel rather than in series. Her classifications of memory based on knowledge (semantic memory) as opposed to events (episodic memory) helped understanding of how the brain organises its knowledge base and the categories of information that it uses, and led to the identification of a new neurological condition, semantic dementia.
The development of non-invasive methods that allow the visualization of the structure and the function of the living intact brain is one of the major achievements of the latter part of the twentieth century. British scientists played key roles in the discovery and development of the various forms of “imaging” that are now available and that have been widely adopted in many branches of medicine.
Richard Frackowiak founded the influential Wellcome Department of Imaging Neurosciences’ Functional Imaging Laboratory at the Institute of Neurology in 1994. A clinician by training he has investigated the physiology of normal and diseased human brains with positron emission tomography (PET) and subsequently magnetic resonance imaging (MRI) and he established the quantitative steady-state method for measuring human cerebral blood flow and oxygen extraction. He has investigated the pathophysiology of dementia; the evolution of acute cerebral ischemia; demonstrated that foetal cell implants for the treatment of Parkinson’s disease become functional, and has pioneered investigation of plastic mechanisms that underpin recovery after brain injury. He has shown that scanning pre-symptomatically may provide a reliable bio-marker of neurodegeneration associated with ageing.
Terry Jones is a pioneer of PET. He showed how short lived oxygen-15 labelled gases and water could be used to image and measure tissue perfusion and oxygen extraction in a number of organs. His initial experiments were carried out using planar (2 -dimensional) gamma cameras, and he subsequently worked to develop the then new detection technique of PET, which allowed the quantitative measurement of biologically relevant processes. His emphasis on non-invasiveness and the biological relevance of imaging signals led to many methodological advances at the MRC Cyclotron Unit which he headed. He was also a major collaborator with industry, influencing the design and capabilities of new generations of PET scanners.
Peter Mansfield, Nobel Laureate 2003, was responsible for some of the key advances leading to the development of MRI. He showed that when biological tissues were placed in a high magnetic field, gradients in that field reflected precise differences in the arrangement of hydrogen atoms in tissue water molecules, which could rapidly be analysed and transformed into an image, an essential step to obtain a practical diagnostic technique. His major contribution was to devise the universally used method for spatially encoding MRI signals to permit 3-dimensional imaging. Mansfield also showed that extremely rapid imaging could be achieved by very fast gradient variations (the so-called echo-planing imaging, EPI). This was a key component in developing medical scanners that became available a decade later.
Roger Ordidge was one of Mansfield’s post-doctoral students in the late 1970s. Mansfield’s EPI had been difficult to implement, and Ordidge’s initial work identified theoretical difficulties and practical modifications of the technique which formed the basis of a critical patent. He constructed the equipment required to make EPI work and presented the first undistorted images at the 1980 meeting of the British Radio Spectroscopy Group. Subsequent improvements enabled him to obtain the first reasonable images of human limbs and the first MRI movie images of a beating rabbit heart. Ater modifications have now become integral parts of many current MR machines, and he has invented equally significant and influential methods for use in MR spectroscopy.
Each interview is available as text, freely downloadable as a pdf, and also as an audio podcast and as a video via YouTube. Details and links are given on each individual page. The unedited transcripts, all the original film rushes and other correspondence have been deposited in the Wellcome Library. Scientific publications of each interviewee can be retrieved by interrogating the free PubMedCentral database at http://www.ncbi.nlm.nih.gov/pmc/
Tilli Tansey & Les Iversen: grant holders & editors
Richard Thomas: producer, interviewer & editor
Michael Sanders: camera & sound
Carole Reeves: podcast & video-clips editor
Alan Yabsley: web editor & multimedia manager