Category Archives: Physiology News

Articles pulled from our magazine, Physiology News.

Tales of a Nazi-fighting Nobel Prize winner

You probably haven’t heard of AV Hill, but if you’ve ever ridden a bike, watched the football or lifted a finger, you should thank him. The introduction real-estate buffs get of AV Hill, whose Highgate home has recently gone up for sale, certainly illustrates the universal impact of physiology! The house itself sports a Blue Plaque describing A.V. simply as ‘Physiologist,’ unveiled in 2015 in the presence of The Physiological Society. David Miller, Chair of our History & Archives Committees & Hon. Res. Fellow of the University of Glasgow, UK, wrote for Physiology News about the ceremony commemorating the ‘Nazi-fighting Nobel Prize winner.’ 

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The Blue Plaque. Photo credit: David Miller

The [unveiling of AV Hill’s Blue Plaque], sponsored by Atelier and the estate agents Savills, was attended by a number of AV’s extended family, together with dozens of other guests and dignitaries. Jonathan Ashmore, Fran Ashcroft and I represented The Society. Brief speeches were made by Greg Dyke (Chairman of The Football Association and former Director General of the BBC), Dr Julie Maxton (Executive Director, Royal Society), Prof Nicholas Humphrey (psychologist and philosopher), Stephen Wordsworth (CARA – Council for Assisting Refugee Academics) and Sir Ralph Kohn FRS (founder of the Kohn Foundation) who had proposed the Blue Plaque to honour AV’s memory.  Amongst the speeches, Nicholas Humphrey (a grandson of AV) described that regular guests at the house included many Nobel laureates, AV’s brother-in-law, the economist John Maynard Keynes, and friends as varied as Stephen Hawking and Sigmund Freud. The afterdinner conversations involved passionate debates about science and politics. ‘Every Sunday [as a child] we would have to attend a tea party at grandpa’s house and apart from entertaining some extraordinary guests, he would devise some great games for us, such as frog racing in the garden or looking through the lens of a [dissected] sheep’s eye.

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AV Hill in 1955. Photo credit: Harold Lewis

Archibald Vivian Hill (1886-1977)–known to all as ‘AV’–was the first British winner of the Nobel Prize for Physiology or Medicine (in 1922/3), honoured for his early work on heat production in muscle. He is widely regarded as a founder of the discipline of biophysics, bringing his command of mathematics and physical principles to his work in physiology.  His research work was fundamental in areas as varied as hormone-, neurotransmitter- and drug-receptor physiology, enzyme kinetics, muscle metabolism, nerve function, the mechanism of muscle mechanical function and more. One reason for the speech from Greg Dyke, representing the FA at the unveiling, is that aspects of AV’s work are also recognised as foundations of Sports Science: AV was himself a gifted athlete. He was mentor to several generations of leading physiologists. He led the physiology department at Manchester University (1920-23) and then at University College London (1923-1951). He joined The Society in 1912 and filled many major roles (Secretary 1927-33, Foreign Secretary 1934-45, served many years on the Editorial Board of The Journal of Physiology). He was elected a Fellow of The Royal Society in 1918, going on to fill several senior roles (Council from 1932-4, Biological Secretary 1935-45, Foreign Secretary 1946) and held a Royal Society Foulerton Professorship. In World War II, he served as the (independent) MP for Cambridge University, his alma mater, and on government wartime science and technical committees.

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A.V. Hill’s Nobel Prize certificate

Beyond his research, mentoring, government work, science administration and teaching, AV’s humanitarian work was exemplary. He played a leading role in setting up CARA (in 1933, with Ernest Rutherford, William Beveridge and others) and thus in the work to assist and support scientists escaping persecution in Nazi Germany. At the Blue Plaque ceremony, Sir Ralph Kohn referred to this endeavour: whilst still a child, Sir Ralph himself had escaped (together with his parents) from Leipzig in 1935. Sir Ralph reminded me that Bernard Katz had also escaped Leipzig the same year. He became a PhD student of AV and lived for some years as a lodger at AV’s home: thus there is a case for a further physiologist’s Blue Plaque at 16 Bishopswood Road.

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The unveiling of the Blue Plaque, September 2015. Credit: David Miller

Hill said and wrote much that is worthy of being quoted. As a champion of the value of unfettered original research, he observed in his Inaugural Lecture for the Jodrell Chair of Physiology at UCL in 1923 (when he succeeded Ernest Starling), ‘Medicine is continually demanding more information and help in the grievous and urgent problems which it has to solve – useful information, practical information, information which is likely to help heal … minds and bodies. It is impossible not to be moved by this appeal, and in their hearts there are few physiologists who do not hope that their work may prove, in some sense and at some good time, of service to mankind in the maintenance of health, in the prevention of disease, and in the art of science and healing. One’s heart, however, is not always one’s best guide; more useful in the end is the intellectual faith … which urges Tom, Dick and Harry in their humble way to explore each his own little strange and miraculous phenomenon, whether in the organic or inorganic world.’ [as quoted by Brian Jewell in Physiology News, Summer 2008, p12].

Stressing out the immune system

Excerpt from a Physiology News feature by Natalie Riddell, School of Biosciences and Medicine, University of Surrey, UK, @N_Riddell_Immun

Natalie Riddell LatitudeStress can get under our skin. It can influence each and every physiological system, and all of the major contemporary diseases in the UK, including cardiovascular disease, inflammatory disorders, metabolic syndrome, infectious diseases and cancer, have been associated with stress. Stress affects everyone, and levels of anxiety and mental health disorders are increasing with work-related stress now being the second most commonly reported illness in the UK workforce. Over the last four decades, research in the area of Psychoneuroimmunology (PNI) has identified stress induced immune alterations as a potential mediator between chronic stress and ill-health.

In the 1970s, Holmes and Rahe developed a scale to subjectively grade stress, [which inspired our recent survey of stress in modern Britain]. They ranked over 40 different types of life stressors, such as the death of someone close to you, changes in relationship status, work-related stress, even Christmas, and they assigned each stressor a score. The total tally of stress scores that a person had experienced in the last year could accurately predict the likeliness of future illness. This demonstrated that stress and illness were closely related. In the 1990’s, Cohen et al., eloquently demonstrated that psychological stress increased the rates of respiratory infections and clinical symptoms in participants inoculated with the common cold (Cohen, Tyrrell et al. 1993). Subsequent studies revealed that every organ, tissue and cell of the immune system could be altered by psychological stress. The involvement of immune alterations in stress induced diseases was recognised and the field of PNI was born.

Defining stress

Stress is highly subjective. Something that I may class as stressful (watching Arsenal this season), may not be stressful to other people (Tottenham supporters). So how can we define stress? In the 1960s, the psychologist Richard Lazarus introduced the concept that stress is a process consisting of three distinct steps. First, a stimulus (i.e., the stressor) has to be present and perceived. Second, the stimulus initiates a conscious or sub-conscious process whereby the stressor is evaluated in relation to available coping options. If the demands of the situation exceed the ability to cope, then the situation is perceived as stressful. Thirdly, this results in a stress response involving emotional (e.g., anxiety, embarrassment) and biological (e.g., autonomic-endocrine) adaptations. Put simply; stress is a situation or event that exceeds, or is perceived to exceed, the individual’s ability to cope, that then triggers an emotional and biological response.

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Image: Darryl Leja, NHGRI

The stress adaptation response and immunity

The biological adaptation to stress is activation of the sympathetic nervous system. The same biological response is induced whether the stressor is psychological, such as anxiety or embarrassment, or physical, for example, exercise, trauma or fever. In the case of psychological stress, the individual perceives an inability to cope and this results in the amygdala, a part of the brain that contributes to emotion processing, sending a distress signal to the nearby hypothalamus. The hypothalamus can communicate with the rest of the body via either of two arms of the involuntary nervous system: “rest and digest” (parasympathetic) or “fight or flight” (sympathetic). During stress, this “fight or flight” system is triggered and various physiological changes occur, including an increase in heart rate, respiration and energy production. This promotes survival of the individual by maximising physical capacity to cope with the stressor.

During stress, signalling from the “fight or flight” sympathetic nervous system causes the adrenal gland to secrete the two main stress hormones; adrenaline and cortisol. These hormones can spread and act throughout the body via the circulation. The sympathetic nervous system innervates all of the organs of the immune system, and individual immune cells can directly respond to changes in circulating levels of adrenaline and cortisol. Stress is therefore able to alter every process of immunity, from the initial development of stem cells into early immune cells in the bone marrow, through to the triggering of immune responses to specific antigens in the lymph nodes. Even when in the peripheral tissues, such as the skin or gut, where mature immune cells are most likely to encounter infections, the cells can be regulated by stress hormones. It is therefore unsurprising that the immune system is a modifiable target of stress.

Read Natalie’s full article in our magazine Physiology News to find out how acute stress changes the composition of the blood, and why our Stone Age brain can’t cope with the constant stress of modern life. Her feature takes a more detailed dive into the effects of stress on the immune system’s day-night (circadian) rhythm, and points to stress management as an easy and affordable way to make us healthier.

Reference

Cohen, S., D. A. Tyrrell and A. P. Smith (1993). Negative life events, perceived stress, negative affect, and susceptibility to the common cold. J Pers Soc Psychol 64(1): 131-140.

 

 

The open science movement: Revolution is underway

By Keith Siew, @keithsiew, University of Cambridge

‘Information is power. But like all power, there are those who want to keep it for themselves. The world’s entire scientific and cultural heritage, published over centuries in books and journals, is increasingly being digitized and locked up by a handful of private corporations.’ Aaron Swartz, in Guerilla Open Access Manifesto, 2008

The world’s first academic science journal, Philosophical Transactions, was published by the Royal Society in 1665. At last count there were some 11,365 science journals spanning over 234 disciplines by 2015, and yet the primary model of scientific publishing remained largely unchanged throughout the centuries.

As a fresh-faced, naïve PhD student, I recall the horror I felt upon learning that my hard work would be at the mercy of a veiled, political peer-review process, that I’d be left with little option but to sign away my rights to publishers, and too often forced to choose between burning a hole in my wallet or forgoing access to a potentially critical paper!

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Derivative of ‘Open Access Explained!’ [https://www.youtube.com/watch?v=L5rVH1KGBCY] by ©PhDComics.com Licensed under CC BY.

The open science movement offers an alternative to this unjust system. In its purest form, the movement advocates for making scientific research and its dissemination an entirely transparent process, freely accessible to all levels of society.

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Read more here in Physiology News about some of the more radical elements of the movement, existing open science opportunities and the reasons behind life scientists’ relatively slow adoption of open science. The full article also discusses the ongoing struggle for open access, the growing angst towards closed peer review and fundamental shifts on the horizon in both the ways we communicate (i.e. preprints) and carry out science (i.e. open data and open notebook science).

The dangers of careless press releases

by Simon Cork, Imperial College London, @simon_c_c

This article originally appeared in Physiology News

Simon Cork

You open the morning paper and are excited to find an article about a newly published study in your area of interest. You start reading it and quickly realise that the journalist has completely taken the press release out of context. What was originally some preliminary cell culture work has turned into a front page splash solving an age-old problem or heralding a new cure. Sound familiar?

We live in a world of 24-hour rolling news coverage. The necessity to write punchy news headlines and be the first to break stories has never been greater. Because of this, it’s very easy for journalists to take press releases out of their original scientific context, and ‘sex’ them up in a way that sells. This is particularly the case for my own area of research, obesity.

The world is suffering from an obesity epidemic especially (but not exclusively) in the Western world. Reports suggest around two-thirds of people are dieting at any one time, and most of these diets don’t work. This is why stories about miracle weight loss cures and therapies are cat nip to journalists and readers alike.

Frustrated by the misrepresentation of obesity in the press, I decided to sign up to the Science Media Centre (SMC), not knowing it would lead to my television debut.

The remit of the SMC is to provide journalists with expert quotes on scientific studies that are likely to garner media attention. In the world of obesity and diabetes, this usually involves studies showing that eating too much of X will lead to diabetes, or that cutting Y out of your diet reduces body weight.

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I recently commented on a new study, which had followed approximately 20,000 children over a 10-year period, some born via caesarean and some born naturally, and found that those who were born via caesarean were more likely to be obese in later life. I was asked to comment whether or not the conclusions of the study were sound, and offer a possible explanation for the findings. In fact, this study adds to other literature supporting this relationship, and the most likely cause is exposure to different microbes when born naturally versus via caesarean, although the link hasn’t fully been proven.

Since the study used a large cohort, the results were more statistically significant. However, since it was an observational study there isn’t a causative link.

My comments were picked up by a number of news agencies, including The Guardian, Daily Mail and the BBC News website. Nerve-rackingly, I even got a call from the producer of BBC Radio 4’s Today Programme, who was interested in picking this piece up and wondered if I would pop into the studio the next morning. This was swiftly followed by Sky News, Jeremy Vine and BBC News.

Now all of this was a far cry from the ELISA that I was planning on carrying out that day, but was an interesting insight into the angle journalists take on scientific stories. Having received the call asking if I’d like to go on the Today programme at 11 pm the previous evening, I spent a number of hours doing a comprehensive PubMed search of all the most recent meta-analysis studies investigating caesarean births and obesity risk. Turns out all they’re really interested in is why. If the Brexit debate has taught us anything, it’s that the public switch-off at the sight of a percentage symbol or talk of numbers. What people want to know is why and how it affects them. So my interviews mostly revolved around why caesarean births seem to increase the risk of obesity and whether there is anything we can do to mitigate the risk. That and trying to politely convince a caller to the Jeremy Vine Show that her child’s obesity was probably more the result of her confessed feeding of copious amounts of chocolate to him, rather than his method of birth.

If, like me, you find yourself at odds with journalistic reporting of science stories, I would urge you to join the database at the Science Media Centre. You’re not guaranteed to get TV time, but you might get your name in the paper. Just make sure that you at least know enough about whatever it is you’re commenting on to make it through a 30-minute conversation with Jeremy Vine and John Humphrys!

Mindfulness matters to physiologists

Excerpt from a Physiology News feature by Lee de-Wit, @leedewitInstitute of Continuing Education, University of Cambridge, UK & Psychology and Language Sciences, University College London, UK

Our minds are often busy planning the future or thinking about the past. Mindfulness involves becoming more aware of what is happening right now. That might involve becoming more aware of feelings in your body. It might involve becoming aware of the sensations of your breath. It might simply involve becoming more conscious of the fact one’s mind is thinking about the future or the past.

This practise of mindfulness has proved effective in treating certain clinical conditions, and can influence behaviour on a range of tasks. In parallel to this, there is also a large body of evidence showing that mindfulness has a range of measurable outcomes on both neural activity and even neural structures. Research on mindfulness not only helps us to understand this practise per se, but has also increased our understanding of plasticity and localization of functions within the adult human brain. […]

Secular mindfulness without Buddhism

Mindfulness is a relatively recent approach that extracts some of the core teachings from Buddhism and reformulates them as a secular practise to help patients recovering from chronic pain or to deal with stress. This approach was first pioneered by Jon Kabat-Zinn at the Massachusetts University Hospital. […] Jon Kabat-Zinn developed a secular program of mindfulness training that focused on developing some of the key skills involved in Buddhist meditation and awareness training. He formalised this approach as an 8-week Mindfulness-Based Stress Reduction (MBSR) course. This model was then further developed by Mark Williams and colleagues at Oxford, who developed the 8-week Mindfulness-Based Cognitive Therapy (MBCT) course. This 8-week MBCT course was developed over 10 years ago, as a treatment to prevent the relapse of patients who have suffered multiple episodes of depression. Two recent meta-analyses have provided evidence that MBCT offers an effective treatment in preventing relapse for patients who have had depression (Kuyken et al., 2016), and in the treatment of mood and anxiety problems in clinical populations (Hofmann et al., 2010).

At its most simple, mindfulness is about becoming more aware of one’s experience of feelings, emotions, thoughts and mental and bodily state in the present moment. […] When you first start, you’ll realise just how much the mind wanders off when you try and focus on a simple aspect of your present moment experience. Critically however, mindfulness doesn’t mean one starts judging oneself for having a mind that wanders off, rather one seeks to acknowledge one’s wandering mind and patiently learn the skill of bringing it back to the present moment.

To really develop this practise, it can be useful to have extended periods of meditation where you focus on areas of your body, or the sensation of your breathing in a formal meditation posture. Mindfulness isn’t just something you do sitting on a mat on the floor however. You can mindfully eat your dinner, mindfully draw a picture, mindfully read an article about mindfulness.

How meditation can change your brain

I sometimes think that one of the most important and under-communicated (to the general public) findings of the last 50 years is just how remarkably similar our brains are. More recently however, there has been an increasing recognition that our brains sometimes differ in ways that have interesting functional and theoretical consequences. […]

In 2004, meditation joined the list of factors that were associated with changes in the brain’s structure. Building on work from the previous year, showing that the brains of experienced meditators had higher levels of coherent activity (Lutz et al., 2004), researchers at Harvard, Yale, MIT and Massachusetts General Hospital found that there were also large-scale differences in the structure of certain areas of the brains of experienced meditators (Lazar et al., 2005). These changes were not random, they were found in areas of the brain that could be logically interpreted given the skills practised in meditation. In particular, one of the areas that was larger in experienced meditators was the insula. This is an area of the brain that we know is important in interoception, the perception (visceral, not visual) of our own body. Given that mindfulness often involves the development of a greater awareness of one’s present moment bodily experience, it seems logical that the area of the brain that seems to be involved in that would be one of the areas to be influenced by long-term mindfulness practise.

Read the full article in Physiology News.

References:

Hofmann SG, Sawyer AT, Witt AA, Oh D (2010). The effect of mindfulness-based therapy on anxiety and depression: a meta-analytic review. J Consult Clin Psychol 78, 169-183 doi:10.1037/a0018555

Kuyken W, et al. (2016). Efficacy of mindfulness-based cognitive therapy in prevention of depressive relapse: an individual patient data meta-analysis from randomized trials. JAMA Psychiatry 73, 565–574 doi:10.1001/jamapsychiatry.2016.0076

Lazar SW, et al. (2005). Meditation experience is associated with increased cortical thickness. Neuroreport 16, 1893–1897.

Lutz A, Greischar LL, Rawlings NB, Ricard M, Davidson RJ (2004). Long-term meditators self-induce high-amplitude gamma synchrony during mental practice. Proc Natl Acad Sci USA 101, 16369–16373 doi:10.1073/pnas.0407401101

 

The science of laughter

Excerpt from a Physiology News feature by Sophie Scott, Institute of Cognitive Neuroscience, UCL, London, UK, @sophiescott

Human vocal communication is primarily studied in the form of human speech – a remarkable talent and evolutionarily highly specialised motor act that involves high levels of precise motor control over the articulators and over breathing. However, we do not solely communicate vocally with speech: when we are in the grips of more extreme emotion, we frequently start to produce non-verbal vocalisations, often in a relatively involuntary fashion. This includes vocal behaviours such as screaming, sobbing and laughing.

The physiology of laughter

I first started working with these kinds of vocal acts in the 1990s, when I was collaborating with colleagues who were studying neuropsychological patients who had specific deficits in the perception of emotions. […] The characteristic ‘ha ha ha’ sound is driven by the involvement of the intercostal muscles: normally used smoothly to pull air into and out of the lungs during metabolic breathing, and to produce a constant sub glottal pressure, to vibrate the vocal folds during speech and song, the intercostal muscles and diaphragm start to produce large contractions during laughter, each of which contributes to a single ‘ha’ burst, as air is forcibly exhaled (NB it is also possible for these contractions to be largely acoustically silent).

Laughter is more like a different way of breathing than it is a different way of speaking.

If these contractions start to run into one another, then the laughter can start to sound more like silent wheezing. From this perspective, laughter is more like a different way of breathing than it is a different way of speaking. Another physiological change is a constricting of the pharynx, meaning that some sounds are made during laughter as a consequence of this constriction (e.g. glottal whistles). The intercostal contractions made during laughter are much greater than those used to control breathing during speech production, and this also affects the noises made during laughter, with very high pitched noises being produced, which would be difficult or unlikely to produce under voluntary control. My laugh can be very high pitched, and I can hit pitches when laughing that I would be unable to produce while singing.

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Rats don’t laugh at jokes, and neither do we

Laughter is an interesting human behaviour to study, even in isolation: it appears to be a universal emotional expression, however claims that only humans laugh have transpired to be incorrect. Laughter has been reported in gorillas, chimpanzees and orangutans, where it can look and sound quite similar to human laughter. However, we are unable to hear many of the noises made by other animals, meaning that there may be many more examples out there: it’s also probably true that no one is out there looking for laughter. Certainly a vocal behaviour which is contextually identical to laughter has been described in rats: rats make a distinctive chirping sound when they are playing together, and when they are being tickled, and when they are anticipating being tickled. Indeed, at its heart, Panksepp has argued, laughter can be considered an invitation to play.

We are 30 times more likely to laugh with someone else than if we are on our own.

As all mammals play when juveniles, and some continue to play through into adulthood (dogs, humans, otters), this argument would suggest that laughter is likely to be widely found across mammals. This role in play seems counterintuitive to humans adults, who strongly associate laughter with humour, jokes and comedy, however Robert Provine has shown that even in humans, laughter is primarily a social behaviour, which is strongly primed by other people – we are 30 times more likely to laugh with someone else than if we are on our own.

We are laughing to show that we like people, understand them, agree with them.

What this means in practice is that we are laughing mostly when we are in the company of others – and we are still not laughing at jokes. Indeed we laugh mostly at comments and statements and although we report laughing because we are amused, we are laughing to show that we like people, understand them, agree with them, are affiliated to them as much as if not more than because something is ‘funny’. Within conversations, laughter is very tightly co-ordinated, with members of a conversation laughing together at the end of sentences, even if the conversation is in sign language rather than a vocal language, and in theory people could be laughing all the way through if they wished to. We also laugh much more often than we report: all studies that have compared actual to reported laughter find that people laugh more than they say they do. Indeed, laughter is probably the most commonly encountered non-verbal vocal emotional expression, occurring at around 7 times per 10 minutes of conversation. Provine has also noted that laughter is highly behaviourally contagious, and people will frequently laugh simply because others are laughing. Like other such contagious behaviours, such as yawning, contagious laughter is modified by social factors, and people are much more likely to catch a laugh (or a yawn) from someone they know than from a stranger.

Read the full article in Physiology News.

Watch Sophie’s TED talk, Why we laugh.