Wellcome Trust Centre for the History of Medicine

PURPOSE: A new strain of H1N1 influenza, also known as swine flu was confirmed in the UK in May 2009 and has spread to over 100 countries around the world causing the World Health Organization to declare a global flu pandemic. The primary objectives of this review are to identify the key demographic and attitudinal determinants of three types of protective behaviour during a pandemic: preventive, avoidant, and management of illness behaviours, in order to describe conceptual frameworks in which to better understand these behaviours and to inform future communications and interventions in the current outbreak of swine flu and subsequent influenza pandemics. METHODS: Web of Science and PubMed databases were searched for references to papers on severe acute respiratory syndrome, avian influenza/flu, H5N1, swine influenza/flu, H1N1, and pandemics. Forward searching of the identified references was also carried out. In addition, references were gleaned from an expert panel of the Behaviour and Communications sub-group of the UK Scientific Pandemic Influenza Advisory Group. Papers were included if they reported associations between demographic factors, attitudes, and a behavioural measure (reported, intended, or actual behaviour). RESULTS: Twenty-six papers were identified that met the study inclusion criteria. The studies were of variable quality and most lacked an explicit theoretical framework. Most were cross-sectional in design and therefore not predictive over time. The research shows that there are demographic differences in behaviour: being older, female and more educated, or non-White, is associated with a higher chance of adopting the behaviours. There is evidence that greater levels of perceived susceptibility to and perceived severity of the diseases and greater belief in the effectiveness of recommended behaviours to protect against the disease are important predictors of behaviour. There is also evidence that greater levels of state anxiety and greater trust in authorities are associated with behaviour. CONCLUSIONS: The findings from this review can be broadly explained by theories of health behaviour. However, theoretically driven prospective studies are required to further clarify the relationship between demographic factors, attitudes, and behaviour. The findings suggest that intervention studies and communication strategies should focus on particular demographic groups and on raising levels of perceived threat of the pandemic disease and belief in the effectiveness of measures designed to protect against it.

The Human Genome Project has been the first major foray of the biological and medical research communities into “big science.” In this Viewpoint, we present some of our experiences in organizing and managing such a complicated, publicly funded, international effort. We believe that many of the lessons we learned will be applicable to future large-scale projects in biology.

Recent imaging studies show that the orbitofrontal cortex (OFC) is activated during a wide variety of paradigms, including guessing tasks, simple delayed matching tasks and sentence completion. We suggest that, as with other regions of the prefrontal cortex, activity in the OFC is most likely to be observed when there is insufficient information available to determine the appropriate course of action. In these circumstances the OFC, rather than other prefrontal regions, is more likely to be activated when the problem of what to do next is best solved by taking into account the likely reward value of stimuli and responses, rather than their identity or location. We suggest that selection of stimuli on the basis of their familiarity and responses on the basis of a feeling of 'rightness' are also examples of selection on the basis of reward value. Within the OFC, the lateral regions are more likely to be involved when the action selected requires the suppression of previously rewarded responses.

Body ownership refers to the special perceptual status of one's own body, which makes bodily sensations seem unique to oneself. We studied the neural correlates of body ownership by controlling whether an external object was accepted as part of the body or not. In the rubber hand illusion (RHI), correlated visuotactile stimulation causes a fake hand to be perceived as part of one's own body. In the present study, we distinguished between the causes (i.e., multisensory stimulation) and the effect (i.e., the feeling of ownership) of the RHI. Participants watched a right or a left rubber hand being touched either synchronously or asynchronously with respect to their own unseen right hand. A quantifiable correlate of the RHI is a shift in the perceived position of the subject's hand toward the rubber hand. We used positron emission tomography to identify brain areas whose activity correlated with this proprioceptive measure of body ownership. Body ownership was related to activity in the right posterior insula and the right frontal operculum. Conversely, when the rubber hand was not attributed to the self, activity was observed in the contralateral parietal cortex, particularly the somatosensory cortex. These structures form a network that plays a fundamental role in linking current sensory stimuli to one's own body and thus also in self-consciousness.

Age-related neurodegenerative and neurochemical changes are thought to underlie decline in motor and cognitive functions, but compensatory processes in cortical and subcortical function may allow maintenance of performance level in some people. Our objective was to investigate age-related changes in the motor system of the human brain using functional MRI. Twenty six right handed volunteers were scanned whilst performing an isometric, dynamic, visually paced hand grip task, using dominant (right) and non-dominant (left) hands in separate sessions. Hand grip with visual feedback activated a network of cortical and subcortical regions known to be involved in the generation of simple motor acts. In addition, activation was seen in a putative human 'grasping circuit', involving rostral ventral premotor cortex (Brodmann area 44) and intraparietal sulcus. Within this network, a number of regions were more likely to be activated the older the subject. In particular, age-related changes in task- specific activations were demonstrated in left deep anterior central sulcus when using the dominant or non-dominant hand. Additional age-related increases were seen in caudal dorsal premotor cortex, caudal cingulate sulcus, intraparietal sulcus, insula, frontal operculum and cerebellar vermis. We have demonstrated a clear age-related effect in the neural correlates of motor performance, and furthermore suggest that these changes are non-linear. These results support the notion that an adaptable and plastic motor network is able to respond to age-related degenerative changes in order to maintain performance levels.

We investigated whether the proinflammatory T cell cytokines IL-17 and IL-22 are induced by human mycobacterial infection. Remarkably, >20% of specific cytokine-producing CD4(+) T cells in peripheral blood of healthy, mycobacteria-exposed adults expressed IL-17 or IL-22. Specific IL-17- and IL-22-producing CD4(+) T cells were distinct from each other and from Th1 cytokine-producing cells. These cells had phenotypic characteristics of long-lived central memory cells. In patients with tuberculosis disease, peripheral blood frequencies of these cells were reduced, whereas bronchoalveolar lavage fluid contained higher levels of IL-22 protein compared with healthy controls. IL-17 was not detected in this fluid, which may be due to suppression by Th1 cytokines, as PBMC IL-17 production was inhibited by IFN-gamma in vitro. However, Th1 cytokines had no effect on IL-22 production in vitro. Our results imply that the magnitude and complexity of the anti-mycobacterial immune response have historically been underestimated. IL-17- and IL-22-producing CD4(+) T cells may play important roles in the human immune response to mycobacteria.

The purpose of the Medical Termination of Pregnancy Bill, published on 15 June 1966, was to amend and clarify the law relating to termination of pregnancy by a registered medical practitioner. When David Steel, a young Liberal MP from the Scottish Borders, put this bill forward, some suggested that a Scottish politician had no need to introduce abortion reform since Scots law was already satisfactory in this regard. Certainly, abortion law in Scotland was more flexible than its English counterpart, and the number of prosecutions few. The line between criminal and non-criminal abortion was, however, just as indistinct, with great medical uncertainty in this area. On becoming law, the 1967 Abortion Act was the first piece of abortion-related legislation to cover Scotland, England and Wales collectively. None the less, for a variety of legal and moral reasons, abortion policy and practice continued to differ on either side of the Border.

In the 1830s the obstetrician Robert Lee made a series of observations on the gravid uterus that ran counter to received wisdom. This paper recounts the way in which Lee's work was handled by the premier scientific institution of the day, the Royal Society.

While he was working at the Royal Postgraduate Medical School, Ian Donald (later Regius Professor of Midwifery, University of Glasgow and a pioneer of diagnostic ultrasound) collaborated with Albert Claireaux and Robert Steiner on histological and radiological studies of hyaline membrane disease. In 1953, Donald and Steiner published thefirst radiological study of a series of cases. The success of this research stimulated Donald's interest in imaging technologies.

This is a major synthesis of the knowledge and practice of early modern English medicine in its social and cultural contexts. The book vividly maps out some central areas: remedies (and how they were made credible), notions of disease, advice on preventive medicine and on healthy living, and how surgeons worked upon the body and their understanding of what they were doing. The structures of practice and knowledge examined in the first part of the book came to be challenged in the later seventeenth century, when the 'new science' began to overturn the foundation of established knowledge. However, as the second part of the book shows, traditional medical practice was so well entrenched in English culture that much of it continued into the eighteenth century. Various changes did however occur, which set the agenda for later medical treatment and which are discussed in the final chapter

Grey matter volume in the posterior hippocampus of London taxi drivers is greater than in age-matched controls, and the size of this increase correlates positively with time spent taxi driving (E.A. Maguire et al., 2000. Proc Natl Acad Sci USA 97: 4398-4403). This change suggests that increased posterior hippocampal grey matter volume is acquired in response to increased taxi driving experience, perhaps reflecting their detailed representation of the city. However, an alternate hypothesis is that the difference in hippocampal volume is instead associated with innate navigational expertise, leading to an increased likelihood of becoming a taxi driver. To investigate this possibility, we used structural brain imaging and voxel-based morphometry (VBM) to examine a group of subjects who were not taxi drivers. Despite this group showing a wide range of navigational expertise, there was no association between expertise and posterior hippocampal grey matter volume (or, indeed, grey matter volume throughout the brain). This failure to find an association between hippocampal volume and navigational expertise thus suggests that structural differences in the human hippocampus reflect the detail and/or duration of use of the spatial representation acquired, and not innate navigational expertise per se.

The ability to identify and react to novelty within the environment is fundamental to survival. Computational models emphasize the potential role of the hippocampus in novelty detection, its unique anatomical circuitry making it ideally suited to act as a comparator between past and present experience. The hippocampus, therefore, is viewed to detect associative mismatches between what is expected based on retrieval of past experience and current sensory input. However, direct evidence that the human hippocampus performs such operations is lacking. We explored brain responses to novel sequences of objects using functional magnetic resonance imaging (fMRI), while subjects performed an incidental target detection task. Our results demonstrate that hippocampal activation was maximal when prior predictions concerning which object would appear next in a sequence were violated by sensory reality. In so doing, we establish the biological reality of associative match-mismatch computations within the human hippocampus, a process widely held to play a cardinal role in novelty detection. Our results also suggest that the hippocampus may generate predictions about how future events will unfold, and critically detect when these expectancies are violated, even when task demands do not require it. The present study also offers broader insights into the nature of essential computations carried out by the hippocampus, which may also underpin its unique contribution to episodic memory.

The time-scale of hippocampal involvement in supporting episodic memory remains a keenly debated topic, with disagreement over whether its role is temporary or permanent. Recently, there has been interest in how navigation by hippocampally-compromised patients in environments learned long ago speaks to this issue. However, identifying patients with damage that is primarily hippocampal, control subjects matched for navigation experience, and testing their in situ navigation, present substantial problems. We met these challenges by using a highly accurate and interactive virtual reality simulation of central London (UK) to assess the navigation ability of a licensed London taxi driver who had sustained bilateral hippocampal damage. In this test, patient TT and matched control taxi drivers drove a virtual London taxi along the streets they had first learned 40 years before. We found that the hippocampus is not required for general orientation in the city either in first person or survey perspectives, detailed topographical knowledge of landmarks and their spatial relationships, or even for active navigation along some routes. However, in his navigation TT was very reliant on main artery or 'A' roads, and became lost when navigation depended instead on non-A roads. We conclude that the hippocampus in humans is necessary for facilitating navigation in places learned long ago, particularly where complex large-scale spaces are concerned, and successful navigation requires access to detailed spatial representations.

interesting problem, to which I hope to return." Thus, in 1915,

En prenant comme modele d'etude l'artisan botaniste qui reflete la science populaire, l'A. concretise la relation existant entre la culture litteraire et l'experience pratique, et s'inspire de la theorie de l'habitus de Bourdieu (P.)

Previous imaging studies have used mostly perceptually abstracted, idealized, or static stimuli to show segregation of function in the cerebral cortex. We wanted to learn whether functional segregation is maintained during more natural, complex, and dynamic conditions when many features have to be processed simultaneously, and identify regions whose activity correlates with the perception of specific features. To achieve this, we used functional magnetic resonance imaging (fMRI) to measure brain activity when human observers viewed freely dynamic natural scenes (a James Bond movie). The intensity with which they perceived different features (color, faces, language, and human bodies) was assessed psychometrically in separate sessions. In all subjects different features were perceived with a high degree of independence over time. We found that the perception of each feature correlated with activity in separate, specialized areas whose activity also varied independently. We conclude that even in natural conditions, when many features have to be processed simultaneously, functional specialization is preserved. Our method thus opens a new way of brain mapping, which allows the localization of a multitude of brain areas based on a single experiment using uncontrolled, natural stimuli. Furthermore, our results show that the intensity of activity in a specialized area is linearly correlated with the intensity of its perceptual experience. This leads us to suggest that each specialized area is directly responsible for the creation of a feature-specific conscious percept (a microconsciousness). Hum. Brain Mapp. 21:75-83, 2004.

We used the technique of functional magnetic resonance imaging to chart the colour pathways in the human brain beyond V4. We asked subjects to view objects that were dressed in natural and unnatural colours as well as their achromatic counterparts and compared the activity produced in the brain by each condition. The results showed that both naturally and unnaturally coloured objects activate a pathway extending from V1 to V4, though not overlapping totally the activity produced by viewing abstract coloured Mondrian scenes. Normally coloured objects activated, in addition, more anterior parts of the fusiform gyrus, the hippocampus and the ventrolateral frontal cortex. Abnormally coloured objects, by contrast, activated the dorsolateral frontal cortex. A study of the cortical covariation produced by these activations revealed that activity in large parts of the occipital lobe covaried with each. These results, considered against the background of previous physiological and clinical studies, allow us to discern three broad cortical stages of colour processing in the human brain. The first is based on V1 and possibly V2 and is concerned mainly with registering the presence and intensity of different wavelengths, and with wavelength differencing. The second stage is based on V4 and is concerned with automatic colour constancy operations, without regard to memory, judgement and learning. The third stage, based on the inferior temporal and frontal cortex, is more concerned with object colours. The results we report, as well as the schema that we suggest, also allow us to reconcile the computational theory of Land, implemented without regard to cognitive factors such as memory and learning, and the cognitive systems of Helmholtz and Hering, which view such factors as critical in the determination of colours.

Like it or not, a big picture of the history of science is something which we cannot avoid. Big pictures are, of course, thoroughly out of fashion at the moment; those committed to specialist research find them simplistic and insufficiently complex and nuanced, while postmodernists regard them as simply impossible. But however specialist we may be in our research, however scornful of the immaturity of grand narratives, it is not so easy to escape from dependence – acknowledged or not – on a big picture. When we define our research as part of the history of science, we implicitly invoke a big picture of that history to give identity and meaning to our specialism. When we teach the history of science, even if we do not present a big picture explicitly, our students already have a big picture of that history which they bring to our classes and into which they fit whatever we say, no matter how many complications and refinements and contradictions we put before them – unless we offer them an alternative big picture.

A double-blind placebo trial was conducted to determine the effect of moderate to high loads of Trichuris trichiura (whipworm) infection on the cognitive functions of 159 school children (age 9-12 years) in Jamaica. Infected children were randomly assigned to Treatment or Placebo groups. A third group of randomly selected uninfected children were assigned to a Control for comparative purposes. The improvement in cognitive function was evaluated using a stepwise multiple linear regression, designed to control for any confounding variables. The expulsion of worms led to a significant improvement in tests of auditory short-term memory (P less than 0.02; P less than 0.01), and a highly significant improvement in the scanning and retrieval of long-term memory (P less than 0.001). After 9 weeks, treated children were no longer significantly different from an uninfected Control group in these three tests of cognitive function. The removal of T. trichiura was more important than Ascaris lumbricoides in determining this improvement. The results suggest that whipworm infection has an adverse effect on certain cognitive functions which is reversible by therapy.

Visual neglect occurs most frequently and persistently after lesions that include the right supramarginal gyrus (SMG), a part of the inferior parietal lobule. Patients with this syndrome make very few saccades to the left, and show abnormal performance on tasks in which they must covertly shift their attention to the left, suggesting that the right SMG is involved in the generation of saccades and attention shifts. Functional imaging studies of saccades and covert attention shifts in the normal brain, however, have shown weak or absent responses in both SMGs. We used event-related functional MRI to re-examine the responses to saccades and attention shifts within a single experiment, and to assess responses to left- and right-sided stimuli independently. When subjects made saccades to peripheral stimuli, the expected responses were seen in striate and prestriate cortex, the superior parietal lobules, the frontal eye fields, the supplementary motor area and the anterior insulae. In addition there was a response in the right SMG but not in the left SMG, as predicted from the clinical literature. When subjects made a covert visual assessment of the peripheral stimulus without any saccade, greater activity was seen in all of the areas in the frontoparietal network. Each area showed a bias towards contralateral stimuli, with two exceptions: the anterior insulae gave mainly ipsilateral responses, whilst the right SMG gave equal responses to right- and left-sided stimuli. These findings are discussed in the context of current theories pertaining to the clinical syndrome of neglect.